In this study, we analyzed a cohort of 167 septic ICU patients with hematological malignancies characterized by a predominant representation of lymphoma and acute leukemia. A substantial proportion of the patients had progressive or refractory disease status, and they had a notable history of previous HSCT. In our study, hyperlactatemia at ICU admission was frequent in all septic patients with hematological malignancies. Additionally, lactate levels at 0, 6th, and 12th hours, and hyperlactatemia frequency at 0, 6th, and 12th hours were higher in ICU non-survivors than survivors. However, there was no difference in LC between ICU survivors and non-survivors at any point LC was calculated. Invasive mechanical ventilation, requirement of vasopressors, lactate levels at the 6th hour, and APACHE II score were independent risk factors for ICU mortality.
The complexities of lactate dynamics and their impact on outcomes in septic ICU patients with hematological malignancies are highlighted by the findings of this study. It was observed that non-survivors presented with higher lactate levels at 0, 6th, and 12th hours compared to survivors. This result indicates a potential association between elevated lactate and adverse outcomes, similar to those observed in prior studies (11–13). The observed pattern of hyperlactatemia frequency over the first 24 hours, with a decline from 64–36%, indicates the dynamic nature of lactate levels in this population. This may be influenced by factors such as the response to therapeutic interventions, disease progression, and the resolution of sepsis-related derangements. Moreover, we found that lactate levels at the 6th hour were an independent risk factor for mortality. Identifying lactate levels at the 6th hour as an independent risk factor for mortality suggests that early assessment during the critical hours of septic progression may offer more timely and valuable prognostic information than measurements taken at ICU admission or during later stages of hyperlactatemia in this patient population.
Remarkably, despite these differences in lactate levels at various time points, no significant difference in LC was observed between ICU survivors and non-survivors in our cohort. This exciting discovery underlines the complexities of lactate kinetics in sepsis among individuals with hematological malignancies, challenging common assumptions. The lack of a significant difference in LC between ICU survivors and non-survivors raises questions. Traditionally, LC has been considered a reliable prognostic marker in sepsis, reflecting the effectiveness of resuscitative efforts (7, 14–16). However, when considering hematological malignancies, this perspective might be more complicated. To evaluate the findings related to LC in our study, it would be meaningful to examine the outcomes from different perspectives. First, please consider the limitations of LC in the general septic ICU patient population, and second, understand the differences within the context of hematological malignancies.
From the first point of view, the complex nature of lactate, serving as a molecule, substrate, energy source, ingredient of certain intravenous fluids, and a regulator of cellular bioenergetics during physiological stress, is quite challenging (17). This complexity makes it difficult to determine a specific purpose for which it should serve as a marker or target. Additionally, approximately 20–30% of septic shock cases may present with normal lactate levels (< 2 mmol/L), rendering LC measurements ineffective (15). Likewise, in our study, nearly one-third of the patients did not present with hyperlactatemia on ICU admission. Additionally, various factors can confound lactate measurements, including using Ringer's lactate as a resuscitative fluid, exogenous lactate production (e.g., metformin use), and large-volume packed red blood cell transfusion (15). There was a frequent need for blood product transfusion in our patients (81%). However, the absence of data indicating the lack of timing data showing the relationship between transfusion and lactate measurements has prevented our ability to demonstrate this association. Moreover, we didn’t have specific data regarding the amount and type of fluid therapy given during the initial resuscitation of sepsis or shock. Similarly, in several studies, numerous potential factors that could interact with lactate dynamics cannot be thoroughly examined in all aspects (10–12). For all these reasons, while the current data suggest the superiority of LC over lactate levels in ICU patients with shock, there are also studies that do not support this idea, and it remains uncertain whether lactate kinetics outperform lactate values (15, 16, 18). Additionally, LC is a more robust prognostic marker when severe hyperlactatemia is present (12). On the contrary, only 12% of our patients had severe hyperlactatemia on ICU admission. The presence of milder hyperlactatemia in our patient population may contribute to underestimating the predictive value of LC.
A study by Bruno et al. found that the 6th-hour LC was an independent predictor for outcome prediction in 3299 septic ICU patients (19). They only knew the acute disease state in the form of SOFA scores and had no information about the comorbidities in their cohort. When we address the results of another study by Fuernau et al. involving a distinct patient cohort, they compared lactate values at admission and after 8 hours with LC for mortality prediction in 781 patients with cardiogenic shock (18). They found arterial lactate after 8 hours superior in mortality prediction in comparison with baseline lactate and LC. These discordant results observed among two large cohorts, unselected septic patients and those in cardiogenic shock, express a meaningful message regarding the second point of view. This message is about the complex nature of lactate values and LC as biomarkers, susceptible to influence from diverse conditions like underlying diseases, treatment modalities, and acute states of illness. Considering the specificity of our patient cohort, septic patients with hematological malignancies, the inconsistency in lactate levels and clearance may arise from the baseline characteristics, previous treatment modalities, or underlying malignancy-related factors. Moreover, the impact of chemotherapy-induced organ dysfunction and immunosuppression on lactate metabolism should be considered, potentially clouding the prognostic importance of changing lactate levels. Additionally, the underlying mechanism of hyperlactatemia involves significant differences in lactate metabolism between hematological malignancies and tissue hypoxia (20). Thus, it could impact the findings of our study, especially regarding variations in LC within our patient cohort.
These results highlight the importance of developing customized prognostic markers for this population, considering the complexities of disease and treatment-specific characteristics and treatment approaches. Future research should explore novel biomarkers or combinations of indicators that better capture the complexity of sepsis in the context of hematological malignancies. Refining risk stratification models specific to this population may enhance our ability to predict outcomes and guide targeted interventions.
Despite the valuable insights gained from this study, several limitations may impact the generalizability of our findings. The first one is the retrospective nature and single-center design of this study. Moreover, the study did not explore certain aspects that could contribute to lactate variability, such as the specific types of hematological malignancies, variations in chemotherapy regimens, and the impact of immunosuppression on lactate metabolism. Additionally, we had no precise data about the timing of blood product transfusions, fluid therapy, and its balance, which can impact the relationship between lactate measurements and ICU outcomes.