F. Wallet

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.

Preload dependence indices to titrate volume expansion during septic shock: a randomized controlled trial

IntroductionIn septic shock, pulse pressure or cardiac output variation during passive leg raising are preload dependence indices reliable at predicting fluid responsiveness. Therefore, they may help to identify those patients who need intravascular volume expansion, while avoiding unnecessary fluid administration in the other patients. However, whether their use improves septic shock prognosis remains unknown. The aim of this study was to assess the clinical benefits of using preload dependence indices to titrate intravascular fluids during septic shock.MethodsIn a single-center randomized controlled trial, 60 septic shock patients were allocated to preload dependence indices-guided (preload dependence group) or central venous pressure-guided (control group) intravascular volume expansion with 30 patients in each group. The primary end point was time to shock resolution, defined by vasopressor weaning.ResultsThere was no significant difference in time to shock resolution between groups (median (interquartile range) 2.0 (1.2 to 3.1) versus 2.3 (1.4 to 5.6) days in control and preload dependence groups, respectively). The daily amount of fluids administered for intravascular volume expansion was higher in the control than in the preload dependence group (917 (639 to 1,511) versus 383 (211 to 604) mL, P = 0.01), and the same held true for red cell transfusions (178 (82 to 304) versus 103 (0 to 183) mL, P = 0.04). Physiologic variable values did not change over time between groups, except for plasma lactate (time over group interaction, P <0.01). Mortality was not significantly different between groups (23% in the preload dependence group versus 47% in the control group, P = 0.10). Intravascular volume expansion was lower in the preload dependence group for patients with lower simplified acute physiology score II (SAPS II), and the opposite was found for patients in the upper two SAPS II quartiles. The amount of intravascular volume expansion did not change across the quartiles of severity in the control group, but steadily increased with severity in the preload dependence group.ConclusionsIn patients with septic shock, titrating intravascular volume expansion with preload dependence indices did not change time to shock resolution, but resulted in less daily fluids intake, including red blood cells, without worsening patient outcome.Trial registrationClinicaltrials.gov NCT01972828. Registered 11 October 2013.

Effects of a continuous low-dose clonidine epidural regimen on pain, satisfaction and adverse events during labour: a randomized, double-blind, placebo-controlled trial.

Background and objective Epidural clonidine has been proposed as an adjunct for anaesthetic mixtures during labour. Administered as a bolus, clonidine may have side effects such as sedation and hypotension; its continuous infusion could be attractive in this respect. We, therefore, conducted a randomized, double-blind trial using patient-controlled epidural analgesia with a background infusion using a low dose of clonidine during labour. Methods A total of 128 healthy parturients in active labour received a patient-controlled epidural analgesia solution of 0.0625% levobupivacaine and sufentanil 0.25 μg ml−1 with or without clonidine 2 μg ml−1. Ninety-five parturients were analysed. The pain score over time was evaluated as well as drug volume utilization; supplementation bolus and side effects were recorded. The primary endpoint was maternal satisfaction [ClinicalTrials.gov Identifier (NCT00437996)]. Results Three patients in the control group failed to achieve satisfactory epidural analgesia owing to a technical issue. Although the primary endpoint was not statistically significant, analgesia was more pronounced and obtained earlier in the clonidine group. The area under the curve for the visual analogue pain score was significantly lower in the clonidine group. In this group, hourly doses of levobupivacaine and sufentanil were reduced (13.9 ± 4.3 vs. 16.3 ml ± 4.0; P = 0.005) as well as rescue supplementation and pruritus incidence (18 vs. 46%; P = 0.004). Maternal blood pressure was significantly lower, over time, in the clonidine group but remained within the normal range. Sedation was similar in both groups (4.3 vs. 2.0%; not significant). Conclusion The addition of clonidine to epidural levobupivacaine and sufentanil for patient-controlled epidural analgesia in labour improved analgesia, reduced the supplementation rate and reduced pruritus without improvement in maternal satisfaction. Blood pressure was significantly lower in the clonidine group over time but without clinical consequence.

