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EMJ Online First, published on March 9, 2015 as 10.1136/emermed-2014-204305 Original article
Lactate level, aetiology and mortality of adult patients in an emergency department: a cohort study Mathilde Pedersen, Vibeke Schnack Brandt, Jon Gitz Holler, Annmarie Touborg Lassen ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ emermed-2014-204305). Department of Emergency Medicine, Odense University Hospital, Odense C, Denmark Correspondence to Mathilde Pedersen, Department of Emergency Medicine, Odense University Hospital, Sdr. Boulevard 29, entrance 130, 1. Floor, Odense C 5000, Denmark; [email protected] MP and VSB are shared firstauthorship. Received 5 September 2014 Revised 12 February 2015 Accepted 15 February 2015
ABSTRACT Background Increased lactate is associated with high mortality among patients with suspected infection or trauma in the emergency department (ED), but the association with patients with other aetiologies is less well described. The aim of this study was to describe the relation between lactate, aetiology and 7-day mortality in adult ED patients. Methods A retrospective cohort study of all adult patients who had a lactate measured within 4 h after arrival to the ED at Odense University Hospital between June 2012 and May 2013. The categorisation of suspected aetiology was based on discharge diagnoses. Results 5360 patients were included; 51.7% were men, and the median age was 67 years (IQR 50–79). 77.2% had low lactate (0–1.9 mmol/L), 16.2% intermediate lactate (2–3.9 mmol/L), and 6.6% high lactate (≥4 mmol/L). 7-day mortality was 2.9% (95% CI 2.4% to 3.5%) for patients with low lactate, 7.8% (95% CI 6.1% to 9.8%) for patients with intermediate lactate, and 23.9% (95% CI 19.6% to 28.8%) for patients with high lactate. The association between lactate level and mortality varied across different diagnostic groups. Based on Area Under the Curve in receiver operating characteristic analysis, lactate level showed to be useful in patients with infection (0.78, 95% CI 0.73 to 0.84), trauma (0.78, 95% CI 0.65 to 0.92), cardiac diseases (0.83, 95% CI 0.75 to 0.91) and gastrointestinal diseases (0.83, 95% CI 0.68 to 0.98). Lactate level was not useful in neurological (0.58, 95% CI 0.50 to 0.67) and respiratory disease (0.64, 95% CI 0.55 to 0.74), and of uncertain value in the remaining diagnostic groups. Conclusions Among adult ED patients, the prognostic value of lactate varies between diagnostic groups.
INTRODUCTION
▸ http://dx.doi.org/10.1136/ emermed-2013-203541
To cite: Pedersen M, Brandt VS, Holler JG, et al. Emerg Med J Published Online First: [ please include Day Month Year] doi:10.1136/emermed-2014204305
The lactate level is often interpreted as a marker of tissue hypoperfusion and is used in the definition of shock.1 Lactate is produced by anaerobic metabolism when cellular oxygen usage fails, but other factors, such as decreased clearance can also influence the lactate level.2 3 Increased lactate is associated with high mortality among patients with suspected infection or trauma in the emergency department (ED),4–11 but the risk of an adverse outcome might depend on the underlying condition of hyperlactatemia, which can differ according to aetiology.2 3 Elevated lactate levels have been found associated with overall mortality in a broad cohort of adult patients as well as the elderly over 65 years of age, independent of the presence of infection.12 13 Apart from these two studies, the association
Key messages What is already known on this subject? Numerous observational studies have proved that increased lactate among patients diagnosed with suspected infection or trauma is associated with high mortality in the emergency department (ED). Until now, the association between other diagnosed categories in the ED with elevated lactate is sparsely described. What might this study add? Our study suggests that mortality risk, due to an elevated lactate, differs between different diagnostic groups in the ED, depending on the cause of hyperlactatemia. among patients with elevated lactate and aetiologies other than infection and trauma is only sparsely described. Increased time to normalise lactate have also been found to predict higher mortality rates6 and have been used in treatment guidance.14 As knowledge of the prognostic value of an elevated lactate level among undifferentiated ED patients could be clinically useful in order to identify critically ill patients for intensive resuscitation, the aim of the present study was to describe the relation between lactate, aetiology and 7-day mortality in adult ED patients.
METHOD Study design and setting We performed a hospital-based cohort-study at Odense University Hospital between 1 June 2012 and 31 May 2013. The ED at Odense University Hospital serves a mixed rural–urban population (n=288 000 adults). It provides 24-hour acute care and acts as primary hospital for the local area. The department operated as an open general ED for unselected patients as well as the primary department for virtually all patients admitted acutely to the hospital. Exceptions are patients with prehospital-identified severe heart disease, pregnant patients past 16th week of gestation, patients in haemodialysis, patients in active chemotherapy or radiation therapy, and children with medical conditions.
