Lactate and Glucose in Critically III Patients: What Goes Around, Comes Around* Paui A. van Beest, MD, PhD
with mortality when both BCC and lactate were entered into logistic regression models (8). These results were consistent in patients without hypoglycemia suggesting that prognostic models evaluating the effect of BCC in ICU patients should also take lactate into account. This is not surprising because lactate has been around as a prognostic indicator since the early Peter E. Spronk, MD, PhD, FCCP 1960s. Excess lactate was found to correspond with severity of Department of Intensive Care Medicine circulatory failure, that is, particularly lactate levels greater than Geire Hcspital Apeidocrn; and 4 mmol/L were associated with bad outcome (9). Since then a HERMES Critical Care Group huge amount of literature consistently reported a relationship Apeidocrn, The Netherlands between lactate levels and organ failure or mortality (10). Also, early clearance of lactate has been suggested as a treatment goal during early resuscitation of critically ill patients (11). ntensive insulin therapy (IIT) in critically ill patients has been strongly debated since the original studies in Leuven, Nevertheless, partially due to the complex and partially unraveled lactate metabolism, the therapeutic role of lactate remains particularly after publication of the Normoglycemia in unclear (10). It is tempting to consider entering another variIntensive Care Evaluation-Survival Using Clucose Algorithm able in the equation, that is, dynamic lactate indices outperRegulation trial (1,2). Consensus seems nowadays to maintain form static lactate indices and improve the performance of the blood glucose concentrations (BCCs) between 72 and 180mg/ dL, avoiding hypoglycemia and aiming for minimal BGC fluc- Acute Physiology and Chronic Health Evaluation (APACHE) II score (12). Also, in the early phase of acute illness, lactate values tuations (3). Indeed, hyperglycemia has been independently are strongly related to the sequential organ failure assessment associated with mortality (4, 5) and normalizing glucose levels (SOEA) score (13). The SOFA score incorporates bilirubin as seemed reasonable at least. However, the apparent role of hypermirror for liver function. Thus, maybe we should consider liver glycemia only tells half the story. First, literature lacks proof of function, or lack thereof, together with lactate and glucose in a causality between hyperglycemia and clinical outcome (6). Secmodel of outcome prediction for critically ill patients. ond, acute hyperglycemia happens for a reason in acute illness. The vast majority of glucose uptake is noninsulin dependent Because of the retrospective nature of the study, clear idenwhich demands a concentration gradient for diffusion from tifiers of circulatory shock are unfortunately lacking, such as the blood fiow into the cell, particularly in sepsis when this is Svo^, cardiac index, and effects of volume infusion. This makes reduced (7). This mechanism may be partially responsible for it difficult to identify patients with low output states from the results of the initial Leuven trial where continuous IV glu- those with sepsis-related shunting or cytopathic hypoxia as cose loads equivalent to 2-3 L glucose (10%) were administered causes for increased lactate levels. Also, the authors could not per day in addition to insulin infusions. Indeed, the hyperglyidentify patients with preexisting feeding deficits or starvation cemia reflects stress-induced changes in carbohydrate metabostates. Another point to consider is the lack of standardization lism in which glucose is a key player together with lactate. This is of BGC measurement (3). Different glucose values produced the biological fundament for the article presented by Kaukonen by various methods will lead to different insulin doses. This et al (8) in this issue of Critical Care Medicine. could result in clinically relevant variations in glucose concentrations between patients. Of note, glucose meters are less preIn their study, Kaukonen et al (8) analyzed static and cise than blood gas analyzers and various biases between two time-weighted simultaneous measurements of glucose and lactate from 7,925 consecutive patients during their stay in the types of glucose meters have been described (14). Nevertheless, the article by Kaukonen et al (8) elegantly ICU. All glycémie and lactate metrics were significantly lower in provides a probable explanation for the failure of IIT to survivors than in nonsurvivors. Both glucose and lactate were improve outcome in the NICE-SUGAR trial (1). As such independently associated with mortality. However, their main it may be considered an intriguing hypothesis-generating finding was that BCC ceased to be independently associated article warranting prospective studies aiming to unravel the relationship between BGC, lactate levels, and outcome in dif'Seealsop. 