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Hyperglycaemia in critically ill patients: marker or mediator of mortality?
Anouk M Corstjens, Iwan CC van der Horst, Jan G Zijlstra, AB Johan Groeneveld, Felix Zijlstra, Jaap E Tulleken, Jack JM Ligtenberg
Critical Care , 2006, DOI: 10.1186/cc4957
Abstract: Acute hyperglycaemia is frequently present in situations of stress, both in diabetic and in nondiabetic patients [1-3]. Because it is so common, it could be viewed as a physiologic adaptation during the 'fight or flight' response. On the other hand, it has been associated with complications, prolonged intensive care unit (ICU) and hospital stay, and increased mortality. The important issue is whether hyperglycaemia is just related to disease severity or is an independent risk factor that contributes to morbidity and mortality [4]. If hyperglycaemia is an independent risk factor, then tight glucose control (TGC) may have beneficial effects on morbidity and mortality. Conversely, if hyperglycaemia is not a risk factor per se, then the risks associated with glucose control may outweigh the benefits. We made an inventory of the prevalence and prognostic value of hyperglycaemia, and of the effects of glucose control in different groups of critically ill patients, in order to evaluate the available evidence.Table 1 provides an overview of various situations in which a correlation between hyperglycaemia and mortality has been demonstrated. Different authors use different threshold values to define hyperglycaemia.Among patients admitted to a general hospital, 38% exhibited increased blood glucose (BG) values, defined as either fasting BG values above 7 mmol/l or two random values above 11.1 mmol/l [5]. In that retrospective study 16% of 223 patients admitted with new onset hyperglycaemia (without a history of diabetes mellitus) died during their stay in hospital, as compared with only 1.7% of 1168 patients without hyperglycaemia (P < 0.001). The cause of death in the hyperglycaemia group was more often related to infection (33% versus 20% without hyperglycaemia) or acute neurological complications (19% versus 10%). Patients with new onset hyperglycaemia had a longer hospital stay and were more often admitted to the ICU (29% versus 9%). In this study, diabetic patients had a
Stress hyperglycaemia in critically ill patients: Potential role of incretin hormones; a preliminary study
Llompart-Pou,J. A.; Fernández-de-Castillo,A. G.; Burguera,B.; Pérez-Bárcena,J.; Marsé,P.; Rodríguez-Yago,M.; Barceló,A.; Raurich,J. M.a;
Nutrición Hospitalaria , 2012,
Abstract: background: stress hyperglycaemia is common in the intensive care unit (icu) setting and has been related to a worst outcome. objective: the objective was to characterize the association of glucoregulatory hormones, mainly incretins, with the levels of glycaemia, and its relationship with outcome in icu patients. methods: we prospectively studied 60 patients. stress hyperglycaemia was diagnosed when glycaemia was < 115 mg/dl. at icu admission we determined glycaemia, insulin, glucagon, cortisol, glucose-dependent insulinotropic polypeptide (gip) and glucagon-like peptide-1 (glp-1) plasma levels. groups were compared using kruskal-wallis test. the association between glycaemia levels and glucoregulatory hormones was evaluated using linear regression. results: forty-five patients (75%) had hyperglycaemia. we observed no differences in glucoregulatory hormones levels between normo- and hyper- glycaemia groups. glycaemia levels were not significantly correlated with insulin, glucagon, cortisol or gip levels, but were correlated with glp-1 (p = 0.04). glp-1 was also correlated with cortisol (p = 0.01), but failed to show a significant correlation with insulin, glucagon or gip levels. lower levels of plasma glp-1 were found in patients with stress hyperglycaemia requiring vasoactive support (p = 0.02). conclusions: glycaemia levels were correlated with glp-1 levels in icu patients. glp-1 levels were also associated with cortisol. patients with stress hyperglycaemia who required vasoactive support had lower incretin levels compared with those patients with stress hyperglycaemia who were hemodynamically stables. (clinicaltrials.gov identifier: nct01087372).
Tight blood glucose control: a recommendation applicable to any critically ill patient?
