Standards for the use of enteral nutrition in patients with diabetes or stress hyperglycaemia: expert consensus
Abstract
Background: Hyperglycaemia that occurs during enteral nutrition (EN) should be prevented and treated appropriately since it can have important consequences for morbidity and mortality. However, there are few quality studies in the literature regarding the management of EN in this situation. The objective of this project was to attempt to respond, through a panel of experts, to those clinical problems regarding EN in patients with diabetes or stress hyperglycaemia (hereinafter referred to only as hyperglycaemia) for which we do not have conclusive scientific evidence; (2) Methods: The RAND/UCLA Appropriateness Method, a modified Delphi panel method, was applied. A panel of experts made up of 10 clinical nutrition specialists was formed, and they scored on the appropriateness of EN in hyperglycaemia, doing so in two rounds. A total of 2992 clinical scenarios were examined, which were stratified into five chapters: type of formula used, method of administration, infusion site, treatment of diabetes, and gastrointestinal complications. (3) Results: consensus was detected in 36.4% of the clinical scenarios presented, of which 23.7% were deemed appropriate scenarios, while 12.7% were deemed inappropriate. The remaining 63.6% of the scenarios were classified as uncertain; (4) Conclusions: The recommendations extracted will be useful for improving the clinical management of these patients. However, there are still many uncertain scenarios reflecting that the criteria for the management of EN in hyperglycaemia are not completely standardised. More studies are required to provide quality recommendations in this area.
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Citation: Rebollo-Pérez, M.I.; Florencio Ojeda, L.; García-Luna, P.P.; Irles Rocamora, J.A.; Olveira, G.; Lacalle Remigio, J.R.; Arraiza Irigoyen, C.; Calañas Continente, A.; Campos Martín, C.; Fernández Soto, M.L.; et al. Standards for the Use of Enteral Nutrition in Patients with Diabetes or Stress Hyperglycaemia: Expert Consensus. Nutrients 2023,15, 4976. https://doi.org/10.3390/ nu15234976 Academic Editor: Iwona Rudkowska Received: 15 September 2023 Revised: 24 November 2023 Accepted: 28 November 2023 Published: 30 November 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). nutrients Article Standards for the Use of Enteral Nutrition in Patients with Diabetes or Stress Hyperglycaemia: Expert Consensus María I. Rebollo-Pérez 1,†, Luna Florencio Ojeda 1,† , Pedro P. García-Luna 2,3 , JoséA. Irles Rocamora 3,4 , Gabriel Olveira 5,6,7,8,* , Juan Ramón Lacalle Remigio 3,*, Carmen Arraiza Irigoyen 9, Alfonso Calañas Continente 10, Cristina Campos Martín11, María Luisa Fernández Soto 12,13, JoséManuel García Almeida 5,14 , María Laínez López 1, Concepción Losada Morell 15, Luis Miguel Luengo Pérez 16 , Teodosia Muñoz de Escalona Martínez 17, JoséL. Pereira-Cunill 2,3 , Francisco J. Vílchez-López 18 and Juana M. Rabat-Restrepo 3,11 1Endocrinology and Nutrition Clinical Management Unit, University Hospital Juan Ramón Jiménez, 21005 Huelva, Spain; [email protected] (M.I.R.-P.); [email protected] (L.F.O.); [email protected] (M.L.L.) 2Regional Andalusian Health Service, Service of Endocrinology and Nutrition, University Hospitals Virgen del Rocío, 41013 Seville, Spain; [email protected] (P.P.G.-L.); jper[email protected] (J.L.P.-C.) 3Faculty of Medicine, University of Seville, 41009 Seville, Spain; [email protected] (J.A.I.R.); [email protected] (J.M.R.-R.) 4Endocrinology and Nutrition Clinical Management Unit, University Hospital Valme, 41014 Seville, Spain 5Biomedical Research Institute of Málaga (IBIMA), 29010 Málaga, Spain; jgar[email protected] 6 Endocrinology and Nutrition Clinical Management Unit, Regional University Hospital of Málaga/University of Málaga, 29010 Málaga, Spain 7Biomedical Network Research Centre for Diabetes and Associated Metabolic Diseases (CIBERDEM) (CB07/08/0019), Health institute Carlos III, 28029 Madrid, Spain 8Medicine and Dermatology Department, Faculty of Medicine, University of Málaga, 29010 Málaga, Spain 9University Hospital of Jaén, 23007 Jaén, Spain; [email protected] 10 Endocrinology and Nutrition Clinical Management Unit, University Hospital Reina Sofia, 14004 Córdoba, Spain; [email protected] 11 Endocrinology and Nutrition Clinical Management Unit, University Hospital Virgen Macarena, 41009 Seville, Spain 12 Endocrinology and Nutrition Clinical Management Unit, University Hospital San Cecilio, 18012 Granada, Spain; [email protected] 13 Biosanitary Institute of Granada, Medicine Department, Faculty of Medicine of Granada, University of Granada, 18010 Granada, Spain 14 Endocrinology and Nutrition Clinical Management Unit, University Hospital Virgen de la Victoria, 29010 Málaga, Spain 15 Endocrinology and Nutrition Clinical Management Unit, Internal Medicine Clinical Management Unit, Hospital Infanta Margarita, 14940 Cabra, Córdoba, Spain; [email protected] 16 University Hospital of Badajoz, 06080 Badajoz, Spain; [email protected] 17 Endocrinology and Nutrition Clinical Management Unit, University Hospital Torrecárdenas, 04009 Almeria, Spain; [email protected] 18 Endocrinology and Nutrition Clinical Management Unit, Biomedical Research and Innovation Institute of Cádiz, University Hospital Puerta del Mar, 11009 Cádiz, Spain; [email protected] *Correspondence: [email protected] (G.O.); [email protected] (J.R.L.R.) †These authors contributed equally to this work. Abstract: (1) Background: Hyperglycaemia that occurs during enteral nutrition (EN) should be prevented and treated appropriately since it can have important consequences for morbidity and mortality. However, there are few quality studies in the literature regarding the management of EN in this situation. The objective of this project was to attempt to respond, through a panel of experts, to those clinical problems regarding EN in patients with diabetes or stress hyperglycaemia (hereinafter referred to only as hyperglycaemia) for which we do not have conclusive scientific evidence; (2) Methods: The RAND/UCLA Appropriateness Method, a modified Delphi panel method, was applied. A panel of experts made up of 10 clinical nutrition specialists was formed, and they scored on the appropriateness of EN in hyperglycaemia, doing so in two rounds. A total of 2992 clinical scenarios were examined, which were stratified into five chapters: type of formula used, method of administration, infusion site, treatment of diabetes, and gastrointestinal complications. Nutrients 2023,15, 4976. https://doi.org/10.3390/nu15234976 https://www.mdpi.com/journal/nutrients
