|Year : 2017 | Volume
| Issue : 1 | Page : 21-27
Arterial lactate level is associated with mortality rate in unscheduled surgical intensive care admissions
Min-Hsin Huang1, Chao-Han Lai1, Ping-I Lin2, Wu-Wei Lai1
1 Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
2 Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center; Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
|Date of Web Publication||28-Feb-2017|
Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Sheng.Li Road, Tainan 70403
Source of Support: None, Conflict of Interest: None
Background: Lactate is a widely used biomarker for patients with conditions such as infection or trauma. The value of lactate level in risk stratification is rarely investigated for patients admitted to the surgical Intensive Care Unit (ICU), regardless of diagnosis.
Purposes: This study examines whether arterial lactate levels at the approximate time of admission can predict short-term mortality in all unscheduled surgical ICU patients.
Materials and Methods: A retrospective cohort study of all unscheduled surgical ICU admissions from July 2010 to June 2013 was conducted. Patients were stratified into low (<2.0 mmol/L), intermediate (2.0–3.9 mmol/L), and high (≥4.0 mmol/L) lactate groups according to initial lactate measurements. The primary endpoint was 28-day mortality.
Results: Of 1404 eligible admissions, 163 (11.6%) of them died within 28 days. Admission lactate levels were significantly higher in nonsurvivors than in survivors (P < 0.001). Multiple regression analysis showed that both intermediate and high lactate levels were independent risk factors for mortality. Patients with a high lactate level had an odds ratio (OR) of 1.81 (95% confidence interval [CI] 1.12–2.91; P = 0.015) relative to patients with a low lactate level. Patients with an intermediate lactate level had an OR of 1.73 (95% CI 1.07–2.79; P = 0.025) relative to patients with a low lactate level. Other independent predictors of mortality included Acute Physiology and Chronic Health Evaluation II score, existence of malignancy, and thrombocytopenia.
Conclusion: An admission arterial lactate level of 2.0 mmol/L or higher at the time of ICU admission can be used to identify high-risk surgical patients.
Keywords: Intensive care, lactate, mortality, surgery
|How to cite this article:|
Huang MH, Lai CH, Lin PI, Lai WW. Arterial lactate level is associated with mortality rate in unscheduled surgical intensive care admissions. Formos J Surg 2017;50:21-7
|How to cite this URL:|
Huang MH, Lai CH, Lin PI, Lai WW. Arterial lactate level is associated with mortality rate in unscheduled surgical intensive care admissions. Formos J Surg [serial online] 2017 [cited 2019 May 22];50:21-7. Available from: http://www.e-fjs.org/text.asp?2017/50/1/21/201187
| Introduction|| |
Lactate is a widely used biomarker for risk stratification in patients with infection or severe trauma in emergency medicine.,,,,,,,,, A high lactate level, defined as a blood lactate level of 4.0 mmol/L or more, is assessed during the management of patients with severe sepsis or septic shock to identify those who need aggressive therapy., However, there are limited data regarding the usability of an intermediate lactate level (2.0–3.9 mmol/L) for risk stratification in critically ill patients, regardless of diagnosis.,,,, Several recent studies have demonstrated that intermediate and high lactate levels are associated with undesirable outcomes for patients admitted to medical or pediatric Intensive Care Units (ICUs).,, However, it remains unclear whether lactate levels can be used to identify high-risk patients in all critically ill surgical patients.
Among all surgical ICU admissions, a substantial amount are admitted to the ICU following a scheduled surgery. In contrast to unscheduled admissions, the risk of death for patients admitted to the ICU following scheduled surgery is extremely low because these patients are mostly admitted for intensive monitoring, not for management of organ dysfunction., Risk profiles are obviously different between scheduled and unscheduled admissions in the surgical ICU; therefore, it is logical to separate these two groups when investigating lactate usefulness in risk stratification for surgical ICU admissions.
This study aims to evaluate whether an elevated lactate level in surgical ICU patients is associated with the likelihood of mortality. We hypothesize that patients with a lactate level ≥2.0 mmol/L should be associated with an increased risk of mortality over a period of 28 days in unscheduled surgical ICU admissions. We further hypothesize that hyperlactatemia can be an independent predictor of death, regardless of the presence of infection or shock.
| Materials and Methods|| |
This study was an observational cohort study. It was conducted at three surgical ICUs, including 24-bed mixed surgical ICU, 10-bed neurosurgical ICU, and 8-bed cardiovascular surgical ICU, in National Cheng Kung University Hospital, a 1300-bed medical center in Taiwan. The clinical management of patients admitted to these ICUs was provided collaboratively by an intensivist and a surgeon. Because of the observational design of the study with normal clinical management, it was approved by the Institutional Review Board of the hospital (Approval No.: A-ER-102-172), and the requirement for individual written informed consent was waived.
