Serum lactate as a predictor of mortality in patients hospitalised with COVID-19
Date First Published:
February 6, 2021
Last Updated:
April 8, 2021
Report by:
Corinna Ekebuisi, Medical Student (University of Liverpool)
Search checked by:
Justin Newstone, University of Liverpool
Three-Part Question:
In [patients admitted to hospital with confirmed or suspected COVID-19] is [the level of serum lactate] able to [predict mortality]?
Clinical Scenario:
A 40 year old male attends the emergency department with a persistent dry cough and fever. He tested positive for COVID-19 infection five days ago and has been isolating ever since. On examination his heart rate is 120 beats per minute, respiratory rate is 20 and his oxygen saturations are 94% on room air. Would measuring his serum lactate help you to risk stratify this patient and determine his requirement for medical intervention?
Search Strategy:
PubMed search: 2019 – 09 October 2020 and 2019 – 25 November 2020
Scopus search: 2019 – 09 October 2020 and 2019 – 25 November 2020
Web of Science search: 2019 – 09 October 2020 and 2019 – 25 November 2020
Scopus search: 2019 – 09 October 2020 and 2019 – 25 November 2020
Web of Science search: 2019 – 09 October 2020 and 2019 – 25 November 2020
Search Details:
((COVID-19 OR Coronavirus OR SARS-CoV-2) AND (Lactate OR Lactic Acid) AND NOT dehydrogenase)
Outcome:
After the removal of duplicates from the primary search, 99 titles and abstracts were reviewed. 10 of these were deemed to be relevant to the clinical question. An additional 3 papers were identified during the second literature search. Of the 13 included studies, there were 12 cohort studies and 1 retrospective case series.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Prognostic Factors for 30-Day Mortality in Critically Ill Patients With Coronavirus Disease 2019: An Observational Cohort Study Ferrando-Vivas et al. 2020 United Kingdom | 9,990 patients hospitalised with COVID-19. (Median age 60 years) |
Cohort study (2b) | 30-day ICU mortality | There were 3,933 ICU deaths. Highest serum lactate measurement in the first 24 hours of ICU admission was associated with 30-day ICU mortality (HR 1.499, 95% CI: 1.301 – 1.729; p<0.0001). Mortality increased steeply with increasing lactate up to approximately 2mmol/L, then increased more gradually in the Cox proportional-hazard regression model. | Missing data. Baseline medications not considered. Co-infections not considered. The method of confirming a COVID-19 case was not defined. |
| Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study Goodall et al. 2020 England | 981 patients hospitalised with COVID-19. A COVID-19 case was defined as a positive result on RT-PCR test for SARS-CoV-2. (Median age 69 years) |
Retrospective cohort study (2b) | In-hospital mortality | There were 354 in-hospital deaths. Higher lactate levels were associated with an increased risk of death in the multivariable Cox proportional-hazard model analysis (adjusted HR 2.67, 95% CI: 1.65 – 4.33; p<0.001) | Single-centre study. Missing data. Co-infections not considered. Retrospective study design. |
| Early predictors of in-hospital mortality in patients with COVID-19 in a large American cohort Bahl et al. 2020 USA | 1461 patients hospitalised with COVID-19. A COVID-19 case was defined as a positive result on RT-PCR test for SARS-CoV-2. (Median age 62 years) |
Cohort Study (2b) | Missing data. Baseline medications not considered. |
||
| Lactate Kinetics Reflect Organ Dysfunction and Are Associated with Adverse Outcomes in Intensive Care Unit Patients with COVID-19 Pneumonia: Preliminary Results from a GREEK Single-Centre Study Vassiliou et al. 2020 Greece | 45 patients hospitalised with COVID-19. A COVID-19 case was defined as a positive result on RT-PCR test for SARS-CoV-2. (Mean age 64 years) |
Retrospective Cohort Study (2b) | 28-day ICU mortality | There were 11 ICU deaths. Maximum lactate on admission was independently associated with 28-day ICU mortality (P = 0.008, multivariate Cox regression analysis). Mean daily lactate levels were higher in non-survivors (p<0.0001) on the mixed model analysis. | Single-centre study. Small sample size. Baseline medications not considered. Co-infections not considered. Retrospective study design. |
| Prognostic factors associated with mortality risk and disease progression in 639 critically ill patients with COVID-19 in Europe Garcia et al. 2020 European | 639 patients hospitalised with COVID-19. A COVID-19 case was defined as a positive result on RT-PCR test for SARS-CoV-2. (Median age 63 years) |