Nutrients 2023,15, 4976 2 of 26 (3) Results: consensus was detected in 36.4% of the clinical scenarios presented, of which 23.7% were deemed appropriate scenarios, while 12.7% were deemed inappropriate. The remaining 63.6% of the scenarios were classified as uncertain; (4) Conclusions: The recommendations extracted will be useful for improving the clinical management of these patients. However, there are still many uncertain scenarios reflecting that the criteria for the management of EN in hyperglycaemia are not completely standardised. More studies are required to provide quality recommendations in this area. Keywords: enteral nutrition; diabetes; stress hyperglycaemia; expert consensus; Delphi 1. Introduction Medical nutrition therapy (enteral and parenteral) is one of the most recognised causes of hyperglycaemia in the hospital setting, along with other factors such as stress due to illness or the use of hyperglycaemic drugs. The degree of hyperglycaemia is related to the severity of the disease and is an important prognostic marker [1,2]. Expert recommendations recognise that there are few studies that evaluate the prevalence of hyperglycaemia in patients receiving EN, with reported values ranging from 30% to 47% and with half of the patients lacking a previous diagnosis of diabetes mellitus (DM) [ 3 , 4 ]. Abuin-Fernandez (2020) estimated the prevalence of DM to be 31.8% for patients receiving home enteral nutrition (HEN) through a feeding tube [ 5 ]. For patients receiving medical nutrition therapy, hyperglycaemia has been associated with increased morbidity and mortality [6,7]. At the time this project began, the evidence from clinical trials on the management of hyperglycaemia in patients receiving EN was scant, coming predominantly from studies conducted on specific EN formulas [8,9]. Given the lack of evidence, professionals must resort to other sources to guide their clinical practice, including consensus statements that collect and systematise expert opinions. The objective of this project was to identify and respond to those problems for which we do not have scientific evidence in the use of EN for patients with hyperglycaemia, through an expert consensus, using the RAND/UCLA Appropriateness Method. 2. Materials and Methods The consensus method—the RAND/UCLA Appropriateness Method (RAM) [ 10 ]— was used to establish criteria for the appropriate use of medical treatments. Decisions about the design of the project were the responsibility of the steering group, which consisted of professionals with experience in clinical nutrition (M.I.-R., J.M.-R., P.P.-G.L., J.A.-I., and G.-O.), with methodological support (J.R.-L.R.). The phases and tasks carried out to develop the panel were completed in accordance with what is indicated in the RAM [11] manual, and they are summarised below: 2.1. Literature Review A bibliographic search of articles on the management of EN in hyperglycaemia was carried out. The search was performed in PubMed, filtering for clinical trials, meta-analyses, systematic reviews, and expert recommendations, with the keywords enteral nutrition AND diabetes or enteral nutrition AND hyperglycaemia. The steering group selected publications that, in their opinion, could serve as support for the panel discussions. 2.2. Preparation of the Clinical Scenarios or Indicatios A questionnaire was prepared (Appendix A), and it comprised 32 open questions about nutrient intake targets, administration regimens, the use of specific EN formulas for hyperglycaemia or other concomitant specific pathologies, the treatment of hyperglycaemia in patients with EN and the management of complications of EN. The questionnaire
Nutrients 2023,15, 4976 3 of 26 was sent by email to 11 specialists in clinical nutrition from hospitals in Andalusia and Extremadura (panel members). The responses were used to identify the most relevant clinical variables for decision-making on the use of EN in hyperglycaemia (collected in Appendix B). The clinical scenarios were created by combining the categories of those variables (Figures 1–3). The steering group reviewed all the scenarios and eliminated those that they considered not to occur in clinical practice. Finally, a total of 2992 clinical scenarios were included. Figure 4shows the appearance of some of the scenarios, as they were presented to the panel members. Nutrients2023,15,xFORPEERREVIEW3of27 2.2.PreparationoftheClinicalScenariosorIndicatios Aquestionnairewasprepared(AppendixA),anditcomprised32openquestions aboutnutrientintaketargets,administrationregimens,theuseofspecificENformulasfor hyperglycaemiaorotherconcomitantspecificpathologies,thetreatmentofhyperglycaemiainpatientswithENandthemanagementofcomplicationsofEN.Thequestionnaire wassentbyemailto11specialistsinclinicalnutritionfromhospitalsinAndalusiaand Extremadura(panelmembers).Theresponseswereusedtoidentifythemostrelevant clinicalvariablesfordecision-makingontheuseofENinhyperglycaemia(collectedin AppendixB). Theclinicalscenarioswerecreatedbycombiningthecategoriesofthosevariables (Figures1–3).Thesteeringgroupreviewedallthescenariosandeliminatedthosethatthey considerednottooccurinclinicalpractice.Finally,atotalof2992clinicalscenarioswere included.Figure4showstheappearanceofsomeofthescenarios,astheywerepresented tothepanelmembers. Figure1.OrganisationchartofthevariablesusedtobuildtheclinicalscenariosforChapters1,2 and3.BMI:bodymassindex;PU:pressureulcer;HbA1c:glycosylatedhaemoglobin. Figure 1. Organisation chart of the variables used to build the clinical scenarios for Chapters 1, 2 and 3. BMI: body mass index; PU: pressure ulcer; HbA1c: glycosylated haemoglobin. Nutrients2023,15,xFORPEERREVIEW3of27 2.2.PreparationoftheClinicalScenariosorIndicatios Aquestionnairewasprepared(AppendixA),anditcomprised32openquestions aboutnutrientintaketargets,administrationregimens,theuseofspecificENformulasfor hyperglycaemiaorotherconcomitantspecificpathologies,thetreatmentofhyperglycaemiainpatientswithENandthemanagementofcomplicationsofEN.Thequestionnaire wassentbyemailto11specialistsinclinicalnutritionfromhospitalsinAndalusiaand Extremadura(panelmembers).Theresponseswereusedtoidentifythemostrelevant clinicalvariablesfordecision-makingontheuseofENinhyperglycaemia(collectedin AppendixB). Theclinicalscenarioswerecreatedbycombiningthecategoriesofthosevariables (Figures1–3).Thesteeringgroupreviewedallthescenariosandeliminatedthosethatthey considerednottooccurinclinicalpractice.Finally,atotalof2992clinicalscenarioswere included.Figure4showstheappearanceofsomeofthescenarios,astheywerepresented tothepanelmembers. Figure1.OrganisationchartofthevariablesusedtobuildtheclinicalscenariosforChapters1,2 and3.BMI:bodymassindex;PU:pressureulcer;HbA1c:glycosylatedhaemoglobin. Figure 2. Flowchart of the variables used to build the clinical scenarios for Chapter 4. BMI: body mass index; HbA1c: glycosylated haemoglobin; EN: enteral nutrition.
