Purpose of review To summarize the advances in literature that support the best current practices... more Purpose of review To summarize the advances in literature that support the best current practices regarding glucose control in the critically ill. Recent findings There are differences between patients with and without diabetes regarding the relationship of glucose metrics during acute illness to mortality. Among patients with diabetes, an assessment of preadmission glycemia, using measurement of Hemoglobin A1c (HgbA1c) informs the choice of glucose targets. For patients without diabetes and for patients with low HgbA1c levels, increasing mean glycemia during critical illness is independently associated with increasing risk of mortality. For patients with poor preadmission glucose control the appropriate blood glucose target has not yet been established. New metrics, including stress hyperglycemia ratio and glycemic gap, have been developed to describe the relationship between acute and chronic glycemia. Summary A ‘personalized’ approach to glycemic control in the critically ill, with recognition of preadmission glycemia, is supported by an emerging literature and is suitable for testing in future interventional trials.
ContextThe outcome of patients requiring intensive care can be influenced by the presence of prev... more ContextThe outcome of patients requiring intensive care can be influenced by the presence of previously undiagnosed diabetes (undiagDM).ObjectiveThis work aimed to define the clinical characteristics, glucose control metrics, and outcomes of patients admitted to the intensive care unit (ICU) with undiagDM, and compare these to patients with known DM (DM).MethodsThis case-control investigation compared undiagDM (glycated hemoglobin A1c [HbA1c] ≥ 6.5%, no history of diabetes) to patients with DM. Glycemic ratio (GR) was calculated as the quotient of mean ICU blood glucose (BG) and estimated preadmission glycemia, based on HbA1c ([28.7 × HbA1c] – 46.7 mg/dL). GR was analyzed by bands: less than 0.7, 0.7 to less than or equal to 0.9, 0.9 to less than 1.1, and greater than or equal to 1.1. Risk-adjusted mortality was represented by the Observed:Expected mortality ratio (OEMR), calculated as the quotient of observed mortality and mortality predicted by the severity of illness (APACHE IV prediction of mortality).ResultsOf 5567 patients 294 (5.3%) were undiagDM. UndiagDM had lower ICU mean BG (P < .0001) and coefficient of variation (P < .0001) but similar rates of hypoglycemia (P = .08). Mortality and risk-adjusted mortality were similar in patients with GR less than 1.1 comparing undiagDM and DM. However, for patients with GR greater than or equal to 1.1, mortality (38.5% vs 10.3% [P = .0072]) and risk-adjusted mortality (OEMR 1.18 vs 0.52 [P < .0001]) were higher in undiagDM than in DM.ConclusionThese data suggest that DM patients may develop tolerance to hyperglycemia that occurs during critical illness, a protective mechanism not observed in undiagDM, for whom hyperglycemia remains strongly associated with higher risk of mortality. These results may shed light on the natural history of diabetes.