Philippe Devos, Jean-Charles Preiser
Critical Care , 2004, DOI: 10.1186/cc2989
Abstract: Until the end of the past millenium, relatively little attention was given to control of blood sugar levels. In critically ill patients, hyperglycaemia was considered to be physiological because it results from the metabolic and hormonal changes that accompany the stress response to injury. In most intensive care units (ICUs), blood sugar was checked every 4–6 hours and hyperglycaemia (defined as blood sugar levels >10–12 mmol/l [180–216 mg/dl]) was corrected by subcutaneous or intravenous insulin. The presence of pre-existing diabetes mellitus or post-neurosurgical status often prompted more intense control of hyperglycaemia. Furthermore, the issue of glucose control was discussed in few sessions or satellite symposia during intensive care meetings.The deleterious effects of hyperglycaemia during critical illness have been characterized over the past few years, and include an increased susceptibility to infections and thromboses, macrovascular and microvascular changes, and delayed wound healing, among other effects (for review [1]). Renewed interest in control of hyperglycaemia in critically ill patients (Fig. 1) followed the publication of a study conducted by Van den Berghe and coworkers in 2001 [2]. Those investigators reported a 43% decrease in relative intensive care mortality as well as consistent decreases in several surrogate markers of disease severity in patients randomly assigned to tight glucose control by intensive intravenous insulin therapy. A post hoc multivariate logistic regression analysis of these data suggested that control of hyperglycaemia played a more important role than did the amount of insulin administered [3]. Interestingly enough, at least two recent retrospective, large-scale studies [4,5] confirmed that outcome was improved in patients whose average blood glucose was maintained below 8 mmol/l (144 mg/dl; Table 1).Although the findings reported by Van den Berghe and coworkers are impressive, some concern arose regarding the applicabi
Exogenous glucagon-like peptide-1 attenuates the glycaemic response to postpyloric nutrient infusion in critically ill patients with type-2 diabetes
Adam M Deane, Matthew J Summers, Antony V Zaknic, Marianne J Chapman, Robert JL Fraser, Anna E Di Bartolomeo, Judith M Wishart, Michael Horowitz
Critical Care , 2011, DOI: 10.1186/cc9983
Abstract: Eleven critically ill mechanically-ventilated patients with known type-2 diabetes received intravenous infusions of GLP-1 (1.2 pmol/kg/minute) and placebo from t = 0 to 270 minutes on separate days in randomised double-blind fashion. Between t = 30 to 270 minutes a liquid nutrient was infused intraduodenally at a rate of 1 kcal/min via a naso-enteric catheter. Blood glucose, serum insulin and C-peptide, and plasma glucagon were measured. Data are mean ± SEM.GLP-1 attenuated the overall glycaemic response to nutrient (blood glucose AUC30-270 min: GLP-1 2,244 ± 184 vs. placebo 2,679 ± 233 mmol/l/minute; P = 0.02). Blood glucose was maintained at < 10 mmol/l in 6/11 patients when receiving GLP-1 and 4/11 with placebo. GLP-1 increased serum insulin at 270 minutes (GLP-1: 23.4 ± 6.7 vs. placebo: 16.4 ± 5.5 mU/l; P < 0.05), but had no effect on the change in plasma glucagon.Exogenous GLP-1 in a dose of 1.2 pmol/kg/minute attenuates the glycaemic response to small intestinal nutrient in critically ill patients with type-2 diabetes. Given the modest magnitude of the reduction in glycaemia the effects of GLP-1 at higher doses and/or when administered in combination with insulin, warrant evaluation in this group.ANZCTR:ACTRN12610000185066The management of hyperglycaemia in the critically ill is an important, and contentious, issue [1,2]. In critically ill patients the ideal glycaemic range is uncertain, but is likely to be ≤ 10 mmol/l [1]. When compared to critically ill patients with so-called 'stress hyperglycaemia' those with known diabetes are at greater risk of complications from hypoglycaemia, yet appear to be less vulnerable to the toxicity of hyperglycaemia [2]. The mechanisms underlying hyperglycaemia in critically ill patients with known diabetes are complex, but include relative insulin insufficiency, insulin resistance and hyperglucagonaemia [3].Glucagon-like peptide-1 (GLP-1), secreted from enteroendocrine L-cells in response to intestinal nutrient, has the capac
