Jacques Levraut

Low exogenous lactate clearance as an early predictor of mortality in normolactatemic critically ill septic patients

ObjectiveTo evaluate the prognostic value of lactate clearance and lactate production in severely ill septic patients with normal or mildly elevated blood lactate concentration. DesignProspective, observational study. SettingNineteen-bed mixed medicosurgical intensive care unit. PatientsFifty-six patients with severe sepsis and blood lactate concentration <3 mmol/L. Measurements and Main ResultsLactate metabolism was evaluated in all patients. Lactate clearance was measured by modeling the change in arterial blood lactate over time induced by an infusion of 1 mmol/kg sodium lactate for 15 mins. Lactate production was calculated as the product of lactate clearance times the blood lactate concentration before the infusion. Outcome was taken to be mortality at 28 days after the beginning of the septic episode. A logistic regression model taking into account different risk factors was constructed. Among the 56 patients, 17 (30.3%) died before the 28th day. Basal blood lactate concentration was not different between survivors and nonsurvivors, whereas lactate clearance and production were higher in survivors (0.86 ± 0.32 vs. 0.58 ± 0.18 L/hr/kg, p < .005, and 1.19 ± 0.63 vs. 0.89 ± 0.24 mmol/hr/kg, p = .055, respectively). An increase in blood lactate 45 mins after the end of the lactate infusion (&Dgr;lact-T60) ≥0.6 mmol/L was predictive of 28-day mortality with 53% sensitivity and 90% specificity. Multivariate analysis showed that only three factors were independently and significantly correlated with 28-day mortality: presence of more than two organ failures (odds ratio, 27;p = .04), age >70 yrs (odds ratio, 5.7;p = .032), and &Dgr;lact-T60 ≥0.6 mmol/L (odds ratio, 14.2;p = .042). ConclusionLow lactate clearance in severely ill septic patients with normal or mildly elevated blood lactate is predictive of poor outcome independently of other known risk factors such as age and number of organ failures.

Effect of continuous venovenous hemofiltration with dialysis on lactate clearance in critically ill patients

OBJECTIVE To evaluate the effect of continuous venovenous hemofiltration with dialysis on lactate elimination by critically ill patients. DESIGN Prospective, clinical study. SETTING Surgical intensive care unit of a university hospital. PATIENTS Ten critically ill patients with acute renal failure and stable blood lactate concentrations. INTERVENTIONS Two-stage investigation: a) measurement of lactate concentrations in samples of serum and ultradiafiltrate from patients receiving continuous venovenous hemofiltration with dialysis to calculate lactate clearance by the hemofilter; b) evaluation of total plasma lactate clearance by infusing sodium L-lactate (1 mmol/kg of body weight) over 15 mins. MEASUREMENTS AND MAIN RESULTS Arterial lactate concentration was determined before, during, and after the infusion. Lactate elimination variables were calculated from the plasma curve using model-independent and model-dependent estimates (by software). At the end of the infusion, median blood lactate concentration increased from 1.4 mmol/L (range 0.8 to 2.6) to 4.8 mmol/L (range 2.4 to 5.7) and returned to 1.6 mmol/L (range 0.9 to 3.4) 60 mins later. The median total plasma lactate clearance was 1379 mL/min (range 753.7 to 1880.7) and the median filter lactate clearance was 24.2 mL/min (range 7.1 to 35.6). Thus, filter lactate clearance accounted for < 3% of total lactate clearance. CONCLUSIONS Continuous venovenous hemofiltration with dialysis cannot mask lactate overproduction, and its blood concentration remains a reliable marker of tissue oxygenation in patients receiving this renal replacement technique.