OBJECTIVES: To determine the associations of relative hypoglycemia and hemoglobin A1c-adjusted ti... more OBJECTIVES: To determine the associations of relative hypoglycemia and hemoglobin A1c-adjusted time in blood glucose (BG) band (HA-TIB) with mortality in critically ill patients. DESIGN: Retrospective cohort investigation. SETTING: University-affiliated adult medical-surgical ICU. PATIENTS: Three thousand six hundred fifty-five patients with at least four BG tests and hemoglobin A1c (HbA1c) level admitted between September 14, 2014, and November 30, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were stratified for HbA1c bands of &lt;6.5%; 6.5–7.9%; greater than or equal to 8.0% with optimal affiliated glucose target ranges of 70–140, 140–180, and 180–250 mg/dL, respectively. HA-TIB, a new glycemic metric, defined the HbA1c-adjusted time in band. Relative hypoglycemia was defined as BG 70–110 mg/dL for patients with HbA1c ≥ 8.0%. Further stratification included diabetes status-no diabetes (NO-DM, n = 2,616) and preadmission treatment with or without insulin (DM-INS, n = 352; DM-No-INS, n = 687, respectively). Severity-adjusted mortality was calculated as the observed:expected mortality ratio (O:EMR), using the Acute Physiology and Chronic Health Evaluation IV prediction of mortality. Among NO-DM, mortality and O:EMR, decreased with higher TIB 70–140 mg/dL (p &lt; 0.0001) and were lowest with TIB 90–100%. O:EMR was lower for HA-TIB greater than or equal to 50% than less than 50% and among all DM-No-INS but for DM-INS only those with HbA1 greater than or equal to 8.0%.Among all patients with hba1c greater than or equal to 8.0% And no bg less than 70 mg/dl, mortality was 18.0% For patients with relative hypoglycemia (bg, 70–110 mg/dl) (p &lt; 0.0001) And was 0.0%, 12.9%, 13.0%, And 34.8% For patients with 0, 0.1–2.9, 3.0–11.9, And greater than or equal to 12.0 Hours of relative hypoglycemia (p &lt; 0.0001). CONCLUSIONS: These findings have considerable bearing on interpretation of previous trials of intensive insulin therapy in the critically ill. Moreover, they suggest that BG values in the 70–110 range may be deleterious for patients with HbA1c greater than or equal to 8.0% and that the appropriate target for BG should be individualized to HbA1c levels. These conclusions need to be tested in randomized trials.
Annales Francaises D Anesthesie Et De Reanimation, Mar 1, 2014
J.-Y. Lefrant *, D. Hurel , N.J. Cano , C. Ichai , J.-C. Preiser , F. Tamion h a Services des réa... more J.-Y. Lefrant *, D. Hurel , N.J. Cano , C. Ichai , J.-C. Preiser , F. Tamion h a Services des réanimations, division anesthésie réanimation douleur urgence, CHU de Nîmes, place du Pr-Robert-Debré, 30029 Nîmes cedex 9, France b Service de réanimation médico-chirurgicale, centre hospitalier François-Quesnay, 2, boulevard Sully, 78201 Mantes-la-Jolie cedex, France c Service de nutrition, CHU de Clermont-Ferrand, 63003 Clermont-Ferrand cedex, France d Unité de nutrition humaine, Clermont université, université d’Auvergne, BP 10448, 63000 Clermont-Ferrand, France e Inra, UMR 1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France f Service de réanimation médico-chirurgicale, hôpital Saint-Roch, CHU de Nice, 5, rue Pierre-Dévoluy, 06006 Nice cedex 1, France g Service des soins intensifs, hôpital universitaire Erasme, 808, route de Lennik, 1070 Bruxelles, Belgique h Service de réanimation médicale, hôpital Charles-Nicolle, CHU de Rouen, 1, rue de Germont, 76081 Rouen cedex, France
Systemic inflammatory response syndrome (SIRS) can be related to acute inflammatory conditions th... more Systemic inflammatory response syndrome (SIRS) can be related to acute inflammatory conditions that can be sometimes missed and inappropriately managed as severe infections. We report a case of Churg Strauss Syndrome (CSS), presenting as septic shock with acute onset of fever and multiple organ failure including pulmonary involvement with severe hypoxemia, hypotension requiring vasoactive support and acute renal failure. Antibiotics were discontinued and intravenous steroids allowed a rapid clinical improvement in close relationship with the fall in circulating eosinophils count.
Over the last ten years, much progress has been achieved in intensive care medicine. Large random... more Over the last ten years, much progress has been achieved in intensive care medicine. Large randomized studies, most often their multicentric, were performed and their results were translated into rules to be followed for the most appropriate treatment of life-threatening organ failures. The place of non-invasive ventilation in the management of hypercapnic or hypoxic respiratory insufficiencies was thus defined, and the methods for less traumatic mechanical ventilation were specified. The techniques of renal replacement therapy were compared and the optimal doses of dialysis or hemofiltration were established. The metabolic support of the patients was also altered following landmark studies, such as the management of blood glucose, which deeply influenced the approach to critically ill patients.
