Early Lactate Clearance as a Determinant of Survival in Patients with Sepsis: Findings from a Low-resource Country

Data were collected via file reviews for six months from the date of getting exemption from the ethical review committee (ref- 2019-1589-4058) following variables, were considered: demographics, the suspected source of infection, vital signs, initial and repeat serum lactate concentrations, initially at admission and then 6 hours later, use of vasopressin, and intravenous fluid, information on comorbid conditions, hospital length of stay and outcome information. Illness severity was defined using the presence of individual organ system failures as assessed by the worst recorded values for each organ system: cardiovascular = initial Systolic BP less than 90 mmHg; pulmonary = new oxygen requirement or PaO2/FIO2 less than 300; renal = serum creatinine more than 2.0 mg/dL; hepatic = serum bilirubin greater than 2.0 mg/dL; hematologic = platelets less than 100,000/2L or international normalized ratio more than 1.5 sec; neurologic = a new finding of altered mental status (history or physical exam) and calculation of the Sequential Organ Failure Assessment (SOFA) score.

To describe the characteristics of the study population, we reported frequencies and proportions, SPSS 23.0 was used to analyze the data. More specifically, we reported frequencies and proportions to describe the characteristics of the study population for the categorical variables such as gender, presence of diabetes or hypertension, etc. We checked the normality assumption for continuous variables by histograms superimposed with the normal curve. We used a Chi-squared test or Fisher’s exact to assess the frequency distribution and the relationship between covariates and survival or organ dysfunction for categorical variables. We performed univariable logistic regression analysis to determine the individual effect of each significant predictor on survival or organ dysfunction. We considered a p-value of less than 0.05 for significant results. Finally, we conducted a multivariable logistic regression analysis to determine the adjusted effect of each determinant on survival or organ dysfunction. We presented the results of regression analysis by crude/unadjusted Odds ratio (OR) and adjusted odds ratio (AOR) with 95% Confidence Intervals (CIs).

A total 198 patients were included in the study. The study findings illustrated that almost half of the patients (45.54%) were older than 60 years and a quarter (25.75%) were young of 20 to 40 years old as sown in Table 1. The ratio of males and females was almost one to one with 51% being male and 49% females. A little over a quarter (27.8%) of the patients were diabetic, almost one-third (35.4%) were hypertensive, 14.6% had chronic kidney disease, 18.2% had ischemic heart disease, 19.7% suffered from lung disease, and 5.1% had chronic liver disease. Almost all of the admitted patients (84.3%) had undergone one or other surgical or therapeutic procedures during a hospital stay and one quarter (25.8%) stayed for more than a week in the hospital. A greater proportion of the patients (83.3%) had a platelet count of more than 100,000 and 11.1% had a previous history of blood transfusion (Table 1). Around 83% of the patients (n= 165) were discharged from the hospital and 17% of the patients died (n=33). Pneumonia was the most common cause of sepsis in 48.9%(97) (Table-2). There were missing data for 25.8% of the patients for the lactate clearance, whereas 55% of the patients had early lactate clearance and 19.7% had delayed lactate clearance. On the other hand, 18.69% (37) of the patients had multiple organ dysfunction, 47.47%(94) had single organ dysfunction, and 33.84%(67) had no organ dysfunction.

Table 3 describes the characteristics of the patients by survival or mortality. We found that a higher proportion of the patients who died (57.6%) were older than 60 years old when compared with 43.0% of the patients discharged from the hospital. Similarly, 54.5% of the patients died and 22.4% of their counterparts were diabetic (p-value: <0.001). A significantly higher proportion of patients who died (60.6%) were hypertensive compared with patients discharged from the hospital (30.3%; p-value: 0.001). Mortality rate was higher in patients with delayed lactate clearance 38.4% (18/39) as compared to 16.6% (18/108) in patients with early clearance. About 45.5% of the patients who died had delayed lactate clearance when compared with 21.1% of patients discharged (p-value: 0.005) as shown in Table 3. Around 39.4% of the patients who died had undergone any procedure done as opposed to 10.9 % of the patients who were discharged from the hospital. A significantly higher proportion of the patients (63.6%) who died suffered from chronic kidney disease as opposed to 10.3% of the patients discharged. However, there were no significant differences between patients who died and those who were discharged by blood transfusion and gender.