Effects of dopamine and norepinephrine on systemic and hepatosplanchnic hemodynamics, oxygen exchange, and energy balance in vasoplegic septic patients

Dopamine is widely used to improve systemic and hepatosplanchnic hemodynamics and oxygenation during sepsis. However, some studies have suggest that norepinephrine may have beneficial effects on regional blood flow and metabolism, whereas dopamine might have deleterious effects related to redistribution of blood flow away from the intestinal mucosa or by decreasing directly the cell redox state. In 12 vasoplegic septic patients, we compared the effects of norepinephrine and dopamine on systemic and hepatosplanchnic hemodynamics, oxygenation, and energy metabolism. Catecholamines were administered in a crossover randomized order to maintain mean arterial pressure (MAP) at 80 mmHg. Hepatosplanchnic blood flow (Qspl) was determined using a continuous infusion of indocyanine green dye. Despite a similar MAP, the cardiac index was higher with dopamine than with norepinephrine (6.3 [5.3-7.3] vs. 4.3 [3.8-4.9] L·min−1·m−2) (P < 0.001). Qspl was similar with both catecholamines, but the ratio of Qspl to cardiac output was significantly lower with dopamine (23.9% [17.5-33.5]) than with norepinephrine (33.5% [25.8-37]) (P < 0.05). Although global O2 delivery and O2 consumption were higher with dopamine (782 [707-859] vs. 553 [512-629] mL·min−1·m−2, P < 0.001 and 164 [134-192] vs. 128 [111-149] mL·min−1·m−2, P < 0.001, respectively), hepatosplanchnic O2 delivery and consumption were not different. Hepatic lactate uptake was lower (0.47 [0.3-0.89] vs. 1.01 [0.69-1.34] mmol·min−1) (P < 0.01), and hepatic venous lactate-to-pyruvate ratio was higher (15.3 [7.6-21.1] vs. 11.2 [6.6-15.1], P < 0.05) with dopamine than with norepinephrine. In vasoplegic septic patients, maintaining mean arterial pressure, hepatosplanchnic hemodynamics, and oxygen exchange with dopamine requires a consequent increased cardiac output, which is responsible for an increased global oxygen demand when compared with norepinephrine. In addition, dopamine impairs the hepatic energy balance. Its position as a preferential treatment compared with norepinephrine in this context may therefore be questionable.

Initial effect of sodium bicarbonate on intracellular pH depends on the extracellular nonbicarbonate buffering capacity.

ObjectiveThe effect of sodium bicarbonate on intracellular pH under conditions close to those in vivo, with both bicarbonate and nonbicarbonate buffering systems, is unknown. We postulated that this effect depends on the nonbicarbonate buffering capacity because the alkali-induced back-titration of these buffers results in a concentration-dependent release of CO2 in the extracellular space, leading to a decrease in intracellular pH. DesignThe study was conducted in two stages. First, human hepatocytes were perfused with pH 7 bicarbonate-buffered medium (5 mM HCO3−, 20 torr Pco2) containing no nonbicarbonate buffer or small amounts (5 mM 4-[2-hydroxyethyl]-1-piperazineethanesulfonic acid [HEPES]) or large amounts (20 mM HEPES) of nonbicarbonate buffer. Second, the changes in intracellular pH of hepatocytes placed in acidotic human blood (pH 7, 5 mM HCO3−, 20 torr Pco2) at three hematocrits (40%, 20%, and 5%) were measured. SettingResearch laboratory at a medical university. SubjectsCryopreserved human hepatocytes thawed the day before the experiments. InterventionsSodium bicarbonate was infused for 10 mins to increase the HCO3− concentration from 5 to 30 mM. In the second part, 20 mM sodium bicarbonate was added directly to the blood bathing the cells. Measurements and Main Results The intracellular pH was measured with the pH-sensitive fluorescent dye bis-carboxyethyl carboxy-fluorescein in its esterified form, acetoxy-methyl ester, by using a single-cell imaging technique. Gas analyses were performed before and during the sodium bicarbonate load. Sodium bicarbonate caused a decrease in intracellular pH with all media except the artificial medium containing no HEPES. This decrease was small in media with low nonbicarbonate buffering capacity (5 mM HEPES and 5% hematocrit blood) and large in media with high nonbicarbonate buffering capacity (20 mM HEPES and 40% hematocrit blood). The change in intracellular pH was linked closely to the change in Pco2 caused by the sodium bicarbonate. ConclusionsThe effect of sodium bicarbonate on intracellular pH depends on changes in Pco2 in the medium bathing the cells. The increase in Pco2 is correlated with the extracellular nonbicarbonate buffering capacity because of the release of H+ ions coming from the back-titration of these buffers. We conclude that sodium bicarbonate may exacerbate cell acidosis under buffering conditions close to those in vivo and that the initial changes in cell pH caused by sodium bicarbonate depend on the extracellular nonbicarbonate buffering capacity.