We evaluated all patients who were consecutively admitted to the study ICUs from July 2010 to June 2013. Patients were deemed eligible for the initial cohort if they were aged 18 years or older, had stayed in the ICU for more than 24 h, and had at least one lactate measurement within the first 24 h of admission. We excluded patients with incomplete demographic data or with apparent brain death at the time of ICU admission. If a patient was admitted to the ICU more than once during the same hospitalization, only the data from first ICU admission were used.
Eligible admissions were divided into two groups according to the reason of admission. Patients admitted to the ICU after elective operations were categorized as the scheduled admission group, and other patients were categorized as the unscheduled admission group. Only patients in the unscheduled admission group were included in the final cohort.
All study ICUs were equipped with electronic patient monitoring and recording systems (Philips IntelliVue Clinical Information Portfolio; Philips Medical Systems, Andover, MA 01810, USA). Data associated with clinical care were entered into the information system by the caring nurses, doctors, and respiratory therapists. In the study, clinical and laboratory data from the first 24 h of ICU admission were retrieved from this database. Other demographic data were retrieved from the hospital administration database.
All patients were monitored using arterial catheters during their ICU stay. For lactate measurements, blood samples were drawn from an arterial catheter and were measured using GEM Premier 3000 Blood Gas/Electrolyte Analyzers (Instrumentation Laboratory Co., 113, Hartwell Avenue, Lexington, MA 02421, USA). The analyzers were maintained and calibrated regularly in accordance with hospital regulations. Lactate is not routinely measured in the study ICUs. The timing and indications of lactate measurements are decided by the managing clinicians. The analyzers' maximal detection limit for lactate is 15.0 mmol/L. When lactate results are ≥15.0 mmol/L, the results are arbitrarily recorded as 15.0. Because the analyzers are designed to measure arterial blood gas and lactate levels simultaneously, each time the caring physician orders an arterial blood gas analysis, lactate level is also measured and recorded in the database.
According to the admission lactate level, patients were stratified into three groups (low, 0.1–1.9 mmol/L; intermediate, 2.0–3.9 mmol/L; and high, ≥4.0 mmol/L) consistent with the ranges used in previous studies., The severity of illness is assessed within the first 24 h according to the Acute Physiology and Chronic Health Evaluation (APACHE) II score. In addition to lactate, other biochemical and clinical data with possible associations with infection and shock were collected. These parameters included hematocrit, leukocyte count, serum urea, platelet count, the occurrence of hypotension, and the occurrence of fever. Hypotension is defined as either administration of any vasopressor or an episode of mean arterial pressure of &360;65 mmHg. Fever is defined as a body temperature higher than 38.0°C. The primary outcome was 28-day mortality. The secondary outcomes were hospital mortality, ICU length of stay, hospital length of stay, and the use of renal replacement therapy during ICU stay.
We used descriptive statistics to describe the study population. Data were presented as median and interquartile ranges for continuous variables, and number of subjects (%) for categorical variables. Survivors and nonsurvivors in the final cohort were compared using the Mann–Whitney U-test for continuous variables and using Fisher's exact test for categorical variables. Logistic regression was used to describe the relationship between risk factors and 28-day mortality. Odds ratio (OR) and 95% confidence intervals (CIs) were used to report the results from the logistic regression analysis. Two-tailed P < 0.05 identifies statistical significances between groups. We did not correct for multi-testing corrections due to the correlations among different predictors.
| Results|| |
We screened 4413 consecutive admissions during the study period. Of the 3338 eligible admissions, 2867 (85.9%) had lactate measurements during the first 24 h and were included in the initial cohort [Figure 1]. A total of 1463 patients were admitted after scheduled operation, and the other 1404 patients were unscheduled ICU admissions. Of the 1463 scheduled admissions, only 40 (2.7%) patients died within 28 days of ICU admission. There was no significant association between initial lactate levels and 28-day mortality rates (2.8% in the low lactate group, 2.0% in the intermediate lactate group, 3.6% in the high lactate group; P = 0.37). Therefore, scheduled admissions were excluded from subsequent analyses. Only unscheduled admissions were included in the final study cohort.
