Study of the X-ray radiation interaction with a multislit collimator for the creation of microbeams in radiation therapy.

Microbeam radiation therapy (MRT) is a developing radiotherapy, based on the use of beams only a few tens of micrometres wide, generated by synchrotron X-ray sources. The spatial fractionation of the homogeneous beam into an array of microbeams is possible using a multislit collimator (MSC), i.e. a machined metal block with regular apertures. Dosimetry in MRT is challenging and previous works still show differences between calculated and experimental dose profiles of 10-30%, which are not acceptable for a clinical implementation of treatment. The interaction of the X-rays with the MSC may contribute to the observed discrepancies; the present study therefore investigates the dose contribution due to radiation interaction with the MSC inner walls and radiation leakage of the MSC. Dose distributions inside a water-equivalent phantom were evaluated for different field sizes and three typical spectra used for MRT studies at the European Synchrotron Biomedical beamline ID17. Film dosimetry was utilized to determine the contribution of radiation interaction with the MSC inner walls; Monte Carlo simulations were implemented to calculate the radiation leakage contribution. Both factors turned out to be relevant for the dose deposition, especially for small fields. Photons interacting with the MSC walls may bring up to 16% more dose in the valley regions, between the microbeams. Depending on the chosen spectrum, the radiation leakage close to the phantom surface can contribute up to 50% of the valley dose for a 5 mm × 5 mm field. The current study underlines that a detailed characterization of the MSC must be performed systematically and accurate MRT dosimetry protocols must include the contribution of radiation leakage and radiation interaction with the MSC in order to avoid significant errors in the dose evaluation at the micrometric scale.

Significant dose reduction using synchrotron radiation computed tomography: first clinical case and application to high resolution CT exams.

Since the invention of Computed Tomography (CT), many technological advances emerged to improve the image sensitivity and resolution. However, no new source types were developed for clinical use. In this study, for the first time, coherent monochromatic X-rays from a synchrotron radiation source were used to acquire 3D CTs on patients. The aim of this work was to evaluate the clinical potential of the images acquired using Synchrotron Radiation CT (SRCT). SRCTs were acquired using monochromatic X-rays tuned at 80 keV (0.350 × 0.350 × 2 mm3 voxel size). A quantitative image quality comparison study was carried out on phantoms between a state of the art clinical CT and SRCT images. Dedicated iterative algorithms were developed to optimize the image quality and further reduce the delivered dose by a factor of 12 while keeping a better image quality than the one obtained with a clinical CT scanner. We finally show in this paper the very first SRCT results of one patient who received Synchrotron Radiotherapy in an ongoing clinical trial. This demonstrates the potential of the technique in terms of image quality improvement at a reduced radiation dose for inner ear visualization.

How tumour-induced vascular changes alter angiogenesis: Insights from a computational model.

A computational model was developed to describe experimentally observed vascular changes induced by the introduction of a tumour on a mouse equipped with a dorsal skinfold chamber. The vascular structure of the host tissue was segmented from in vivo images and transposed into the computational framework. Simulations of tumour-induced vascular changes were performed and include the destabilizing effects of the growth factor VEGF on the integrity of the vessels walls. The integration of those effects, that include alteration of the vessel wall elasticity and wall breaching, were required to realistically reproduce the experimental observations. The model was then used to investigate the importance of the vascular changes for oxygen delivery and tumour development. To that end, we compared simulations obtained with a dynamic vasculature with those obtained with a static one. The results showed that the tumour growth was strongly impeded by the constant vascular changes. More precisely, it is the angiogenic process itself that was affected by vascular changes occurring in bigger upstream vessels and resulting in a less efficient angiogenic network for oxygen delivery. As a consequence, tumour cells are mostly kept in a non-proliferative hypoxic state. Tumour dormancy thus appears as one potential consequence of the intense vascular changes in the host tissue.

Synchrotron X-ray microtransections: a non invasive approach for epileptic seizures arising from eloquent cortical areas.

Synchrotron-generated X-ray (SRX) microbeams deposit high radiation doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. We made such image-guided SRX microtransections in the left somatosensory cortex in a rat model of generalized epilepsy using high radiation doses (820 Gy) in thin (200 µm) parallel slices of tissue. This procedure, targeting the brain volume from which seizures arose, altered the abnormal neuronal activities for at least 9 weeks, as evidenced by a decrease of seizure power and coherence between tissue slices in comparison to the contralateral cortex. The brain tissue located between transections stayed histologically normal, while the irradiated micro-slices remained devoid of myelin and neurons two months after irradiation. This pre-clinical proof of concept highlights the translational potential of non-invasive SRX transections for treating epilepsies that are not eligible for resective surgery.

