Patients with a poor neurological outcome after CA had higher lactate values on admission and over the first 2 days than patients with a favourable outcome. Blood lactate concentration on admission remained a significant predictor of poor outcome even after adjustment for major confounders. Nonetheless, the relative decrease in lactate at 6, 12 and 24 h was not related to neurological outcome. In a linear regression model, use of vasopressors, PaO2, time to ROSC and renal SOFA were independently associated with high admission blood lactate concentration.
The pathophysiology of hyperlactataemia is complex and can involve tissue hypoperfusion, adrenergic hyperstimulation  and altered lactate clearance by the liver . Interestingly, high lactate concentrations in our study were associated with renal dysfunction, which was probably a marker of organ failure  more than the kidney’s inability to clear lactate . There was no association between lactate levels and the intensity of therapy (i.e. ECMO or IABP), although the number of treated patients was relatively limited. There was also no association of lactate on admission and hepatic dysfunction as assessed by the hepatic SOFA subscore. Moreover, increased PaO2 values were predictive of high lactate concentration on admission. Recent studies have suggested that very high PaO2 values (> 300 mmHg) may aggravate post-anoxic brain injury . However, a specific threshold for oxygen toxicity has not yet been identified in clinical practice and the mechanisms relating oxygen toxicity to lactate production need to be further evaluated in this setting.
A high blood lactate concentration on admission was significantly correlated with poor neurological outcome. Similarly, in a large cohort of 443 patients, Lee et al. reported that a high blood lactate measured within 1 h of ROSC was correlated with CPC 3–5 at hospital discharge . In 394 CA survivors enrolled over a 10-year period, Kliegel et al.  found a significant correlation between lactate at baseline, 24 and 48 h and neurological outcome. Moreover, blood lactate concentrations have been included, along with initial rhythm, estimated no-flow and low-flow intervals and creatinine levels, in a hospital admission predictive score for good neurological recovery after successful resuscitation from OHCA .
A decrease in lactate concentrations over time is a reliable marker of effective treatment in critically ill patients with shock [22,23,24,25]. As expected, we found that the higher the lactate on admission, the greater the decrease over time . However, there was no relationship between lactate decrease and neurological outcome. Our findings contrast with those of Donnino et al.  who reported that lactate decrease at 6 and 12 h was more pronounced in survivors than in non-survivors, but no data on neurological recovery were available. Two studies have reported that the decrease in lactate at 12 h was an independent marker of good neurological outcome [8, 9]. The differences between these studies and our results may be explained by a lower median lactate on admission in our study (4.3 mEq/L in our study vs. 6 to 15 mEq/L in [8, 9, 14]), which is probably explained by a shorter duration of CA in our cohort of patients.
Of note, we also reported data in patients with IHCA, whereas most previous studies included only OHCA patients. Only Karagiannis et al. , in a small group of 28 patients after IHCA, described higher lactate concentrations at 6, 18 and 24 h after ROSC in non-survivors than in survivors, and a significantly lower percentage decrease in lactate at 6 and 12 h in non-survivors. In our cohort, lactate levels were similar in IHCA and OHCA patients at all time points. This is of interest because IHCA is usually secondary to different aetiologies than OHCA and associated with severe pre-existing comorbidities, which may alter the generalizability of outcome predictors for OHCA to the IHCA setting. Blood lactate values were also similar regardless of the initial rhythm, despite the fact that patients with non-shockable rhythms are more likely to have prior hypoxia or hypotension and, in general, a longer time from arrest to CPR [28, 29]. This suggests that the prognostic value of lactate levels on admission is independent of these CA characteristics and applicable to a wide CA population.
Our study has some limitations. First, given the retrospective design, we could not reliably account for some variables that may have influenced lactate concentrations, especially on admission, particularly CPR quality, total doses of adrenaline during CPR and fluid administration or fluid balance. However, consistent management in a single centre can reasonably exclude important differences in treatment strategies among patients. Moreover, we provided time to ROSC, but could not differentiate between “no-flow” and “low-flow” times, which could further influence the initial lactate levels (e.g. prolonged “no-flow” times should be associated with higher lactate values). Second, we evaluated a limited cohort of patients, including a heterogeneous population of patients with IHCA and OHCA, which may limit the generalizability of our findings. Third, our model could account for only one-third of the variability in lactate concentrations on admission, indicating that other factors that we did not account for—e.g. no-flow period, total dose of adrenaline given during CPR, vasopressors given during the ICU stay—may be involved in the pathophysiology of high lactate concentrations in this setting. Fourth, baseline lactate concentration may be related to the quality of resuscitation during CA, whereas lactate concentration at 12 or 24 h may be related more to the quality of critical care provided. Although this statement sounds logical, we have almost no data in the literature to confirm this hypothesis and the retrospective nature of our study precludes any additional analysis. Furthermore, the interpretation of baseline lactate could also be confounded by underlying conditions (e.g. sepsis) and/or aetiology of arrest (e.g. prolonged hypoxaemia before arrest). Fifth, lactate concentrations were available to the treating clinicians; although lactate concentrations are not used as a marker of poor prognosis in this setting, we cannot exclude that persistently high lactate concentrations may have encouraged limitation of invasive therapies in some of these patients, thus raising the risk of “self-fulfilling prophecy”. Finally, we evaluated liver function using the hepatic SOFA subscore, which is based on total bilirubin levels. Hypoxic hepatitis, as observed after CA, is, however, defined as an elevation of aminotransferases; nevertheless, the occurrence of hypoxic hepatitis is rare  and generally occurs 1–2 days after CA, which would be of limited interest for interpretation of admission lactate levels.