Evaluation of Recruited Lung Volume at Inspiratory Plateau Pressure With PEEP Using Bedside Digital Chest X-ray in Patients With Acute Lung Injury/ARDS

BACKGROUND: We wanted to assess whether there was a significant relationship between recruited lung volume (Vrec) and change in density on digital processed chest x-ray measured at 2 different levels of inspiratory plateau pressure corresponding to 2 PEEP levels in patients with acute lung injury or ARDS. METHODS: In 14 subjects, PEEP 5 cm H2O and 15 cm H2O were prospectively applied in a random order for 10 min. At the end of each period, chest x-ray was taken using a digital portable device, and a pressure-volume curve of the respiratory system was performed. We also assessed PaO2, and the static and the dynamic (Cdyn,rs) compliance of the respiratory system. Change in end-expiratory lung volume between tidal breath and relaxation volume of the respiratory system was determined. Radiological attenuation was measured on chest x-rays in 4 regions of interest in the right lung, and in 3 regions of interest in the left lung, drawn in posterior intercostal spaces from top to bottom, by using dedicated software. The ratio of lung density in each region between PEEP 15 and PEEP 5 (rP15/P5) and their arithmetic mean (μP15/P5) were computed. Vrec was determined from the pressure-volume curves. RESULTS: The median value of rP15/P5 in the 98 lung levels was 0.91 (0.80–1.01), which was significantly different from 1 (P < .001). The values of rP15/P5 were not significantly different between the lung levels. The median values of Vrec and μP15/P5 were 288 (173–402) mL and 0.90 (0.80–0.97), respectively. There was a significant negative correlation between Vrec and μP15/P5 (R = −0.77, P = .01). The reduction in μP15/P5 tended to correlate with the increase in Cdyn,rs (R = −0.49, P = .077) or in PaO2 (R = −0.53, P = .05) between PEEP 15 cm H2O and PEEP 5 cm H2O. CONCLUSIONS: Digital chest x-ray done at the bedside in acute lung injury/ARDS subjects was able to detect a reduction in density between PEEP 5 cm H2O and PEEP 15 cm H2O, which correlated with Vrec.

Management and Long-Term Outcome of Patients With Chronic Neuromuscular Disease Admitted to the Intensive Care Unit for Acute Respiratory Failure: A Single-Center Retrospective Study

BACKGROUND: Patients with chronic neuromuscular disease represent less than 10% of those receiving mechanical ventilation in the intensive care unit (ICU). Little has been reported regarding either ICU management of acute respiratory failure (ARF) in the era of noninvasive mechanical ventilation (NIV) or long-term outcomes. OBJECTIVE: To describe the respiratory management of patients with chronic neuromuscular diseases admitted to our university hospital ICU for ARF, and the long-term outcomes. METHODS: We retrospectively analyzed patients with chronic neuromuscular diseases admitted to our ICU for a first episode of ARF between January 1, 1996, and February 27, 2007. We assessed severity of illness on ICU admission, respiratory management during ICU stay, and outcomes on June 15, 2008. RESULTS: During the study period, 87 patients (44 with hereditary and 43 with acquired neuromuscular diseases) had their first ARF episode that required ICU admission. In the hereditary-diseases group and the acquired-diseases group, respectively, the rates of NIV use during the ICU stay were 82% and 63% (P = .040), the intubation rates were 30% and 56% (P = .02), and the tracheotomy rates were 9% and 12% (difference not significant). At the final assessment (median 3 years) the mortality rate was 58%, and mortality was not significantly related to the type of neuromuscular disease. At final assessment, 46% of the patients were on NIV and 29% had tracheotomy. CONCLUSIONS: In our ICU, chronic neuromuscular disease is an uncommon cause of ARF, for which we often use NIV. These patients had a low probability of death in the ICU. Long-term outcome was independent of the type of neuromuscular disease.