Synchrotron X-ray microbeams: A promising tool for drug-resistant epilepsy treatment.

Epilepsy is one of the most important neurological diseases. It concerns about 1% of the population worldwide. Despite the discovery of new molecules, one third of epileptic patients are resistant to anti-epileptic drugs and among them only a few can benefit from resective surgery. In this context, radiotherapy is an interesting alternative to the other treatments and several clinical devices exist (e.g., Gamma Knife(®)). The European Synchrotron Radiation Facility offers the possibility to develop new methods of radiosurgery and to study their antiepileptic effects. Here, we discuss several studies that we performed recently to test and try to understand the antiepileptic effects of X-ray synchrotron microbeams in different animal models of epilepsy. We showed a decrease of seizures after Interlaced Microbeam Radiotherapy (IntMRT) of the somatosensory cortex, known as the seizure generator, in a genetic model of absence epilepsy. These antiepileptic effects were stable over 4 months and with low tissular and functional side-effects. The irradiated pyramidal neurons still displayed their physiological activity but did not synchronize anymore. We also obtained a lasting suppression of seizures after IntMRT of the dorsal hippocampus in a mouse model of mesiotemporal lobe epilepsy. However, an important variability of antiepileptic efficiency was observed probably due to the small size of the targeted structure. Despite these encouraging proofs-of-concepts, there is now a need to adapt IntMRT to other models of epilepsy in rodents which are close to refractory forms of epilepsy in human patients and to implement this approach to non-human primates, before moving to clinical trials.

Impact of exercise training without caloric restriction on inflammation, insulin resistance and visceral fat mass in obese adolescents.

BACKGROUND: Exercise training has been shown to improve cardiometabolic health in obese adolescents. OBJECTIVES: Evaluate the impact of a 12-week exercise-training programme (without caloric restriction) on obese adolescents' cardiometabolic and vascular risk profiles. METHODS: We measured systemic markers of oxidation, inflammation, metabolic variables and endothelial function in 20 obese adolescents (OB) (age: 14.5 ± 1.5 years; body mass index: 34.0 ± 4.7 kg m(-2) ) and 20 age- and gender-matched normal-weight adolescents (NW). Body composition was assessed by magnetic resonance imagery. Peak aerobic capacity and maximal fat oxidation were evaluated during specific incremental exercise tests. OB participated in a 12-week exercise-training programme. RESULTS: OB presented lower peak aerobic capacity (24.2 ± 5.9 vs. 39.8 ± 8.3 mL kg(-1) min(-1) , P < 0.05) and maximal fat oxidation compared with NW (P < 0.05). OB displayed greater F2t-Isoprostanes (20.5 ± 6.7 vs. 13.4 ± 4.2 ng mmol(-1) creatinine), Interleukin-1 receptor antagonist (IL-1Ra) (1794.8 ± 532.2 vs. 835.1 ± 1027.4 pg mL(-1) ), Tumor Necrosis Factor-α (TNF-α) (2.1 ± 1.2 vs. 1.5 ± 1.0 pg mL(-1) ), Soluble Tumor Necrosis Factor-α Type II Receptor (sTNFαRII), leptin, insulin, homeostasis model assessment of insulin resistance, version 2 (HOMA2-IR), high-sensitive C-reactive protein, triglycerides and lower adiponectin and high-density lipoprotein cholesterol (all P < 0.05). After exercise training, despite lack of weight loss, VO2peak (mL.kg(-1) .min(-1) ) and maximal fat oxidation increased (P < 0.05). IL-1Ra and IFN-gamma-inducible protein 10 (IP-10) decreased (P < 0.05). Insulin and HOMA2-IR decreased (14.8 ± 1.5 vs. 10.2 ± 4.2 µUI mL(-1) and 1.9 ± 0.8 vs. 1.3 ± 0.6, respectively, P < 0.05). Change in visceral fat mass was inversely associated with change in maximal fat oxidation (r = -0.54; P = 0.024). The subgroup of participants that lost visceral fat mass showed greater improvements in triglycerides, insulin resistance and maximal fat oxidation. CONCLUSION: Our data confirms the role of exercise training on improving the inflammatory profile and insulin resistance of OB in the absence of weight loss. However, those who lost a greater amount of visceral fat mass showed greater benefits in terms of insulin profile, triglycerides and maximal fat oxidation.

