Carole Ichai

Clinical practice guideline on diagnosis and treatment of hyponatraemia

Hyponatraemia, defined as a serum sodium concentration <135 mmol/l, is the most common disorder of body fluid and electrolyte balance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from subtle to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay in patients presenting with a range of conditions. Despite this, the management of patients remains problematic. The prevalence of hyponatraemia in widely different conditions and the fact that hyponatraemia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and speciality-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA), represented by European Renal Best Practice (ERBP), have developed the Clinical Practice Guideline on the diagnostic approach and treatment of hyponatraemia as a joint venture of three societies representing specialists with a natural interest in hyponatraemia. In addition to a rigorous approach to methodology and evaluation, we were keen to ensure that the document focused on patient-important outcomes and included utility for clinicians involved in everyday practice.

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.

ESPEN endorsed recommendations: nutritional therapy in major burns.

BACKGROUND & AIMS Nutrition therapy is a cornerstone of burn care from the early resuscitation phase until the end of rehabilitation. While several aspects of nutrition therapy are similar in major burns and other critical care conditions, the patho-physiology of burn injury with its major endocrine, inflammatory, metabolic and immune alterations requires some specific nutritional interventions. The present text developed by the French speaking societies, is updated to provide evidenced-based recommendations for clinical practice. METHODS A group of burn specialists used the GRADE methodology (Grade of Recommendation, Assessment, Development and Evaluation) to evaluate human burn clinical trials between 1979 and 2011. The resulting recommendations, strong suggestions or suggestions were then rated by the non-burn specialized experts according to their agreement (strong, moderate or weak). RESULTS Eight major recommendations were made. Strong recommendations were made regarding, 1) early enteral feeding, 2) the elevated protein requirements (1.5-2 g/kg in adults, 3 g/kg in children), 3) the limitation of glucose delivery to a maximum of 55% of energy and 5 mg/kg/h associated with moderate blood glucose (target ≤ 8 mmol/l) control by means of continuous infusion, 4) to associated trace element and vitamin substitution early on, and 5) to use non-nutritional strategies to attenuate hypermetabolism by pharmacological (propranolol, oxandrolone) and physical tools (early surgery and thermo-neutral room) during the first weeks after injury. Suggestion were made in absence of indirect calorimetry, to use of the Toronto equation (Schoffield in children) for energy requirement determination (risk of overfeeding), and to maintain fat administration ≤ 30% of total energy delivery. CONCLUSION The nutritional therapy in major burns has evidence-based specificities that contribute to improve clinical outcome.

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.

Metabolic response to the stress of critical illness

The metabolic response to stress is part of the adaptive response to survive critical illness. Several mechanisms are well preserved during evolution, including the stimulation of the sympathetic nervous system, the release of pituitary hormones, a peripheral resistance to the effects of these and other anabolic factors, triggered to increase the provision of energy substrates to the vital tissues. The pathways of energy production are altered and alternative substrates are used as a result of the loss of control of energy substrate utilization by their availability. The clinical consequences of the metabolic response to stress include sequential changes in energy expenditure, stress hyperglycaemia, changes in body composition, and psychological and behavioural problems. The loss of muscle proteins and function is a major long-term consequence of stress metabolism. Specific therapeutic interventions, including hormone supplementation, enhanced protein intake, and early mobilization, are investigated. This review aims to summarize the pathophysiological mechanisms, the clinical consequences, and therapeutic implications of the metabolic response to stress.

International recommendations for glucose control in adult non diabetic critically ill patients.

IntroductionThe purpose of this research is to provide recommendations for the management of glycemic control in critically ill patients.MethodsTwenty-one experts issued recommendations related to one of the five pre-defined categories (glucose target, hypoglycemia, carbohydrate intake, monitoring of glycemia, algorithms and protocols), that were scored on a scale to obtain a strong or weak agreement. The GRADE (Grade of Recommendation, Assessment, Development and Evaluation) system was used, with a strong recommendation indicating a clear advantage for an intervention and a weak recommendation indicating that the balance between desirable and undesirable effects of an intervention is not clearly defined.ResultsA glucose target of less than 10 mmol/L is strongly suggested, using intravenous insulin following a standard protocol, when spontaneous food intake is not possible. Definition of the severe hypoglycemia threshold of 2.2 mmol/L is recommended, regardless of the clinical signs. A general, unique amount of glucose (enteral/parenteral) to administer for any patient cannot be suggested. Glucose measurements should be performed on arterial rather than venous or capillary samples, using central lab or blood gas analysers rather than point-of-care glucose readers.ConclusionsThirty recommendations were obtained with a strong (21) and a weak (9) agreement. Among them, only 15 were graded with a high level of quality of evidence, underlying the necessity to continue clinical studies in order to improve the risk-to-benefit ratio of glucose control.