Factors associated with noninvasive ventilation failure in postoperative acute respiratory insufficiency: an observational study.

Background and objective Few data are available on the efficacy of noninvasive ventilation (NIV) in postoperative patients with acute respiratory failure (ARF). Methods Seventy-two patients coming from the surgical wards with postoperative ARF were retrospectively evaluated. The major characteristics of patients who were intubated were compared with the characteristics of those who were not after a trial of NIV. Predictive factors for failure of NIV were analysed. Results Out of 72 patients with ARF after surgery who were treated with NIV, 42 avoided intubation (58%). On a univariate analysis, a decrease in the paO2/FiO2 ratio after 1 h of NIV (223 ± 84 to 160 ± 68 mmHg, P < 0.05) was associated with NIV failure and need for tracheal intubation because of nosocomial pneumonia and an increased simplified acute physiology score (SAPS) 2. In a multivariate analysis, nosocomial pneumonia [odds ratio (OR) 4.189; 95% confidence interval (CI) 1.383–12.687] and SAPS 2 higher than 35 (OR 4.969; 95% CI 1.627–15.172) were independent predictive factors of NIV failure. NIV success was associated with a reduced ICU stay (16.8 vs. 26.1 days, P < 0.001). Conclusion NIV could be considered in postoperative patients who presented with ARF. Nosocomial pneumonia is predictive of NIV failure.

A Perioperative Clinical Pathway Can Dramatically Reduce Failure-to-rescue Rates After Cytoreductive Surgery for Peritoneal Carcinomatosis: A Retrospective Study of 666 Consecutive Cytoreductions

Objective: To determine whether a perioperative, standardized clinical pathway could impact the failure-to-rescue rate after cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) in a tertiary center. Summary of Background Data: Morbidity and mortality remain significant after CRS for PC. Clinical pathways have been associated with better outcomes after surgery. The failure-to-rescue rate is a useful metric for evaluating quality in surgery. Materials and Methods: This study included 666 patients that received CRS for PC between 2009 and 2014. Starting in 2012, a standardized perioperative clinical pathway was introduced, which focused on patient selection, nutrition, renal protection, pain management, prevention, and early detection of complications. Complications were evaluated with the National Cancer Institutes Common Terminology Criteria for Adverse Events. We used multivariate analyses to evaluate clinicopathological and perioperative factors for associations with major complications and failure-to-rescue. Complication rates were compared before and after the clinical pathway implementation. Results: Major complications occurred in 341 patients (51%), leading to 15 deaths. The complication rate was similar before and after clinical pathway introduction (54.75% vs 48.9%, respectively; P = 0.138). Only prolonged surgery (longer than 240 mins) was independently associated with major complications. The failure-to-rescue rate was 4.4% for the entire period, but it significantly decreased after introducing the clinical pathway (9.02% vs 1.02%; P < 0.001). On multivariate analysis, only renal complications were associated with the failure-to-rescue. Conclusion: Morbidity after CRS remains significant, but standardized management facilitated a reduction in the failure-to-rescue rate and improved the quality of care. Specific effort should be dedicated to preventing postoperative renal failure.

Complications after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis: Risk factors for ICU admission and morbidity prognostic score

BACKGROUND AND OBJECTIVES For patients suffering from peritoneal carcinomatosis, cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the only curative option. We focused on severe complications in the postoperative course of HIPEC. METHODS We studied perioperative data from patients who underwent HIPEC between January 2010 and August 2011. Our primary objective was to identify perioperative risk factors for ICU admission. Our secondary objective was to identify patient that may be re-admitted to the ICU thanks to a prognostic score. RESULTS 122 patients underwent HIPEC. 32 presented severe adverse events (26.2%) and 7 died (5.7%). Reasons for ICU admission were septic shock in 28.1% of patients, hemorrhagic shock for 21.9%, hemodynamic instability for 15.6%, respiratory causes for 6.2% and post-operative acidosis for 6.2%. Vasopressors were required for 34% and 40.6% were mechanically ventilated. CONCLUSION Peritoneal cancer index, diaphragmatic peritonectomy, the need of vasopressive therapy, total volume of fluid leakage collected in drains and total volume of fluid therapy administered at day 1 reported on ideal body weight were the 5 significant variables that we combined to build a morbidity prognostic score. One patient over 4 is likely to present severe complications. A predictive morbidity score provide informative data for clinicians.