The final study cohort consisted of 1404 unscheduled surgical ICU admissions. The median age was 62.1 (49.9–75.3) years, and 916 (65.2%) patients were male. The median APACHE II score was 17 (12–23), and the 28-day mortality was 11.6%. A total of 727 (51.8%) patients were admitted after an emergency operation.
Comparisons of characteristics for survivors and nonsurvivors are summarized in [Table 1]. Admission lactate levels were significantly higher in nonsurvivors than in survivors (median 3.5 mmol/L [2.0–7.1] in nonsurvivors, median 1.9 mmol/L [1.1–3.6] in survivors; P < 0.001). In addition, nonsurvivors had significantly higher APACHE II scores (P < 0.001), a higher proportion of malignancy (P = 0.03), lower hematocrit levels (P < 0.001), higher urea levels (P < 0.001), lower platelet counts (P < 0.001), and were more likely to have hypotensive episodes during the first 24 h following ICU admission (P < 0.001).
|Table 1: Comparison between survivors and nonsurvivors in unscheduled surgical intensive care admissionsa|
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For subsequent analyses, we stratified patients into low, intermediate, and high lactate groups according to initial lactate levels. A total of 389 (27.7%) patients had an intermediate lactate level and 349 (24.9%) patients had a high lactate level. Twenty-eight-day mortality rates were 6.0% for the low lactate group, 12.9% for the intermediate lactate group, and 20.9% for the high lactate group. The Kaplan–Meier estimates of overall survival for patients with low, intermediate, and high lactate levels are depicted in [Figure 2]. Elevated lactate levels were significantly associated with an increased risk of mortality within 28 days (low vs. intermediate, P < 0.001; low vs. high, P < 0.001; intermediate vs. high, P = 0.003). The causes of death for these patients are analyzed in [Table 2]. Patients who died of sepsis/septic shock or hypovolemic shock might be more likely to have higher admission arterial lactate levels, and patients who died of respiratory failure were less likely to have higher admission arterial lactate levels.
|Figure 2: Kaplan–Meier curves of probability of survival for low (<2.0 mmol/L), intermediate (2.0–3.9 mmol/L), and high (≥4.0 mmol/L) lactate groups showed that there were significant between-group differences in mortality rates at 28 days|
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|Table 2: Causes of death in patients who died within 28 days of unscheduled surgical Intensive Care Unit admissions|
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Factors significantly associated with mortality in univariate analysis were then subjected to a multiple logistic regression analysis [Table 3]. Both intermediate and high lactate levels were still independently associated with 28-day mortality. The OR were 1.73 (95% CI, 1.07–2.79; P = 0.025) for intermediate lactate levels and 1.81 (95% CI, 1.12–2.91; P = 0.015) for high lactate levels, respectively. Other independent predictors of mortality were APACHE II scores (OR, 1.12; 95% CI, 1.05–1.15; P < 0.001), the presence of malignancy (OR, 2.07; 95% CI, 1.31–3.27; P = 0.002), and platelet count < 100 × 109/L (OR, 2.88; 95% CI, 1.91–4.34; P < 0.001).
|Table 3: Multiple regression analysis of predictors for 28-day mortality in unscheduled surgical intensive care admissions|
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In addition to 28-day mortality, [Table 4] demonstrates that patients with intermediate and high lactate levels had significantly higher hospital mortality rates (P < 0.001). ICU length of stay was also significantly longer for these two groups in comparison to the low lactate group (P < 0.001). However, there was no significant difference in hospital length of stay (P = 0.39) or in the proportion of patients receiving renal replacement therapy during ICU stay (P = 0.17) among three groups.
|Table 4: Comparison of outcome variables between low, intermediate, and high lactate groupsa|
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| Discussion|| |
In this large observational study of unscheduled surgical ICU admissions, intermediate and high arterial lactate levels at admission are associated with increased risk of 28-day mortality. This association is independent of disease severity, sepsis, hypotension, and comorbidities. Our results are consistent with several previous reports that indicate an elevated lactate level in the ICU is associated with increased mortality.,,,, Our study expands this association between elevated lactate levels and mortality to all critically ill surgical patients.
Lactate is one of the most commonly used biomarkers in acutely ill patients. Blood lactate level is dependent on the balance between its production and metabolism. Both processes are extremely complex, found in almost every organ, and can be affected by stress levels., Although the overall production and metabolism of lactate in critical illness is a complex process, its prognostic value has already been confirmed in certain subgroups of critically ill patients. Previous studies have demonstrated an association between elevated lactate levels and mortality in patients admitted to the ICU, but most of the studies were limited by small sizes (<500 patients).,, Studies have been carried out in mixed medical-surgical populations, but their analyses did not include detailed physiological and biochemical data from the time of ICU admission., The few studies that have collected and analyzed detailed clinical data in a large population were conducted in medical or pediatric ICUs.,, Our study is the first to investigate the association between hyperlactatemia and outcome in a large group of surgical ICU admissions. Our results suggest that lactate is a useful biomarker to identify high-risk patients in a surgical ICU.