Cohort study (2b) | ICU mortality | There were 97 ICU deaths. Lactate on admission was independently associated with ICU-mortality on multivariable Cox proportional-hazard regression model (p = 0.009). | Differences across centres. Missing data. Baseline medications not considered. |
| Clinical Characteristics and Predictors of 28-Day Mortality in 352 Critically Ill Patients with COVID-19: A Retrospective Study Alharthy et al. 2020 Saudi Arabia | 352 patients hospitalised with COVID-19. A COVID-19 case was defined as a positive result on RT-PCR test for SARS-CoV-2. (Mean age 51 years) |
Retrospective cohort study (2b) | 28-day ICU mortality | There were 113 ICU deaths. An increased serum lactate level was a predictor for 28-day ICU mortality in the multivariate regression analysis (OR 3.9, 95% CI: 2.4 – 4.9; p = 0.035) Non-survivors had a significantly higher serum lactate level than survivors in the Student’s t-test (2.13 ±0.34 vs. 1.61 ±0.33, p = 0.0001). | Single-centre study. Missing data. Baseline medications not considered. Retrospective study design. |
| Epidemiological & clinical characteristic & early outcome of COVID-19 patients in a tertiary care teaching hospital in India: A preliminary analysis Kayina et al. 2020 India | 235 patients hospitalised with COVID-19. A COVID-19 case was defined as a positive result on RT-PCR test for SARS-CoV-2. (Mean age 51 years) |
Cohort study (2b) | 24-hour ICU mortality | There were 20 ICU deaths. Non-survivors had a higher baseline serum lactate compared with survivors (p<0.01, n=122). | Single-centre study. Preliminary analysis. Missing data. Baseline medications not considered. Co-infections not considered. |
| Clinical characteristics of 25 death cases with COVID-19: A retrospective review of medical records in a single medical center, Wuhan, China Li et al. 2020 China | 25 patients hospitalised with COVID-19. A COVID-19 case was defined as a positive result on RT-PCR test for SARS-CoV-2. (Median age 73 years) |
Retrospective cohort study (2b) | In-hospital mortality | There were 25 in-hospital deaths. Lactate level increased in 100% (n=12) of patients with repeat measurements, from the first test (median = 1.35, IQR: 0.68 – 1.5) to the last test (median = 2.75, IQR: 1.83 – 3.55) taken before death. | Single-centre study. Small sample size. Missing data. No comparison with survivors. In-hospital treatment not considered. Descriptive analysis only - no analysis to determine statistical significance of findings. Retrospective study design |
| Summary of 20 tracheal intubation by anesthesiologists for patients with severe COVID-19 pneumonia: retrospective case series Zhang et al. 2020 China | 20 patients hospitalised with COVID-19. A COVID-19 case was defined as positive on RT-PCR for SARS-CoV-2 AND positive chest CT findings AND clinical symptoms of COVID-19. (Median age 71 years) |
Retrospective case series (4) | 7-day mortality post tracheal intubation | There were 7 deaths post tracheal intubation. Non-survivors had a significantly higher lactate than survivors, both before and after tracheal intubation (Student’s t-test, p = 0.001). | Single-centre study. Small sample size. Baseline medications not considered. Co-infections not considered. Retrospective study design. |
| Changes in the Clinical Characteristics of 62 Patients Who Died from Coronavirus Disease 2019 Chen et al. 2020 China | 62 patients hospitalised with COVID-19. A COVID-19 case was defined as a positive result on RT-PCR test for SARS-CoV-2. (Median age 72 years) |
Retrospective cohort study (2b) | In-hospital mortality | There were 62 in-hospital deaths. Lactic acid levels at the last follow-up before death were significantly worse than on admission (Student’s t-test, p = 0.013). | Single-centre study. Small sample size. Baseline medications not considered. No comparison with survivors. Retrospective study design. |
| Validation of Predictors of Disease Severity and Outcomes in COVID-19 Patients: A Descriptive and Retrospective Study Tan et al. 2020 China | 142 patients hospitalised with COVID-19. A COVID-19 case was defined as a positive result on RT-PCR test for SARS-CoV-2. (Mean age 56 years) |
