Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Hyperglycemia and diabetes mellitus

Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: Hiperglucemia y diabetes mellitus

C. Vaquerizo Alonso^a, T. Grau Carmona^b and M. Juan Díaz^c

^aHospital Universitario de Fuenlabrada. Madrid. Spain.
^bHospital Universitario 12 de Octubre. Madrid. Spain.
^cHospital General Universitario. Ciudad Real. Spain.

ABSTRACT

Hyperglycemia is one of the main metabolic disturbances in critically-ill patients and is associated with increased morbidity and mortality. Consequently, blood glucose levels must be safely and effectively controlled, that is, maintained within a normal range, avoiding hypoglycemia on the one hand and elevated glucose concentrations on the other. To accomplish this aim, insulin is often required, avoiding protocols designed to achieve tight glycemic control.
To prevent hyperglycemia and its associated complications, energy intake should be adjusted to patients' requirements, avoiding overnutrition and excessive glucose intake. Protein intake should be adjusted to the degree of metabolic stress.
Whenever patients require artificial feeding, the enteral route, if not contraindicated, should be used since parenteral nutrition is associated with a higher frequency of hyperglycemia and greater insulin requirements. Enteral nutrition should be administered early, preferably within the first 24 hours of admission to the intensive care unit, after hemodynamic stabilization. Specific diets for hyperglycemia, containing low glycemic index carbohydrates and fibre and enriched with monounsaturated fatty acids, can achieve good glycemic control with lower insulin requirements.

Key words: Hyperglycemia. Diabetes mellitus. Artificial nutrition. Glycemic control.

RESUMEN

La hiperglucemia es una de las alteraciones metabólicas predominantes en los pacientes críticos y se asocia con un aumento de la morbimortalidad. por ello, es necesario realizar un control efectivo y a su vez seguro de la glucemia, esto es, mantener la normoglucemia en un rango que evite el riesgo de desarrollar hipoglucemia, por un lado, y las cifras elevadas de glucemia, por otro. Para conseguirlo, en la mayoría de los casos es necesario el tratamiento con insulina evitando protocolos dirigidos a conseguir cifras estrictas de glucemias. ]]> Con el fin de prevenir la hiperglucemia y sus complicaciones asociadas, el aporte energético debe adecuarse a los requerimientos de los pacientes, evitando la sobrenutrición y el aporte excesivo de glucosa. El aporte proteico se ajustará al nivel de estrés metabólico. Siempre que el enfermo requiera nutrición artificial y no esté contraindicada debe emplearse la vía enteral, ya que la nutrición parenteral se asocia a mayor frecuencia de hiperglucemia y mayores necesidades de insulina. La administración de la nutrición enteral debe ser precoz, preferiblemente dentro de las primeras 24 h de ingreso en UCI, tras la estabilización hemodinámica. Las dietas específicas para hiperglucemia que contienen hidratos de carbono de bajo índice glucémico, fibra y ricas en ácidos grasos monoinsaturados podrían conseguir un mejor control glucémico con menores necesidades de insulina.

Palabras clave: Hiperglucemia. Diabetes mellitus. Nutrición artificial. Control de glucemia.

Introduction

In critically-ill patients the development of hyperglycemia secondary to the acute lesion stress is common even in non-diabetics. Hyperglycemia and the metabolic consequences of insulin resistance increase morbidity and mortality in critically-ill patients¹, because they enhance the occurrence of infections and multiple organ failure, mainly due to proinflammatory effects and cell toxicity per se of high glycemia values.

What should be the nutritional support route and when should it be started?

Whe never the gastrointestinal tract is intact and the patient requires artificial feeding, the enteral route must be used in the first 24-48 hours of stay, over the parenteral, which is associated with a higher frequency of hyperglycemia and insulin needs². Although it is known that gastroparesis of diabetic patients can make gastrointestinal tolerance more difficult³, the enteral route allows for a better control of blood sugar levels and prevents complications derived from hyperglycemia in critically-ill diabetic patients or those with stress hyperglycemia² (Ia).

What should be the characteristics of energy supply?

One of the most controversial issues is the distribution of the total calorie requirements and, particularly, the carbohydrate/lipid ratio. The American Diabetes Association (ADA)⁵ sets out that critically-ill diabetic patients may receive either a standard formula (50% carbohydrates) or a formula low in carbohydrates (33-40%). In contrast, the European Association for the Study of Diabetes⁶ recommends that fat content in diet should not exceed 35% and that carbohydrate intake should be within 45-60% of the daily calorie needs.