Although measuring lactate levels is not routine during ICU admission at our hospital, it is measured when the caring physician orders either a lactate measurement or an arterial blood gas analysis. Our data are representative for admission lactate levels because over 85% of the patients had lactate measurements performed within the first 24 h of their ICU stay. In addition to single lactate values, parameters derived from serial lactate measurements, such as time of sustained hyperlactatemia and lactate clearance have also been investigated in previous studies.,,,, Some studies suggested that parameters derived from serial lactate measurements might be superior to single lactate measurements. However, there is no agreement on the optimal time interval between serial lactate samplings. Furthermore, additional computation is required for generating these parameters. The universal use of such parameters in all critically ill patients would be difficult because of the cumbersome computational requirements.
A blood lactate level of 4.0 mmol/L or more is a widely accepted threshold to identify high-risk patients in management of severe sepsis or septic shock., Recently, an intermediate lactate level was found to be associated with increased mortality in medical or pediatric ICUs., Our study is the first to confirm that an intermediate lactate level is also a predictor of short-term mortality in critically ill surgical patients. Our results suggest that using a lactate level of 4.0 mmol/L as a threshold for risk stratification could exclude a substantial number of high-risk patients whose initial lactate levels are between 2.0 and 3.9 mmol/L in unscheduled surgical ICU admissions.
An elevated lactate level is frequently associated with sepsis and tissue hypoperfusion in literature. Whether hyperlactatemia is merely a marker of sepsis and shock or an independent predictor of death remains controversial. Their relationships were thoroughly examined in our study; we included laboratory and clinical variables possibly associated with sepsis or tissue hypoperfusion in the multiple regression analysis. Patients who died of sepsis/septic shock or hypovolemic shock were more likely to have hyperlactatemia at the time of ICU admission. The multiple regression analysis demonstrated that intermediate and high lactate levels were independently associated with increased mortality. Therefore, we suggest that patients admitted to surgical ICUs due to sepsis or hypovolemic shock with elevated arterial lactate levels warrant close clinical attention because they are associated with an increased risk of death. However, ICU clinicians should pay attention to any patient admitted with elevated lactate levels because other conditions may also contribute to hyperlactatemia and affect patient outcome.
Optimal management for patients with elevated arterial lactate levels remains uncertain. Lactate clearance may prove to be a reasonable therapeutic target, given its prognostic value and use with regard to septic shock., We, therefore, suggest that ICU clinicians who encounter patients with a lactate level of 2.0 mmol/L or higher at the time of ICU admission should look for any remediable causes of physiological derangements. Aggressive lactate measurements to obtain lactate clearance until hyperlactatemia is resolved may be helpful for subsequent management in these patients.
There are several limitations in our study. First, the study is a single-center, retrospective cohort study, making it difficult to control or identify every source of bias. However, the use of a prospectively collected clinical database should minimize the biases and errors. Second, since lactate measurements are not routine at the time of ICU admission, the timing and indications of lactate measurements varied greatly among patients in the study cohort. Third, certain medications can affect lactate levels, but we did not collect detailed data about medication. Fourth, for postoperative ICU patients, it is possible that hyperlactatemia had already been recognized in the operating theater, and then corrected by an anesthesiologist before ICU admission. For these patients, the initial lactate levels at the time of ICU admission may have been affected by perioperative care. However, without the relevant information, these patients would be indistinguishable from other patients in our study.
| Conclusion|| |
Intermediate and high arterial lactate levels at the approximate time of ICU admission were independent predictors of 28-day mortality within a large mixed cohort of critically ill surgical patients. Our study confirmed that hyperlactatemia can be used to identify high-risk patients in all unscheduled surgical ICU admissions.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Bakker J, Nijsten MW, Jansen TC. Clinical use of lactate monitoring in critically ill patients. Ann Intensive Care 2013;3:12.
Okorie ON, Dellinger P. Lactate: Biomarker and potential therapeutic target. Crit Care Clin 2011;27:299-326.
Kruse O, Grunnet N, Barfod C. Blood lactate as a predictor for in-hospital mortality in patients admitted acutely to hospital: A systematic review. Scand J Trauma Resusc Emerg Med 2011;19:74.