Nutrients 2023,15, 4976 4 of 26 Nutrients2023,15,xFORPEERREVIEW4of27 Figure2.FlowchartofthevariablesusedtobuildtheclinicalscenariosforChapter4.BMI:body massindex;HbA1c:glycosylatedhaemoglobin;EN:enteralnutrition. Figure3.FlowchartofthevariablesusedtobuildtheclinicalscenariosforChapter5.BMI:body massindex;PU:pressureulcer;HbA1c:glycosylatedhaemoglobin;EN:enteralnutrition. Figure4.Fragmentofoneofthespreadsheetswiththescenariosandscalesusedtorateappropriateness. Thescenariosweregroupedintochaptersaccordingtotheclinicalvariableschosen toassessaspecificaspectofENuse.Forthisreason,thenumberofscenariosisdifferent ineachchapter. Thecontentsofthechaptersarelistedbelow: Chapter1:typesofformulasused(768clinicalscenarios); Figure 3. Flowchart of the variables used to build the clinical scenarios for Chapter 5. BMI: body mass index; PU: pressure ulcer; HbA1c: glycosylated haemoglobin; EN: enteral nutrition. Nutrients2023,15,xFORPEERREVIEW4of27 Figure2.FlowchartofthevariablesusedtobuildtheclinicalscenariosforChapter4.BMI:body massindex;HbA1c:glycosylatedhaemoglobin;EN:enteralnutrition. Figure3.FlowchartofthevariablesusedtobuildtheclinicalscenariosforChapter5.BMI:body massindex;PU:pressureulcer;HbA1c:glycosylatedhaemoglobin;EN:enteralnutrition. Figure4.Fragmentofoneofthespreadsheetswiththescenariosandscalesusedtorateappropriateness. Thescenariosweregroupedintochaptersaccordingtotheclinicalvariableschosen toassessaspecificaspectofENuse.Forthisreason,thenumberofscenariosisdifferent ineachchapter. Thecontentsofthechaptersarelistedbelow: Chapter1:typesofformulasused(768clinicalscenarios); Figure 4. Fragment of one of the spreadsheets with the scenarios and scales used to rate appropriateness. The scenarios were grouped into chapters according to the clinical variables chosen to assess a specific aspect of EN use. For this reason, the number of scenarios is different in each chapter. The contents of the chapters are listed below: •Chapter 1: types of formulas used (768 clinical scenarios); •Chapter 2: method of administration (288 clinical scenarios); •Chapter 3: infusion site (192 clinical scenarios); •Chapter 4: treatment of diabetes (1104 clinical scenarios);
Nutrients 2023,15, 4976 5 of 26 •Chapter 5: management of complications (640 clinical scenarios). 2.3. Selection of the Members of the Panel of Experts The 10 members of the panel were selected from the nutrition specialists who were working in public hospitals in Andalusia and Extremadura, and all of them had more than 10 years of experience and spent at least 80% of their working time in clinical nutrition. 2.4. Rounds to Score Indications The panellists scored each scenario anonymously in two rounds and at different times. In the second round, the panellists were provided with information about the responses of the other panellists in the first round, along with the panellist’s own score. This information is explained below. 2.4.1. Definition of Appropriateness The panellists expressed their opinions in each scenario by scoring on a nine-point Likert-type scale that ranged from one (very inappropriate) to nine (very appropriate). The scores reflected how appropriate, according to the panellist, the use of the procedure was in that scenario. A procedure was considered appropriate if, in using the procedure, the potential benefits clearly outweighed the negative consequences that could occur. Conversely, the use of a procedure was inappropriate if the expected risks clearly outweighed the expected potential benefits. The benefits and risks were related to people’s health, regardless of financial or organisational costs. 2.4.2. First Round All panellists received the same documentation by email at the same time, and it included: the references selected after reviewing the literature on EN and hyperglycaemia; the definitions of the terms used in the list of indications (Appendix C); instructions for the scoring process; and the spreadsheet files containing the scenarios. In addition, they were given a list of the definitions of the variables used to create the scenarios. 2.4.3. Second Round Once all the scores from the first round were received and processed by us, a new document containing the scenarios was prepared, together with the results of the first round. This document was personalised for each panellist because the scores they had assigned in the first round were included. The key to interpreting the outputs and information that were presented to each panellist are shown in Figure 5. Colour coding was used to reflect whether an indication was rated as inappropriate (yellow), uncertain (pink) or appropriate (green). Nutrients2023,15,xFORPEERREVIEW6of27 Figure5.Theappearanceofascenariowiththeresultsthatwerepresentedtoapanellistindicating theelementsthatwererepresented. Then,thepanellistswereinvitedtoaface-to-facemeetinginwhicheachpanellist receivedtheaforementioneddocuments.Duringthesession,thepanellistsdiscussedthe resultsofthefirstround,anonymouslyscoringthesamescenariosagain.Twomoderators ledthediscussions;theirroleswerelimitedtocontrollingthedebatesandtheydidnot voteorinfluencetheopinionsofthepanelmembers. Asaresultofthediscussions,thepanellistsproposedthatthescenariosforChapters 4and5shouldbemodified.Thesemodifiedscenarioswerevotedonintwonewrounds, bothofwhichwerelimitedtothosechapters. 2.5.StatisticalCriteriaforConsensus Aftereachround,thescoresofthepanellistswerestatisticallyprocessed.Asaresult, ineachscenario,thedegreeofagreementbetweenthepanellistsandtheiropinionsonthe useoftheprocedurewasmeasured. Itwasdefinedthattherewasagreementwithinthepanelifthescoresofallthepanellists,afterexcludingthehighestandthelowest,werewithinthesamethree-pointinterval.Itwasdefinedthattherewasdisagreementiffourormorepanellistsvotedinthe intervalfromonetothreeandanotherfourormorevotedintheintervalfromsevento nine.Thosescenariosthatwerenotclassifiedasagreementordisagreementwereconsidereduncertain. Finally,eachindicationwasclassifiedasoneofthefollowingcategoriesaccordingto thedegreeofagreementandthemedianofthescores: Appropriateindicationifthemedianwasintheintervalfromseventonine,without disagreement. Uncertainindicationifthemedianwasintheintervalfromfourtosix,orwhenthere wasdisagreementamongthepanellists,independentofthemedian; Inappropriateindicationifthemedianwasintheintervalofonetothree,without disagreement. 3.Results Tables1–5summarisethemainresultsofthepanel,specificallythoseclinicalscenariosinwhichtherewasconsensusonbothanappropriateandinappropriateindication, withsomecontributionsresultingfromthediscussionofthepanelmembers. Figure 5. The appearance of a scenario with the results that were presented to a panellist indicating the elements that were represented.
Nutrients 2023,15, 4976 6 of 26 Then, the panellists were invited to a face-to-face meeting in which each panellist received the aforementioned documents. During the session, the panellists discussed the results of the first round, anonymously scoring the same scenarios again. Two moderators led the discussions; their roles were limited to controlling the debates and they did not vote or influence the opinions of the panel members. As a result of the discussions, the panellists proposed that the scenarios for Chapters 4 and 5 should be modified. These modified scenarios were voted on in two new rounds, both of which were limited to those chapters. 2.5. Statistical Criteria for Consensus After each round, the scores of the panellists were statistically processed. As a result, in each scenario, the degree of agreement between the panellists and their opinions on the use of the procedure was measured. It was defined that there was agreement within the panel if the scores of all the panellists, after excluding the highest and the lowest, were within the same three-point interval. It was defined that there was disagreement if four or more panellists voted in the interval from one to three and another four or more voted in the interval from seven to nine. Those scenarios that were not classified as agreement or disagreement were considered uncertain. Finally, each indication was classified as one of the following categories according to the degree of agreement and the median of the scores: • Appropriate indication if the median was in the interval from seven to nine, without disagreement. • Uncertain indication if the median was in the interval from four to six, or when there was disagreement among the panellists, independent of the median; • Inappropriate indication if the median was in the interval of one to three, without disagreement. 3. Results Tables 1–5summarise the main results of the panel, specifically those clinical scenarios in which there was consensus on both an appropriate and inappropriate indication, with some contributions resulting from the discussion of the panel members. Table 1. Summary of the results from chapter 1: types of formulas used. Appropriate Inappropriate •Use of a normal-calorie and normal-protein diabetes specific formula in stable outpatients •Use of a high-protein and normal-calorie diabetes-specific formula in unstable inpatients with no other comorbidities •The presence of PU determines the appropriate indication of a high-protein formula or a PU-specific formula • The presence of constipation makes it appropriate to use a standard formula with fibre if there is good glycaemic control in stable patients (for both outpatients and inpatients) •The use of specific formulas for kidney disease is prioritised in all clinical scenarios •The use of protein modules is appropriate when there is a PU or in the case of malnourished obese patients •High-protein and high-calorie diabetes specific formulas: #By protein content *: In pre-dialysis kidney disease in almost all clinical outpatient and inpatient scenarios; exception: stressful situations, especially in malnourished patients #By calorie content *: Obese outpatients without malnutrition Stable, obese inpatients •Standard formulas with/without fibre: #Patients with poor glycaemic control #Fibre formulas are inappropriate in the case of gastroparesis, and formulas without fibre are inappropriate in the case of constipation PU: pressure ulcer. * Plausible explanation of the results obtained according to the opinions of the panel experts.