There are specific enteral formulae for diabetics containing fewer carbohydrates (35-40%) and more fats (40-50%), with predominance of monounsaturated fatty acids (MUFA) (> 60% of the total fat content). New formulae have been developed that, in addition to reducing fat content, increase their low glycemic index carbohydrates⁶. In studies performed in non-criticallyill patients, both types of formulae reduce the glycemic and insulinemic response to intake and, furthermore, diets rich in slow-digestion carbohydrates do not raise post-prandial triglyceride levels, unlike diets rich in fats^7,8. Therefore, it is recommended to use lowglycemic index carbohydrates, such as starch (preferably), fructose at lower doses, and more recently, isomaltulose and sucromalt, amongst others⁸ (Ib).

With regard to lipids, it is recommended to increase MUFA, as they improve glycemic control, lipid metabolism and insulin secretion in non-critically-ill patients with type 2 diabetes⁷ (Ib), ⁸ (IIa). Furthermore, it is recommended to reduce polyunsaturated fatty acids (PUFA) of the ω-6 series to prevent proinflammatory eicosanoids to increase⁹.

Regarding PN, the use of mixtures of carbohydrates with fructose or polyols (xylitol) offers conflicting results regarding a better glycemic control when compared to mixtures with glucose^10,11 and currently are scantly used.

In general, patients with type 2 diabetes benefit from fat-high diets, as diets very rich in carbohydrates affect the lipid profile of the patient and increase the risk of cardiovascular diseases.³

What should be the protein intake and its characteristics?

Seriously ill patients with hyperglycemia and particularly diabetics show deep metabolic changes in the absence of insulin, such as an increased basal energy expenditure (BEE) and a negative net protein balance. Both insulin and amino acids stimulate protein synthesis, though its effects depend on its relative concentration. In hyperaminoacidemia states, it has been suggested that additional insulin doses do not increase protein synthesis, probably related to the insulin resistance level of each patient¹².

There is no adequate evidence to define a specific nitrogen supply to critically-ill diabetic patients or those with stress hyperglycemia. It is recommended to adjust protein needs to the metabolic stress level of the patient: 1.3-1.7 g of proteins/kg/day according to their metabolic state, in order to prevent exacerbation of protein catabolism.

Do other specific nutrients play any role in nutritional-metabolic support in these patients?

The parenteral administration of glutamine has been associated with an improved glycemic control¹³ through several potential mechanisms: a) through the metabolism of glutamine to glucose in the glucose-glutamine cycle; b) increasing insulin secretion; c) improving the sensitivity to insulin of the striate muscle; d) increasing the oxidation of free fatty acids, and e) decreasing the inflammatory response. It has been proven that glutamine improves insulin sensitivity in seriously ill patients¹⁴, and 2 multicenter clinical trials have shown that patients receiving TPN enriched with glutamine have fewer infectious complications and better metabolic tolerability^15,16 (Ib).

Eicosapentaenoic acid and gamma linolenic acid

There are no studies with enteral nutrition (EN) or PN that show significant effects of ω-3 fatty acids on glycemic control.

Fiber

The ADA recommends administration of dietary fiber in diabetic patients, due to its lower glycemic index⁵. A metaanalysis showed no significant benefits in seriously ill patients¹⁶ (Ia), though a subsequent study demonstrated that specific diets containing fiber improved glycemic control, though without emphasis in seriously ill patients⁷ (Ib).

Trace elements and vitamins

There is no evidence that antioxidant vitamins at doses higher than the requirements are safe or beneficial¹⁷ (IIb). The contribution of oxidative stress in diabetic complications and, particularly in seriously ill patients, is not evident, as tissue damage occurs in diabetic patients but not in patients with insulin resistance, as in the case of stress hyperglycemia occurring in critically-ill patients. There are no evidences of the efficacy of antioxidants in the prevention or control of the complications associated with hyperglycemia¹⁸ (IV).

Specific enteral diets for the control of hyperglycemia are characterized as rich in MUFA and containing low-glycemic index carbohydrates and fiber¹⁹. Very few studies have been performed to date and, though they show no differences in morbidity-mortality with the use of a conventional diet, they achieve a better control of glycemia and a lower need for insulin¹⁹ (Ib), ^20,21 (III). A recent study evidences also a lower variability in blood sugar levels when a specific enteral diet is used in patients with type 2 diabetes²² (III).

Should blood glucose values be normalized in critically-ill patients?

Different studies have shown that hyperglycemia is an independent risk factor for a poorer prognosis in critically-ill patients^23,24.

The outcomes of a study in a population of criticallyill surgical patients maintaining a tight glycemic control, from 80 to 110 mg/dl by continuous perfusion of insulin²⁵ and demonstrating a reduction of 3.4% of the risk of death at the ICU, could not be reproduced in subsequent studies^26,27. Even subsequent publications evidence an increased mortality in the group of patients maintaining strict blood glucose levels (80-110 mg/dl), mortality related to the high incidence of severe hypoglycemia^{28- 30} (Ib).