The metabolic response to stress have been selected as an adaptive response to survive critical i... more The metabolic response to stress have been selected as an adaptive response to survive critical illness. Several mechanisms well preserved over the evolution, including the stimulation of the sympathetic nervous system, the release of pituitary hormones, a peripheral resistance to the effects of these and other anabolic factors are triggered to increase the provision of energy substrates to the vital tissues. After an acute insult, alternative substrates are used as a result of the loss of control of energy substrate utilization. The clinical consequences of the metabolic response to stress include sequential changes in energy expenditure, stress hyperglycemia, changes in body composition, psychological and behavioral problems. The loss of muscle proteins and function is a major long-term consequence of stress metabolism. Specific therapeutic interventions, including hormone supplementation, enhanced protein intake and early mobilization are investigated.
Background: Interventional studies investigating blood glucose (BG) management in intensive care ... more Background: Interventional studies investigating blood glucose (BG) management in intensive care units (ICU) have been inconclusive. New insights are needed. We assessed the ability of a new metric, the Glycemic Ratio (GR), to determine the relationship of ICU glucose control relative to preadmission glycemia and mortality. Methods: Retrospective cohort investigation (n = 4790) in an adult medical-surgical ICU included patients with minimum four BGs, hemoglobin (Hgb), and hemoglobin A1c (HbA1c). The GR is the quotient of mean ICU BGs (mBG) and estimated preadmission BG, derived from HbA1c. Results: Mortality displayed a J-shaped curve with GR (nadir GR 0.9), independent of background glycemia, consistent for HbA1c <6.5% vs >6.5%, and Hgb >10 g/dL vs <10 g/dL and medical versus surgical. An optimal range of GR 0.80 to 0.99 was associated with decreased mortality compared with GR above and below this range. The mBG displayed a linear relationship with mortality at lower Hb...
Purpose of review To summarize the advances in literature that support the best current practices... more Purpose of review To summarize the advances in literature that support the best current practices regarding glucose control in the critically ill. Recent findings There are differences between patients with and without diabetes regarding the relationship of glucose metrics during acute illness to mortality. Among patients with diabetes, an assessment of preadmission glycemia, using measurement of Hemoglobin A1c (HgbA1c) informs the choice of glucose targets. For patients without diabetes and for patients with low HgbA1c levels, increasing mean glycemia during critical illness is independently associated with increasing risk of mortality. For patients with poor preadmission glucose control the appropriate blood glucose target has not yet been established. New metrics, including stress hyperglycemia ratio and glycemic gap, have been developed to describe the relationship between acute and chronic glycemia. Summary A ‘personalized’ approach to glycemic control in the critically ill, with recognition of preadmission glycemia, is supported by an emerging literature and is suitable for testing in future interventional trials.
ContextThe outcome of patients requiring intensive care can be influenced by the presence of prev... more ContextThe outcome of patients requiring intensive care can be influenced by the presence of previously undiagnosed diabetes (undiagDM).ObjectiveThis work aimed to define the clinical characteristics, glucose control metrics, and outcomes of patients admitted to the intensive care unit (ICU) with undiagDM, and compare these to patients with known DM (DM).MethodsThis case-control investigation compared undiagDM (glycated hemoglobin A1c [HbA1c] ≥ 6.5%, no history of diabetes) to patients with DM. Glycemic ratio (GR) was calculated as the quotient of mean ICU blood glucose (BG) and estimated preadmission glycemia, based on HbA1c ([28.7 × HbA1c] – 46.7 mg/dL). GR was analyzed by bands: less than 0.7, 0.7 to less than or equal to 0.9, 0.9 to less than 1.1, and greater than or equal to 1.1. Risk-adjusted mortality was represented by the Observed:Expected mortality ratio (OEMR), calculated as the quotient of observed mortality and mortality predicted by the severity of illness (APACHE IV prediction of mortality).ResultsOf 5567 patients 294 (5.3%) were undiagDM. UndiagDM had lower ICU mean BG (P < .0001) and coefficient of variation (P < .0001) but similar rates of hypoglycemia (P = .08). Mortality and risk-adjusted mortality were similar in patients with GR less than 1.1 comparing undiagDM and DM. However, for patients with GR greater than or equal to 1.1, mortality (38.5% vs 10.3% [P = .0072]) and risk-adjusted mortality (OEMR 1.18 vs 0.52 [P < .0001]) were higher in undiagDM than in DM.ConclusionThese data suggest that DM patients may develop tolerance to hyperglycemia that occurs during critical illness, a protective mechanism not observed in undiagDM, for whom hyperglycemia remains strongly associated with higher risk of mortality. These results may shed light on the natural history of diabetes.