Hyperglycaemia results from beta-cell dysfunction in critically ill children with respiratory and cardiovascular failure: a prospective observational study
Catherine M Preissig, Mark R Rigby
Critical Care , 2009, DOI: 10.1186/cc7732
Abstract: C-peptide and blood glucose (BG) levels were assessed in 41 children aged 2 to 18 years old who were admitted to our paediatric intensive care unit (PICU). Patients who developed CIH, defined as persistent BG above 7.7 mmol/L, were treated with insulin infusion to achieve BG levels between 4.4 and 7.7 mmol/L. C-peptide levels were compared with respect to CIH development and degree of organ failure in all patients. Respiratory and cardiovascular failure were defined as need for mechanical ventilation and need for vasoactive infusions, respectively. Clinical and laboratory parameters, including c-peptide levels, were assessed.Of 41 children enrolled, 18 had respiratory failure only, 11 had both respiratory and cardiovascular failure, and 12 had neither respiratory or cardiovascular failure. Nine patients with respiratory failure only, 10 with both respiratory and cardiovascular failure, and none with no respiratory or cardiovascular failure developed CIH. Patients with CIH and respiratory and cardiovascular failure (n = 10) had very low c-peptide levels (4.4 ng/mL) despite significantly elevated mean BG levels (10.8 mmol/L), while those with CIH and respiratory failure only had very high c-peptide levels (11.5 ng/mL) with mean BG of 9.9 mmol/L. Low endogenous insulin production in those with respiratory and cardiovascular failure was associated with rapid onset of CIH, illness severity, higher insulin requirement and longer mechanical ventilation days, PICU length of stay and CIH duration.Primary beta-cell dysfunction as defined by low endogenous c-peptide production appears to be prevalent in critically ill children with both respiratory and cardiovascular failure who develop CIH, whereas elevated insulin resistance appears to be the prominent cause of CIH in children with respiratory failure only. Our finding that beta-cell dysfunction is present in a subset of critically ill children with CIH challenges the assertion from adult studies that CIH is primarily the re
Recommendations of the GARIN group for managing non-critically ill patients with diabetes or stress hyperglycaemia and artificial nutrition Recomendaciones del grupo GARIN para el manejo de pacientes no críticos con diabetes o hiperglucemia de estrés y nutrición artificial
G. Olveira,P. P. García-Luna,J. L. Pereira,I. Rebollo
Nutrición Hospitalaria , 2012,
Abstract: Background & aims: By means of this update, the GARIN working group aims to define its position regarding the treatment of patients with diabetes or stress hyperglycaemia and artificial nutrition. In this area there are many aspects of uncertainty, especially in non-critically ill patients. Methods: Bibliographical review, and specific questions in advance were discussed and answered at a meeting in the form of conclusions. Results: We propose a definition of stress hyperglycaemia. The indications and access routes for artificial nutrition are no different in patients with diabetes/stress hyperglycaemia than in non-diabetics. The objective must be to keep pre-prandial blood glucose levels between 100 and 140 mg/dl and post-prandial levels between 140 and 180 mg/dl. Hyperglycemia can be prevented through systematic monitoring of capillary glycaemias and adequately calculate energy-protein needs. We recommend using enteral formulas designed for patients with diabetes (high monounsaturated fat) to facilitate metabolic control. The best drug treatment for treating hyperglycaemia/diabetes in hospitalised patients is insulin and we make recommendations for adapt the theoretical insulin action to the nutrition infusion regimen. We also addressed recommendations for future investigation. Conclusions: This recommendations about artificial nutrition in patients with diabetes or stress hyperglycaemia can add value to clinical work. Introducción y objetivos: En el tratamiento de los pacientes con diabetes o hiperglucemia de estrés y la nutrición artificial existen muchas áreas de incertidumbre, sobre todo en pacientes no críticos. El grupo de trabajo GARIN tiene como objetivo definir su posición en este campo. Material y métodos: Revisión bibliográfica previa y reunión presencial