The largest multicenter study conducted to date (NICESUGAR)³⁰ included 6,104 patients from mixed ICUs and compared 2 ranges of blood glucose levels: 80-108 mg/dL (strict) versus < 180 mg/dL (conventional). The incidence of severe hypoglycemia was higher in the strict control group (6.8 vs 0.5%; p < 0.001) and 90-day mortality in the strict control group was significantly higher (27.5%) than in the conventional group (24.9%) (95% CI, 1.02-1.28; p = 0.02)³⁰ (Ib). The mean blood glucose achieved in the strict control group was 114 mg/dL vs the conventional group 144 mg/dL.

Two recent metaanalyses shows that in all criticallyill patients, the strict control of blood glucose levels (80-110 mg/dl) significantly increased severe hypoglycemia, without improving survival as compared to the conventional control group^31,32 (Ia).

It has been demonstrated that the variability of blood glucose levels along the patient evolution may affect mortality, even if it occurs between blood glucose ranges considered as appropriate³³. In the cohort of 66,184 patients evaluated by the ANZICS (Australian and New Zealand Intensive Care Society), the variability of blood sugar levels over the first days of evolution was associated with an increased adjusted mortality when compared to the appearance of severe hypoglycemia²⁴ (III).

- It is recommended to monitor blood glucose values in all critically-ill patients (A).

- It is recommended, as most appropriate, to maintain blood glucose levels below 150 mg/dl (C).

- It is recommended to start treatment with insulin when blood glucose levels exceed 150 mg/dL (C).

- Continuous insulin perfusion protocols, will be designed to prevent strict blood glucose levels (80-110 mg/dL) in order to reduce the risk of severe hypoglycemia (B).

- It is recommended that continuous insulin perfusion protocols should be designed to avoid the variability of blood glucose levels (C).

- Energy supply should meet patient requirements avoiding overnutrition (C).

- Specific diets for hyperglycemia may decrease insulin requirements in these patients (B).

- In patients with parenteral nutrition it is recommended to use glutamine supplements in order to contribute to hyperglycemia control (B).

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Conflict of interests

The authors declare that they have participated in activities funded by the pharmaceutical industry for marketing of nutritional products (clinical studies, educational programmes and attendance to scientific events). No pharmaceutical industry has participated in the preparation, discussion, writing, and establishing of evidences in any phase of this article.

References

1. McMahon MM, Miles JM. Glycemic control and nutrition in the intensive care unit. Curr Opin Clin Nutr Metab Care 2006; 9: 120-3.         [ Links ]

2. Gramlich L, Kichian K, Pinilla J, Rodych NJ, Dhaliwal R, Heyland DK. Does enteral nutrition compared to parenteral nutrition result in better outcomes in critically ill adult patients? A systematic review of the literature. Nutrition 2004; 20: 43-8.         [ Links ]

3. Coulston AM. Enteral nutrition in the patient with diabetes mellitus. Curr Opin Clin Nutr Metab Care 2000; 3: 11-5.         [ Links ]

4. Grau T, Bonet A. Caloric intake and liver dysfunction in critically ill patients. Curr Opin Clin Nutr Metab Care 2009; 12: 175-9.         [ Links ]

5. American Diabetes Association. Nutrition Recommendations and Interventions for Diabetes: a position statement of the American Diabetes Association. Diabetes Care 2007; 30 (Suppl. 1): S48-65.         [ Links ]

6. Elia M, Ceriello A, Laube H, Sinclair AJ, Engfer M, Stratton RJ. Enteral nutritional support and use of diabetes-specific formulas for patients with diabetes: a systematic review and metaanalysis. Diabetes Care 2005; 28: 2267-79.         [ Links ]

7. Vanschoonbeek K, Lansink M, Van Laere KM, Senden JM, Verdijk LB, Van Loon LJ. Slowly digestible carbohydrate sources can be used to attenuate the postprandial glycemic response to the ingestion of diabetes-specific enteral formulas. Diabetes Educ 2009; 35: 631-40.         [ Links ]

8. Yokoyama J, Someya Y, Yoshihara R, Ishii H. Effects of highmonounsaturated fatty acid enteral formula versus high-carbohydrate enteral formula on plasma glucose concentration and insulin secretion in healthy individuals and diabetic patients. J Int Med Res 2008; 36: 137-46.         [ Links ]

9. Moore FA. Caution: use fat emulsions judiciously in intensive care patients. Crit Care Med 2001; 29: 1644-5.         [ Links ]

10. López Martínez J, Sánchez Castilla M, De Juana Velasco P, Díaz Abad R, Rodríguez Roldán JM, García de Lorenzo y Mateos A, et al. Non-glucose carbohydrates in the parenteral nutrition of patients with systemic inflammatory response syndrome. Nutr Hosp 1999; 14: 71-80.         [ Links ]