Treatment of metabolic acidosis.

Metabolic acidosis is characterized by a decrease of the blood pH associated with a decrease in the bicarbonate concentration. This may be secondary to a decrease in the strong ion difference or to an increase in the weak acids concentration, mainly the inorganic phosphorus. From a conceptual point of view, two types of nontoxic metabolic acidosis must be differentiated: the mineral metabolic acidosis that reveals the presence of an excess of nonmetabolizable anions, and the organic metabolic acidosis that reveals an excess of metabolizable anions. Significance and consequences of these two types of acidosis are radically different. Mineral acidosis is not caused by a failure in the energy metabolic pathways, and its treatment is mainly symptomatic by correcting the blood pH (alkali therapy) or accelerating the elimination of excessive mineral anions (renal replacement therapy). On the other hand, organic acidosis gives evidence that a severe underlying metabolic distress is in process. No reliable argument exists to prove that this acidosis is harmful under these conditions in humans. Experimental data even show that hypoxic cells are able to survive only if the medium is kept acidic. The management of an acute organic metabolic acidosis is therefore primarily based on the cause of the acidosis, and no scientific argument exists to justify the correction of the acid–base imbalance in this context.

Long-Term β-Blocker Therapy Decreases Blood Lactate Concentration in Severely Septic Patients.

Objectives:Measurement of blood lactate concentration in the early management of sepsis is an important step in severity assessment. High blood lactate levels in the early phase of sepsis have classically been thought to be related to tissue hypoxia, but other factors could intervene. We hypothesized that the activation of glycolysis through &bgr;-adrenergic stimulation by endogenous catecholamines plays an important role in lactate production and that long-term &bgr;-blocker therapy could affect the lactate concentration in patients with severe sepsis and septic shock. Design:Retrospective cohort study. Setting:Emergency department. Patients:Two hundred sixty patients with severe sepsis or septic shock were included. Twenty-five percent were previously treated with &bgr;-blockers. Interventions:None. Measurements and Main Results:We recorded initial vital signs, the source of infection, mortality at 28 days, blood lactate concentration, and Predisposition Insult Response of Organ failure and Sequential Organ Failure Assessment scores using an electronic database. Blood lactate concentration was significantly lower in patients previously treated with &bgr;-blockers (3.9 ± 2.3 mmol/L vs 5.6 ± 3.6 mmol/L; p < 0.001). This difference was still significant after controlling for mortality (p < 0.005), for the level of the Predisposition Insult Response of Organ failure (p < 0.05) and Sequential Organ Failure Assessment (p < 0.05) scores, and for the source of infection (p < 0.05). Nearly four times more patients treated with &bgr;-blockers had normal blood lactate levels (p< 0.001). Only two factors were significantly and independently associated with normal blood lactate concentration during severe sepsis and septic shock: survival (p = 0.03) and &bgr;-blocker therapy (p = 0.01). Conclusions:Long-term &bgr;-blocker therapy decreases blood lactate concentration of severely ill septic patients at presentation. We conclude that the use of blood lactate measurement as a triage tool in the initial assessment of septic patients with &bgr;-blocker therapy may underestimate the severity of the sepsis.

L’acidose lactique reste une complication grave du traitement par metformine

We report 4 cases of lactic acidosis in diabetic patients usually treated with metformin. For the first 3 patients, the clinical history was similar because lactic acidosis was precipitated by gastro-intestinal disorders whereas all of them were simultaneously treated with several nephrotoxic drugs. These 3 patients presented with acute renal failure on arrival at hospital. Their issue was fatal whereas any obvious cause of overproduction of lactate was found. The fourth case, which was due to a voluntary intoxication, was the only one presenting with a favourable evolution. The metformin plasma and red blood cell levels were performed for 2 of 4 patients and confirmed the overdose. These observations remind that metformin-associated lactic acidosis remains a serious complication, and that medical doctors must respect strictly contra-indications and guidelines for withdrawing metformin.