Nutrients 2023,15, 4976 7 of 26 Table 2. Summary of the results from chapter 2: method of administration. Appropriate Inappropriate •Intermittent EN administration in almost all outpatients and stable inpatients •Continuous administration is appropriate in the most unstable patients •Panellists showed a trend to consider intermittent administration more appropriate for inpatients in the case of constipation •There was no agreement on cyclical management in any scenario • Intermittent EN administration in the case of gastroparesis for all clinical scenarios EN: enteral nutrition. Table 3. Summary of the results from chapter 3: infusion site. Appropriate Inappropriate The indications and routes of access for enteral nutrition in patients with hyperglycaemia are similar to those in patients without hyperglycaemia * • Gastric infusion of enteral nutrition in all clinical scenarios except gastroparesis •Post-pyloric infusion of enteral nutrition in patients with gastroparesis •Gastric infusion in gastroparesis * Opinion of the panel members. Table 4. Summary of the results from chapter 4: treatment of hyperglycaemia. Appropriate Inappropriate Oral Antidiabetic Drugs •Metformin: most clinical scenarios: #<70 years old, with no comorbidities or with CV risk #>70 years old, with no comorbidities and with a BMI of >40 or with CV risk •Sulfonylureas: none •Glynides: none scenario. According to the experts, there could be a place for their use in EN administered in bolus (no consensus) * •Metformin: usual contraindications: >70 years old with kidney or liver disease •Sulfonylureas: the usual contraindications: heart failure, liver or kidney disease, CV risk, or a BMI of >40 •Glinides: liver disease and a BMI of >40 Insulin •In continuous/cyclic EN: #Insulin glargine in almost all clinical situations evaluated adding: Regular rapid-acting insulin as a fixed bolus if high glycaemia Extra bolus of rapid-acting regular insulin according to glycaemic level #Insulin glargine without associated rapid-acting insulin regimen in stable patients (continuous EN) #Insulin detemir combined with an extra bolus of rapid-acting regular insulin according to glycaemic levels #Insulin degludec adding: Extra bolus of rapid-acting regular insulin according to glycaemic level Rapid Regular rapid-acting insulin as a fixed bolus in cyclic EN if high glycaemia and metabolic stress •In intermittent EN: #Insulin glargine in almost all clinical situations, adding: Regular rapid-acting insulin as a fixed bolus if high glycaemia Extra bolus of rapid-acting regular insulin according to glycaemic level #Insulin glargine in almost all clinical situations, adding: Ultra-rapid-acting insulin as a fixed bolus if high glycaemia and metabolic stress (unstable patient) Extra bolus of ultra-rapid-acting insulin if controlled glycaemia with or without stress or high glycaemia without stress #Insulin detemir; adding rescue insulin: Extra bolus of rapid-acting regular insulin if controlled glycaemia and metabolic stress or high glycaemia without metabolic stress Extra bolus of ultra-rapid-acting insulin if high glycaemia and metabolic stress •In continuous EN: #Regular/ultra-rapid-acting insulin in a fixed bolus exclusively •In intermittent EN: #Insulin glargine exclusively without fixed or corrective regimen in the case of controlled glycaemia with stress fixed #Insulin detemir exclusively in a single dose for high glycaemia or metabolic stress •With any method of administration of EN: #Any exclusively basal insulin without a fixed or corrective regimen in the case of high glycaemia and metabolic stress #Regular insulin as a fixed bolus without basal insulin in the case of high glycaemia and metabolic stress #Ultra-rapid-acting insulin without basal insulin in any scenario CV: cardiovascular; BMI: body mass index; EN: enteral nutrition; * Plausible explanation of the results obtained according to the opinions of the panel experts.
Nutrients 2023,15, 4976 8 of 26 Table 5. Summary of the results from chapter 5: management of complications of enteral nutrition. Appropriate Inappropriate Diarrhoea •Specific normal-calorie and normal-protein formula for diabetes (with a high percentage of soluble fibre) for patients with poor glycaemic control and no associated comorbidity (for both outpatients (HbA1c > 8%) and inpatients with normal nutrition (high glycaemia)) •Specific high-calorie and high-protein formulas for diabetes (higher osmolarity *) for patients with kidney failure (due to protein content *) and in the case of gastroparesis (due to fibre *) (for both outpatients and inpatients) •Standard formula (with or without fibre) for patients with poor glycaemic control (HbA1c >8% or high glycaemia); the formula with fibre would be inappropriate in the case of gastroparesis, regardless of glycaemic control •Standard formula with fibre for patients with good glycaemic control but with pressure ulcers or kidney failure Constipation •Specific normal-calorie and normal-protein formula for diabetes for patients with normal nutrition and no comorbidity (both for outpatients (regardless of glycaemic control) and inpatients (with high glycaemia and without stress)) •Specific high-calorie and high-protein formula for diabetes for: #Outpatients with PU and inpatients with PU (normonourished and without stress) # With high glycaemia and stress without PUs •Standard formula with fibre for outpatients with normal nutrition, who are over 70 years old, without comorbidity, and with HbA1c < 8% (stable elderly patients) •Specific high-calorie and high-protein diabetes formula for patients with kidney failure (for protein content *), for patients with normal nutrition (due to calorie content *), and in cases of gastroparesis (due to fibre content *) •Standard formula (with or without fibre) for patients with HbA1c >8% or high glycaemia; the formula with fibre would be inappropriate in the case of gastroparesis •Use of standard formula with fibre for patients with controlled glycaemia but with gastroparesis (due to fibre content *) or PU (due to protein content *) •Peptide formula (without fibre) HbA1c: glycosylated haemoglobin. PU: pressure ulcer. * Plausible explanation for the results obtained according to the opinions of the panel experts. The detailed results are reported in Appendix D. The full information on the scores for all scenarios is available upon request. In Chapters 1–3, the scores of nine panellists were collected (the files of one panellist were unrecoverable). These chapters were discussed in a different session than the one held for Chapters 4 and 5, where there were 10 panellists. In Appendix E, the means of the median, the median absolute deviation, the proportion of agreement and disagreement, and the percentages of the scenarios rated as appropriate, inappropriate or uncertain are presented. In most of the scenarios, the panellists agreed (90.4%), although we found that agreement was reached because, above all, they voted in the interval from four to six, and those scenarios were classified as uncertain (63.6%). The rest of the scenarios (36.4%) were classified as appropriate (23.7%) or inappropriate (12.7%). Figure 6shows the proportions of the appropriate, inappropriate and uncertain scenarios for each chapter.