Participants All patients ≥18 years of age who had an arterial blood gas (ABG) sample drawn within 4 h of arrival to the ED were included. If the same patient had more than one contact to the ED during the study period they were only included at first visit. Foreign
Pedersen M, et al. Emerg Med J 2015;0:1–7. doi:10.1136/emermed-2014-204305
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd under licence.
1
Downloaded from http://emj.bmj.com/ on March 24, 2015 - Published by group.bmj.com
Original article or emigrated patients who did not have an active Personal Identification Number (PRN) that is unique to all Danish citizens,15 were excluded. So were all ABG analyses without registration of the patient’s PRN or lactate measurement.
did not meet an a priori-defined criterion of a minimum number of 50 patients in a category and were transposed to the category ‘other diseases’.
Statistical methods Procedure for lactate measurement Lactate measurements were performed using ABG samples according to a clinical decision based on the patient’s condition. All ABG samples were performed bedside, analysed and registered in an ABL machine (ABL 800 Flex, Radiometer medical ApS, Åkandevej 21, DK-2700 Brønshøj, Denmark).
Quantitative variables On the basis of previous studies and definitions of shock, initial arterial lactate level was a priori defined as low (2).16 Age was grouped into three categories in a natural order (18–49, 50–79 and ≥80 years).
Data sources Data was extracted from the ABL machines located at the ED as well as from the electronic patient records. Using the Danish unique PRN, information on included patients was also retrieved from the Danish National Patient Register and the Civil Registration System.15 17 From the National Patient Register, we identified all discharge diagnoses (action-diagnoses) based on the International Classification of Diseases 10th revision (ICD-10),18 for the last 10 years, which we used for the Charlson Comorbidity Score. From the Civil Registration System, we gathered information regarding gender and age as well as 7-day mortality.
Definition of disease categories The presumed aetiological categories were based on the patient discharge diagnosis for the entire admission period. A protocol of criteria for categorisation was made a priori (see online supplementary appendix 1). Two of the researchers, a priori, performed categorisation of all 982 different discharge diagnoses independently and blinded to each other, as well as the individual patient records (see online supplementary appendix 2). The κ-score for interobserver agreement, in classification of the ICD-10 codes, was 0.95 (95% CI 0.94 to 0.97). The categorisation was defined according to a clinical approach, physiological features and theoretical pathogenesis of lactate production,3 19 including either a disease in an organ system or a systemic condition. Diseases in organ systems were defined as neurological, intestinal, cardiac, respiratory, endocrine and haematological diseases. Nephrological and hepatological diseases were considered as one category due to the function of lactate clearance.19 Systemic conditions were defined and prioritised as infection, trauma, hypovolemic condition, malignant diseases, intoxication and allergic conditions. Systemic conditions were prioritised over diseases related to organ systems. For example, a patient with pneumonia was allocated to the category of infection instead of respiratory diseases, and a patient with gastrointestinal bleedings was allocated to the category of hypovolemic conditions that covers all acute bleedings, dehydration, burns and tissue corrosions regardless of which organ is affected. Discharge diagnoses that did not match the criteria for the above-mentioned groups, were categorised into ‘other diseases’. The categories haematology and allergy 2
Baseline characteristics are presented for patients with low, intermediate and high lactate levels. Categorical variables are expressed as percentages with 95% CIs based on the binominal distribution. All continuous variables were non-normally distributed, and are described as medians with IQR. Pearson’s χ2 test was used to compare categorical variables. A logistic regression model was used to assess the relationship (OR) between 7-day mortality and lactate level. For all calculations of OR, the low lactate level was used as reference. A multivariate logistic regression model was performed including age, sex, comorbidity and discharge categories as predefined potential confounding variables. An interaction analysis was performed to test the interaction between lactate and discharge categories in the multivariate regression model. In the different discharge categories, Cuzick’s test for trend was used to test the trend in 7-day mortality for increasing lactate values. p Values 0.75 and a lower CI 95% >0.5 was considered useful. AUC 0.5. AUC for neurological diseases was 0.58 (95% CI 0.50 to 0.67), and AUC for respiratory diseases was 0.64 (95% CI 0.55 to 0.74). This indicates that lactate has no prognostic value in these diagnostic groups, as AUC was
EMJ Online First, published on March 9, 2015 as 10.1136/emermed-2014-204305 Original article