Applicability of Pulse Pressure Variation during Unstable Hemodynamic Events in the Intensive Care Unit: A Five-Day Prospective Multicenter Study

Pulse pressure variation can predict fluid responsiveness in strict applicability conditions. The purpose of this study was to describe the clinical applicability of pulse pressure variation during episodes of patient hemodynamic instability in the intensive care unit. We conducted a five-day, seven-center prospective study that included patients presenting with an unstable hemodynamic event. The six predefined inclusion criteria for pulse pressure variation applicability were as follows: mechanical ventilation, tidal volume >7 mL/kg, sinus rhythm, no spontaneous breath, heart rate/respiratory rate ratio >3.6, absence of right ventricular dysfunction, or severe valvulopathy. Seventy-three patients presented at least one unstable hemodynamic event, with a total of 163 unstable hemodynamic events. The six predefined criteria for the applicability of pulse pressure variation were completely present in only 7% of these. This data indicates that PPV should only be used alongside a strong understanding of the relevant physiology and applicability criteria. Although these exclusion criteria appear to be profound, they likely represent an absolute contraindication of use for only a minority of critical care patients.

High-flow nasal oxygen vs. standard oxygen therapy in immunocompromised patients with acute respiratory failure: study protocol for a randomized controlled trial

BackgroundAcute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in immunocompromised patients. High-flow nasal oxygen (HFNO) therapy is an alternative to standard oxygen. By providing warmed and humidified gas, HFNO allows the delivery of higher flow rates via nasal cannula devices, with FiO2 values of nearly 100%. Benefits include alleviation of dyspnea and discomfort, decreased respiratory distress and decreased mortality in unselected patients with acute hypoxemic respiratory failure. However, in preliminary reports, HFNO benefits are controversial in immunocompromised patients in whom it has never been properly evaluated.Methods/designThis is a multicenter, open-label, randomized controlled superiority trial in 30 intensive care units, part of the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique (GRRR-OH). Inclusion criteria will be: (1) adults, (2) known immunosuppression, (3) ARF, (4) oxygen therapy ≥ 6 L/min, (5) written informed consent from patient or proxy. Exclusion criteria will be: (1) imminent death (moribund patient), (2) no informed consent, (3) hypercapnia (PaCO2 ≥ 50 mmHg), (4) isolated cardiogenic pulmonary edema, (5) pregnancy or breastfeeding, (6) anatomical factors precluding insertion of a nasal cannula, (7) no coverage by the French statutory healthcare insurance system, and (8) post-surgical setting from day 1 to day 6 (patients with ARF occurring after day 6 of surgery can be included).The primary outcome measure is day-28 mortality. Secondary outcomes are intubation rate, comfort, dyspnea, respiratory rate, oxygenation, ICU length of stay, and ICU-acquired infections.Based on an expected 30% mortality rate in the standard oxygen group, and 20% in the HFNO group, error rate set at 5%, and a statistical power at 90%, 389 patients are required in each treatment group (778 patients overall). Recruitment period is estimated at 30 months, with 28 days of additional follow-up for the last included patient.DiscussionThe HIGH study will be the largest multicenter, randomized controlled trial seeking to demonstrate that survival benefits from HFNO reported in unselected patients also apply to a large immunocompromised population.Trial registrationClinicalTrials.gov, ID: NCT02739451. Registered on 15 April 2016.