Nutrients 2023,15, 4976 9 of 26 Nutrients2023,15,xFORPEERREVIEW10of27 Figure6.Proportionofappropriate,inappropriateanduncertainindicationsbychapter.Yellow representsinappropriate,pinkrepresentsuncertain,andgreenrepresentsappropriate. 4.Discussion Theopinionsexpressedbyexpertsinclinicalnutritioninthisworkreflectthatthe criteriaforthemanagementofENinhyperglycaemiaarenotstandardised.Ofthetotal presentedscenarios,36.4%wereagreeduponasbeingappropriateorinappropriate.The mostrelevantresultsfromeachchapterarediscussedbelow. 4.1.TypesofFormulasUsed AnyENformulacanbeusedindiabetesorhyperglycaemiaifthehypoglycaemic therapyisappropriatelyadjusted.However,mostpublicationsrecommendtheuseofspecificdietsfordiabetessincetheyseemtoprovideaddedvalueforthemetaboliccontrolof thesepatientscomparedtostandardformulas[8,9,12,13]. RegardingtheopinionsofthepanelexpertsontheuseofdifferenttypesofENformulasindifferentclinicalscenarios,thepresenceofpressureulcers(PU)determinedthe appropriateindicationofaspecifichigh-proteinformulafordiabetesorofaspecificformulaforPU(formulasenrichedwithdefinednutrientsthatpromotehealing,suchasarginine),bothforoutpatientsandinpatients. Coincidingwithwhatwaspublished[14],therewasagreementthattheuseofaspecifichigh-proteinformulafordiabeteswasinappropriateinmostscenarioswithpre-dial- ysiskidneyfailure,withscenarioswithassociatedmetabolicstressarisingasuncertain. Thismayhavebeenduetothefactthatpatientswithmetabolicstressmaypresentthe protein-energywastingsyndromeassociatedwithkidneyfailureandrequiretheuseofa high-proteinformulainthissituation.Accordingtothelatestrecommendationsofthe AmericanDiabetesAssociation(ADA),therecommendedproteinintakeforpatientswith chronickidneydiseasewhoarenotondialysisshouldbeapproximately0.8gr/kg weight/day[15].Inalltheclinicalscenarioswithkidneyfailure,therewasagreementin consideringthespecificformulasforthiscomorbiditytobeappropriate.Someofthese kidney-failure-specificenteralformulasincludelow-glycaemic-indexcarbohydrates, prebioticsandahighpercentageoffat,andthesemaybeappropriateforpeoplewith hyperglycaemia. Therewasalsoagreementthatthespecifichigh-calorieandhigh-proteinformulasfor diabeteswouldbeinappropriateforinpatientswithgoodglycaemiccontrolandwithout metabolicstress,whoalsohaveaBMIofover40kg/m2,andforoutpatientswithnormal nutrition,whoalsohaveaBMIofover40kg/m2.Thismayhavebeenduetothecalorie contentofthistypeofformula.However,therewasnoagreementamongthepanellists regardingitsuseforpatientswithBMIsofover40kg/m2whowereinpatientswith Figure 6. Proportion of appropriate, inappropriate and uncertain indications by chapter. Yellow represents inappropriate, pink represents uncertain, and green represents appropriate. 4. Discussion The opinions expressed by experts in clinical nutrition in this work reflect that the criteria for the management of EN in hyperglycaemia are not standardised. Of the total presented scenarios, 36.4% were agreed upon as being appropriate or inappropriate. The most relevant results from each chapter are discussed below. 4.1. Types of Formulas Used Any EN formula can be used in diabetes or hyperglycaemia if the hypoglycaemic therapy is appropriately adjusted. However, most publications recommend the use of specific diets for diabetes since they seem to provide added value for the metabolic control of these patients compared to standard formulas [8,9,12,13]. Regarding the opinions of the panel experts on the use of different types of EN formulas in different clinical scenarios, the presence of pressure ulcers (PU) determined the appropriate indication of a specific high-protein formula for diabetes or of a specific formula for PU (formulas enriched with defined nutrients that promote healing, such as arginine), both for outpatients and inpatients. Coinciding with what was published [ 14 ], there was agreement that the use of a specific high-protein formula for diabetes was inappropriate in most scenarios with predialysis kidney failure, with scenarios with associated metabolic stress arising as uncertain. This may have been due to the fact that patients with metabolic stress may present the protein-energy wasting syndrome associated with kidney failure and require the use of a high-protein formula in this situation. According to the latest recommendations of the American Diabetes Association (ADA), the recommended protein intake for patients with chronic kidney disease who are not on dialysis should be approximately 0.8 gr/kg weight/day [ 15 ]. In all the clinical scenarios with kidney failure, there was agreement in considering the specific formulas for this comorbidity to be appropriate. Some of these kidney-failure-specific enteral formulas include low-glycaemic-index carbohydrates, prebiotics and a high percentage of fat, and these may be appropriate for people with hyperglycaemia. There was also agreement that the specific high-calorie and high-protein formulas for diabetes would be inappropriate for inpatients with good glycaemic control and without metabolic stress, who also have a BMI of over 40 kg/m 2 , and for outpatients with normal nutrition, who also have a BMI of over 40 kg/m 2 . This may have been due to the calorie content of this type of formula. However, there was no agreement among the panellists regarding its use for patients with BMIs of over 40 kg/m 2 who were inpatients with metabolic stress or who were malnourished outpatients. Although there are no good-
Nutrients 2023,15, 4976 16 of 26 h. For patients with DM and hypertriglyceridemia over 400 mg/dl, what kind of formula would you use? Justify the answer; i. For patients with DM and EN by nasogastric tube presenting gastroparesis, what formula would you use? Justify the answer; j. In case of severe gastroparesis that requires infusion of nutrition into the jejunum; what formula would you use? Justify the answer; k. In what situations do you consider it necessary to use micronutrient supplementation in people with DM? Justify the answer. •Treatment of diabetes in EN: a. What would be the ideal oral hypoglycaemic agents (OHAs) treatment in patients with DM2 and HEN? b. Do the new drugs (GLP-1-1 analogues; SGLT-2) have a role in the management of patients with EN and DM2? c. Do you use the glycaemic load calculation and the sensitivity index to calculate bolus insulin in people with a bolus or who are critically ill? Respond yes or no and justify the answer; d. Which insulin do you consider most appropriate as basal insulin? As night-time or daytime EN, as continuous 24-h EN and as EN in bolus or by gravity. Justify the answer; e. Which insulin do you consider most appropriate as bolus insulin? As night-time or daytime EN, as continuous 24-h EN and as EN in bolus or by gravity. Justify the answer; f. Which insulin do you consider most appropriate as a correction or rescue insulin? As night-time or daytime EN, as continuous 24-h EN and as EN in bolus or by gravity. Justify the answer; g. What do you think influences you the most when prescribing EN to a patient (select the top three): i. Type of formula: macronutrient composition; ii. Formula type: calorie density; iii. Formula Type: flavouring; iv. Price; v. Characteristics of the container (size, weight, grip, opening and closing, etc.) and connections; vi. Patient preferences; vii. Marketing of the manufacturing company; viii. Clinical studies of the formula. Appendix B •Variables used to create the scenarios in chapters 1, 2 and 3: a. Patient point of care: outpatient or inpatient; b. Age (only in outpatients): under 70 years or 70 years or older; c. Glycaemia (only in inpatients): controlled or high; d. Metabolic stress (only in inpatients): without stress or with stress; e. Glycaemia (only in outpatients): glycosylated haemoglobin greater than 8% or glycosylated haemoglobin under 8%; f. Nutritional status: malnourished or normonourished; g. Body Mass Index (BMI): BMI < 40 kg/m2or BMI > 40 kg/m2; h. Kidney failure (KF) (only in patients with BMI < 40): without kidney failure (KF) or with KF; i. Comorbidity (only in patients with BMI < 40 and without KF): no comorbidities, gastroparesis, pressure ulcer or constipation. •Variables used to build the scenarios in chapter 4 (for antidiabetic drugs): a. Patient point of care: outpatient;