Table 3 describes the characteristics of the patients by organ dysfunction. We found that a higher proportion of the patients with multiple organ dysfunction (33.3%) had delayed lactate clearance when compared with 31.9% of the patients with single organ dysfunction and 15.7% of the patients who did not have any organ dysfunction at all (p-value: 0.09). Similarly, 24.3% of the patients with multiple organ dysfunction had chronic kidney disease when compared with 16.0 % of the patients with single organ dysfunction and 7.5% of the patients with no organ dysfunction at all (p-value: <0.059). A significantly higher proportion of patients with multiple organ dysfunction (27.0%) had lung disease when compared with 23.4 % of the patients with single organ dysfunction and 10.4% of the patients with not any organ dysfunction at all (p-value: 0.05). About 13.5% of the patients with multiple organ dysfunction had severe worsening of the score on the Glasgow coma scale when compared with 2.1% of patients with single organ dysfunction and 3% with no organ dysfunction (p-value: 0.05) as shown in Table 3. Around 29.7 of the patients with multiple organ dysfunction had undergone any procedure done as opposed to 13.4 % of the patients with no organ dysfunction. Whereas there were no significant differences between patients with and without organ dysfunction by blood transfusion, age, gender, ischemic heart disease, hypertension, and diabetes mellitus (Table 3).

Table 4 shows the findings of factors associated with mortality with a special focus on the association between delayed lactate clearance and mortality. We found that patients with delayed lactate clearance were 3.12 times (OR = 3.12; [95% CI: 1.37-7.09]) more likely to die when compared to patients with early lactate clearance (Table 3). Likewise, patients who were diabetic were 4.15 times more likely to die when compared to the non-diabetic patients (OR = 4.15; [95% CI:1.91-9.03]). Similarly, hypertensive patients were 3.54 times more likely to die when compared to their counterparts (OR = 3.54; [95% CI:1.63-7.67]). Furthermore, patients with lung disease were 2.46 (OR = 2.46; [95% CI: 1.075.61]) times likely to die when compared to those without lung disease. Patients with ischemic heart disease were 2.80 (OR = 2.80; [95% CI: 1.21-6.48]) times more likely to die than patients without ischemic heart disease (Table 4). Similarly, patients with any procedure done were 5.31 (OR = 5.31; [95% CI: 2.26-12.45]) times likely to die when compared to those without any procedure done. Patients with prolonged stay and platelet count of less than 10,000 were 6.65 (OR = 6.65; [95% CI: 2.98-14.8]) and 3.25(OR = 3.25; [95% CI: 1.38-7.61]) times likely to die respectively as opposed to their counterparts (Table 4).

Table 4 shows the findings of factors associated with organ dysfunction with a special focus on the association between delayed lactate clearance and organ dysfunction. The study findings revealed that patients with delayed lactate clearance were 2.56 (OR = 2.56; [95% CI: 1.07-6.13]) times likely to have organ dysfunction when compared to patients with early lactate clearance. Similarly, patients with chronic kidney disease were 2.78 (OR = 2.78; [95% CI: 1.01-7.66]) times more likely to have organ dysfunction than patients without chronic kidney disease (Table 4). We did not find any significant differences between patients with and without organ dysfunction on factors such as age, gender, hypertension, any procedure is done, lung disease, platelet count, and length of stay as shown in table 4.

The results of the multivariable analysis were adjusted for patient’s age, comorbid such as DM, HTN, and is-chemic heart disease, platelet count, and length of stay. The adjusted results demonstrated a positive relationship between delayed lactate clearance and mortality, meaning that after adjusting for potential confounders, patients with delayed lactate clearance were more than 8 times more likely to die than patients with early lactate clearance [aOR = 7.67; 95% CI:1.11-53.26)]. Other statistically significant factors predicted the mortality included DM (aOR = 8.56; [95% CI :1.18-62.01]), HTN (AOR = 56.36; [95% CI :3.57-889.83]), (aOR = 1.37; [95% CI (0.52-3.66]) and platelet count as well as patient’s level of consciousness as shown in Table 4.

The results of the multivariable analysis were adjusted for the patient’s comorbidities. The results demonstrated that there was no statistically significant association between delayed lactate clearance [aOR = 2.18; 95% CI: 0.87-5.49)] and organ dysfunction in the final adjusted model after controlling for potential confounders. However, there was a statistically significant association between chronic kidney disease (aOR = 6.13; [95% CI:1.72-21.86]) and organ dysfunction after controlling for potential confounders persisted in the adjusted model, however, 95% CI for these associations were not precise as shown in Table 4.