Olivier Mimoz

Prospective, randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients

OBJECTIVES To compare the efficacy of a newly available antiseptic solution (composed of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, and 4% benzyl alcohol), with 10% povidone iodine, on the prevention of central venous or arterial catheter colonization and infection. DESIGN Prospective, randomized clinical trial. SETTING Surgical-trauma intensive care unit (ICU) in a university hospital. PATIENTS All patients admitted to the ICU and requiring the insertion of a central venous and/or an arterial catheter from July 1, 1992 to October 31, 1993. INTERVENTIONS Patients were randomly assigned to one of two groups according to the antiseptic solution used for insertion and catheter care. The same solution was used for skin disinfection from the time of catheter insertion to the time of removal of each catheter. MEASUREMENTS AND MAIN RESULTS Catheter distal tips were quantitatively cultured when catheters were no longer necessary, if there was a suspicion of catheter-related infection, and routinely after 7 days of use for arterial catheters, or after 15 days of use for central venous catheters. The rate of significant catheter colonization (i.e., > or = 10(3) colony-forming units [cfu]/mL by quantitative culture), and catheter-related sepsis (as defined by sepsis abating following catheter removal per 1,000 catheter-days), were significantly lower in the chlorhexidine group (12 vs. 31 [relative risk 0.4, 95% confidence interval 0.1 to 0.9, p < .01] and 6 vs. 16 [relative risk 0.4, 95% confidence interval 0.1 to 1, p = 0.5], respectively). The rate of central venous catheter colonization and central venous catheter-related sepsis per 1,000 catheter-days were also significantly lower in the chlorhexidine group (8 vs. 31 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .03] and 5 vs. 19 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .02], respectively). Finally, the rate of arterial catheter colonization per 1,000 catheter-days was significantly lower in the chlorhexidine group (15 vs. 32 [relative risk 0.5, 95% confidence interval 0.1 to 1, p = .05]), whereas the rate of arterial catheter-related sepsis per 1,000 catheter-days was similar for the two study groups (8 in the chlorhexidine group vs. 10 in the povidone iodine group [relative risk 0.8, 95% confidence interval 0.1 to 2.2, p = .6]). The 0.25% chlorhexidine solution was superior to the 10% povidone iodine solution in preventing catheter colonizations and catheter-related sepsis due to Gram-positive bacteria (5 vs. 20 [p < .001], and 2 vs. 10 [p < .001], respectively), whereas the activity of the 0.25% chlorhexidine solution was nonsignificantly superior in preventing Gram-negative infections (7 vs. 4 [p = .5], and 4 vs. 2 [p = .8], respectively). CONCLUSIONS The 4% alcohol-based solution of 0.25% chlorhexidine gluconate and 0.025% benzalkonium chloride was more effective than 10% povidone iodine for insertion site care of short-term central venous and arterial catheters. This effect appeared related to a more efficacious prevention of infections with Gram-positive bacteria.

Procalcitonin and C-reactive protein during the early posttraumatic systemic inflammatory response syndrome

Objectives: To describe the initial evolution of serum procalcitonin (PCT) and C-reactive protein (CRP) in previously healthy adult trauma patients and to compare the relationship of the expression of these two proteins with indicators of trauma severity. Design: Prospective, descriptive, longitudinal study.Setting: Surgical ICU in an university hospital.Patients: Twenty-one patients admitted during the first posttraumatic 3 h exhibiting an Injury Severity Score (ISS) between 16 and 50 were enrolled.Measurements: Blood sampling was performed on admission and on posttraumatic days 0.5,1, 2 and 3 to assess serum levels of PCT and CRP. Total creatine kinase (CKtot) and lactate dehydrogenase (LDHtot) activities in the serum were used as tissue damage indicators.Results: PCT exhibited an early and transient increase in serum levels similar to a more delayed change of CRP levels. Peak PCT and peak CRP were related to the ISS, the extent of tissue damage and the amount of fluid replacement during the first day. During the first 3 posttraumatic days, 90 % of the patients exhibited a generalized inflammatory syndrome without infection.Conclusions: An early and transient release of PCT into the circulation was observed after severe trauma and the amount of circulating PCT seemed proportional to the severity of tissue injury and hypovolemia, yet unrelated to infection. The predictive value of both PCT and CRP for a forthcoming multiple organ failure still remains to be clarified.

