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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.57 no.6 Campinas Nov./Dec. 2007
Lactate as a predictor of mortality and multiple organ failure in patients with the systemic inflammatory response syndrome*
Lactato como pronóstico de mortalidad y falencia orgánica en pacientes con síndrome de la respuesta inflamatoria sistémica
Domingos Dias Cicarelli, TSAI; Joaquim Edson Vieira, TSAII; Fábio Ely Martins BenseñorII
IIAnestesiologista do HC-FMUSP; Professor Colaborador da Disciplina de Anestesiologia da FMUSP
OBJECTIVES: The systemic inflammatory response syndrome (SIRS) is common
in the postoperative period of critically ill patients. The objective of this
study was to investigate the correlation between lactate level, multiple organ
dysfunction, and mortality in patients with SIRS.
METHODS: This prospective study evaluated 24 patients with a postoperative diagnosis of SIRS (American College of Chest Physicians/Society of Critical Care Medicine) in the surgical ICU. Lactate levels were determined in the first 24 hours after the diagnosis of SIRS and daily, for 7 days. Patients were divided in 2 groups: LE Group (lactate > 2 mmol.L-1) and LN Group (lactate < 2 mmol.L-1). Multiple organ failure was evaluated by the SOFA (Sequential Organ Failure Assessment) score daily, for 7 days. After the 7-day follow-up period patients were followed for up to 28 days, until discharge from the hospital or death.
RESULTS: Thirteen patients were included in the LE Group after the diagnosis of SIRS and 11 patients in the LN Group. The relative risk (RR) of death in 7 days for the LE Group was 4.23 (CI 95% 2.25-7.95) times greater than in the LN Group in the first day of the study. The RR of death in 28 days was 1.7 times greater for the LE Group (CI 95% 0.84-3.46). The SOFA score was similar in both groups.
CONCLUSIONS: Patients with elevated lactate in the first 24 hours after the diagnosis of SIRS did not have more organic dysfunction than patients with normal lactate levels, but they had an increased risk of death in 7 days.
Key Words: INTENSIVE CARE MEDICINE: multiple organ failure; METABOLISM: lactate, inflammation.
Y OBJETIVOS: El síndrome de la respuesta inflamatoria sistémica
(SRIS) es común en pacientes en estado crítico en el postoperatorio.
El objetivo de este estudio fue investigar la correlación entre dosificación
de lactato, disfunción de múltiplos órganos y mortalidad
en pacientes con diagnóstico de SRIS.
MÉTODO: Estudio prospectivo que evaluó 24 pacientes con diagnóstico de SRIS (Colegio Americano de Cirujanos Torácicos/Sociedad Americana de Medicina Intensiva) en el postoperatorio en UTI quirúrgica. El lactato fue dosificado en las primeras 24 horas después del diagnóstico de SIRS y diariamente durante 7 días. Los pacientes fueron divididos en 2 grupos: Grupo LE (lactato > 2 mmol.L-1) y Grupo LN (lactato < 2 mmol.L-1). La falencia de múltiples órganos se evaluó por la puntuación SOFA (Sequential Organ Failure Assessment) diariamente por 7 días. Después del seguimiento por 7 días, los pacientes fueron acompañados hasta su alta u óbito en 28 días.
RESULTADOS: Trece pacientes fueron incluidos en el Grupo LE después del diagnóstico de SRIS y 11 pacientes en el Grupo LN. El riesgo relativo (RR) de óbito en 7 días para el Grupo LE fue 4.23 (IC 95% 2.25-7.95) veces mayor que el Grupo LN, el primero día del estudio. El RR de óbito en 28 días fue 1.7 veces mayor para el Grupo LE (IC 95% 0.84-3.46). Los grupos fueron similares con relación al SOFA durante el estudio.
CONCLUSIONES: Los pacientes con lactato elevado en las primeras 24 horas después del diagnóstico de SRIS no presentaron más disfunción orgánica que los pacientes con lactato normal, pero tuvieron riesgo aumentado de óbito en 7 días.
The systemic inflammatory response syndrome (SIRS) is a clinical manifestation of acute endothelial inflammation, which is common in the postoperative period of severely ill patients. The systemic inflammatory response syndrome might be related with infection, trauma, burns, pancreatitis, or lung diseases. However, it is one of the first manifestations in patients with sepsis, which is SIRS with a known infection. This syndrome can be defined by two or more of the symptoms listed here: fever (temperature > 38°C) or hypothermia (< 36°C); tachycardia (> 90 bpm); tachypnea (> 20 bpm) or hyperventilation (PaCO2 < 32 mmHg); and leukocytosis or leucopenia (> 12,000 cells.µL-1 or < 4,000 cells.µL-1), or a left shift (more than 10% of immature neutrophils) 1,2.
