Critical Care

Blood lactate in mild and moderate ARDS secondary to SARS COV 2

a b s t r a c t

Background and objectives: Elevated Blood lactate levels are associated with poor outcome in several critical con- ditions. Patients with SARS-CoV-2 rarely develop hyperlactatemia. The purpose of this study is to evaluate the trend of lactatemia in patients affected by mild/moderate SARS-Co V-2-ARDS and if it affected prognosis.

Methods: We analyzed blood lactate levels in thirty-eight patients with severe SARS-CoV-2 infection admitted to COVID Care Unit of Santa Maria delle Grazie Hospital, Pozzuoli.

Results: Twenty patients survived and were discharged at home and 18 patients died. Despite severe hypoxia that affected all patients enrolled, T0 lactate was within normal values. All survivors showed a significant increase in lactate concentration the day prior to clinical improvement. In not-survivors levels of lactate did not increase significantly.

Conclusion: In our study, patients who survive SARS CoV-2 ARDS have a fleeting increase in lactate, which precedes clinical improvement by one day.

(C) 2023

  1. Background and objectives

Elevated blood lactate levels are associated with poor outcome in sev- eral critical conditions. Hyperlactatemia in critically ill patients is often due to tissue hypoperfusion, tissue hypoxia and the subsequent activa- tion of anaerobic glycolysis. In sepsis, a blood lactate level >2 mmol/l de- spite adequate volume resuscitation is associated with increased mortality [1]. In acute heart failure, 24-h time-weighted lactate is predic- tor of poor outcome [2]. It remains unclear whether high values of blood lactate are predictors of adverse outcome in patients affected by COVID-

19. Prior investigations suggest that SARS-CoV-2-acute respiratory dis- tress syndrome (ARDS) is associated with lower blood lactate concentra- tion than nonSARS-CoV-2 ARDS [3,4]. Patients with SARS-CoV-2 rarely develop hyperlactatemia, usually only in the late stages of the most se- vere clinical pictures [5,6]. The purpose of this study is to evaluate the trend of lactatemia in patients affected by mild/moderate SARS-CoV-2 ARDS and evaluate for any association with prognosis [7].

  1. Methods

We analyzed blood lactate levels in patients with SARS-CoV-2 infec- tion admitted to COVID Care Unit of Santa Maria delle Grazie Hospital,

* Corresponding author at: via Scalea 17 b, Portici (NA) 80055, Italy.

E-mail address: [email protected] (A. Pagano).

Pozzuoli, Italy, from March to April 2021. Our Covid Unit is a sub- intensive unit that does provide for the hospitalization of patients who need non-invasive mechanical ventilation, high-flow nasal cannu- las and conventional oxygen therapy. This Unit does not provide for the hospitalization of patients in invasive mechanical ventilation. All en- rolled patients were older than 18 years affected by mild-to-moderate ARDS requiring non-invasive ventilatory support. Intubated patients were excluded. SARS-CoV-2 infection was diagnosed through real- time reverse transcription polymerase reaction (RT-PCR) on nasal swab. Every patient underwent arterial blood analysis, processed and instantly analyzed through a mobile point of care system (Cobas b 123, Roche). oxygenation status was assessed using partial pressure of O2, partial pressure of CO2 and haemoglobin oxygen saturation. The ox- ygen partial pressure/oxygen inspiratory fraction (PaO2/FiO2) ratio was calculated to compare different values of arterial pO2 in patients receiv- ing different FiO2. Among the other parameters, pH and Bicarbonate concentration (HCO3-) were measured for the evaluation of acid-base disorders. arterial blood lactate concentrations were also recorded. At least one arterial blood sample per day was available for each enrolled patient. Lactate evaluation was performed at least once a day as part of the blood gas evaluation. All patients underwent chest CT. typical findings are ground glass opacity, crazy paving pattern and consolida- tion. A semi-quantitative CT severity score (CT SS) was calculated [8]. CT severity score was calculated by assessing the degree of lobe involve- ment for each of the five lung lobes separately on a scale of 0-5, with 0

https://doi.org/10.1016/j.ajem.2023.01.032

0735-6757/(C) 2023

indicating no involvement, 1 indicating <5% involvement, 2 indicating 5-25% involvement, 3 indicating 26-49% involvement, 4 indicating

Table 1

Characteristic of patients at baseline.