Chlorhexidine versus povidone iodine in preventing colonization of continuous epidural catheters in children: a randomized, controlled trial.

BackgroundChlorhexidine is better than povidone iodine for skin preparation before intravascular device insertion or blood culture collection, but it is not known whether chlorhexidine is superior in reducing colonization of continuous epidural catheters. MethodsChildren requiring an epidural catheter for postoperative analgesia longer than 24 h were randomly assigned to receive skin preparation with an alcoholic solution of 0.5% chlorhexidine or an aqueous solution of 10% povidone iodine before catheter insertion. Using surgical aseptic techniques, catheters were inserted into either the lumbar or the thoracic epidural space based on the preferences of the anesthesia team, on clinical indication, or both. Immediately before epidural catheter removal, their insertion site and hub were qualitatively cultures. After their removal, the catheter tips were quantitatively cultured. Catheters were classified as colonized when their tips yielded 1,000 or more colony-forming units/ml in cultures. ResultsOf 100 randomly assigned patients, 96 were evaluable. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters were kept in place for a median (range) duration of 50 (range, 21–100) h. Catheters inserted after skin preparation with chlorhexidine were one sixth as likely and less quickly to be colonized as catheters inserted after skin preparation with povidone iodine (1 of 52 catheters [0.9 per 100 catheter days]vs. 5 of 44 catheters [5.6 per 100 catheter days]; relative risk, 0.2 [95% confidence interval, 0.1–1.0];P = 0.02). Coagulase-negative staphylococci were the only colonizing microorganisms recovered, and the skin surrounding the catheter insertion site was the origin of all the colonizing microorganisms. ConclusionsCompared with aqueous povidone iodine, the use of alcoholic chlorhexidine for cutaneous antisepsis before epidural catheter insertion reduces the risk of catheter colonization in children.

Accuracy of a continuous noninvasive hemoglobin monitor in intensive care unit patients.

Objective:To determine whether noninvasive hemoglobin measurement by Pulse CO-Oximetry could provide clinically acceptable absolute and trend accuracy in critically ill patients, compared to other invasive methods of hemoglobin assessment available at bedside and the gold standard, the laboratory analyzer. Design:Prospective study. Setting:Surgical intensive care unit of a university teaching hospital. Patients:Sixty-two patients continuously monitored with Pulse CO-Oximetry (Masimo Radical-7). Interventions:None. Measurements and Results:Four hundred seventy-one blood samples were analyzed by a point-of-care device (HemoCue 301), a satellite lab CO-Oximeter (Siemens RapidPoint 405), and a laboratory hematology analyzer (Sysmex XT-2000i), which was considered the reference device. Hemoglobin values reported from the invasive methods were compared to the values reported by the Pulse CO-Oximeter at the time of blood draw. When the case-to-case variation was assessed, the bias and limits of agreement were 0.0 ± 1.0 g/dL for the Pulse CO-Oximeter, 0.3 ± 1.3g/dL for the point-of-care device, and 0.9 ± 0.6 g/dL for the satellite lab CO-Oximeter compared to the reference method. Pulse CO-Oximetry showed similar trend accuracy as satellite lab CO-Oximetry, whereas the point-of-care device did not appear to follow the trend of the laboratory analyzer as well as the other test devices. Conclusion:When compared to laboratory reference values, hemoglobin measurement with Pulse CO-Oximetry has absolute accuracy and trending accuracy similar to widely used, invasive methods of hemoglobin measurement at bedside. Hemoglobin measurement with pulse CO-Oximetry has the additional advantages of providing continuous measurements, noninvasively, which may facilitate hemoglobin monitoring in the intensive care unit.

Randomized Controlled Trial of Chlorhexidine Dressing and Highly Adhesive Dressing for Preventing Catheter-related Infections in Critically Ill Adults