11. Valero MA, León-Sanz M, Escobar I, Gomis P, De la Cámara A, Moreno JM. Evaluation of nonglucose carbohydrates in paren teral nutrition for diabetic patients. Eur J Clin Nutr 2001; 55: 1111-6.         [ Links ]

12. Hebert SL, Nair KS. Protein and energy metabolism in type 1 diabetes. Clin Nutr 2010; 29: 13-7.         [ Links ]

13. Borel MJ, Williams PE, Jabbour K, Levenhagen D, Kaizer E, Flakoll PJ. Parenteral glutamine infusion alters insulin-mediated glucose metabolism. JPEN J Parenter Enteral Nutr 1998;22: 280-5.         [ Links ]

14. Bakalar B, Duska F, Pachl J, Fric M, Otahal M, Pazout J, et al. Parenterally administered dipeptide alanylglutamine prevents worsening of insulin sensitivity in multiple-trauma patients. Crit Care Med 2006; 34: 381-6.         [ Links ]

15. Déchelotte P, Hasselmann M, Cynober L, Allaouchiche B, Coëffier M, Hecketsweiler B et al. L-alanyl-L-glutamine dipeptidesupplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study. Crit Care Med 2006; 34: 598-604.         [ Links ]

16. Del Olmo D, López del Val T, Martínez de Icaya P, De Juana P, Alcázar V, Koning A et al. Fiber in enteral nutrition: systematic review of the literature. Nutr Hosp 2004; 19: 167-74.         [ Links ]

17. Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care 2003; 26: 1277-94.         [ Links ]

18. Scott JA, King GL. Oxidative stress and antioxidant treatment in diabetes. Ann NY Acad Sci 2004; 1031: 204-13.         [ Links ]

19. Mesejo A, Acosta JA, Ortega C, Vila J, Fernández M, Ferreres J et al. Comparison of a high-protein disease-specific enteral formula with a high-protein enteral formula in hyperglycemic critically ill patients. Clin Nutr 2003; 22: 295-305.         [ Links ]

20. De Azevedo JR, De Araujo LO, Da Silva WS, De Azevedo RP. A carbohydrate-restrictive strategy is safer and as efficient as intensive insulin therapy in critically ill patients. J Crit Care 2010; 25: 84-9.         [ Links ]

21. Pohl M, Mayr P, Mertl-Roetzer M, Lauster F, Haslbeck M, Hipper B et al. Glycemic control in patients with type 2 diabetes mellitus with a disease-specific enteral formula: stage II of a randomized, controlled multicenter trial. JPEN J Parenter Enteral Nutr 2009; 33: 37-49.         [ Links ]

22. Alish CJ, Garvey WT, Maki KC, Sacks GS, Hustead DS, Hegazi RA et al. A diabetes-specific enteral formula improves glycemic variability in patients with type 2 diabetes. Diabetes Technol Ther 2010; 12: 419-25.         [ Links ]

23. Krinsley JS. Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin Proceed 2003; 78: 1471-8.         [ Links ]

24. Bagshaw SM, Egi M, George C, Bellomo R; Australia New Zealand Intensive Care Society Database Management Committee. Early blood glucose control and mortality in critically ill patients in Australia. Crit Care Med 2009; 37: 463-70.         [ Links ]

25. Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M et al. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001; 345: 1359-67.         [ Links ]

26. Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006; 354: 449-61.         [ Links ]

27. Arabi YM, Tamin HM, Rishu AH. Hypoglucemia with intensive insulin therapy in critically ill patient: predisposing factors and association with mortality. Crit Care Med 2009; 37: 2536-44.         [ Links ]

28. Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N et al; German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008; 358: 125-39.         [ Links ]

29. Preiser JC, Devos P, Ruiz-Santana S, Mélot C, Annane D, Groeneveld J et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med 2009; 35: 1738-48.         [ Links ]

30. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V et al; NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360: 1283-97.         [ Links ]

31. Griesdale DE, De Souza R, Van Dam R, Heyland DK, Cook DJ, Malhotra A, et al. Intensive insuline therapy and mortality among critically ill patients. A meta-analysis including NICESUGAR study data. CMAJ 2009; 180: 821-7.         [ Links ]

32. Marik PE, Preiser JC. Toward understanding tight glycemic control in the ICU: a systematic review and metaanalysis. Chest 2010; 137: 544-51.         [ Links ]

33. Krinsley JS. Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med 2008; 36: 3008-13.         [ Links ]

Correspondence:
C. Vaquerizo Alonso.
Hospital Universitario de Fuenlabrada.
Madrid. Spain.
E-mail: cvaquerizo.hflr@salud.madrid.org