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1.  Quasi-Experimental Study of Sodium Citrate Locks and the Risk of Acute Hemodialysis Catheter Infection among Critically Ill Patients 
Antimicrobial Agents and Chemotherapy  2014;58(10):5666-5672.
Critically ill patients who require renal replacement therapy (RRT) are vulnerable to catheter-related bloodstream infections (CRBSI). This study compared the risks of dialysis catheter infection according to the choice of locking solution in the intensive care unit (ICU). A prospective quasi-experimental study with marginal structural models (MSM) and 2:1 greedy propensity-score matching (PSM) was conducted at nine university-affiliated hospitals and three general hospitals. A total of 596 critically ill patients received either saline solution or heparin lock solution (the standard of care [SOC]) from 2004 to 2007 in the Cathedia cohort (n = 464 for MSM; n = 124 for PSM) or 46.7% citrate lock from 2011 to 2012 in the citrate (CLock) cohort (n = 132 for MSM; n = 62 for PSM) to perform RRT using intermittent hemodialysis. Catheter-tip colonization and CRBSI were analyzed. The mean duration (standard deviation [SD]) of catheterization was 7.1 days (6.1) in the SOC group and 7.0 days (5.9) in the CLock group (P = 0.84). The risk of dialysis catheter-tip colonization was lower in the CLock group (20.5 versus 38.7 per 1,000 catheter-days in the SOC group; hazard ratio [HR] from MSM, 0.73; 95% confidence interval [CI], 0.57 to 0.93; P < 0.02). Consistent findings were found from PSM (HR, 0.46; 95% CI, 0.22 to 0.95; P < 0.04). The risk of CRBSI was nonsignificantly different in the CLock group (1.1 versus 1.8 per 1,000 catheter-days in the SOC group; HR from MSM, 0.48; 95% CI, 0.12 to 1.87; P = 0.29). By reducing the risk of catheter-tip colonization, citrate lock has the potential to improve hemodialysis safety in the ICU. Additional studies are warranted before the routine use of citrate locks can be recommended in the ICU.
PMCID: PMC4187910  PMID: 24982071
2.  Initial use of one or two antibiotics for critically ill patients with community-acquired pneumonia: impact on survival and bacterial resistance 
Critical Care  2013;17(6):R265.
Several guidelines recommend initial empirical treatment with two antibiotics instead of one to decrease mortality in community-acquired pneumonia (CAP) requiring intensive-care-unit (ICU) admission. We compared the impact on 60-day mortality of using one or two antibiotics. We also compared the rates of nosocomial pneumonia and multidrug-resistant bacteria.
This is an observational cohort study of 956 immunocompetent patients with CAP admitted to ICUs in France and entered into a prospective database between 1997 and 2010.
Patients with chronic obstructive pulmonary disease were excluded. Multivariate analysis adjusted for disease severity, gender, and co-morbidities was used to compare the impact on 60-day mortality of receiving adequate initial antibiotics and of receiving one versus two initial antibiotics.
Initial adequate antibiotic therapy was significantly associated with better survival (subdistribution hazard ratio (sHR), 0.63; 95% confidence interval (95% CI), 0.42 to 0.94; P = 0.02); this effect was strongest in patients with Streptococcus pneumonia CAP (sHR, 0.05; 95% CI, 0.005 to 0.46; p = 0.001) or septic shock (sHR: 0.62; 95% CI 0.38 to 1.00; p = 0.05). Dual therapy was associated with a higher frequency of initial adequate antibiotic therapy. However, no difference in 60-day mortality was found between monotherapy (β-lactam) and either of the two dual-therapy groups (β-lactam plus macrolide or fluoroquinolone). The rates of nosocomial pneumonia and multidrug-resistant bacteria were not significantly different across these three groups.
Initial adequate antibiotic therapy markedly decreased 60-day mortality. Dual therapy improved the likelihood of initial adequate therapy but did not predict decreased 60-day mortality. Dual therapy did not increase the risk of nosocomial pneumonia or multidrug-resistant bacteria.
PMCID: PMC4056004  PMID: 24200097
3.  How caregivers view patient comfort and what they do to improve it: a French survey 
Intensive care unit (ICU) patients are exposed to many sources of discomfort. Most of these are related to the patient’s condition, but ICU design or how care is organized also can contribute. The present survey was designed to describe the opinions of ICU caregivers on sources of patient discomfort and to determine how they were dealt with in practice. The architectural and organizational characteristics of ICUs also were analyzed in relation to patient comfort.
An online, closed-ended questionnaire was developed. ICU caregivers registered at the French society of intensive care were invited to complete this questionnaire.