RATIONALE Most vascular catheter-related infections (CRIs) occur extraluminally in patients in the intensive care unit (ICU). Chlorhexidine-impregnated and strongly adherent dressings may decrease catheter colonization and CRI rates. OBJECTIVES To determine if chlorhexidine-impregnated and strongly adherent dressings decrease catheter colonization and CRI rates. METHODS In a 2:1:1 assessor-masked randomized trial in patients with vascular catheters inserted for an expected duration of 48 hours or more in 12 French ICUs, we compared chlorhexidine dressings, highly adhesive dressings, and standard dressings from May 2010 to July 2011. Coprimary endpoints were major CRI with or without catheter-related bloodstream infection (CR-BSI) with chlorhexidine versus nonchlorhexidine dressings and catheter colonization rate with highly adhesive nonchlorhexidine versus standard nonchlorhexidine dressings. Catheter-colonization, CR-BSIs, and skin reactions were secondary endpoints. MEASUREMENTS AND MAIN RESULTS A total of 1,879 patients (4,163 catheters and 34,339 catheter-days) were evaluated. With chlorhexidine dressings, the major-CRI rate was 67% lower (0.7 per 1,000 vs. 2.1 per 1,000 catheter-days; hazard ratio [HR], 0.328; 95% confidence interval [CI], 0.174-0.619; P = 0.0006) and the CR-BSI rate 60% lower (0.5 per 1,000 vs. 1.3 per 1,000 catheter-days; HR, 0.402; 95% CI, 0.186-0.868; P = 0.02) than with nonchlorhexidine dressings; decreases were noted in catheter colonization and skin colonization rates at catheter removal. The contact dermatitis rate was 1.1% with and 0.29% without chlorhexidine. Highly adhesive dressings decreased the detachment rate to 64.3% versus 71.9% (P < 0.0001) and the number of dressings per catheter to two (one to four) versus three (one to five) (P < 0.0001) but increased skin colonization (P < 0.0001) and catheter colonization (HR, 1.650; 95% CI, 1.21-2.26; P = 0.0016) without influencing CRI or CR-BSI rates. CONCLUSIONS A large randomized trial demonstrated that chlorhexidine-gel-impregnated dressings decreased the CRI rate in patients in the ICU with intravascular catheters. Highly adhesive dressings decreased dressing detachment but increased skin and catheter colonization. Clinical trial registered with www.clinicaltrials.gov (NCT 01189682).

Prevention of central venous catheter-related infection in the intensive care unit

This article is one of ten reviews selected from the Yearbook of Intensive Care and Emergency Medicine 2010 (Springer Verlag) and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/yearbook. Further information about the Yearbook of Intensive Care and Emergency Medicine is available from http://www.springer.com/series/2855.

Skin antisepsis with chlorhexidine–alcohol versus povidone iodine–alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, two-by-two factorial trial

BACKGROUND Intravascular-catheter-related infections are frequent life-threatening events in health care, but incidence can be decreased by improvements in the quality of care. Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections. We hypothesised that chlorhexidine-alcohol would be more effective than povidone iodine-alcohol as a skin antiseptic to prevent intravascular-catheter-related infections. METHODS In this open-label, randomised controlled trial with a two-by-two factorial design, we enrolled consecutive adults (age ≥18 years) admitted to one of 11 French intensive-care units and requiring at least one of central-venous, haemodialysis, or arterial catheters. Before catheter insertion, we randomly assigned (1:1:1:1) patients via a secure web-based random-number generator (permuted blocks of eight, stratified by centre) to have all intravascular catheters prepared with 2% chlorhexidine-70% isopropyl alcohol (chlorhexidine-alcohol) or 5% povidone iodine-69% ethanol (povidone iodine-alcohol), with or without scrubbing of the skin with detergent before antiseptic application. Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were. The primary outcome was the incidence of catheter-related infections with chlorhexidine-alcohol versus povidone iodine-alcohol in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01629550 and is closed to new participants. FINDINGS Between Oct 26, 2012, and Feb 12, 2014, 2546 patients were eligible to participate in the study. We randomly assigned 1181 patients (2547 catheters) to chlorhexidine-alcohol (594 patients with scrubbing, 587 without) and 1168 (2612 catheters) to povidone iodine-alcohol (580 patients with scrubbing, 588 without). Chlorhexidine-alcohol was associated with lower incidence of catheter-related infections (0·28 vs 1·77 per 1000 catheter-days with povidone iodine-alcohol; hazard ratio 0·15, 95% CI 0·05-0·41; p=0·0002). Scrubbing was not associated with a significant difference in catheter colonisation (p=0·3877). No systemic adverse events were reported, but severe skin reactions occurred more frequently in those assigned to chlorhexidine-alcohol (27 [3%] patients vs seven [1%] with povidone iodine-alcohol; p=0·0017) and led to chlorhexidine discontinuation in two patients. INTERPRETATION For skin antisepsis, chlorhexidine-alcohol provides greater protection against short-term catheter-related infections than does povidone iodine-alcohol and should be included in all bundles for prevention of intravascular catheter-related infections. FUNDING University Hospital of Poitiers, CareFusion.