Predictors of long-term mortality in patients with cirrhosis undergoing cardiac surgery.

AIM: Little is known regarding the long-term outcome in cirrhotic patients undergoing cardiac surgery. The objective of this study was to identify preoperative and postoperative mortality risk factors and to determine the best predictors of long-term outcome. METHODS: Fifty-eight consecutive cirrhotic patients requiring cardiac surgery between January 2004 and January 2009 were prospectively studied at our institution. Seven patients (12%) died. A complete follow-up was performed in the whole survival group until November 2012 (mean 46±28 months). Variables usually measured on admission and during the first 24 h of the postoperative period were evaluated together with cardiac surgery scores (Parsonnet, EuroSCORE), liver scores (Child-Turcotte-Pugh, Model for End-Stage Liver Disease, United Kingdom End-Stage Liver Disease score), and ICU scores (Acute Physiology and Chronic Health Evaluation II and III, Simplified Acute Physiology Score II and III, Sequential Organ Failure Assessment). RESULTS: Twelve patients (23.5%) died during follow-up; six were Child class A and six class B. Comparing survivors vs. non-survivors using univariate analysis, variables associated with better long-term outcome were lower arterial lactate 24 h after admission (1.7±0.4 vs. 2.1±0.7 mmol·L(-1), P=0.03) and higher urine output in the first 24 h (2029±512 vs. 1575±627 mL, P=0.03). The receiver operating characteristic curve showed that the Simplified Acute Physiology Score III score had the best predictive value for long-term outcome (AUC: 77.4±0.76%; sensitivity: 83.3%; specificity: 64.9%, P=0.005). Multivariate analysis identified Simplified Acute Physiology Score III score (P=0.02) and urine output in the first 24 h (P=0.02) as independent factors associated with long-term outcome. Long-term survival was 82.4% for Child A, 47.6% for Child B and 33.3% for Child C (P=0.001). CONCLUSION: Long-term survival in cirrhotic patients requiring cardiac surgery is a more valuable prognostic measure than short-term survival. Urine output in the first 24 h may be a valuable predictor of long-term outcome in these patients. The Simplified Acute Physiology Score III is also useful.

Potential advantages of using synchrotron X-ray based techniques in pediatric research.

Synchrotron radiation (SR), which combines extremely high intensity, high collimation, tunability, and continuous energy spectrum, allows the development of advanced X-ray based techniques that are becoming a uniquely useful tool in life science research, along providing exciting opportunities in biomedical imaging and radiotherapy. This review summarize emerging techniques and their potential to greatly enhance the exploration of dynamical biological process occurring across various spatial and temporal regimes, from whole body physiology, down to the location of individual chemical species within single cells. In recent years pediatric research and clinic practice have started to profit from these new opportunities, particularly by extending the diagnostic and therapeutic capabilities of these X-ray based techniques. In diagnosis, technical advances in DEI and KES imaging modalities have been demonstrated as particularly valuable for children and women since SR allows dose minimization, with significant reductions compared to conventional approaches. However, the greatest expectations are in the field of SR based radiotherapy, increasingly studies are demonstrating SR radiotherapy provides improved chances of recovery; this is especially the case for pediatric patients. In addition, we report on the applicability of advanced X-ray microscopy techniques that offer exceptional spatial and quantitative resolution in elemental detection. These techniques, which are useful for in vitro studies, will be particularly advantageous where investigators seek deeper understanding of diseases where mismetabolism of metals, either physiological important (i.e. Cu, Zn) or outright toxic (i.e. Pb), underlies pathogenesis.

Monochromatic minibeam radiotherapy: theoretical and experimental dosimetry for preclinical treatment plans.