A total of 915 staff members (55% nurses) from 264 adult and 28 pediatric ICUs completed the questionnaire. Analysis of the answers reveals that: 68% of ICUs had only single-occupancy rooms, and 66% had natural light in each room; ICU patients had access to television in 59% of ICUs; a clock was present in each room in 68% of ICUs. Visiting times were <4 h in 49% of adult ICUs, whereas 64% of respondents considered a 24-h policy to be very useful or essential to patients’ well-being. A nurse-driven analgesia protocol was available in 42% of units. For caregivers, the main sources of patient discomfort were anxiety, feelings of restraint, noise, and sleep disturbances. Paramedics generally considered discomfort related to thirst, lack of privacy, and the lack of space and time references, whereas almost 50% of doctors ignored these sources of discomfort. Half of caregivers indicated they assessed sleep quality. A minority of caregivers declared regular use of noise-reduction strategies. Twenty percent of respondents admitted to having non-work-related conversations during patient care, and only 40% indicated that care often was or always was provided without closing doors. Family participation in care was planned in very few adult ICUs.
Results of this survey showed that ICUs are poorly equipped to ensure patient privacy and rest. Access by loved ones and their participation in care also is limited. The data also highlighted that some sources of discomfort are less often taken into account by caregivers, despite being considered to contribute significantly.
PMCID: PMC3700816  PMID: 23815804
Intensive care unit; Comfort; Survey; Organization; Opinions
4.  Diagnostic accuracy of early urinary index changes in differentiating transient from persistent acute kidney injury in critically ill patients: multicenter cohort study 
Critical Care  2013;17(2):R56.
Urinary indices have limited effectiveness in separating transient acute kidney injury (AKI) from persistent AKI in ICU patients. Their time-course may vary with the mechanism of AKI. The primary objective of this study was to evaluate the diagnostic value of changes over time of the usual urinary indices in separating transient AKI from persistent AKI.
An observational prospective multicenter study was performed in six ICUs involving 244 consecutive patients, including 97 without AKI, 54 with transient AKI, and 93 with persistent AKI. Urinary sodium, urea and creatinine were measured at ICU admission (H0) and on 6-hour urine samples during the first 24 ICU hours (H6, H12, H18, and H24). Transient AKI was defined as AKI with a cause for renal hypoperfusion and reversal within 3 days.
Significant increases from H0 to H24 were noted in fractional excretion of urea (median, 31% (22 to 41%) and 39% (29 to 48%) at H24, P < 0.0001), urinary urea/plasma urea ratio (15 (7 to 28) and 20 (9 to 40), P < 0.0001), and urinary creatinine/plasma creatinine ratio (50 (24 to 101) and 57 (29 to 104), P = 0.01). Fractional excretion of sodium did not change significantly during the first 24 hours in the ICU (P = 0.13). Neither urinary index values at ICU admission nor changes in urinary indices between H0 and H24 performed sufficiently well to recommend their use in clinical setting (area under the receiver-operating characteristic curve ≤0.65).
Although urinary indices at H24 performed slightly better than those at H0 in differentiating transient AKI from persistent AKI, they remain insufficiently reliable to be clinically relevant.
PMCID: PMC3733426  PMID: 23531299
5.  Prognostic consequences of borderline dysnatremia: pay attention to minimal serum sodium change 
Critical Care  2013;17(1):R12.
To assess the prevalence of dysnatremia, including borderline changes in serum sodium concentration, and to estimate the impact of these dysnatremia on mortality after adjustment for confounders.
Observational study on a prospective database fed by 13 intensive care units (ICUs). Unselected patients with ICU stay longer than 48 h were enrolled over a 14-year period were included in this study. Mild to severe hyponatremia were defined as serum sodium concentration < 135, < 130, and < 125 mmol/L respectively. Mild to severe hypernatremia were defined as serum sodium concentration > 145, > 150, and > 155 mmol/L respectively. Borderline hyponatremia and hypernatremia were defined as serum sodium concentration between 135 and 137 mmol/L or 143 and 145 respectively.
A total of 11,125 patients were included in this study. Among these patients, 3,047 (27.4%) had mild to severe hyponatremia at ICU admission, 2,258 (20.3%) had borderline hyponatremia at ICU admission, 1,078 (9.7%) had borderline hypernatremia and 877 (7.9%) had mild to severe hypernatremia. After adjustment for confounder, both moderate and severe hyponatremia (subdistribution hazard ratio (sHR) 1.82, 95% CI 1.002 to 1.395 and 1.27, 95% CI 1.01 to 1.60 respectively) were associated with day-30 mortality. Similarly, mild, moderate and severe hypernatremia (sHR 1.34, 95% CI 1.14 to 1.57; 1.51, 95% CI 1.15 to 1.99; and 2.64, 95% CI 2.00 to 3.81 respectively) were independently associated with day-30 mortality.