50-75% involvement, and 5 indicating >75% involvement. The sum of

Survivors

Not-survivors

p

the five lobe scores ranged from 0 (no involvement) to 25 (maximum

involvement), giving a total lung CT score. All patients were treated

AGE CT SS

63+-10

17+-5

70+-13

20+-3

0.05

0,02

with dexamethasone 6 mg daily and enoxaparin 100 u/kg; antibiotics

P/F

150+-56

76+-28

0,01

were reserved only for patients with suspected bacterial superinfection.

LACTATE t0

1,7+-0,5

1,9+-1

0,5

Collected data were evaluated by performing parametric and

non-parametric tests as appropriate. Student’s t-test was performed to compare the differences of continuous variables between groups. The chi-square test was used to compare categorical variables.

  1. Results

Thirty-eight patients (30 men, 8 women) were enrolled. Mean age was 66 +- 12 years. At admission, mean PaO2/FiO2 ratio was 112 +-

85. None had hemodynamic instability or required vasopressor or ino- tropic support. Mean CT severity score was 18 +- 4. Mean lactate con- centration was 1.8 +- 0.7 mmol/dl. Twenty patients survived and were discharged home and 18 patients died, of whom seven patients under- went orotracheal intubation and mechanical ventilation. There was no statistically significant difference between groups in terms of age and lactate at admission. Non-survivors showed a lower PaO2/FiO2 ratio (76 +- 28 vs 150 +- 56, p 0.01) and a CTSS higher (17 +- 5 vs 20 +- 3) than survivors. All patients in the survivors group showed a signifi- cant increase in lactate concentration the day prior to clinical improve- ment (lactate T0 1.7 +- 0.5 mmol/l, lactate max 3.1 +- 0.9 mmol/l, p < 0.001) (Fig. 1). In non-survivors, levels of lactate did not increase significantly (1.9 +- 1 mmol/l vs 2.6+-1.1 mmol/l p > 0.05). (See Table 1)

  1. Discussion

In our study, despite moderate hypoxia (mean PaO2/FiO2 112 +- 85) that affected all patients enrolled, T0 lactate was within normal values. This result agrees with those published by Alfano and colleagues [12]. Furthermore, our results suggest the presence of a different pattern in lactatemia between COVID patients who survive and are discharged at home and patients who have poor outcomes. Hypoxia and consequent alteration in mitochondrial oxidation are the main causes of lactate overproduction. Aerobic glycolysis is another considerable mechanism of lactate production in stress condition as sepsis, severe trauma, in re- sponse to elevated levels of epinephrine. Despite severe hypoxia, usu- ally, in severe SARS-CoV-2 infection, lactate levels do not increase significantly [9,10]. The mechanisms are not completely explained. We hypothesized that increased hepatic and renal clearance of lactate through the Cori cycle could prevent hyperlactatemia in these patients. The increase in LDH, which has frequently been found in patients with COVID 19, could reinforce this idea, since this enzyme is also involved in the conversion of lactate to pyruvate in the Cori cycle [13]. Neverthe- less, we found no significant differences in liver or kidney function parameters between the survivors and not-survivors. Other authors

Fig. 1. Daily lactate level in surviors (Group 1) and non-survivors (Group 2).

claimed that lactate produced is consumed by a binding mitochondrial antiviral signaling protein [11]. All survivors developed a fleeting but significant increase in blood lactate 24-h before respiratory improve- ment. Another possible explanation of this trend in lactate concentra- tions could be related to the fact that clinical improvement causes a reduction in energy demands and consequently a reduction in lactate consumption for gluconeogenesis. Further studies are needed to evalu- ate the trend of blood lactate levels in patients with respiratory insuffi- ciency due to COVID-19. A limit of our study is that we have excluded intubated patients.

  1. Conclusion

In our study, patients who survive SARS CoV 2 – ARDS have a fleeting increase in lactate, which precedes clinical improvement by one day.

Funding source

None.

CRediT authorship contribution statement

A. Pagano: Writing – original draft, Supervision. G. Porta: Writing – review & editing. G. Bosso: Conceptualization. E. Allegorico: Conceptu- alization. C. Serra: Investigation. V. Mercurio: Writing – review & editing, Supervision. G. Sansone: Investigation. S. Orefice: Investigation.

F.G. Numis: Supervision, Conceptualization.

Declaration of Competing Interest

All authors have not conflicts of interest.

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