Monochromatic x-ray minibeam radiotherapy is a new radiosurgery approach based on arrays of submillimetric interlaced planar x-ray beams. The aim of this study was to characterize the dose distributions obtained with this new modality when being used for preclinical trials. Monte Carlo simulations were performed in water phantoms. Percentage depth-dose curves and dose profiles were computed for single incidences and interleaved incidences of 80 keV planar x-ray minibeam (0.6 × 5 mm) arrays. Peak to valley dose ratios were also computed at various depths for an increasing number of minibeams. 3D experimental polymer gel (nPAG) dosimetry measurements were performed using MRI devices designed for small animal imaging. These very high spatial resolution (50 µm) dose maps were compared to the simulations. Preclinical minibeams dose distributions were fully characterized. Experimental dosimetry correlated well with Monte Carlo calculations (Student t-tests: p > 0.1). F98 tumor-bearing rats were also irradiated with interleaved minibeams (80 keV, prescribed dose: 25 Gy). This associated preclinical trial serves as a proof of principle of the technique. The mean survival time of irradiated glioma-bearing rats increased significantly, when compared to the untreated animals (59.6 ± 2.8 days versus 28.25 ± 0.75 days, p < 0.001).

Dosimetry protocol for the forthcoming clinical trials in synchrotron stereotactic radiation therapy (SSRT).

PURPOSE: An adequate dosimetry protocol for synchrotron radiation and the specific features of the ID17 Biomedical Beamline at the European Synchrotron Radiation Facility are essential for the preparation of the forthcoming clinical trials in the synchrotron stereotactic radiation therapy (SSRT). The main aim of this work is the definition of a suitable protocol based on standards of dose absorbed to water. It must allow measuring the absolute dose with an uncertainty within the recommended limits for patient treatment of 2%-5%. METHODS: Absolute dosimetry is performed with a thimble ionization chamber (PTW semiflex 31002) whose center is positioned at 2 g cm(-2) equivalent depth in water. Since the available synchrotron beam at the ESRF Biomedical Beamline has a maximum height of 3 mm, a scanning method was employed to mimic a uniform exposition of the ionization chamber. The scanning method has been shown to be equivalent to a broad beam irradiation. Different correction factors have been assessed by using Monte Carlo simulations. RESULTS: The absolute dose absorbed to water at 80 keV was measured in reference conditions with a 2% global uncertainty, within the recommended limits. The dose rate was determined to be in the range between 14 and 18 Gy/min, that is to say, a factor two to three times higher than the 6 Gy/min achievable in RapidArc or VMAT machines. The dose absorbed to water was also measured in a RW3 solid water phantom. This phantom is suitable for quality assurance purposes since less than 2% average difference with respect to the water phantom measurements was found. In addition, output factors were assessed for different field sizes. CONCLUSIONS: A dosimetry protocol adequate for the specific features of the SSRT technique has been developed. This protocol allows measuring the absolute dose absorbed to water with an accuracy of 2%. It is therefore satisfactory for patient treatment.

Treatment plans optimization for contrast-enhanced synchrotron stereotactic radiotherapy.

PURPOSE: Synchrotron stereotactic radiotherapy (SSRT) is a treatment that involves the targeting of high-Z elements into tumors followed by stereotactic irradiation with monochromatic x-rays from a synchrotron source, tuned at an optimal energy. The irradiation geometry, as well as the secondary particles generated at a higher yield by the medium energy x-rays on the high-Z atoms (characteristic x-rays, photoelectrons, and Auger electrons), produces a localized dose enhancement in the tumor. Iodine-enhanced SSRT with systemic injections of iodinated contrast agents has been successfully developed in the past six years in the team, and is currently being transferred to clinical trials. The purpose of this work is to study the impact on the SSRT treatment of the contrast agent type, the beam quality, the irradiation geometry, and the beam weighting for defining an optimized SSRT treatment plan. METHODS: Theoretical dosimetry was performed using the MCNPX particle transport code. The simulated geometry was an idealized phantom representing a human head. A virtual target was positioned in the central part of the phantom or off-centered by 4 cm. The authors investigated the dosimetric characteristics of SSRT for various contrast agents: Iodine, gadolinium, and gold; and for different beam qualities: Monochromatic x-ray beams from a synchrotron source (30-120 keV), polychromatic x-ray beams from an x-ray tube (80, 120, and 180 kVp), and a 6 MV x-ray beam from a linear accelerator. Three irradiation geometries were studied: One arc or three noncoplanar arcs dynamic arc therapy, and an irradiation with a finite number of beams. The resulting dose enhancements, beam profiles, and histograms dose volumes were compared for iodine-enhanced SSRT. An attempt to optimize the irradiation scheme by weighing the finite x-ray beams was performed. Finally, the optimization was studied on patient specific 3D CT data after contrast agent infusion. RESULTS: It was demonstrated in this study that an 80 keV beam energy was a good compromise for treating human brain tumors with iodine-enhanced SSRT, resulting in a still high dose enhancement factor (about 2) and a superior bone sparing in comparison with lower energy x-rays. This beam could easily be produced at the European Synchrotron Radiation Facility medical beamline. Moreover, there was a significant diminution of dose delivered to the bone when using monochromatic x-rays rather than polychromatic x-rays from a conventional tube. The data showed that iodine SSRT exhibits a superior sparing of brain healthy tissue in comparison to high energy treatment. The beam weighting optimization significantly improved the treatment plans for off-centered tumors, when compared to nonweighted irradiations. CONCLUSIONS: This study demonstrated the feasibility of realistic clinical plans for low energy monochromatic x-rays contrast-enhanced radiotherapy, suitable for the first clinical trials on brain metastasis with a homogeneous iodine uptake.