Lactate level, aetiology and mortality of adult patients in an emergency department: a cohort study Mathilde Pedersen, Vibeke Schnack Brandt, Jon Gitz Holler, Annmarie Touborg Lassen ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ emermed-2014-204305). Department of Emergency Medicine, Odense University Hospital, Odense C, Denmark Correspondence to Mathilde Pedersen, Department of Emergency Medicine, Odense University Hospital, Sdr. Boulevard 29, entrance 130, 1. Floor, Odense C 5000, Denmark; [email protected] MP and VSB are shared firstauthorship. Received 5 September 2014 Revised 12 February 2015 Accepted 15 February 2015
ABSTRACT Background Increased lactate is associated with high mortality among patients with suspected infection or trauma in the emergency department (ED), but the association with patients with other aetiologies is less well described. The aim of this study was to describe the relation between lactate, aetiology and 7-day mortality in adult ED patients. Methods A retrospective cohort study of all adult patients who had a lactate measured within 4 h after arrival to the ED at Odense University Hospital between June 2012 and May 2013. The categorisation of suspected aetiology was based on discharge diagnoses. Results 5360 patients were included; 51.7% were men, and the median age was 67 years (IQR 50–79). 77.2% had low lactate (0–1.9 mmol/L), 16.2% intermediate lactate (2–3.9 mmol/L), and 6.6% high lactate (≥4 mmol/L). 7-day mortality was 2.9% (95% CI 2.4% to 3.5%) for patients with low lactate, 7.8% (95% CI 6.1% to 9.8%) for patients with intermediate lactate, and 23.9% (95% CI 19.6% to 28.8%) for patients with high lactate. The association between lactate level and mortality varied across different diagnostic groups. Based on Area Under the Curve in receiver operating characteristic analysis, lactate level showed to be useful in patients with infection (0.78, 95% CI 0.73 to 0.84), trauma (0.78, 95% CI 0.65 to 0.92), cardiac diseases (0.83, 95% CI 0.75 to 0.91) and gastrointestinal diseases (0.83, 95% CI 0.68 to 0.98). Lactate level was not useful in neurological (0.58, 95% CI 0.50 to 0.67) and respiratory disease (0.64, 95% CI 0.55 to 0.74), and of uncertain value in the remaining diagnostic groups. Conclusions Among adult ED patients, the prognostic value of lactate varies between diagnostic groups.
INTRODUCTION
▸ http://dx.doi.org/10.1136/ emermed-2013-203541
To cite: Pedersen M, Brandt VS, Holler JG, et al. Emerg Med J Published Online First: [ please include Day Month Year] doi:10.1136/emermed-2014204305
The lactate level is often interpreted as a marker of tissue hypoperfusion and is used in the definition of shock.1 Lactate is produced by anaerobic metabolism when cellular oxygen usage fails, but other factors, such as decreased clearance can also influence the lactate level.2 3 Increased lactate is associated with high mortality among patients with suspected infection or trauma in the emergency department (ED),4–11 but the risk of an adverse outcome might depend on the underlying condition of hyperlactatemia, which can differ according to aetiology.2 3 Elevated lactate levels have been found associated with overall mortality in a broad cohort of adult patients as well as the elderly over 65 years of age, independent of the presence of infection.12 13 Apart from these two studies, the association
Key messages What is already known on this subject? Numerous observational studies have proved that increased lactate among patients diagnosed with suspected infection or trauma is associated with high mortality in the emergency department (ED). Until now, the association between other diagnosed categories in the ED with elevated lactate is sparsely described. What might this study add? Our study suggests that mortality risk, due to an elevated lactate, differs between different diagnostic groups in the ED, depending on the cause of hyperlactatemia. among patients with elevated lactate and aetiologies other than infection and trauma is only sparsely described. Increased time to normalise lactate have also been found to predict higher mortality rates6 and have been used in treatment guidance.14 As knowledge of the prognostic value of an elevated lactate level among undifferentiated ED patients could be clinically useful in order to identify critically ill patients for intensive resuscitation, the aim of the present study was to describe the relation between lactate, aetiology and 7-day mortality in adult ED patients.
METHOD Study design and setting We performed a hospital-based cohort-study at Odense University Hospital between 1 June 2012 and 31 May 2013. The ED at Odense University Hospital serves a mixed rural–urban population (n=288 000 adults). It provides 24-hour acute care and acts as primary hospital for the local area. The department operated as an open general ED for unselected patients as well as the primary department for virtually all patients admitted acutely to the hospital. Exceptions are patients with prehospital-identified severe heart disease, pregnant patients past 16th week of gestation, patients in haemodialysis, patients in active chemotherapy or radiation therapy, and children with medical conditions.
