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author:("ichi, Carole")
1.  Early and persistent high level of PS 100β is associated with increased poor neurological outcome in patients with SAH: is there a PS 100β threshold for SAH prognosis? 
Critical Care  2016;20:33.
Protein S100β (PS100 β) and neuron specific enolase (NSE) have been described as biological markers of neuronal damage. The purpose of our study was to assess the prognosis thresholds of these biomarkers in subarachnoid aneurysmal hemorrhage (SAH).
Forty eight patients admitted following SAH were treated by endovascular coiling. Initial neurologic severity was assessed using the World Federation Neurologic Surgeons (WFNS), Fisher grades, initial Glasgow coma scale (GCS) and SAPS II. PS100β and NSE plasma concentration were measured daily within the first week. The primary endpoint of the study was the 6-month Glasgow Outcome Score (GOS) dichotomized as poor (GOS 1–3) or good (GOS 4–5).
A poor outcome at 6-months was associated with significant higher levels of S100β value from day 1 to day 7, whereas NSE values were significantly higher from day 5 to day 7. Best threshold value, for prognosis, was obtained at day 5 for PS100β >0.13 μg/L (specificity 0.95 95 % confidence interval (CI) 0.74–1; sensitivity 0.83 95 % CI 0.65–0.93) and day 7 for NSE >14.5 μg/L (specificity 0.90 95 % CI 0.67–0.98); sensitivity (0.69 95 % CI 0.51–0.83)). After multivariate logistic analysis, only PS100β at day 5 and SAPS II enabled to predict neurological outcome at 6 months (p <0.05).
PS100β >0.13 μg/L at day 5 is an independent predicting factor of poor neurological outcome at 6 months following SAH. This result could support the use of this biomarker at the acute phase of SAH to help physician determine the prognosis.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-016-1200-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4738799  PMID: 26843206
Surrogate marker; Aneurysmal subarachnoid hemorrhage; S100 protein; Neuron specific enolase; Outcome
2.  Sodium lactate for fluid resuscitation: the preferred solution for the coming decades? 
Critical Care  2014;18(4):163.
In a recent issue of Critical Care, 0.5 M sodium lactate infusion for 24 hours was reported to increase cardiac output in patients with acute heart failure. This effect was associated with a concomitant metabolic alkalosis and a negative water balance. Growing data strongly support the role of lactate as a preferential oxidizable substrate to supply energy metabolism leading to improved organ function (heart and brain especially) in ischemic conditions. Due to its sodium/chloride imbalance, this solution prevents hyperchloremic acidosis and limits fluid overload despite the obligatory high sodium load. Sodium lactate solution therefore shows many advantages and appears a very promising means for resuscitation of critically ill patients. Further studies are needed to establish the most appropriate dose and indications for sodium lactate infusion in order to prevent the occurrence of severe hypernatremia and metabolic alkalosis.
PMCID: PMC4095570  PMID: 25043707
3.  Nutrition in Critical Care 
Critical Care  2014;18(3):311.
PMCID: PMC4223554
4.  Perioperative cardiovascular monitoring of high-risk patients: a consensus of 12 
Critical Care  2015;19(1):224.
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.
PMCID: PMC4424585  PMID: 25953531
5.  Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU patients 
Critical Care  2015;19(1):153.
In a randomized controlled trial comparing tight glucose control with a computerized decision support system and conventional protocols (post hoc analysis), we tested the hypothesis that hypoglycemia is associated with a poor outcome, even when controlling for initial severity.
We looked for moderate (2.2 to 3.3 mmol/L) and severe (<2.2 mmol/L) hypoglycemia, multiple hypoglycemic events (n ≥3) and the other main components of glycemic control (mean blood glucose level and blood glucose coefficient of variation (CV)). The primary endpoint was 90-day mortality. We used both a multivariable analysis taking into account only variables observed at admission and a multivariable matching process (greedy matching algorithm; caliper width of 10−5 digit with no replacement).
A total of 2,601 patients were analyzed and divided into three groups: no hypoglycemia (n =1,474), moderate hypoglycemia (n =874, 34%) and severe hypoglycemia (n =253, 10%). Patients with moderate or severe hypoglycemia had a poorer prognosis, as shown by a higher mortality rate (36% and 54%, respectively, vs. 28%) and decreased number of treatment-free days. In the multivariable analysis, severe (odds ratio (OR), 1.50; 95% CI, 1.36 to 1.56; P =0.043) and multiple hypoglycemic events (OR, 1.76, 95% CI, 1.31 to 3.37; P <0.001) were significantly associated with mortality, whereas blood glucose CV was not. Using multivariable matching, patients with severe (53% vs. 35%; P <0.001), moderate (33% vs. 27%; P =0.029) and multiple hypoglycemic events (46% vs. 32%, P <0.001) had a higher 90-day mortality.