[Synchroton radiotherapy]. / Radiothérapie par rayonnement synchrotron.

Radiation therapy is commonly used in the treatment of cancer. The normal tissue tolerance can be a limit to deliver enough dose to the tumor to be curative. The synchrotron beam presents some interesting physical properties, which could decrease this limitation. Synchrotron beam is a medium energy X-ray nearly parallel beam with high intensity. Three methods are under preclinical investigations: the microbeam, the minibeam and the stereotactic radiotherapy. The first two use a geometric irradiation effect called spatial fractioning. The last one use highly conformational irradiation geometry combined with a dose enhancement due to the presence of high-Z element in the target. Synchrotron radiotherapy preclinical experiments have shown some curative effect on rodent glioma models. Following these encouraging results a phase I/II clinical trial of iodinated enhanced stereotactic synchrotron radiotherapy is currently being prepared at the European Synchrotron Radiation Facility.

Simulation of dose deposition in stereotactic synchrotron radiation therapy: a fast approach combining Monte Carlo and deterministic algorithms.

A hybrid approach, combining deterministic and Monte Carlo (MC) calculations, is proposed to compute the distribution of dose deposited during stereotactic synchrotron radiation therapy treatment. The proposed approach divides the computation into two parts: (i) the dose deposited by primary radiation (coming directly from the incident x-ray beam) is calculated in a deterministic way using ray casting techniques and energy-absorption coefficient tables and (ii) the dose deposited by secondary radiation (Rayleigh and Compton scattering, fluorescence) is computed using a hybrid algorithm combining MC and deterministic calculations. In the MC part, a small number of particle histories are simulated. Every time a scattering or fluorescence event takes place, a splitting mechanism is applied, so that multiple secondary photons are generated with a reduced weight. The secondary events are further processed in a deterministic way, using ray casting techniques. The whole simulation, carried out within the framework of the Monte Carlo code Geant4, is shown to converge towards the same results as the full MC simulation. The speed of convergence is found to depend notably on the splitting multiplicity, which can easily be optimized. To assess the performance of the proposed algorithm, we compare it to state-of-the-art MC simulations, accelerated by the track length estimator technique (TLE), considering a clinically realistic test case. It is found that the hybrid approach is significantly faster than the MC/TLE method. The gain in speed in a test case was about 25 for a constant precision. Therefore, this method appears to be suitable for treatment planning applications.

Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials.

Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.

Quantitative functional imaging and kinetic studies with high-Z contrast agents using synchrotron radiation computed tomography.

1. There is an increasing demand in diagnostic radiology for extracting additional morphological and functional quantitative parameters from three-dimensional computed tomography (CT) images. Synchrotron radiation computed tomography (SRCT) is the state-of-the-art method in preclinical X-ray CT, because its performance is close to the theoretical limits in terms of accuracy and precision. 2. The SRCT method with monochromatic X-ray beams yields absolute high-Z element contrast agent concentrations, without errors arising from beam hardening or scatter artefacts, by using digital subtraction techniques of the sinograms. Each pixel of the reconstructed difference images provides a quantitative concentration versus time curve of inhaled or injected high-Z contrast agents (xenon or iodine) with a high sensitivity. This is the key point of two functional imaging techniques that were developed at the European Synchrotron Radiation Facility: brain perfusion and lung function (ventilation and perfusion). 3. These two imaging techniques provide parametric images expressed in absolute perfusion parameters (blood volume, blood flow, mean transit time and capillary permeability) or ventilation parameters (lung volume, regional lung ventilation, bronchial lumen size, regional airway and lung compliance) with a high accuracy and precision. 4. The aim of the present brief review is to give a snapshot of the status and perspectives of these two imaging techniques, with emphasis on the performances and interests for functional imaging. Two separate sections will then describe the results obtained so far using SRCT as an in vivo functional imaging tool for measuring changes in haemodynamics and ventilation, in the investigation of experimental pathophysiology and in the effects of therapeutic intervention.