1379. ferent types of ICU patients. Future trials should probably Key Words: glucose; outcome; tight glycémie control focus on early lactate normalization (11,15) accompanied by The authors have disclosed that they do not have any potential contlicts various glycémie targets, including tolerant management of ot interest. stress hyperglycemia (6). Department of Anesfhesiology University Medical Center Grcningen University cf Grcningen Grcningen, The Netherlands
I
Copyright © 2014 by the Society ot Critical Care Medicine and Lippincott Williams & Wilkins
DOI:10.1097/CCM.0000000000000271 Critical Care Medicine
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Editorials
REFERENCES I.The NICE-SUGAR Study Investigators: Intensive versus oonventional glucose control in critically ill patients. N Engi J Med 2009; 360:1283-1297 2. van den Berghe G, Wouters P, Weekers F, et al: Intensive insulin therapy in critically ill patients. N Engi J Med 2001 ; 345:1359-1367 3. Finfer S, Wernerman J, Preiser JC, et al: Ciinioal review: Consensus reoommendations on measurement of blood glucose and reporting glyoemic control in critically ill adults. Crit Care 2013; 17:229 4. Christiansen C, Toft P, Jargensen HS, et ai: Hyperglyoaemia and mortality in critically ill patients. A prospective study, intensive Care Med 2004; 30:1685-1688 5. Laird AM, Miller PR, Kiigo PD, et al: Relationship of early hyperglycemia to mortality in trauma patients. J Trauma 2004; 56:1058-1 062 6. Marik PE, Bellomo R: Stress hyperglyoemia: An essential survival response! Crit Care 2013; 17:305 7. Losser MR, Damoisel C, Payen D: Bench-to-bedside review: Glucose and stress conditions in the intensive care unit. Crit Care 2010; 14:231 8. Kaukonen K-M, Bailey M, Egi M, et al: Stress Hyperlaotatemia Modifies the Relationship Between Stress Hyperglyoemia and
Outcome: A Retrospective Observational Study. Crit Care Med 2014; 42:1379-1385 9. Broder G, Weii M H: Excess laotate: An index of reversibility of shock in human patients. Science 1964; 143:1457-1459 10. Jansen TC, van Bommel J, Bakker J: Blood laotate monitoring in critically ill patients: A systematic health technology assessment. Crit Care Med 2009; 37:2827-2839 11. Nguyen HB, Rivers EP, Knoblich BP, et al: Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004; 32;1637-1642 12. Nichol A, Bailey M, Egi M, et al: Dynamic laotate indices as predictors of outcome in critically ill patients. Crit Care 2011 ; 15:R242 13. Jansen TC, van Bommel J, Woodward R, et al: Association between blood lactate levels. Sequential Organ Failure Assessment subsoores, and 28-day mortality during early and late intensive care unit stay: A retrospective observationai study. Crit Care Med 2009; 37:2369-2374 14. Sacks DB: Intensive glucose control in the ICU: Is SUGAR NICE? A/af Re/2009; 5:473-474 15. van Beest PA, Brander L, Jansen SP, et al: Cumulative laotate and hospital mortality in ICU patients. Ann intensive Care 2013; 3:6
Organ Transplantation and Donation: Why Minority Groups Need More Organs But Donate Less-It's Complex!* Teri Jo Mauch, MD, PhD Department of Pediatrics University of Nebraska Medical Center Lincoln, NE
donation rates would not differ among the study racial/ethnic groups. They reasoned that the relatively larger proportion of Hispanics (48%) and American Indians (10%) in NM compared with other states, combined with provision of at least some of their healthcare experiences by their own racial/ethnic Susan L. Bratton, MD, MPH community, would enhance their trust in the medical system Department of Pediatrics to levels similar to levels enjoyed by non-Hispanic whites, leadUniversity of Utah ing to similar rates of deceased donation. African Americans Salt Lake City, UT compose a very small fraction of the NM population and were not evaluated. n this issue of Critical Care Medicine, the study by Moore Analyzing data obtained from the statewide organ proet al (1) evaluated