In a large cohort of ICU patients, severe hypoglycemia and multiple hypoglycemic events were associated with increased 90-day mortality.
Trial registration Identifier: NCT01002482. Registered 26 October 2009.
PMCID: PMC4470320  PMID: 25888011
6.  Effect of N-Acetylcysteine Pretreatment of Deceased Organ Donors on Renal Allograft Function: A Randomized Controlled Trial 
Transplantation  2015;99(4):746-753.
Antioxidant donor pretreatment is one of the pharmacologic strategy proposed to prevent renal ischemia-reperfusion injuries and delayed graft function (DGF). The aim of the study was to investigate whether a donor pretreatment with N-acetylcysteine (NAC) reduces the incidence of DGF in adult human kidney transplant recipients.
In this randomized, open-label, monocenter trial, 160 deceased heart-beating donors were allowed to perform 236 renal transplantations from September 2005 to December 2010. Donors were randomized to receive, in a single-blind controlled fashion, 600 mg of intravenous NAC 1 hr before and 2 hr after cerebral angiography performed to confirm brain death. Primary endpoint was DGF defined by the need for at least one dialysis session within the first week or a serum creatinine level greater than 200 μmol/L at day 7 after kidney transplantation.
The incidence of DGF was similar between donors pretreated with or without NAC (39/118; 33% vs. 30/118; 25.4%; P = 0.19). Requirement for at least one dialysis session was not different between the NAC and No NAC groups (17/118; 14.4% vs. 14/118; 11.8%, P = 0.56). The two groups had comparable serum creatinine levels, estimated glomerular filtration rates, and daily urine output at days 1, 7, 15, and 30 after kidney transplantation as well as at hospital discharge. No difference in recipient mortality nor in 1-year kidney graft survival was observed.
Donor pretreatment with NAC does not improve delayed graft function after kidney transplantation.
A prospective, randomized, single-blind study of donor treatment with N-acetylcysteine prior to procurement shows that antioxidant treatment does not influence early renal allograft function for organs from brain-dead donors. Alternative approaches will be necessary to prevent delayed graft function.
PMCID: PMC4376274  PMID: 25250647
7.  Hyperosmolar sodium-lactate in the ICU: vascular filling and cellular feeding 
Critical Care  2014;18(6):599.
Hyperosmolar lactate-based solutions have been used for fluid resuscitation in ICU patients. The positive effects observed with these fluids have been attributed to both lactate metabolism and the hypertonic nature of the solutions. In a recent issue of Critical Care, Duburcq and colleagues studied three types of fluid infused at the same volume in a porcine model of endotoxic shock. The control group was resuscitated with 0.9% NaCl, and the two other groups received either hypertonic sodium-lactate or hypertonic sodium-bicarbonate. The two hypertonic fluids proved to be more effective than 0.9% NaCl for resuscitation in this model. However, some parameters were more effectively corrected by hypertonic sodium-lactate than by hypertonic sodium-bicarbonate, suggesting that lactate metabolism was beneficial in these cases.
PMCID: PMC4331370  PMID: 25673151
8.  Incidence and Characteristics of Acute Kidney Injury in Severe Diabetic Ketoacidosis 
PLoS ONE  2014;9(10):e110925.
Acute kidney injury is a classical complication of diabetic ketoacidosis. However, to the best of our knowledge, no study has reported the incidence and characteristics of acute kidney injury since the consensus definition was issued.
Retrospective study of all cases of severe diabetic ketoacidosis hospitalised consecutively in a medical surgical tertiary ICU during 10 years. Patients were dichotomised in with AKI and without AKI on admission according to the RIFLE classification. Clinical and biological parameters were compared in these populations. Risk factors of presenting AKI on admission were searched for.
Ninety-four patients were included in the study. According to the RIFLE criteria, 47 patients (50%) presented acute kidney injury on admission; most of them were in the risk class (51%). At 12 and 24 hours, the percentage of AKI patients decreased to 26% and 27% respectively. During the first 24 hours, 3 patients needed renal replacement therapy. Acute renal failure on admission was associated with a more advanced age, SAPS 2 and more severe biological impairments. Treatments were not different between groups except for insulin infusion. Logistic regression found 3 risk factors of presenting AKI on admission: age (odds ratio 1.060 [1.020–1.100], p<0.01), blood glucose (odds ratio 1.101 [1.039–1.166], p<0.01) and serum protein (odds ratio 0.928 [0.865–0.997], p = 0.04).