One-third of critically ill patients had a mild to moderate dysnatremia at ICU admission. Dysnatremia, including mild changes in serum sodium concentration, is an independent risk factor for hospital mortality and should not be neglected.
PMCID: PMC4056804  PMID: 23336363
6.  How to deal with dialysis catheters in the ICU setting 
Acute kidney insufficiency (AKI) occurs frequently in intensive care units (ICU). In the management of vascular access for renal replacement therapy (RRT), several factors need to be taken into consideration to achieve an optimal RRT dose and to limit complications. In the medium and long term, some individuals may become chronic dialysis patients and so preserving the vascular network is of major importance. Few studies have focused on the use of dialysis catheters (DC) in ICUs, and clinical practice is driven by the knowledge and management of long-term dialysis catheter in chronic dialysis patients and of central venous catheter in ICU patients. This review describes the appropriate use and management of DCs required to obtain an accurate RRT dose and to reduce mechanical and infectious complications in the ICU setting. To deliver the best RRT dose, the length and diameter of the catheter need to be sufficient. In patients on intermittent hemodialysis, the right internal jugular insertion is associated with a higher delivered dialysis dose if the prescribed extracorporeal blood flow is higher than 200 ml/min. To prevent DC colonization, the physician has to be vigilant for the jugular position when BMI < 24 and the femoral position when BMI > 28. Subclavian sites should be excluded. Ultrasound guidance should be used especially in jugular sites. Antibiotic-impregnated dialysis catheters and antibiotic locks are not recommended in routine practice. The efficacy of ethanol and citrate locks has yet to be demonstrated. Hygiene procedures must be respected during DC insertion and manipulation.
PMCID: PMC3526537  PMID: 23174157
Dialysis catheter; Intensive care unit; Catheter dysfunction; Catheter infection
7.  High creatinine clearance in critically ill patients with community-acquired acute infectious meningitis 
BMC Nephrology  2012;13:124.
A high dose of anti-infective agents is recommended when treating infectious meningitis. High creatinine clearance (CrCl) may affect the pharmacokinetic / pharmacodynamic relationships of anti-infective drugs eliminated by the kidneys. We recorded the incidence of high CrCl in intensive care unit (ICU) patients admitted with meningitis and assessed the diagnostic accuracy of two common methods used to identify high CrCl.
Observational study performed in consecutive patients admitted with community-acquired acute infectious meningitis (defined by >7 white blood cells/mm3 in cerebral spinal fluid) between January 2006 and December 2009 to one medical ICU. During the first 7 days following ICU admission, CrCl was measured from 24-hr urine samples (24-hr-UV/P creatinine) and estimated according to Cockcroft-Gault formula and the simplified Modification of Diet in Renal Disease (MDRD) equation. High CrCl was defined as CrCl >140 ml/min/1.73 m2 by 24-hr-UV/P creatinine. Diagnostic accuracy was performed with ROC curves analysis.
Thirty two patients were included. High CrCl was present in 8 patients (25%) on ICU admission and in 15 patients (47%) during the first 7 ICU days for a median duration of 3 (1-4) days. For the Cockcroft-Gault formula, the best threshold to predict high CrCl was 101 ml/min/1.73 m2 (sensitivity: 0.96, specificity: 0.75, AUC = 0.90 ± 0.03) with a negative likelihood ratio of 0.06. For the simplified MDRD equation, the best threshold to predict high CrCl was 108 ml/min/1.73 m2 (sensitivity: 0.91, specificity: 0.80, AUC = 0.88 ± 0.03) with a negative likelihood ratio of 0.11. There was no difference between the estimated methods in the diagnostic accuracy of identifying high CrCl (p = 0.30).
High CrCl is frequently observed in ICU patients admitted with community-acquired acute infectious meningitis. The estimated methods of CrCl could be used as a screening tool to identify high CrCl.
PMCID: PMC3502432  PMID: 23013403
Critically ill; Glomerular filtration rate; High creatinine clearance; Meningitis
8.  Management of thrombocytopenia in the ICU (pregnancy excluded) 
Thrombocytopenia is a very frequent disorder in the intensive care unit. Many etiologies should be searched, and therapeutic approaches differ according to these different causes. However, no guideline exists regarding optimum practices for these situations in critically ill patients. We present recommendations for the management of thrombocytopenia in intensive care unit, excluding pregnancy, developed by an expert group of the French-Language Society of Intensive Care (Société de Réanimation de Langue Française (SRLF), the French Language Group of Paediatric Intensive Care and Emergencies (GFRUP) and of the Haemostasis and Thrombosis Study Group (GEHT) of the French Society of Haematology (SFH). The recommendations cover six fields of application: definition, epidemiology, and prognosis; diagnostic approach; therapeutic aspects; thrombocytopenia and sepsis; iatrogenic thrombocytopenia, with a special focus on heparin-induced thrombocytopenia; and thrombotic microangiopathy.