Colistin pharmacokinetics: the fog is lifting

Colistin is a re-emerging old antibiotic that is used to treat multidrug-resistant infections in critically ill patients. It corresponds to a mixture of at least 30 different compounds administered as inactive derivatives. Therefore, colistin pharmacokinetics are quite difficult to investigate and complex to predict. However specific chromatographic methods have been made available in recent years, leading to a series of modern pharmacokinetic studies after intravenous administration of the prodrug to critical-care patients; these have been conducted by a few groups and have only been recently published. The objective of this article was to conduct a critical review of these very informative modern pharmacokinetic studies and to provide prospective thoughts.

Circulating cardiac troponin I in trauma patients without cardiac contusion

Objectives: To describe the evolution and the diagnostic value of cardiac troponin I (cTnI) and to relate its concentrations with the indicators of injury in trauma patients.Design: Prospective, observational study of 17 young, previously healthy, mechanically-ventilated patients during the early post-traumatic period in the Surgical ICU of a University Hospital.Methods: Serial measurements of serum cTnI, total creatine kinase activity (CKtot) and its isoenzyme MB (CK-MB) (on admission, 12 h later, then daily for 7 days), clinical data and repeated electrocardiographic (ECG) and transesophageal echocardiography (TEE) recordings.Results: Rhabdomyolysis was observed in all the patients with a significant relationship between CK-MB and CKtot. Despite the fact that no patient demonstrated ECG or TEE signs of myocardial contusion, elevated serum levels of cTnI were observed in six patients (35%) without obvious dilutional interference. As compared with the others, these patients exhibited a more frequent arterial hypotension (83% vs 18%, p=0.035), required greater volume expansion on day 1 (22,000 vs 8,500 ml, p=0.027) and usually demonstrated early (83% vs 9%, p=0.005) and late (66% vs 9%, p=0.028) multiple organ dysfunction syndrome.Conclusions: Taking into account the high reported sensitivity and specificity of cTnI dosage, the present results suggest cTnI can play a role in the evaluation of indirect myocardial injury following traumatic shock.

Pleth variability index predicts fluid responsiveness in critically ill patients.

Objective:To investigate whether the pleth variability index, a noninvasive and continuous tool, can predict fluid responsiveness in mechanically ventilated patients with circulatory insufficiency. Design:Prospective study. Setting:Surgical intensive care unit of a university hospital. Patients:Forty mechanically ventilated patients with circulatory insufficiency in whom volume expansion was planned by attending physician. Exclusion criteria included spontaneous respiratory activity, cardiac arrhythmia, known intracardiac shunt, severe hypoxemia (Pao2/Fio2 <100 mm Hg), contraindication for passive leg raising, left ventricular ejection fraction of <50%, and hemodynamic instability during the procedure. Interventions:Fluid challenge with 500 mL of 130/0.4 hydroxyethyl-starch if respiratory variations in arterial pulse pressure were ≥13% or with passive leg raising if variations in arterial pulse pressure were <13%. Measurements and Main Results:Pleth variability index, variations in arterial pulse pressure, and cardiac output estimated by echocardiography were recorded before and after fluid challenge. Fluid responsiveness was defined as an increase in cardiac output of ≥15%. Twenty-one patients were responders and 19 were nonresponders. Mean ± sd pleth variability index (28% ± 13% vs. 11% ± 4%) and arterial pulse pressure variation (22% ± 11% vs. 5% ± 2%) values at baseline were significantly higher in responders than in nonresponders. The pleth variability index threshold value of 17% allowed discrimination between responders and nonresponders with a sensitivity of 95% (95% confidence interval, 74% to 100%) and a specificity of 91% (95% confidence interval, 70% to 99%). The pleth variability index at baseline correlated (r = .72, p < .0001) with the percentage change in cardiac output induced by fluid challenge, suggesting that a higher pleth variability index at baseline will correlate with a higher percentage change in cardiac output after volume expansion. Conclusions:The pleth variability index can predict fluid responsiveness noninvasively in intensive care unit patients under mechanical ventilation.