Acute kidney injury is frequently associated with severe diabetic ketoacidosis on admission in ICU. Most of the time, this AKI is transient and characterised by a volume-responsiveness to fluid infusion used in DKA treatment. Age, blood glucose and serum protein are associated to the occurrence of AKI on ICU admission.
PMCID: PMC4206473  PMID: 25338064
9.  Early resuscitation of dengue shock syndrome in children with hyperosmolar sodium-lactate: a randomized single-blind clinical trial of efficacy and safety 
Critical Care  2014;18(5):466.
Dengue shock syndrome (DSS) fluid resuscitation by following the World Health Organization (WHO) guideline usually required large volumes of Ringer lactate (RL) that might induce secondary fluid overload. Our objective was to compare the effectiveness of the recommended volume of RL versus a smaller volume of a hypertonic sodium lactate solution (HSL) in children with DSS. The primary end point was to evaluate the effect of HSL on endothelial cell inflammation, assessed by soluble vascular cell adhesion molecule-1 (sVCAM-1) measurements. Secondarily, we considered the effectiveness of HSL in restoring hemodynamic fluid balance, acid–base status, and sodium and chloride balances, as well as in-hospital survival.
A prospective randomized single-blind clinical trial including 50 DSS children was conducted in the Pediatrics Department of Hasan Sadikin Hospital, Bandung, Indonesia. Only pediatric patients (2 to 14 years old) fulfilling the WHO criteria for DSS and new to resuscitation treatments were eligible. Patients were resuscitated with either HSL (5 ml/kg/BW in 15 minutes followed by 1 ml/kg/BW/h for 12 hours), or RL (20 ml/kg/BW in 15 minutes followed by decreasing doses of 10, 7, 5, and 3 ml/kg BW/h for 12 hours).
In total, 50 patients were randomized and included in outcome and adverse-event analysis; 46 patients (8.2 ± 0.5 years; 24.9 ± 1.9 kg; mean ± SEM) completed the protocol and were fully analyzed (24 and 22 subjects in the HSL and RL groups, respectively). Baseline (prebolus) data were similar in both groups. Hemodynamic recovery, plasma expansion, clinical outcome, and survival rate were not significantly different in the two groups, whereas fluid accumulation was one third lower in the HSL than in the RL group. Moreover, HSL was responsible for a partial recovery from endothelial dysfunction, as indicated by the significant decrease in sVCAM-1.
Similar hemodynamic shock recovery and plasma expansion were achieved in both groups despite much lower fluid intake and fluid accumulation in the HSL group.
Trial Registration NCT00966628. Registered 26 August 2009.
PMCID: PMC4172842  PMID: 25189175
10.  Effects of tight computerized glucose control on neurological outcome in severely brain injured patients: a multicenter sub-group analysis of the randomized-controlled open-label CGAO-REA study 
Critical Care  2014;18(5):498.
Hyperglycemia is a marker of poor prognosis in severe brain injuries. There is currently little data regarding the effects of intensive insulin therapy (IIT) on neurological recovery.
A sub-group analysis of the randomized-controlled CGAO-REA study (NCT01002482) in surgical intensive care units (ICU) of two university hospitals. Patients with severe brain injury, with an expected ICU length of stay ≥48 hours were included. Patients were randomized between a conventional glucose management group (blood glucose target between 5.5 and 9 mmol.L−1) and an IIT group (blood glucose target between 4.4 and 6 mmol.L−1). The primary outcome was the day-90 neurological outcome evaluated with the Glasgow outcome scale.
A total of 188 patients were included in this analysis. In total 98 (52%) patients were randomized in the control group and 90 (48%) in the IIT group. The mean Glasgow coma score at baseline was 7 (±4). Patients in the IIT group received more insulin (130 (68 to 251) IU versus 74 (13 to 165) IU in the control group, P = 0.01), had a significantly lower morning blood glucose level (5.9 (5.1 to 6.7) mmol.L−1 versus 6.5 (5.6 to 7.2) mmol.L−1, P <0.001) in the first 5 days after ICU admission. The IIT group experienced more episodes of hypoglycemia (P <0.0001). In the IIT group 24 (26.6%) patients had a favorable neurological outcome (good recovery or moderate disability) compared to 31 (31.6%) in the control group (P = 0.4). There were no differences in day-28 mortality. The occurrence of hypoglycemia did not influence the outcome.