The radiotherapy clinical trials projects at the ESRF: technical aspects.

The radiotherapy clinical trials projects, both aiming at treating aggressive brain tumors, require several major modifications and new constructions at the ESRF ID17 Biomedical beamline. The application of the Stereotactic Synchrotron Radiation Therapy (SSRT) technique mainly necessitates an upgrade of the existing patient positioning system, which was formerly used for the angiography program. It will allow for accurate positioning, translation and rotation of the patient during the treatment. For the Microbeam Radiation Therapy (MRT) clinical trials project, a new white beam hutch will be constructed to accommodate a dedicated patient positioning system. Consequently, the existing control hutches and the related installations will also be completely refurbished. Furthermore, the foreseen installation of a second X-ray source, which will allow doubling the currently available photon flux at high energies, requires a redesign of most optical components to handle the increased power and power densities. Starting from the current ID17 Biomedical beamline layout, the paper will present an update of the different modification/construction projects, including the general organization and planning.

Heavy element enhanced synchrotron stereotactic radiotherapy as a promising brain tumour treatment.

Synchrotron stereotactic radiotherapy (SSR) is a treatment that involves selective accumulation of high-Z elements in tumours followed by stereotactic irradiation, in CT mode, with monochromatic X-rays from a synchrotron source, tuned at an optimal energy. The irradiation geometry, characteristic X-rays, photoelectrons, and Auger electrons generated on high-Z atoms by kilovoltage X-rays produce a localized dose enhancement. Two complimentary SSR approaches have been successfully developed in the past 5 years in our team, and may be promising in high-grade glioma management: iodine-enhanced SSR, with an iodinated contrast agent; and Pt-enhanced SSR; a concomitant radio-chemotherapy treatment with locoregional injection of platinated chemotherapy drugs. The results for iodine-enhanced SSR using contrast agents are presented in this paper. IUdR-enhanced SSR was also tested in this study. Up to 15 Gy, intracarotid infusion of iodine significantly improved the rats' survival compared to irradiation alone. SSR provides the most protracted survivals of F98 glioma-bearing rats. The technique is currently transferred to clinical trials. Iodine-enhanced SSR will be implemented first, because of its simplicity; and pave the way for Pt-enhanced SSR, the most efficient technique, but still needing to be improved in terms of intrinsic toxicity.

Bloodstream infection related to catheter connections: a prospective trial of two connection systems.

Bloodstream infections (BSIs) related to central venous catheters (CVCs) and arterial catheters (ACs) are an increasing problem in the management of critically ill patients. Our objective was to assess the efficacy of a needle-free valve connection system (SmartSite), Alaris Medical Systems, San Diego, CA, USA) in the prevention of catheter-related bloodstream infection (CR-BSI). Patients admitted to an intensive care unit were prospectively assigned to have a CVC and AC connected with either a needle-free valve connection system (NFVCS) or a three-way stopcock connection (3WSC). The characteristics of the patients were similar in the two groups. Before manipulation, the NFVCS was disinfected with chlorhexidine digluconate 0.5% alcoholic solution. The 3WSC was not disinfected between use but it was covered with a protection cap. A total of 799 patients requiring the insertion of a multilumen CVC or AC for >48h from 1 April 2002 to 31 December 2003 were included. CR-BSI rates were 4.61 per 1000 days of catheter use in the disinfected NFVCS group and 4.11 per 1000 days of catheter use in the 3WSC group (P=0.59). When CVC-BSIs and AC-BSIs were analysed separately, the rate of CVC-BSI was 4.26 per 1000 days of catheter use in the NFVCS group, compared with 5.27 in the 3WSC group (P=0.4). The incidence rate of AC-BSI was 5.00 per 1000 days of catheter use in the NFVCS group, compared with 2.83 in the 3WSC group (P=0.08). The use of NFVCS does not reduce the incidence of catheter-related bacteraemia. The arterial catheter (AC) is a significant source of infection in critically ill patients.