the three largest ethnic/racial groups in curement organization and the National Organ Procurement the state of New Mexico (NM), comparing age-adjusted Transplant Network, they found that although NM American rates of organ candidates for transplantation and deceased Indians were 2-3 times more likely to be registered candidates organ donation. They hypothesized that age-adjusted deceased for organ transplantation, they consented to deceased donation much less frequently compared with non-Hispanic whites and Hispanics (0.11-0.13). Additionally, American Indians *Seealso p. 1386. from NM consented to deceased donation significantly less Key Words: minority; organ donation; poverty; transplantation than other U.S. American Indians, whose donation rates are Dr. Mauch served as board member for Aexion Pharmaceuticals (honolower than non-Hispanic whites nationally. However, the rates rarium, travel, and accommodations); is employed by UNMC/Children's of deceased organ donation for NM Hispanics were similar speoialty physicians; lectured for Alexion Pharmaoeuticals and Nebraska AAP; and received support for travel from Children's Hospital of Omaha, to NM non-Hispanic whites, especially among those under American Academy of Pediatrics, Section on Nephrology, and University 40 years, which differs from national data where their rate for of Utah Department of Pediatrics. Her institution received grant support decreased donation is lower than non-Hispanic whites (1). from National Institutes of Health and March of Dimes. Dr. Bratton served as board member for Amerioan Board of Pediatrios Critical Care SubObviously, the gap between needed organs for transplanboard (chair), is employed by the University of Utah, and received support for travel to the 2013 NATCO meeting (speaker). tation and available donors impacts all U.S. racial groups. Minority groups are often disproportionally affected because Copyright © 2014 by the Society of Critical Care Medicine and Lippincoft Wiiiiams & Wilkins frequencies of blood types and human leukocyte antigen DOI: 10.1097/CCM.0000000000000264 alíele combinations differ by race. Greater leukocyte antigen
I
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June 2014 • Volume 42 • Number 6
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
with mortality when both BCC and lactate were entered into logistic regression models (8). These results were consistent in patients without hypoglycemia suggesting that prognostic models evaluating the effect of BCC in ICU patients should also take lactate into account. This is not surprising because lactate has been around as a prognostic indicator since the early Peter E. Spronk, MD, PhD, FCCP 1960s. Excess lactate was found to correspond with severity of Department of Intensive Care Medicine circulatory failure, that is, particularly lactate levels greater than Geire Hcspital Apeidocrn; and 4 mmol/L were associated with bad outcome (9). Since then a HERMES Critical Care Group huge amount of literature consistently reported a relationship Apeidocrn, The Netherlands between lactate levels and organ failure or mortality (10). Also, early clearance of lactate has been suggested as a treatment goal during early resuscitation of critically ill patients (11). ntensive insulin therapy (IIT) in critically ill patients has been strongly debated since the original studies in Leuven, Nevertheless, partially due to the complex and partially unraveled lactate metabolism, the therapeutic role of lactate remains particularly after publication of the Normoglycemia in unclear (10). It is tempting to consider entering another variIntensive Care Evaluation-Survival Using Clucose Algorithm able in the equation, that is, dynamic lactate indices outperRegulation trial (1,2). Consensus seems nowadays to maintain form static lactate indices and improve the performance of the blood glucose concentrations (BCCs) between 72 and 180mg/ dL, avoiding hypoglycemia and aiming for minimal BGC fluc- Acute Physiology and Chronic Health Evaluation (APACHE) II score (12). Also, in the early phase of acute illness, lactate values tuations (3). Indeed, hyperglycemia has been independently are strongly related to the sequential organ failure assessment associated with mortality (4, 5) and normalizing glucose levels (SOEA) score (13). The SOFA score incorporates bilirubin as seemed reasonable at least. However, the apparent role of hypermirror