Nutrients 2023,15, 4976 17 of 26 b. Age: under 70 years or 70 years or older; c. Glycaemia: glycosylated haemoglobin greater than 8% or glycosylated haemoglobin under 8%; d. Nutritional status: malnourished or normonourished; e. Body Mass Index (BMI): BMI < 40 kg/m2or BMI > 40 kg/m2; f. Comorbidity: No comorbidities, kidney failure, liver failure, heart failure or cardiovascular risk. •Variables used to create the scenarios in chapter 4 (for insulins): a. Patient point of care: inpatients; b. Glycaemia: controlled or high; c. Metabolic stress: without stress or with stress; d. Nutritional status: malnourished or normonourished; e. Body Mass Index (BMI): BMI < 40 kg/m2or BMI > 40 kg/m2; f. Enteral nutrition form of administration: continuous or bolus/intermittent or cyclic administration. •Variables used to build the scenarios in chapter 5: a. Patient point of care: outpatient or inpatient; b. Age (only in outpatients): under 70 years or 70 years or older; c. Glycaemia (only in inpatients): controlled or high; d. Metabolic stress (only in inpatients): without stress or with stress; e. Glycaemia (only in outpatients): glycosylated haemoglobin greater than 8% or glycosylated haemoglobin under 8%; f. Nutritional status: malnourished or normonourished; g. Side effects: no comorbidities, gastroparesis, pressure ulcer or kidney failure. Appendix C Term Definition Cyclic administration Administration at a constant rate of enteral nutrition (EN) with a pump for a period of 8–12 h. (it can be during the day with a break at night or vice versa) Continuous administration Administration at a constant rate of EN with a pump, without interruption over 24 h. (also acceptable if there is a 1–2 h break) Bolus/intermittent administration Bolus administration of EN in 3–6 doses per day. It can be with a syringe or by gravity, with a duration of 30 to 120 min per dose. Degludec Insulin analogue over more than 24 h. Malnutrition Clinical situation caused by a nutrient deficit (due to inadequate intake, increased losses, increased requirements, altered absorption and/or inflammation) that entails a change in body composition and that decreases physical and mental functions and has a negative impact on the clinical evolution of the patient. Disease-related malnutrition Malnutrition caused directly or indirectly by suffering from an acute, subacute or chronic disease. Detemir Long-acting insulin analogue (16–24 h) Diarrhoea Producing loose or liquid stools, three or more times a day (or with a greater than normal frequency for the person). Distension Feeling of fullness, nausea, bloating or abdominal pain, due to the accumulation of gas in the stomach and intestine, or accumulation of abdominal fluid. Constipation/equivalent to chronic constipation less than 3 bowel movements a week and/or hard stools in more than 25% of bowel movements, or a feeling of incomplete or very difficult defecations. Low-fat formula Enteral formula with fat content 5–20% of the total energy (TE).
Nutrients 2023,15, 4976 18 of 26 Term Definition High-calorie/high-protein diabetic formula Complete polymeric enteral formula with density >1.2 Kcal/mL, protein content >18% of TE, which contains fermentable fibre in a high or exclusive proportion, low glycaemic index carbohydrates, and/or prebiotics (fructooligosaccharides (FOS), Inulin) and, frequently, a high content of monounsaturated fatty acids. Normal-calorie/high-protein diabetic formula Complete polymeric enteral formula with density >0.9 and <1.2 Kcal/mL, protein content ≥ 18% of TE, which contains fermentable fibre in a high or exclusive proportion, carbohydrates, which contain soluble fibre in a high or exclusive proportion. Low glycaemic index carbohydrates, and/or prebiotics (FOS, Inulin) and, frequently, a high content of monounsaturated fatty acids. Normal-calorie/normal-protein diabetic formula Complete polymeric enteral formula with density >0.9 and <1.2 Kcal/mL, protein content 11–18% of TE, which contains fermentable fibre in a high or exclusive proportion, low glycaemic index carbohydrates, and/or prebiotics (FOS, Inulin) and, frequently, a high content of monounsaturated fatty acids. Standard formula Complete polymeric enteral formula with density >0.9 and <1.2 Kcal/mL, protein content 11–18% of TE, which do not contain fibre. Standard formula with fibre Complete polymeric enteral formula with density >0.9 and <1.2 Kcal/mL, protein content 11–18% of TE, which contain fermentable, non-fermentable fibre or a mixture of fibres. Immunomodulatory formula Complete enteral formula, protein content >18% of TE, enriched to varying degrees with: glutamine, Omega-3 fatty acids, arginine, nucleotides, micronutrients. Peptide formula Complete oligomeric enteral formula, which contains hydrolysed proteins (peptides), in addition to carbohydrates, fats with high medium chain triglycerides (MCT) and micronutrient content. VLCD(very low calorie diet) formulas Omega-3 fatty acids, arginine, nucleotides, micronutrients. Specific formulas Complete enteral formula with a nutrient profile appropriate to metabolic situations or requirements of a specific pathology (diabetes and stress hyperglycaemia, nephropathy, liver disease, stress or immunosuppression, oncology, respiratory failure, cystic fibrosis). Gastroparesis Delayed gastric emptying observed in the absence of gastric obstruction, and accompanied by early satiety, nausea or vomiting, or abdominal pain. Glargine U100 and U300 Long-acting insulin analogue (U100 20–24 h U300 over 24 h). Glinides or meglitinides Group of oral hypoglycaemic drugs that increase insulin secretion. HbA1c Glycosylated haemoglobin. Hyperglycaemia Glycaemia ≥126 mg/dL. Body Mass Index (BMI) Degree of adiposity calculated according to the formula body weight (Kg)/height (m2). Gastric infusion EN infusion through a tube whose distal end is placed in the stomach. Postpyloric infusion Infusion of EN through a tube whose distal end is placed in the duodenum or jejunum. Bolus and rescue insulin Insulin administration in preset doses with established intervals (every 6–8 h, or prandial), adding a higher dose to the preset dose if glycaemia exceeds a preset limit. Rapid-acting insulin Regular insulin duration (5–7 h). Ultra-rapid-acting insulin Insulin analogues (Lispro, aspart, glulisine) duration (2–4 h). Malabsorption Signs and symptoms derived from a deficit in the intestinal absorption of nutrients. Metformin Oral hypoglycaemic drug from the biguanide group that reduces postprandial and basal glycaemia. Normal nutrition Normal nutritional status according to assessment scales such as subjective global assessment (SGA) or clinical and analytical assessment methods. NPH Intermediate-acting insulin (12–16 h). Obesity BMI ≥30 k/m2.