OBJECTIVES: To determine the associations of relative hypoglycemia and hemoglobin A1c-adjusted ti... more OBJECTIVES: To determine the associations of relative hypoglycemia and hemoglobin A1c-adjusted time in blood glucose (BG) band (HA-TIB) with mortality in critically ill patients. DESIGN: Retrospective cohort investigation. SETTING: University-affiliated adult medical-surgical ICU. PATIENTS: Three thousand six hundred fifty-five patients with at least four BG tests and hemoglobin A1c (HbA1c) level admitted between September 14, 2014, and November 30, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were stratified for HbA1c bands of &lt;6.5%; 6.5–7.9%; greater than or equal to 8.0% with optimal affiliated glucose target ranges of 70–140, 140–180, and 180–250 mg/dL, respectively. HA-TIB, a new glycemic metric, defined the HbA1c-adjusted time in band. Relative hypoglycemia was defined as BG 70–110 mg/dL for patients with HbA1c ≥ 8.0%. Further stratification included diabetes status-no diabetes (NO-DM, n = 2,616) and preadmission treatment with or without insulin (DM-INS, n = 352; DM-No-INS, n = 687, respectively). Severity-adjusted mortality was calculated as the observed:expected mortality ratio (O:EMR), using the Acute Physiology and Chronic Health Evaluation IV prediction of mortality. Among NO-DM, mortality and O:EMR, decreased with higher TIB 70–140 mg/dL (p &lt; 0.0001) and were lowest with TIB 90–100%. O:EMR was lower for HA-TIB greater than or equal to 50% than less than 50% and among all DM-No-INS but for DM-INS only those with HbA1 greater than or equal to 8.0%.Among all patients with hba1c greater than or equal to 8.0% And no bg less than 70 mg/dl, mortality was 18.0% For patients with relative hypoglycemia (bg, 70–110 mg/dl) (p &lt; 0.0001) And was 0.0%, 12.9%, 13.0%, And 34.8% For patients with 0, 0.1–2.9, 3.0–11.9, And greater than or equal to 12.0 Hours of relative hypoglycemia (p &lt; 0.0001). CONCLUSIONS: These findings have considerable bearing on interpretation of previous trials of intensive insulin therapy in the critically ill. Moreover, they suggest that BG values in the 70–110 range may be deleterious for patients with HbA1c greater than or equal to 8.0% and that the appropriate target for BG should be individualized to HbA1c levels. These conclusions need to be tested in randomized trials.