Perioperative cardiovascular monitoring of high-risk patients: a consensus of 12

A significant number of surgical patients are at risk of intra- or post-operative complications or both, which are associated with increased lengths of stay, costs, and mortality. Reducing these risks is important for the individual patient but also for health-care planners and managers. Insufficient tissue perfusion and cellular oxygenation due to hypovolemia, heart dysfunction or both is one of the leading causes of perioperative complications. Adequate perioperative management guided by effective and timely hemodynamic monitoring can help reduce the risk of complications and thus potentially improve outcomes. In this review, we describe the various available hemodynamic monitoring systems and how they can best be used to guide cardiovascular and fluid management in the perioperative period in high-risk surgical patients.

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.

Prolonged low-dose dopamine infusion induces a transient improvement in renal function in hemodynamically stable, critically ill patients: a single-blind, prospective, controlled study.

Objective: To evaluate the length of the effects of long‐term (48 hrs), low‐dose dopamine infusion on both renal function and systemic hemodynamic variables in stable nonoliguric critically ill patients. Design: Prospective, single‐blind, controlled clinical study. Setting: University hospital, 19‐bed multidisciplinary intensive care unit. Patients: Eight hemodynamically stable, critically ill patients with a mild nonoliguric renal impairment (creatinine clearance between 30 and 80 mL/min). Interventions: Each patient consecutively received 4 hrs of placebo, followed by a 3 μg/kg/min dopamine infusion during 48 hrs, then a new 4‐hr placebo period. We measured cardiac output and other hemodynamic variables by using a pulmonary artery catheter. The bladder was emptied to determine urine volume and to collect urine samples. Measurements were performed at six times: after the initial control of 4 hrs of placebo (C1); after 4 hrs (H4), 8 hrs (H8), 24 hrs (H24), and 48 hrs (H48) of dopamine infusion; and after the second control of 4 hrs of placebo (C2). Measurements and Main Results: We saw no significant change in systemic hemodynamic variables with dopamine at all times of infusion. Diuresis, creatinine clearance, and the fractional excretion of sodium (FeNa) at C1 and C2 were not different. Urine flow, creatinine clearance, and FeNa increased significantly 4 hrs after starting dopamine (for all these changes, p < .01 vs. C1 and C2). The maximum changes were obtained at H8, with an increase of 50% for diuresis, 37% for creatinine clearance, and 85% for FeNa (for all these changes, p < .01 vs. C1 and C2). But these effects waned progressively from H24, and both creatinine clearance and FeNa at H48 did not differ from control values. Conclusions: In stable critically ill patients, preventive low‐dose dopamine increased creatinine clearance, diuresis, and the fractional excretion of sodium without concomitant hemodynamic change. These effects reached a maximum during 8 hrs of dopamine infusion. But despite a slight persistent increase in diuresis, improvement in creatinine clearance and FeNa disappeared after 48 hrs. According to these data, it is likely that tolerance develops to dopamine‐receptor agonists in critically ill patients at risk of developing acute renal failure.

Reliability of anion gap as an indicator of blood lactate in critically ill patients

Objective: To evaluate the sensitivity, specificity, and predictive values of an elevated anion gap as an indicator of hyperlactatemia and to assess the contribution of blood lactate to the serum anion gap in critically ill patients. Design: Prospective study. Setting: General intensive care unit of a university hospital. Patients: 498 patients, none with ketonuria, severe renal failure or aspirin, glycol, or methanol intoxication. Measurements and results: The anion gap was calculated as [Na+] − [Cl−] − [TCO2]. Hyperlactatemia was defined as a blood lactate concentration above 2.5 mmol/l. The mean blood lactate concentration was 3.7 ± 3.2 mmol/l and the mean serum anion gap was 14.3 ± 4.2 mEq/l. The sensitivity of an elevated anion gap to reveal hyperlactatemia was only 44 % [95 % confidence interval (CI) 38 to 50], whereas specificity was 91 % (CI 87 to 94) and the positive predictive value was 86 % (CI 79 to 90). As expected, the poor sensitivity of the anion gap increased with the lactate threshold value, whereas the specificity decreased [for a blood lactate cut-off of 5 mmol/l: sensitivity = 67 % (CI 58 to 75) and specificity = 83 % (CI 79 to 87)]. The correlation between the serum anion gap and blood lactate was broad (r2 = 0.41, p < 0.001) and the slope of this relationship (0.48 ± 0.026) was less than 1 (p < 0.001). The serum chloride concentration in patients with a normal anion gap (99.1 ± 6.9 mmol/l) was comparable to that in patients with an elevated anion gap (98.8 ± 7.1 mmol/l). Conclusions: An elevated anion gap is not a sensitive indicator of moderate hyperlactatemia, but it is quite specific, provided the other main causes of the elevated anion gap have been eliminated. Changes in blood lactate only account for about half of the changes in anion gap, and serum chloride does not seem to be an important factor in the determination of the serum anion gap.