The systemic inflammatory response syndrome, sepsis, septic shock, and multiple organ failure syndrome (MOFS) have a strong link. The evolution of a patient with this sequence frequently leads to death. However, some patients with SIRS develop MOFS without infection or diagnosis of sepsis. Activation of the inflammatory cascade by an aggressive agent, with or without infection, seems to cause an inflammatory syndrome that is very often auto-sustainable, and the blockade or removal of this agent might not represent guarantee of success in the treatment of SIRS, and it does not avoid evolution of the inflammatory response2.
Endothelial edema secondary to the inflammatory response in the microcirculation increases hydraulic resistance, compromising the blood flow in the microcirculation and reducing the extraction of oxygen, leading to tissue hypoxia, anaerobic metabolism, and production of lactate. Tissue hypoxia favors anaerobic glycolysis and, therefore, increases production of lactate. Several studies have established the use of lactate as diagnostic, therapeutic, and prognostic marker of global tissue hypoxia in hypovolemic shock 3. Increased level of lactate is a marker of the response to metabolic stress, and its intensity and duration are often related with mortality 4.
The objective of this study was to evaluate the relationship between blood levels of lactate in patients with the diagnosis of SIRS in the postoperative period.
A prospective, observational study was conducted at the postoperative ICU of an university hospital. After approval by the Ethics Commission of the Institution informed consents were obtained from the patients or close relatives 5. Patients with a diagnosis of systemic inflammatory response syndrome (SIRS) according to the criteria of the American College of Chest Physicians and the Society of Critical Care Medicine (ACCP/SCCM) were included in this study. Twenty-seven patients admitted to the ICU of the Anesthesiology of the Hospital das Clínicas da Faculdade de Medicina da USP were selected. They were divided in 2 groups: elevated lactate LE (lactate > 2 mmol.L-1) and normal lactate LN (lactate < 2 mmol.L-1).
The severity of the conditions of the patient was determined by the APACHE II (Acute Physiology and Chronic Health Evaluation II) index 6,7. This index was developed to promote an objective evaluation of the severity of patients in intensive care. It is composed of 3 items: acute physiological score (obtained from 12 clinical measurements in the first 24 hours in the ICU). Among those measurements are temperature, mean arterial pressure, heart rate, respiratory rate, arterial pH, serum levels of sodium, potassium, and creatinine, hematocrit and leukocyte count, and Glasgow coma scale. The worse measurement is selected, being attributed a score from 0 to 4 and, if it has not been done, it receives a score of 0, adjusted for age (1 to 6 points are added to patients above 44 years), and for prior health status (points are added for the presence of nephropathies, hepatopathies, cardiopathies, pneumopathies, and immune compromised). According to the score obtained, one can estimate the in-hospital mortality of surgical and non-surgical patients.
After the diagnosis of SIRS, patients were evaluated daily by the SOFA score (Sequential Organ Failure Assessment) 8. This score is composed of 6 subitems that evaluate: respiratory system (PaO2/FiO2 ratio), coagulation (number of platelets), liver function (level of bilirubin), cardiovascular system (mean arterial pressure and need of vasoactive drugs), central nervous system (Glasgow scale), and renal function (creatinine level). Each subitem receives a score of 1 to 4, and higher scores mean increased failure of the system evaluated.
Arterial blood was drawn when the diagnosis of SIRS was made and daily, for 7 days. The same team of physicians followed all patients included in the study. Management protocols of critical patients were not changed during the study. After the 7-day period in the ICU, patients were followed during their stay until they were discharged from the hospital or died, for a maximum of 28 days.
The data are presented as absolute numbers, mean with standard deviation, or percentages. Statistical analysis used the Sigma Stat for Windows, version 2.03 (SPSS Inc). For continuous variables, treatments were compared using the Student t test, Mann-Whitney test, and two-way ANOVA. The relative risk of death in 7 and 28 days was calculated for patients with lactate levels equal or above 2 mmol.L-1 when the diagnosis of SIRS was made (inclusion in the study).
