Transient hyperlactatemia during intravenous administration of glycerol: a prospective observational study

Abstract Background Intravenous glycerol treatment, usually administered in the form of a 5% fructose solution, can be used to reduce intracranial pressure. The administered fructose theoretically influences blood lactate levels, although little is known regarding whether intravenous glycerol treatment causes transient hyperlactatemia. This study aimed to evaluate blood lactate levels in patients who received intravenous glycerol or mannitol. Methods This single-center prospective observational study was performed at a 14-bed general intensive care unit between August 2016 and January 2018. Patients were excluded if they were  2.0 mmol/L). The included patients received intravenous glycerol or mannitol to reduce intracranial pressure and provided blood samples for lactate testing before and after the drug infusion (before the infusion and after 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 150 min). Results Among the 33 included patients, 13 patients received 200 mL of glycerol over 30 min, 13 patients received 200 mL of glycerol over 60 min, and 7 patients received 300 mL of mannitol over 60 min. Both groups of patients who received glycerol had significantly higher lactate levels than the mannitol group (2.8 mmol/L vs. 2.2 mmol/L vs. 1.6 mmol/L, P < 0.0001), with the magnitude of the increase in lactate levels corresponding to the glycerol infusion time. There were no significant inter-group differences in cardiac index, stroke volume, or stroke volume variation. In the group that received the 30-min glycerol infusion, blood lactate levels did not return to the normal range until after 120 min. Conclusions Intravenous administration of glycerol leads to higher blood lactate levels that persist for up to 120 min. Although hyperlactatemia is an essential indicator of sepsis and/or impaired tissue perfusion, physicians should be aware of this phenomenon when assessing the blood lactate levels

Time course of immature platelet count and its relation to thrombocytopenia and mortality in patients with sepsis

<div><p>Introduction</p><p>The pathogenesis of thrombocytopenia in patients with sepsis is not fully understood. The aims of this study were to investigate changes in thrombopoietic activity over time by using absolute immature platelet counts (AIPC) and to examine the impact of platelet production on thrombocytopenia and mortality in patients with sepsis.</p><p>Methods</p><p>This retrospective observational study included adult patients with sepsis admitted to the intensive care unit at a university hospital. Two hundred five consecutive sepsis patients were stratified into four groups according to nadir platelet count: severe (nadir ≤40×10³/μL), moderate (41–80×10³/μL), or mild thrombocytopenia (81–120×10³/μL), or normal-increased platelet count (>120×10³/μL). The development of thrombocytopenia was assessed during the first week; mortality was assessed at day 28.</p><p>Result</p><p>Of the 205 patients included, 61 (29.8%) developed severe thrombocytopenia. On admission, AIPC did not differ among the four groups. In patients with severe thrombocytopenia, AIPC decreased significantly from days 2 to 7, but remained within or above the normal range in the other three groups (overall group comparison, <i>P</i><0.0001). Multivariate analysis including coagulation biomarkers revealed that AIPC was independently associated with the development of severe thrombocytopenia (day 3 AIPC, odds ratio 0.49 [95% confidence interval (CI) 0.35–0.66], <i>P</i><0.0001; day 5 AIPC, 0.59 [95% CI 0.45–0.75], <i>P</i><0.0001). AIPC was a significant predictor of 28-day mortality in Cox hazard models adjusted for Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores (day 3 AIPC, hazard ratio 0.70 [95% CI 0.52–0.89], <i>P</i> = 0.0029; day 5 AIPC, 0.68 [95% CI 0.49–0.87], <i>P</i> = 0.0012).</p><p>Conclusions</p><p>Thrombopoietic activity was generally maintained in the acute phase of sepsis. However, a decrease in AIPC after admission was independently associated with the development of severe thrombocytopenia and mortality, suggesting the importance of suppressed thrombopoiesis in the pathophysiology of sepsis-induced thrombocytopenia.</p></div

Univariate and multivariate Cox regression models to predict 28-day mortality.

<p>Univariate and multivariate Cox regression models to predict 28-day mortality.</p

Time course of coagulation biomarkers from admission (day 1) to day 7 in patients with sepsis.

<p>Septic patients were classified into four groups according to nadir platelet count during the first 7 days of their ICU stay: severe thrombocytopenia (nadir platelet count ≤40×10³/μL); moderate thrombocytopenia (41–80×10³/μL); mild thrombocytopenia (81–120×10³/μL); and normal-increased platelet counts (>120×10³/μL). Data are expressed as mean with the 95% confidence interval shown by the error bars.</p

Univariate/multivariate logistic regression models for severe thrombocytopenia development (nadir platelet count <40×10³/μL).

<p>Univariate/multivariate logistic regression models for severe thrombocytopenia development (nadir platelet count <40×10³/μL).</p

Box plot showing (a) platelet and (b) absolute immature platelet count (AIPC).

<p>Platelet count and AIPC on the day of admission (day 1) and at the nadir during the 7 days are shown. Septic patients were classified into four groups according to nadir platelet count during the first 7 days of their ICU stay: severe thrombocytopenia (nadir platelet count ≤40×10³/μL); moderate thrombocytopenia (41–80×10³/μL); mild thrombocytopenia (81–120×10³/μL); and normal-increased platelet counts (>120×10³/μL). Multiple pairwise comparison used the Steel–Dwass test.</p

Time course of platelet count and absolute immature platelet count (AIPC).

<p>Platelet count and AIPC were measured from admission (day 1) to day 7 in patients with sepsis, classified into four groups according to nadir platelet count during the 7 days: severe thrombocytopenia (nadir platelet count ≤40×10³/μL); moderate thrombocytopenia (41–80×10³/μL); mild thrombocytopenia (81–120×10³/μL); and normal-increased platelet count (>120×10³/μL). Data are expressed as mean with the 95% confidence interval shown by the error bars. Multiple analysis of variance was among the four groups.</p

Baseline characteristics and outcomes of the 205 patients with sepsis.

<p>Baseline characteristics and outcomes of the 205 patients with sepsis.</p