Nutrients 2023,15, 4976 19 of 26 Term Definition Outpatient Patient who receives health care while living in the community (care home or private residence) and who comes to the medical or nursing appointment in person or virtually. Inpatients Patient who remains admitted to hospital for diagnosis or treatment. Metabolic stress Metabolic response to trauma, sepsis, surgery that is associated with increased energy expenditure and muscle catabolism manifested by hyperglycaemia increased urinary nitrogen losses and oxygen consumption. Sulfonylurea Group of oral hypoglycaemic drugs that increase insulin secretion and boost the action of insulin in extrapancreatic tissues. Pressure ulcer Localised area of damage to the skin and underlying tissues caused by pressure, friction, or a combination of both. Appendix D Table A1. Main agreements detected in the panel from chapter 1: types of formulas used. Appropriate Indication 1. Use of a specific formula for diabetes in patients with hyperglycaemia: I. Outpatients: •High-protein and normal-calorie in PU; •High-protein and high-calorie in PU, except in normonourished patients; •Normal-protein and normal-calorie in outpatients, normonourished and without associated comorbidity (regardless of glycaemic control). II. Inpatients: •High-protein and normal-calorie in PU; •High-protein and high-calorie in PU, except in normonourished patients; • High-protein and normal-calorie, in the context of high glycaemia and metabolic stress, normonourished with a BMI under 40 kg/m2and without associated comorbidity. 2. Use of a standard formula with fibre in a patient with hyperglycaemia and constipation: I. Outpatients, under 70 years old, normonourished, with HbA1c under 8%. II. Inpatients, normonourished, with controlled glycaemia and without metabolic stress. 3. Use of a specific formula for kidney failure in patients with hyperglycaemia and kidney failure. 4. Use of a specific formula for PU in patients with hyperglycaemia and PU. 5. Use of protein modules in patients with hyperglycaemia: I. Outpatients: •Malnourished with PU, regardless of metabolic control and age; •Malnourished with a BMI over 40 kg/m2, regardless of metabolic control. II. Inpatients: •With PU, regardless of nutritional status and metabolic control. Inappropriate Indication 1. Use of a specific high-calorie and high-protein formula for diabetes in patients with hyperglycaemia: I. Outpatients: •With pre-dialysis kidney failure; •Under 70 years old, normonourished, with a BMI over 40 kg/m2(regardless of glycaemic control); •With HbA1c under 8% and gastroparesis, regardless of nutritional status and age. II. Inpatients: •With pre-dialysis kidney failure, except in patients with metabolic stress; •With controlled glycaemia and without metabolic stress and a BMI over 40 kg/m2(regardless of nutritional status); •With gastroparesis, regardless of nutritional status.
Nutrients 2023,15, 4976 20 of 26 Table A1. Cont. 2. Use of a specific high-protein and normal-calorie formula for diabetes in patients with hyperglycaemia: I. Inpatients: •With pre-dialysis kidney failure, and with controlled glycaemia, without metabolic stress (regardless of nutritional status). 3. Use of a standard formula without fibre in patients with hyperglycaemia: I. Outpatients: •With constipation; •With HbA1c over 8%. II. Inpatients: •With constipation; •With high glycaemia. 4. Use of a standard formula with fibre in a patient with hyperglycaemia: I. Outpatients: •With gastroparesis; •With HbA1c over 8%. II. Inpatients: •With gastroparesis; •With high glycaemia. 5. Use of protein modules in patients with hyperglycaemia: I. Outpatients: •Normonourished, under 70 years old, with a BMI under 40 kg/m2 and without associated comorbidity (regardless of glycaemic control). II. Inpatients: •Normonourished, with controlled glycaemia and without metabolic stress, without associated comorbidity and with a BMI under 40 kg/m2. PU: pressure ulcer. BMI: body mass index. HbA1c: glycosylated haemoglobin. In the first chapter, 18% were appropriate scenarios, 10% inappropriate and 72% uncertain. Table A2. Main agreements detected in the panel from chapter 2: method of administration. Appropriate Indication 1. Use of EN in continuous administration in patients with hyperglycaemia: I. Outpatients: •With gastroparesis. II. Inpatients: •With gastroparesis; •With high glycaemia and metabolic stress, without constipation (regardless of nutritional status). 2. Use of EN in intermittent administration in patients with hyperglycaemia: I. Outpatients: •Without gastroparesis. II. Inpatients: •Without metabolic stress and with constipation (regardless of glycaemic control or nutritional status). Inappropriate Indication 1. Use of EN in continuous administration in patients with hyperglycaemia: I. Outpatients: •Normonourished, except for gastroparesis; •Malnourished, with HbA1c under 8% and with constipation. 2. Use of EN in intermittent administration in patients with hyperglycaemia: I. Outpatients and inpatients: •With gastroparesis. EN: enteral nutrition. HbA1c: glycosylated haemoglobin. In the second chapter, 10.4% were appropriate scenarios, 21.5% inappropriate and 68.1% uncertain.
Nutrients 2023,15, 4976 21 of 26 Table A3. Main agreements detected in the panel from chapter 3: infusion site. Appropriate Indication 1. Gastric infusion of EN in patients with hyperglycaemia: I. Outpatients and inpatients: •Without gastroparesis. 2. Post-pyloric infusion of EN in patients with hyperglycaemia: I. Outpatients and inpatients: •With gastroparesis. Inappropriate Indication 1. Gastric infusion of EN in patients with hyperglycaemia: I. Outpatients and inpatients: •With gastroparesis. 2. Post-pyloric infusion of EN in patients with hyperglycaemia: I. Outpatients: •Without gastroparesis. II. Inpatients: •With controlled glycemia, without metabolic stress and without associated comorbidities (regardless of nutritional status). EN: enteral nutrition. In the third chapter, there were 19.8% scenarios considered appropriate, 42.2% inappropriate and 38.2% uncertain. Table A4. Main agreements detected in the panel from chapter 4: treatment of hyperglycaemia. Appropriate Indication 1. Use of metformin in patients with hyperglycaemia: • Under 70 years old, without comorbidity or with cardiovascular risk (regardless of nutritional status, glycaemic control or BMI); •Over 70 years old, BMI over 40 kg/m2, without associated comorbidity or with cardiovascular risk. 2. Insulin use in continuous EN in patients with hyperglycaemia: •Basal insulin glargine together with boluses of regular rapid-acting insulin in case of high glycaemia; •Basal insulin glargine together with a rescue regimen of regular rapid-acting insulin in the case of controlled or high glycaemia with metabolic stress and in the case of high glycaemia without metabolic stress; •Exclusive glargine basal insulin without a fixed or corrective regimen of rapid-acting insulin in the case of controlled glycaemia and without metabolic stress; • Insulin detemir together with a rescue regimen of regular rapid-acting insulin in the case of high glycaemia and without metabolic stress; •Insulin degludec together with regular rapid-acting rescue insulin in case of metabolic stress, regardless of glycaemic control. 3. Insulin use in cyclic EN in patients with hyperglycaemia: •Basal insulin glargine together with boluses of regular rapid-acting insulin in case of high glycaemia with metabolic stress; •Basal insulin glargine together with a rescue regimen of regular rapid-acting insulin in the case of controlled or high glycaemia with metabolic stress and in the case of high glycaemia without metabolic stress; •Detemir basal insulin together with a rescue regimen of regular rapid-acting insulin in the case of high glycaemia and without metabolic stress; •Insulin degludec together with boluses of regular rapid-acting insulin in cases of high glycaemia and metabolic stress.