Three patients were excluded from the study due to the loss of lactate parameters after the diagnosis of SIRS. A total of 24 patients were analyzed. The mean age of the 24 patients was 53 ± 18 years (varying from 18 to 77 years). The study included 17 males (71%) and 7 females (29%).The mean age of the LE group was 52 ± 17 years, while in the LN group it was 53 ± 20 years. The APACHE II and SOFA at admission to the study were 15.3 ± 4.4 and 6.8 ± 2.7, respectively. There were no differences between both groups regarding admission APACHE II and SOFA scores (15.3 ± 4.9 and 6.9 ± 2.6 in the LE Group, 15.2 ± 4.1 and 6.7 ± 2.9 in the LN Group). Of the 24 patients, 63% needed treatment with vasopressors, 13% of renal substitution therapy (hemodialysis or hemofiltration), and 63% needed mechanical ventilation. Patients in the study had an initial lactate level of 3.23 ± 2.85 mmol.L-1, with a 7-day mortality of 25% (6 patients) and 28-day mortality rate of 37.5% (9 patients).
The characteristics of the study population at the time of inclusion in the study and the severity of the disease were similar in both groups (Table I).
Thirteen patients were included in the LE Group (lactate level > 2 mmol.L-1) and 11 patients were included in the LN Group (lactate level < 2 mmol.L-1). Using a cutting level of 2 mmol.L-1 or greater of lactate at the moment of inclusion in the study 9,10, the relative risk (RR) of death in seven days was 4.23 (CI 95% 2.25-7.95) and RR in 28 days of 1.7 (CI 95% 0.84-3.46). Among the patients in the LE Group, the 7-day mortality rate was 38.5%, significantly greater than for patients with a normal level of lactate, whose mortality was 9% (p < 0.05). The 28-day mortality rate was 46.1% in the LE Group and 27.3% in the LN Group (p > 0.05). The 7-day and 28-day mortality rate is shown in figure 1. Figure 2 shows the evolution of the level of lactate in both groups during the study.
The sensitivity, specificity, and positive predictive value (PPV) of death in patients with lactate > 2 mmol.L-1 at the time of inclusion in the study were calculated and are presented in table II.
Both groups maintained similar SOFA scores during the study. Differences in the components of the score were not observed: platelet count (coagulation), serum bilirubin levels (liver function), creatinine (renal function), or Glasgow scale (central nervous system dysfunction) (Figure 3).
This study evaluated the level of lactate at the moment the diagnosis of SIRS was made as a postoperative prognostic indicator of mortality and organ failure.
Determination of lactate levels is useful for the early detection of tissue hypoxia, avoiding progressive organ dysfunction and death 9. Lactate is a useful tool that is easy to obtain in the daily medical practice to be used as a marker of tissue hypoxia and disease severity. Persistently high lactate levels have demonstrated to be the best predictor of mortality among the parameters that evaluate oxygen transport 3.
There are several reasons why lactate levels are increased in severely ill patients, including alkalosis, administration of catecholamines, increased metabolic activity, and hepatic or renal failure 10. However, increased lactate associated with poor tissue perfusion seems to be associated with worse evolution 10. In the present study, patients with postoperative lactate levels above 2 mmol.L-1 at the moment SIRS was diagnosed were 4 times more likely to die in 7 days. According to this observation, lactate levels can be used to screen for patients who need more intensive care (earlier and more aggressive therapy), even during or at the end of the surgery. Effective, aggressive treatment of "early shock" may prevent progression to refractory shock and multiple organ failure 9. A delay in volume replacement and inotropic support for myocardial dysfunction increases the risk of death. Under these circumstances, determination of lactate levels, as a prognostic indicator, is very important; it has low cost and is rapidly done. Blood samples for determination of lactate levels can be easily obtained at the operating room, ICU, or emergency room.
Previous studies showed that lactate levels above 4 mmol.L-1 in the presence of SIRS are indicative of a significant increase in mortality 3. In the present study, lactate levels equal or above 2 mmol.L-1 in the first 24 hours after the diagnosis of SIRS were related with an increase in the 7-day mortality. This is similar to the results of other studies demonstrating that the early determination of lactate levels can be predictive of the mortality11-13. Some authors believe that persistent, elevated levels of lactate during the evolution of the disease are more sensitive to predict unfavorable evolution and death 14,15. The results of the present study did not demonstrate a correlation of lactate levels and organic dysfunction evaluated by the SOFA score.
We conclude that lactate levels did not correlate with organic dysfunction; however, elevated lactate levels in the first 24 hours after the diagnosis of SIRS were related with an increase in the risk of death in a seven-day period.
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Dr. Domingos Dias Cicarelli
Av. Piassanguaba, 2.933/71 Planalto Paulista
04060-004 São Paulo, SP
Submitted em 11
de dezembro de 2006
Accepted para publicação em 22 de agosto de 2007
* Received from UTI da Anestesia. Disciplina de Anestesiologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)