In this sub-group analysis of a large multicenter randomized trial, IIT did not appear to alter the day-90 neurological outcome or ICU morbidity in severe brain injured patients or ICU morbidity.
PMCID: PMC4174656  PMID: 25189764
11.  Metformin overdose: time to move on 
Critical Care  2012;16(5):164.
Does metformin-associated lactic acidosis really exist? Despite an old controversy, there is no doubt about it. But do we understand what is going on? Laboratory findings raised several hypotheses explaining the pathophysiology of this disease. The main cause could be an inhibition of either gluconeogenesis or mitochondrial respiratory chain complex I. From bench to bedside, one hypothesis is now confirmed in humans. Metformin poisoning involves, at least partially, a mitochondrial dysfunction.
PMCID: PMC3682282  PMID: 23110819
12.  The Practice of Therapeutic Hypothermia after Cardiac Arrest in France: A National Survey 
PLoS ONE  2012;7(9):e45284.
Cardiac arrest is a major health concern worldwide accounting for 375,000 cases per year in Europe with a survival rate of <10%. Therapeutic hypothermia has been shown to improve patients’ neurological outcome and is recommended by scientific societies. Despite these guidelines, different surveys report a heterogeneous application of this treatment. The aim of the present study was to evaluate the clinical practice of therapeutic hypothermia in cardiac arrest patients.
This self-declarative web based survey was proposed to all registered French adult intensive care units (ICUs) (n = 357). Paediatrics and neurosurgery ICUs were excluded. The different questions addressed the structure, the practical modalities of therapeutic hypothermia and the use of prognostic factors in patients admitted after cardiac arrest.
One hundred and thirty-two out of 357 ICUs (37%) answered the questionnaire. Adherence to recommendations regarding the targeted temperature and hypothermia duration were 98% and 94% respectively. Both guidelines were followed in 92% ICUs. During therapeutic hypothermia, sedative drugs were given in 99% ICUs, mostly midazolam (77%) and sufentanil (59%). Neuromuscular blocking agents (NMBA) were used in 97% ICUs, mainly cisatracurium (77%). Numerous prognostic factors were used after cardiac arrest such as clinical factors (95%), biomarkers (53%), electroencephalography (78%) and evoked potentials (35%).
In France, adherence to recommendations for therapeutic hypothermia after cardiac arrest is higher than those previously reported in other countries. Numerous prognostic factors are widely used even if their reliability remains controversial.
PMCID: PMC3458038  PMID: 23049783
13.  Adjunctive remifentanil infusion in deeply sedated and paralyzed ICU patients during fiberoptic bronchoscopy procedure: a prospective, randomized, controlled study 
Even with an adequate pain assessment, critically ill patients under sedation experience pain during procedures in the intensive care unit (ICU). We evaluated the effects of adjunctive administration of Remifentanil, a short-acting drug, in deeply sedated patient on variation of Bispectral Index (BIS) during a fiberoptic bronchoscopy.
A prospective, randomized, blinded, placebo-controlled study was conducted in 18-bed ICU. Patients needing a tracheal fibroscopy under deep sedation (midazolam (0.1 mg/kg per hour) fentanyl (4 μg/kg per hour)) and neuromuscular blocking (atracurium 0.5 mg/kg) were included in the study. A continuous monitoring of BIS, arterial pressure, and heart rate were realized before, during, and after the fiberoptic exam. An adjunctive continuous placebo or Remifentanil infusion was started just before the fiberoptic exam with a target effect-site concentration of 4 ng/ml using a Base Primea pump.
Mean arterial pressure and heart rates were comparable between the placebo and Remifentanil groups at all times of the procedure. We did not observe differences in the variation of BIS values between the two groups during procedure. We described no change in BIS values relative to the placebo group in this population.
In deeply sedated and paralyzed patients, receiving analgesic support based on a scale score an additional administration of short-acting analgesic drug, such as Remifentanil, seems not to be necessary for acute pain control.
Trial registration
PMCID: PMC3487977  PMID: 22800647
Pain; Intensive care; Bispectral index; Remifentanil
14.  International recommendations for glucose control in adult non diabetic critically ill patients 
Critical Care  2010;14(5):R166.
The purpose of this research is to provide recommendations for the management of glycemic control in critically ill patients.
Twenty-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.
A 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.
Thirty 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.
PMCID: PMC3219261  PMID: 20840773

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