Participants All patients ≥18 years of age who had an arterial blood gas (ABG) sample drawn within 4 h of arrival to the ED were included. If the same patient had more than one contact to the ED during the study period they were only included at first visit. Foreign
Pedersen M, et al. Emerg Med J 2015;0:1–7. doi:10.1136/emermed-2014-204305
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd under licence.
1
Downloaded from http://emj.bmj.com/ on March 24, 2015 - Published by group.bmj.com
Original article or emigrated patients who did not have an active Personal Identification Number (PRN) that is unique to all Danish citizens,15 were excluded. So were all ABG analyses without registration of the patient’s PRN or lactate measurement.
did not meet an a priori-defined criterion of a minimum number of 50 patients in a category and were transposed to the category ‘other diseases’.
Statistical methods Procedure for lactate measurement Lactate measurements were performed using ABG samples according to a clinical decision based on the patient’s condition. All ABG samples were performed bedside, analysed and registered in an ABL machine (ABL 800 Flex, Radiometer medical ApS, Åkandevej 21, DK-2700 Brønshøj, Denmark).
Quantitative variables On the basis of previous studies and definitions of shock, initial arterial lactate level was a priori defined as low (2).16 Age was grouped into three categories in a natural order (18–49, 50–79 and ≥80 years).
Data sources Data was extracted from the ABL machines located at the ED as well as from the electronic patient records. Using the Danish unique PRN, information on included patients was also retrieved from the Danish National Patient Register and the Civil Registration System.15 17 From the National Patient Register, we identified all discharge diagnoses (action-diagnoses) based on the International Classification of Diseases 10th revision (ICD-10),18 for the last 10 years, which we used for the Charlson Comorbidity Score. From the Civil Registration System, we gathered information regarding gender and age as well as 7-day mortality.
Definition of disease categories The presumed aetiological categories were based on the patient discharge diagnosis for the entire admission period. A protocol of criteria for categorisation was made a priori (see online supplementary appendix 1). Two of the researchers, a priori, performed categorisation of all 982 different discharge diagnoses independently and blinded to each other, as well as the individual patient records (see online supplementary appendix 2). The κ-score for interobserver agreement, in classification of the ICD-10 codes, was 0.95 (95% CI 0.94 to 0.97). The categorisation was defined according to a clinical approach, physiological features and theoretical pathogenesis of lactate production,3 19 including either a disease in an organ system or a systemic condition. Diseases in organ systems were defined as neurological, intestinal, cardiac, respiratory, endocrine and haematological diseases. Nephrological and hepatological diseases were considered as one category due to the function of lactate clearance.19 Systemic conditions were defined and prioritised as infection, trauma, hypovolemic condition, malignant diseases, intoxication and allergic conditions. Systemic conditions were prioritised over diseases related to organ systems. For example, a patient with pneumonia was allocated to the category of infection instead of respiratory diseases, and a patient with gastrointestinal bleedings was allocated to the category of hypovolemic conditions that covers all acute bleedings, dehydration, burns and tissue corrosions regardless of which organ is affected. Discharge diagnoses that did not match the criteria for the above-mentioned groups, were categorised into ‘other diseases’. The categories haematology and allergy 2
Baseline characteristics are presented for patients with low, intermediate and high lactate levels. Categorical variables are expressed as percentages with 95% CIs based on the binominal distribution. All continuous variables were non-normally distributed, and are described as medians with IQR. Pearson’s χ2 test was used to compare categorical variables. A logistic regression model was used to assess the relationship (OR) between 7-day mortality and lactate level. For all calculations of OR, the low lactate level was used as reference. A multivariate logistic regression model was performed including age, sex, comorbidity and discharge categories as predefined potential confounding variables. An interaction analysis was performed to test the interaction between lactate and discharge categories in the multivariate regression model. In the different discharge categories, Cuzick’s test for trend was used to test the trend in 7-day mortality for increasing lactate values. p Values 0.75 and a lower CI 95% >0.5 was considered useful. AUC 0.5. AUC for neurological diseases was 0.58 (95% CI 0.50 to 0.67), and AUC for respiratory diseases was 0.64 (95% CI 0.55 to 0.74). This indicates that lactate has no prognostic value in these diagnostic groups, as AUC was