PMCID: PMC3488545  PMID: 22929300
Thrombocytopenia; Critical care; Adults; Expert recommendations
9.  Mortality associated with timing of admission to and discharge from ICU: a retrospective cohort study 
Although the association between mortality and admission to intensive care units (ICU) in the "after hours" (weekends and nights) has been the topic of extensive investigation, the timing of discharge from ICU and outcome has been less well investigated. The objective of this study was to assess effect of timing of admission to and discharge from ICUs and subsequent risk for death.
Adults (≥18 years) admitted to French ICUs participating in Outcomerea between January 2006 and November 2010 were included.
Among the 7,380 patients included, 61% (4,481) were male, the median age was 62 (IQR, 49-75) years, and the median SAPS II score was 40 (IQR, 28-56). Admissions to ICU occurred during weekends (Saturday and Sunday) in 1,708 (23%) cases, during the night (18:00-07:59) in 3,855 (52%), and on nights and/or weekends in 4,659 (63%) cases. Among 5,992 survivors to ICU discharge, 903 (15%) were discharged on weekends, 659 (11%) at night, and 1,434 (24%) on nights and/or weekends. After controlling for a number of co-variates using logistic regression analysis, admission during the after hours was not associated with an increased risk for death. However, patients discharged from ICU on nights were at higher adjusted risk (odds ratio, 1.54; 95% confidence interval, 1.12-2.11) for death.
In this study, ICU discharge at night but not admission was associated with a significant increased risk for death. Further studies are needed to examine whether minimizing night time discharges from ICU may improve outcome.
PMCID: PMC3269385  PMID: 22115194
10.  Acute respiratory failure in kidney transplant recipients: a multicenter study 
Critical Care  2011;15(2):R91.
Data on pulmonary complications in renal transplant recipients are scarce. The aim of this study was to evaluate acute respiratory failure (ARF) in renal transplant recipients.
We conducted a retrospective observational study in nine transplant centers of consecutive kidney transplant recipients admitted to the intensive care unit (ICU) for ARF from 2000 to 2008.
Of 6,819 kidney transplant recipients, 452 (6.6%) required ICU admission, including 200 admitted for ARF. Fifteen (7.5%) of these patients had combined kidney-pancreas transplantations. The most common causes of ARF were bacterial pneumonia (35.5%), cardiogenic pulmonary edema (24.5%) and extrapulmonary acute respiratory distress syndrome (ARDS) (15.5%). Pneumocystis pneumonia occurred in 11.5% of patients. Mechanical ventilation was used in 93 patients (46.5%), vasopressors were used in 82 patients (41%) and dialysis was administered in 104 patients (52%). Both the in-hospital and 90-day mortality rates were 22.5%. Among the 155 day 90 survivors, 115 patients (74.2%) were dialysis-free, including 75 patients (65.2%) who recovered prior renal function. Factors independently associated with in-hospital mortality were shock at admission (odds ratio (OR) 8.70, 95% confidence interval (95% CI) 3.25 to 23.29), opportunistic fungal infection (OR 7.08, 95% CI 2.32 to 21.60) and bacterial infection (OR 2.53, 95% CI 1.07 to 5.96). Five factors were independently associated with day 90 dialysis-free survival: renal Sequential Organ Failure Assessment (SOFA) score on day 1 (OR 0.68/SOFA point, 95% CI 0.52 to 0.88), bacterial infection (OR 0.43, 95% CI 0.21 to 0.90), three or four quadrants involved on chest X-ray (OR 0.44, 95% CI 0.21 to 0.91), time from hospital to ICU admission (OR 0.98/day, 95% CI 0.95 to 0.99) and oxygen flow at admission (OR 0.93/liter, 95% CI 0.86 to 0.99).
In kidney transplant recipients, ARF is associated with high mortality and graft loss rates. Increased Pneumocystis and bacterial prophylaxis might improve these outcomes. Early ICU admission might prevent graft loss.
PMCID: PMC3219351  PMID: 21385434
11.  Oxaliplatin-induced acute renal failure presenting clinically as thrombotic microangiopathy: think of acute tubular necrosis 
NDT Plus  2009;2(3):254-256.
PMCID: PMC4421186  PMID: 25984004
acute renal failure; acute tubular necrosis; microangiopathy; oxaliplatin; thrombocytopenia

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