Annales Francaises D Anesthesie Et De Reanimation, Mar 1, 2014
J.-Y. Lefrant *, D. Hurel , N.J. Cano , C. Ichai , J.-C. Preiser , F. Tamion h a Services des réa... more J.-Y. Lefrant *, D. Hurel , N.J. Cano , C. Ichai , J.-C. Preiser , F. Tamion h a Services des réanimations, division anesthésie réanimation douleur urgence, CHU de Nîmes, place du Pr-Robert-Debré, 30029 Nîmes cedex 9, France b Service de réanimation médico-chirurgicale, centre hospitalier François-Quesnay, 2, boulevard Sully, 78201 Mantes-la-Jolie cedex, France c Service de nutrition, CHU de Clermont-Ferrand, 63003 Clermont-Ferrand cedex, France d Unité de nutrition humaine, Clermont université, université d’Auvergne, BP 10448, 63000 Clermont-Ferrand, France e Inra, UMR 1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France f Service de réanimation médico-chirurgicale, hôpital Saint-Roch, CHU de Nice, 5, rue Pierre-Dévoluy, 06006 Nice cedex 1, France g Service des soins intensifs, hôpital universitaire Erasme, 808, route de Lennik, 1070 Bruxelles, Belgique h Service de réanimation médicale, hôpital Charles-Nicolle, CHU de Rouen, 1, rue de Germont, 76081 Rouen cedex, France
Systemic inflammatory response syndrome (SIRS) can be related to acute inflammatory conditions th... more Systemic inflammatory response syndrome (SIRS) can be related to acute inflammatory conditions that can be sometimes missed and inappropriately managed as severe infections. We report a case of Churg Strauss Syndrome (CSS), presenting as septic shock with acute onset of fever and multiple organ failure including pulmonary involvement with severe hypoxemia, hypotension requiring vasoactive support and acute renal failure. Antibiotics were discontinued and intravenous steroids allowed a rapid clinical improvement in close relationship with the fall in circulating eosinophils count.
Over the last ten years, much progress has been achieved in intensive care medicine. Large random... more Over the last ten years, much progress has been achieved in intensive care medicine. Large randomized studies, most often their multicentric, were performed and their results were translated into rules to be followed for the most appropriate treatment of life-threatening organ failures. The place of non-invasive ventilation in the management of hypercapnic or hypoxic respiratory insufficiencies was thus defined, and the methods for less traumatic mechanical ventilation were specified. The techniques of renal replacement therapy were compared and the optimal doses of dialysis or hemofiltration were established. The metabolic support of the patients was also altered following landmark studies, such as the management of blood glucose, which deeply influenced the approach to critically ill patients.
The metabolic response to stress have been selected as an adaptive response to survive critical i... more The metabolic response to stress have been selected as an adaptive response to survive critical illness. Several mechanisms well preserved over the evolution, including the stimulation of the sympathetic nervous system, the release of pituitary hormones, a peripheral resistance to the effects of these and other anabolic factors are triggered to increase the provision of energy substrates to the vital tissues. After an acute insult, alternative substrates are used as a result of the loss of control of energy substrate utilization. The clinical consequences of the metabolic response to stress include sequential changes in energy expenditure, stress hyperglycemia, changes in body composition, psychological and behavioral problems. The loss of muscle proteins and function is a major long-term consequence of stress metabolism. Specific therapeutic interventions, including hormone supplementation, enhanced protein intake and early mobilization are investigated.
Background: Interventional studies investigating blood glucose (BG) management in intensive care ... more Background: Interventional studies investigating blood glucose (BG) management in intensive care units (ICU) have been inconclusive. New insights are needed. We assessed the ability of a new metric, the Glycemic Ratio (GR), to determine the relationship of ICU glucose control relative to preadmission glycemia and mortality. Methods: Retrospective cohort investigation (n = 4790) in an adult medical-surgical ICU included patients with minimum four BGs, hemoglobin (Hgb), and hemoglobin A1c (HbA1c). The GR is the quotient of mean ICU BGs (mBG) and estimated preadmission BG, derived from HbA1c. Results: Mortality displayed a J-shaped curve with GR (nadir GR 0.9), independent of background glycemia, consistent for HbA1c <6.5% vs >6.5%, and Hgb >10 g/dL vs <10 g/dL and medical versus surgical. An optimal range of GR 0.80 to 0.99 was associated with decreased mortality compared with GR above and below this range. The mBG displayed a linear relationship with mortality at lower Hb...
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