Nutrients 2023,15, 4976 22 of 26 Table A4. Cont. 4. Insulin use in intermittent EN in hyperglycaemic patients: •Basal insulin glargine together with boluses of regular rapid-acting insulin in case of high glycaemia; •Basal insulin glargine together with boluses of ultra-rapid-acting insulin in the case of high glycaemia with metabolic stress; • Basal insulin glargine together with a rescue regimen of regular rapid-acting insulin in the case of controlled glycaemia with metabolic stress and in the case of high glycaemia without metabolic stress; •Basal insulin glargine together with ultra-rapid-acting rescue insulin in the case of controlled glycaemia regardless of metabolic stress and in the case of high glycaemia without metabolic stress; •Insulin detemir together with regular rapid-acting rescue insulin in case of controlled glycaemia and with metabolic stress and high glycaemia without metabolic stress; •Insulin detemir together with ultra-rapid-acting rescue insulin in the case of high glycaemia and metabolic stress. Inappropriate Indication 1. Use of metformin in patients with hyperglycaemia: •With liver failure; •Over 70 years old and kidney failure. 2. Use of sulfonylureas in patients with hyperglycaemia: •With associated comorbidity such as heart failure, liver failure, kidney failure or cardiovascular risk; •No comorbidity associated with BMI over 40 kg/m2, regardless of nutritional status or glycaemic control. 3. Use of glinides in patients with hyperglycaemia: •With liver failure or BMI over 40 kg/m2. 4. Insulin use in continuous EN in patients with hyperglycaemia: • Insulin detemir together with boluses of ultra-rapid-acting insulin in case of controlled glycaemia and without metabolic stress; •Rapid-acting insulin in bolus exclusively (both regular ultra-rapid-acting and rapid-acting insulin). 5. Insulin use in intermittent EN in hyperglycaemic patients: •Insulin glargine as basal insulin exclusively without a fixed or corrective regimen of rapid-acting insulin in the case of controlled glycaemia and with metabolic stress; • Insulin detemir exclusively in a single dose for controlled glycaemia with metabolic stress or high glycaemia regardless of metabolic stress. 6. Use of insulin in any method of EN administration in hyperglycaemic patients: •Basal insulin glargine/detemir/degludec as an exclusive component without a fixed or corrective regimen of rapid-acting insulin in the case of high glycaemia with metabolic stress; •Regular rapid-acting bolus insulin without associated basal component in case of high glycaemia and metabolic stress; •Rapid-acting insulin without associated basal insulin. EN: enteral nutrition. BMI: body mass index. In the fourth chapter, 25.6% of scenarios were appropriate, 12% inappropriate and 62.4% uncertain. Table A5. Main agreements detected in the panel from chapter 5: management of complications. Appropriate Indication 1. Use of a specific normal-calorie and normal-protein formula for diabetes in patients with hyperglycaemia: I. Outpatients: •With diarrhoea, without associated comorbidity and with HbA1c over 8%; •With constipation, without associated comorbidity and normonourished (regardless of glycaemic control). II. Inpatients: •With diarrhoea, without associated comorbidity, normonourished and high glycaemia; •With constipation, without associated comorbidity, normonourished with high glycaemia and without metabolic stress.
Nutrients 2023,15, 4976 23 of 26 Table A5. Cont. 2. Use of a specific high-calorie and high-protein formula for diabetes in patients with hyperglycaemia: I. Outpatients: •With constipation and PU, regardless of nutritional status or glycaemic control. II. Inpatients: •With constipation and PU, without metabolic stress, normonourished; •With constipation, high glycaemia with metabolic stress, without comorbidity or PU. 3. Use of a standard formula with fibre in diabetic patients or with stress hyperglycaemia: I. Outpatients: •With constipation, normonourished, over 70 years old and with HbA1c under 8%, without comorbidity. Inappropriate Indication 1. Use of a specific high-calorie and high-protein formula for diabetes in patients with hyperglycaemia: I. Outpatients: •With diarrhoea, along with gastroparesis or kidney failure; •With constipation and kidney failure; •With constipation, normonourished and gastroparesis. II. Inpatients: •With diarrhoea, along with gastroparesis or kidney failure; •With constipation and kidney failure. 2. Use of a standard formula (without fibre) in patients with hyperglycaemia: I. Outpatients: •With diarrhoea or constipation, HbA1c over 8%, without gastroparesis; •With constipation, malnourished with HbA1c under 8%, along with kidney failure or PU. II. Inpatients: •With diarrhoea or constipation and high glycaemia, without gastroparesis; •With constipation, controlled glycaemia, normonourished without comorbidity or with PU. 3. Use of a standard formula (with fibre) in patients with hyperglycaemia: I. Outpatients: •With diarrhoea and gastroparesis; •With diarrhoea or constipation and HbA1c over 8%; •With diarrhoea, HbA1c under 8% and PU or kidney failure. II. Inpatients: •With diarrhoea and gastroparesis; •With diarrhoea or constipation and high glycaemia; •With diarrhoea, controlled glycaemia and PU; •With constipation, controlled glycaemia, with gastroparesis or PU. 4. Use of a peptide formula (without fibre) in patients with stress hyperglycaemia: I. Outpatients and inpatients: •With constipation. PU: pressure ulcer. HbA1c: glycosylated haemoglobin. In the fifth chapter, 4.5% of scenarios were appropriate, 61.3% inappropriate and 34.2% uncertain. Appendix E Table A6. Median, agreement and appropriateness in all scenarios after the second round. Item Result Median (average) 4.3 Median absolute deviation 1.0 % Scenarios with agreement (n) 90.4 (2706) % Scenarios with disagreement (n) 0.5 (14) % Appropriate scenarios (n) 23.7 (708) % Inappropriate scenarios (n) 12.7 (381) % Uncertain scenarios (n) 63.6 (1903)
Nutrients 2023,15, 4976 24 of 26 Table A7. Median, agreement and appropriateness in the chapter 1 scenarios, after the second round. Item Result Median (average) 4.4 Median absolute deviation 1.0 % Scenarios with agreement (n) 83.7 (643) % Scenarios with disagreement (n) 1.0 (8) % Appropriate scenarios (n) 18.0 (138) % Inappropriate scenarios (n) 10.0 (77) % Uncertain scenarios (n) 72.0 (553) Table A8. Median, agreement and appropriateness in the chapter 2 scenarios, after the second round. Item Result Median (average) 5.1 Median absolute deviation 0.5 % Scenarios with agreement (n) 69.1 (199) % Scenarios with disagreement (n) 0.0 (0) % Appropriate scenarios (n) 10.4 (30) % Inappropriate scenarios (n) 21.5 (62) % Uncertain scenarios (n) 68.1 (196) Table A9. Median, agreement and appropriateness in the chapter 3 scenarios, after the second round. Item Result Median (average) 5.4 Median absolute deviation 3.0 % Scenarios with agreement (n) 84.9 (163) % Scenarios with disagreement (n) 3.1 (6) % Appropriate scenarios (n) 19.8 (38) % Inappropriate scenarios (n) 42.2 (73) % Uncertain scenarios (n) 38.2 (73) Table A10. Median, agreement and appropriateness in the chapter 4 scenarios, after the second round. Item Result Median (average) 4.3 Median absolute deviation 1.5 % Scenarios with agreement (n) 98.1 (1083) % Scenarios with disagreement (n) 1.9 (21) % Appropriate scenarios (n) 25.6 (283) % Inappropriate scenarios (n) 12.0 (132) % Uncertain scenarios (n) 62.4 (689) Table A11. Median, agreement and appropriateness in the chapter 5 scenarios, after the second round. Item Result Median (average) 3.7 Median absolute deviation 1.5 % Scenarios with agreement (n) 96.6 (618) % Scenarios with disagreement (n) 3.4 (22) % Appropriate scenarios (n) 4.5 (29) % Inappropriate scenarios (n) 61.3 (392) % Uncertain scenarios (n) 34.2 (219)
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