for liver function. Thus, maybe we should consider liver glycemia only tells half the story. First, literature lacks proof of function, or lack thereof, together with lactate and glucose in a causality between hyperglycemia and clinical outcome (6). Secmodel of outcome prediction for critically ill patients. ond, acute hyperglycemia happens for a reason in acute illness. The vast majority of glucose uptake is noninsulin dependent Because of the retrospective nature of the study, clear idenwhich demands a concentration gradient for diffusion from tifiers of circulatory shock are unfortunately lacking, such as the blood fiow into the cell, particularly in sepsis when this is Svo^, cardiac index, and effects of volume infusion. This makes reduced (7). This mechanism may be partially responsible for it difficult to identify patients with low output states from the results of the initial Leuven trial where continuous IV glu- those with sepsis-related shunting or cytopathic hypoxia as cose loads equivalent to 2-3 L glucose (10%) were administered causes for increased lactate levels. Also, the authors could not per day in addition to insulin infusions. Indeed, the hyperglyidentify patients with preexisting feeding deficits or starvation cemia reflects stress-induced changes in carbohydrate metabostates. Another point to consider is the lack of standardization lism in which glucose is a key player together with lactate. This is of BGC measurement (3). Different glucose values produced the biological fundament for the article presented by Kaukonen by various methods will lead to different insulin doses. This et al (8) in this issue of Critical Care Medicine. could result in clinically relevant variations in glucose concentrations between patients. Of note, glucose meters are less preIn their study, Kaukonen et al (8) analyzed static and cise than blood gas analyzers and various biases between two time-weighted simultaneous measurements of glucose and lactate from 7,925 consecutive patients during their stay in the types of glucose meters have been described (14). Nevertheless, the article by Kaukonen et al (8) elegantly ICU. All glycémie and lactate metrics were significantly lower in provides a probable explanation for the failure of IIT to survivors than in nonsurvivors. Both glucose and lactate were improve outcome in the NICE-SUGAR trial (1). As such independently associated with mortality. However, their main it may be considered an intriguing hypothesis-generating finding was that BCC ceased to be independently associated article warranting prospective studies aiming to unravel the relationship between BGC, lactate levels, and outcome in dif'Seealsop. 1379. ferent types of ICU patients. Future trials should probably Key Words: glucose; outcome; tight glycémie control focus on early lactate normalization (11,15) accompanied by The authors have disclosed that they do not have any potential contlicts various glycémie targets, including tolerant management of ot interest. stress hyperglycemia (6). Department of Anesfhesiology University Medical Center Grcningen University cf Grcningen Grcningen, The Netherlands
I
Copyright © 2014 by the Society ot Critical Care Medicine and Lippincott Williams & Wilkins
DOI:10.1097/CCM.0000000000000271 Critical Care Medicine
vmwv.ccmjournal.org
1545
Editorials
REFERENCES I.The NICE-SUGAR Study Investigators: Intensive versus oonventional glucose control in critically ill patients. N Engi J Med 2009; 360:1283-1297 2. van den Berghe G, Wouters P, Weekers F, et al: Intensive insulin therapy in critically ill patients. N Engi J Med 2001 ; 345:1359-1367 3. Finfer S, Wernerman J, Preiser JC, et al: Ciinioal review: Consensus reoommendations on measurement of blood glucose and reporting glyoemic control in critically ill adults. Crit Care 2013; 17:229 4. Christiansen C, Toft P, Jargensen HS, et ai: Hyperglyoaemia and mortality in critically ill patients. A prospective study, intensive Care Med 2004; 30:1685-1688 5. Laird AM, Miller PR, Kiigo PD, et al: Relationship of early hyperglycemia to mortality in trauma patients. J Trauma 2004; 56:1058-1 062 6. Marik PE, Bellomo R: Stress hyperglyoemia: An essential survival response! Crit Care 2013; 17:305 7. Losser MR, Damoisel C, Payen D: Bench-to-bedside review: Glucose and stress conditions in the intensive care unit. Crit Care 2010; 14:231 8. Kaukonen K-M, Bailey M, Egi M, et al: Stress Hyperlaotatemia Modifies the Relationship Between Stress Hyperglyoemia and