Hypocapnia does not alter hepatic blood flow or oxygen consumption in patients with head injury

OBJECTIVE To evaluate the effects of hypocapnia on the systemic and hepatic circulations and oxygenation values in patients with head injury. DESIGN Open-label, prospective study. SETTING University hospital, department of anesthesiology and intensive care unit. PATIENTS Eleven mechanically ventilated patients with isolated head trauma and stable hemodynamic status. INTERVENTIONS At the beginning of the study, each patient presented with normocapnic ventilation. Mechanical hyperventilation was then adjusted to obtain stable hypocapnia over an interval of 24 hrs. Cardiac output and other systemic hemodynamic parameters were measured, using a pulmonary artery catheter. Hepatic parameters were measured via a catheter inserted into the hepatic vein. Total hepatic blood flow was determined by the Fick principle using a continuous infusion of indocyanine green. Arterial and hepatic venous blood gases were sampled to determine systemic and hepatic-splanchnic oxygenation. Measurements were done at the end of the four phases: a) 30 mins of normocapnia (N); b) 30 mins of hypocapnia (H0); c) 3 hrs of hypocapnia (H3); and d) 24 hrs of hypocapnia (H24). Intracranial pressure and cerebral perfusion pressure were hourly monitored throughout the study. MEASUREMENTS AND MAIN RESULTS There were no significant changes in systemic hemodynamic parameters. The hepatic blood flow index did not differ from normocapnia (N 1.8 +/- 0.4 L/min/m2) to hypocapnia (H0 1.6 +/- 0.3 L/min/m2; H3 1.7 +/- 0.4 L/min/m2; H24 1.7 +/- 0.4 L/min/m2). The ratio of hepatic blood flow index to cardiac index remained stable throughout the study. Hypocapnia did not affect hepatic-splanchnic oxygen delivery and consumption. CONCLUSIONS Hypocapnic hyperventilation does not alter hepatic hemodynamic parameters in patients with head injury. This result may be related to the lack of changes in cardiac output or in the hepatic vasoreactivity. Moreover, hypocapnia does not modify hepatic-splanchnic oxygenation. Thus, in case of intracranial hypertension, hypocapnia might be used without undesirable effect on the hepatic-splanchnic perfusion.

Tétraplégie flasque aiguë secondaire à une hyperkaliémie

A 57-year-old man with chronic renal failure and multiple vascular diseases presented an acute flaccid tetraplegia. Blood tests revealed renal failure with serum potassium of 9.69 mmol/l. The medullar and brain MRI were normal. The correction of the hyperkalaemia led to a fast and complete neurological recovery. This fact confirmed the diagnosis of secondary hyperkalaemic tetraplegia.

Predicting morphine related side effects in the ED: An international cohort study

Study objectives: Morphine is the reference treatment for severe acute pain in an emergency department. The purpose of this study was to describe and analyse opioid‐related ADRs (adverse drug reactions) in a large cohort of emergency department patients, and to identify predictive factors for those ADRs. Methods: In this prospective, observational, pharmaco‐epidemiological international cohort study, all patients aged 18 years or older who were treated with morphine were enrolled. The study was done in 23 emergency departments in the US and France. Baseline numerical rating scale score and initial and total doses of morphine titration were recorded. Logistic regression analysis was used to study the effects of demographic, clinical and medical history covariates on the occurrence of opioid‐induced ADRs within 6 h after treatment. Results: A total of 1128 patients were included over 10 months. Median baseline initial pain scores were 8/10 (7–10) versus 3/10 (1–4) after morphine administration. Median titration duration was 10 min (IQR, 1–30). The occurrence of opioid‐induced ADRs was 25% and 2% were serious. Patients experienced mainly nausea and drowsiness. Medical history of travel sickness (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.01–2.86) and history of nausea or vomiting post morphine (OR, 3.86; 95% CI, 2.29–6.51) were independent predictors of morphine related ADRs. Conclusion: Serious morphine related ADRs are rare and unpredictable. Prophylactic antiemetic therapy could be proposed to patients with history of travel sickness and history of nausea or vomiting in a postoperative setting or after morphine administration.