Retrospective cohort study (2b) | In-hospital mortality | There were 15 in-hospital deaths. No significant difference was observed between lactic acid levels in non-survivors compared to survivors (p>0.05). | Single-centre study. Small sample size. Missing data. Lactate measurements available for only 15 non-survivors and 23 survivors. In-hospital treatment not considered. Baseline medications not considered. Retrospective study design. |
| Time-dependent changes in the clinical characteristics and prognosis of hospitalized COVID-19 patients in Wuhan, China: A retrospective study Wang et al. 2020 China | 843 patients hospitalised with COVID-19. A COVID-19 case was defined as a positive result on RT-PCR test for SARS-CoV-2. (Median age 60 years) |
Retrospective cohort study (2b) | 12-day in-hospital mortality | There were 77 deaths. Lactic acid level was lowest in the group with the best outcomes and lowest mortality rate (Kruskal-Wallis test, p<0.05). | Single-centre study. Missing data. Baseline medications not considered. Co-infections not considered. Retrospective study design. Only analysed admission laboratory results. |
| Abnormal immunity of non-survivors with COVID-19: predictors for mortality Zhao et al. 2020 China | 539 patients hospitalised with COVID-19. A COVID-19 case was defined as a positive result on 2 or more RT-PCR test for SARS-CoV-2. (Median age 58 years) |
Retrospective cohort study (2b) | In-hospital mortality | There were 125 in-hospital deaths. Lactic acid levels on admission were significantly higher in non-survivors than survivors (2.40 vs. 1.90 mmol/L, p<0.001). | Single-centre study. Missing data. Baseline medications not considered. Co-infections not considered. Retrospective study design. |
Author Commentary:
With the exception of one study (Tan et al.), there was an agreement within the reviewed literature that serum lactate levels correlate with disease progression and mortality in hospitalised COVID-19 patients. Twelve studies out of the thirteen studies found the serum lactate level to be significantly higher in non-survivors compared with survivors (n = 15,192 patients). Specifically, an actively increasing serum lactate was associated with mortality, supporting the use of serial lactate measurements in hospitalised COVID-19 patients in order to detect rising levels. Baseline serum lactate measurements were significantly greater in non-survivors than survivors (n = 12,909 patients), suggesting that a raised serum lactate level on admission is associated with mortality. This identifies serum lactate as not only a predictor of COVID-19 mortality, but an early predictor.
Bottom Line:
A raised or increasing serum lactate level is an early predictor of mortality in patients hospitalised with COVID-19 and thus may be considered in the risk-stratification and management of these patients.
References:
- Ferrando-Vivas et al.. Prognostic Factors for 30-Day Mortality in Critically Ill Patients With Coronavirus Disease 2019: An Observational Cohort Study
- Goodall et al.. Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study
- Bahl et al.. Early predictors of in-hospital mortality in patients with COVID-19 in a large American cohort
- Vassiliou et al.. Lactate Kinetics Reflect Organ Dysfunction and Are Associated with Adverse Outcomes in Intensive Care Unit Patients with COVID-19 Pneumonia: Preliminary Results from a GREEK Single-Centre Study
- Garcia et al.. Prognostic factors associated with mortality risk and disease progression in 639 critically ill patients with COVID-19 in Europe
- Alharthy et al.. Clinical Characteristics and Predictors of 28-Day Mortality in 352 Critically Ill Patients with COVID-19: A Retrospective Study
- Kayina et al.. Epidemiological & clinical characteristic & early outcome of COVID-19 patients in a tertiary care teaching hospital in India: A preliminary analysis
- Li et al.. Clinical characteristics of 25 death cases with COVID-19: A retrospective review of medical records in a single medical center, Wuhan, China
- Zhang et al.. Summary of 20 tracheal intubation by anesthesiologists for patients with severe COVID-19 pneumonia: retrospective case series
- Chen et al.. Changes in the Clinical Characteristics of 62 Patients Who Died from Coronavirus Disease 2019
- Tan et al.. Validation of Predictors of Disease Severity and Outcomes in COVID-19 Patients: A Descriptive and Retrospective Study
- Wang et al.. Time-dependent changes in the clinical characteristics and prognosis of hospitalized COVID-19 patients in Wuhan, China: A retrospective study
- Zhao et al.. Abnormal immunity of non-survivors with COVID-19: predictors for mortality