Outcome: A Retrospective Observational Study. Crit Care Med 2014; 42:1379-1385 9. Broder G, Weii M H: Excess laotate: An index of reversibility of shock in human patients. Science 1964; 143:1457-1459 10. Jansen TC, van Bommel J, Bakker J: Blood laotate monitoring in critically ill patients: A systematic health technology assessment. Crit Care Med 2009; 37:2827-2839 11. Nguyen HB, Rivers EP, Knoblich BP, et al: Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004; 32;1637-1642 12. Nichol A, Bailey M, Egi M, et al: Dynamic laotate indices as predictors of outcome in critically ill patients. Crit Care 2011 ; 15:R242 13. Jansen TC, van Bommel J, Woodward R, et al: Association between blood lactate levels. Sequential Organ Failure Assessment subsoores, and 28-day mortality during early and late intensive care unit stay: A retrospective observationai study. Crit Care Med 2009; 37:2369-2374 14. Sacks DB: Intensive glucose control in the ICU: Is SUGAR NICE? A/af Re/2009; 5:473-474 15. van Beest PA, Brander L, Jansen SP, et al: Cumulative laotate and hospital mortality in ICU patients. Ann intensive Care 2013; 3:6
Organ Transplantation and Donation: Why Minority Groups Need More Organs But Donate Less-It's Complex!* Teri Jo Mauch, MD, PhD Department of Pediatrics University of Nebraska Medical Center Lincoln, NE
donation rates would not differ among the study racial/ethnic groups. They reasoned that the relatively larger proportion of Hispanics (48%) and American Indians (10%) in NM compared with other states, combined with provision of at least some of their healthcare experiences by their own racial/ethnic Susan L. Bratton, MD, MPH community, would enhance their trust in the medical system Department of Pediatrics to levels similar to levels enjoyed by non-Hispanic whites, leadUniversity of Utah ing to similar rates of deceased donation. African Americans Salt Lake City, UT compose a very small fraction of the NM population and were not evaluated. n this issue of Critical Care Medicine, the study by Moore Analyzing data obtained from the statewide organ proet al (1) evaluated the three largest ethnic/racial groups in curement organization and the National Organ Procurement the state of New Mexico (NM), comparing age-adjusted Transplant Network, they found that although NM American rates of organ candidates for transplantation and deceased Indians were 2-3 times more likely to be registered candidates organ donation. They hypothesized that age-adjusted deceased for organ transplantation, they consented to deceased donation much less frequently compared with non-Hispanic whites and Hispanics (0.11-0.13). Additionally, American Indians *Seealso p. 1386. from NM consented to deceased donation significantly less Key Words: minority; organ donation; poverty; transplantation than other U.S. American Indians, whose donation rates are Dr. Mauch served as board member for Aexion Pharmaceuticals (honolower than non-Hispanic whites nationally. However, the rates rarium, travel, and accommodations); is employed by UNMC/Children's of deceased organ donation for NM Hispanics were similar speoialty physicians; lectured for Alexion Pharmaoeuticals and Nebraska AAP; and received support for travel from Children's Hospital of Omaha, to NM non-Hispanic whites, especially among those under American Academy of Pediatrics, Section on Nephrology, and University 40 years, which differs from national data where their rate for of Utah Department of Pediatrics. Her institution received grant support decreased donation is lower than non-Hispanic whites (1). from National Institutes of Health and March of Dimes. Dr. Bratton served as board member for Amerioan Board of Pediatrios Critical Care SubObviously, the gap between needed organs for transplanboard (chair), is employed by the University of Utah, and received support for travel to the 2013 NATCO meeting (speaker). tation and available donors impacts all U.S. racial groups. Minority groups are often disproportionally affected because Copyright © 2014 by the Society of Critical Care Medicine and Lippincoft Wiiiiams & Wilkins frequencies of blood types and human leukocyte antigen DOI: 10.1097/CCM.0000000000000264 alíele combinations differ by race. Greater leukocyte antigen
I
1546
vvww.ccnnjournal.org
June 2014 • Volume 42 • Number 6
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