Puskarich MA, Illich BM, Jones AE. Prognosis of emergency department patients with suspected infection and intermediate lactate levels: A systematic review. J Crit Care 2014;29:334-9.
Shapiro NI, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe RE, et al.
Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med 2005;45:524-8.
Trzeciak S, Dellinger RP, Chansky ME, Arnold RC, Schorr C, Milcarek B, et al.
Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med 2007;33:970-7.
Howell MD, Donnino M, Clardy P, Talmor D, Shapiro NI. Occult hypoperfusion and mortality in patients with suspected infection. Intensive Care Med 2007;33:1892-9.
Guyette F, Suffoletto B, Castillo JL, Quintero J, Callaway C, Puyana JC. Prehospital serum lactate as a predictor of outcomes in trauma patients: A retrospective observational study. J Trauma 2011;70:782-6.
Callaway DW, Shapiro NI, Donnino MW, Baker C, Rosen CL. Serum lactate and base deficit as predictors of mortality in normotensive elderly blunt trauma patients. J Trauma 2009;66:1040-4.
Song YH, Shin TG, Kang MJ, Sim MS, Jo IJ, Song KJ, et al.
Predicting factors associated with clinical deterioration of sepsis patients with intermediate levels of serum lactate. Shock 2012;38:249-54.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al.
Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41:580-637.
Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Lactate clearance vs. central venous oxygen saturation as goals of early sepsis therapy: A randomized clinical trial. JAMA 2010;303:739-46.
Suistomaa M, Ruokonen E, Kari A, Takala J. Time-pattern of lactate and lactate to pyruvate ratio in the first 24 hours of intensive care emergency admissions. Shock 2000;14:8-12.
Nichol AD, Egi M, Pettila V, Bellomo R, French C, Hart G, et al.
Relative hyperlactatemia and hospital mortality in critically ill patients: A retrospective multi-centre study. Crit Care 2010;14:R25.
Khosravani H, Shahpori R, Stelfox HT, Kirkpatrick AW, Laupland KB. Occurrence and adverse effect on outcome of hyperlactatemia in the critically ill. Crit Care 2009;13:R90.
Bai Z, Zhu X, Li M, Hua J, Li Y, Pan J, et al.
Effectiveness of predicting in-hospital mortality in critically ill children by assessing blood lactate levels at admission. BMC Pediatr 2014;14:83.
Juneja D, Singh O, Dang R. Admission hyperlactatemia: Causes, incidence, and impact on outcome of patients admitted in a general medical Intensive Care Unit. J Crit Care 2011;26:316-20.
Morris KP, McShane P, Stickley J, Parslow RC. The relationship between blood lactate concentration, the Paediatric Index of Mortality 2 (PIM2) and mortality in paediatric intensive care. Intensive Care Med 2012;38:2042-6.
Rhodes A, Moreno RP, Metnitz B, Hochrieser H, Bauer P, Metnitz P. Epidemiology and outcome following post-surgical admission to critical care. Intensive Care Med 2011;37:1466-72.
Capuzzo M, Volta C, Tassinati T, Moreno R, Valentin A, Guidet B, et al.
Hospital mortality of adults admitted to Intensive Care Units in hospitals with and without Intermediate Care Units: A multicentre European cohort study. Crit Care 2014;18:551.
Mikkelsen ME, Miltiades AN, Gaieski DF, Goyal M, Fuchs BD, Shah CV, et al.
Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med 2009;37:1670-7.
Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: A severity of disease classification system. Crit Care Med 1985;13:818-29.
Jansen TC, van Bommel J, Mulder PG, Lima AP, van der Hoven B, Rommes JH, et al.
Prognostic value of blood lactate levels: Does the clinical diagnosis at admission matter? J Trauma 2009;66:377-85.
Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL. Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg 1996;171:221-6.
Jansen TC, van Bommel J, Woodward R, Mulder PG, Bakker J. Association between blood lactate levels, Sequential Organ Failure Assessment subscores, and 28-day mortality during early and late Intensive Care Unit stay: A retrospective observational study. Crit Care Med 2009;37:2369-74.
Marty P, Roquilly A, Vallée F, Luzi A, Ferré F, Fourcade O, et al.
Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in Intensive Care Unit: An observational study. Ann Intensive Care 2013;3:3.
Husain FA, Martin MJ, Mullenix PS, Steele SR, Elliott DC. Serum lactate and base deficit as predictors of mortality and morbidity. Am J Surg 2003;185:485-91.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]