en la que se discutieron y contestaron preguntas específicas sobre el tema. Resultados: Proponemos una definición de hiperglucemia de estrés. Las indicaciones y las rutas de acceso a la nutrición artificial no difieren en los pacientes con hiperglucemia de estrés o diabetes respecto a los no diabéticos. El objetivo debe ser mantener los niveles de glucemia preprandial entre 100 y 140 mg/dl y postprandial entre 140 y 180 mg/dl. La hiperglucemia puede prevenirse a través de una monitorización sistemática de las glucemias capilares y un cálculo adecuado de las necesidades energético-proteicas. Recomendamos el uso de fórmulas enterales dise adas para pacientes con diabetes (alto contenido en grasas monoinsaturadas) para facilitar el control metabólico. El mejor tratamiento farmacológico para t
Stress hyperglycaemia in critically ill patients: Potential role of incretin hormones; a preliminary study Hiperglucemia de estrés en el paciente crítico: papel potencial de las incretinas; estudio preliminar  [cached]
J. A. Llompart-Pou,A. G. Fernández-de-Castillo,B. Burguera,J. Pérez-Bárcena
Nutrición Hospitalaria , 2012,
Abstract: Background: Stress hyperglycaemia is common in the intensive care unit (ICU) setting and has been related to a worst outcome. Objective: The objective was to characterize the association of glucoregulatory hormones, mainly incretins, with the levels of glycaemia, and its relationship with outcome in ICU patients. Methods: We prospectively studied 60 patients. Stress hyperglycaemia was diagnosed when glycaemia was < 115 mg/dL. At ICU admission we determined glycaemia, insulin, glucagon, cortisol, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) plasma levels. Groups were compared using Kruskal-Wallis test. The association between glycaemia levels and glucoregulatory hormones was evaluated using linear regression. Results: Forty-five patients (75%) had hyperglycaemia. We observed no differences in glucoregulatory hormones levels between normo- and hyper- glycaemia groups. Glycaemia levels were not significantly correlated with insulin, glucagon, cortisol or GIP levels, but were correlated with GLP-1 (p = 0.04). GLP-1 was also correlated with cortisol (p = 0.01), but failed to show a significant correlation with insulin, glucagon or GIP levels. Lower levels of plasma GLP-1 were found in patients with stress hyperglycaemia requiring vasoactive support (p = 0.02). Conclusions: Glycaemia levels were correlated with GLP-1 levels in ICU patients. GLP-1 levels were also associated with cortisol. Patients with stress hyperglycaemia who required vasoactive support had lower incretin levels compared with those patients with stress hyperglycaemia who were hemodynamically stables. (ClinicalTrials.gov Identifier: NCT01087372). Antecedentes: La hiperglucemia de estrés es habitual en el contexto de la Unidad de cuidados intensivos (UCI) y se ha relacionado con un peor pronóstico. Objetivo: el objetivo fue caracterizar la asociación de hormonas glucorreguladoras, principalmente las incretinas, con las glucemias y su relación con el pronóstico de los pacientes de UCI. Métodos: Estudiamos de forma prospectiva a 60 pacientes. La hiperglucemia de estrés se diagnosticaba cuando la glucemia era < 115 mg/dl. En el ingreso en la UCI, determinamos la glucemia y las concentraciones plasmáticas de insulina, glucagón, cortisol, polipéptido insulinotropo dependiente de glucosa (GIP) y péptido-1 de tipo glucagón (GLP-1). Se compararon los grupos mediante la prueba de Kruskal-Wallis. La asociación entre las glucemias y las hormonas contrarreguladoras se evaluó mediante regresión linear. Resultados: 45 pacientes (75%) tenían hiperglucemia. No observa
Antifungal susceptibility of invasive yeast isolates in Italy: the GISIA3 study in critically ill patients
Giulia Morace, Elisa Borghi, Roberta Iatta, Gerardino Amato, Stefano Andreoni, Gioconda Brigante, Claudio Farina, Giuliana Cascio, Gianluigi Lombardi, Ester Manso, Michele Mussap, Patrizia Pecile, Roberto Rigoli, Elisabetta Tangorra, Maria Valmarin, Maria Montagna
BMC Infectious Diseases , 2011, DOI: 10.1186/1471-2334-11-130
Abstract: 638 yeasts were isolated from the blood, central venous catheters and sterile fluids of 578 patients on general and surgical intensive care units and surgical wards. Etest strips and Sensititre panels were used to test the susceptibility of the isolates to amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole, posaconazole and voriconazole in 13 laboratories centres (LC) and two co-ordinating centres (CC). The Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method was used at the CCs for comparison.Etest and Sensititre (LC/CC) MIC90 values were, respectively: amphotericin B 0.5/0.38, 1/1 mg/L; anidulafungin 2/1.5 and 1/1 mg/L; caspofungin 1/0.75 and 0.5/0.5 mg/L; fluconazole 12/8 and 16/16 mg/L; itraconazole 1/1.5, 0.5/0.5 mg/L; posaconazole 0.5 mg/L and voriconazole 0.25 mg/L for all. The overall MIC90 values were influenced by the reduced susceptibility of Candida parapsilosis isolates to echinocandins and a reduced or lack of susceptibility of Candida glabrata and Candida krusei to azoles, in particular fluconazole and itraconazole. Comparison of the LC and CC results showed good Essential Agreement (90.3% for Etest and 92.9% for Sensititre), and even higher Categorical Agreement (93.9% for Etest and 96% for Sensititre); differences were observed according to the species, method, and antifungal drug. No cross-resistance between echinocandins and triazoles was detected.Our data confirm the different antifungal susceptibility patterns among species, and highlight the need to perform antifungal susceptibility testing of clinically relevant yeasts. With the exception of a few species (e.g. C. glabrata for azoles and C. parapsilosis for echinocandins), the findings of our study suggest that two of the most widely used commercial methods (Etest and Sensititre) provide valid and reproducible results.Severe yeast infections, especially candidaemia, represent a significant health problem in patients at high risk of infectio
Pro/con debate: Is intensive insulin therapy targeting tight blood glucose control of benefit in critically ill patients?
Tobias M Merz, Simon Finfer
Critical Care , 2008, DOI: 10.1186/cc6837
Abstract: Hyperglycaemia is a common accompaniment of acute illness. In published trials insulin treatment was required in more than 98% of ICU patients in whom the goal was to maintain normoglycaemia [1-3]. The hyperglycaemia is thought to result from a number of processes; elevated levels of cortisol, epinephrine, norepinephrine and glucagon increase gluconeogenesis [4-8] and glycogenolysis [9] whilst insulin resistance leads to a decrease in insulin-stimulated uptake of glucose in heart and adipose tissue. In addition, exercise induced uptake of glucose in skeletal muscle is absent in immobilized critically ill patients [10,11]. Hyperglycaemia may cause harm by direct toxicity and through increased intracellular oxidative stress due to higher mitochondrial peroxide production [12,13]. The clinical consequence of hyperglycaemia appears to be an increase in morbidity and mortality in a variety of clinical settings, including heterogeneous populations of critically ill patients [14]. In trauma patients hyperglycaemia is associated with higher mortality and an increased rate of infectious complications [15] as well as with worse neurological outcome in the subset of patients with traumatic brain injury [16]. In patients with sepsis and haematological malignancy, hyperglycaemia at hospital admission predicts higher mortality [17,18]. Hyperglycaemia has also been associated with higher mortality and poor functional recovery in non-diabetic stroke patients [19], and with increased risk of in-hospital mortality, congestive heart failure and cardiogenic shock after myocardial infarction [20]. In summary, hyperglycaemia is common in critically ill patients and its occurrence is clearly associated with a worse outcome; thus, it is natural to ask whether hyperglycaemia is simply a marker of illness severity, or is hyperglycaemia itself harmful, in which case does normalizing blood glucose improve patients' outcomes?The evidence that short-term treatment of hyperglycaemia is beneficial
The critically ill kidney
J.I Piercy
Southern African Journal of Anaesthesia and Analgesia , 2009,
Abstract: Acute kidney injury is a common finding in the critically ill patient. It carries a mortality of up to 60.3%. This review covers the definition, early detection and management of acute kidney injury. The review explores current controversies in the prescribing of renal replacement therapy and focuses on the prevention and management of contrast induced nephropathy.
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