Estimating attributable mortality due to nosocomial infections acquired in intensive care units.

BACKGROUND: The strength of the association between intensive care unit (ICU)-acquired nosocomial infections (NIs) and mortality might differ according to the methodological approach taken. OBJECTIVE: To assess the association between ICU-acquired NIs and mortality using the concept of population-attributable fraction (PAF) for patient deaths caused by ICU-acquired NIs in a large cohort of critically ill patients. SETTING: Eleven ICUs of a French university hospital. DESIGN: We analyzed surveillance data on ICU-acquired NIs collected prospectively during the period from 1995 through 2003. The primary outcome was mortality from ICU-acquired NI stratified by site of infection. A matched-pair, case-control study was performed. Each patient who died before ICU discharge was defined as a case patient, and each patient who survived to ICU discharge was defined as a control patient. The PAF was calculated after adjustment for confounders by use of conditional logistic regression analysis. RESULTS: Among 8,068 ICU patients, a total of 1,725 deceased patients were successfully matched with 1,725 control patients. The adjusted PAF due to ICU-acquired NI for patients who died before ICU discharge was 14.6% (95% confidence interval [CI], 14.4%-14.8%). Stratified by the type of infection, the PAF was 6.1% (95% CI, 5.7%-6.5%) for pulmonary infection, 3.2% (95% CI, 2.8%-3.5%) for central venous catheter infection, 1.7% (95% CI, 0.9%-2.5%) for bloodstream infection, and 0.0% (95% CI, -0.4% to 0.4%) for urinary tract infection. CONCLUSIONS: ICU-acquired NI had an important effect on mortality. However, the statistical association between ICU-acquired NI and mortality tended to be less pronounced in findings based on the PAF than in study findings based on estimates of relative risk. Therefore, the choice of methods does matter when the burden of NI needs to be assessed.

Long-term outcomes of pandemic 2009 influenza A(H1N1)-associated severe ARDS.

BACKGROUND: No data on long-term outcomes of survivors of 2009 influenza A(H1N1) (A[H1N1])-associated ARDS are available. The objective of this study was to compare the 1-year outcomes of survivors of A(H1N1)-associated ARDS, according to use or no use of extracorporeal lung assist (ECLA), using its need as an ARDS severity surrogate. METHODS: Survivors of ARDS (12 with ECLA use vs 25 without, corresponding to 75% and 54% of the eligible patients for each group, respectively) selected from the Réseau Européen de Ventilation Artificielle (REVA) registry had previously been healthy, with only pregnancy and/or moderate obesity (BMI ≤ 35 kg/m²) as known risk factors for A(H1N1) infection. Lung function and morphology, health-related quality of life (HRQoL), and psychologic impairment were evaluated. RESULTS: At 1 year post-ICU discharge for the ECLA and no-ECLA groups, respectively, 50% and 40% reported significant exertion dyspnea, 83% and 64% had returned to work, and 75% and 64% had decreased diffusion capacity across the blood-gas barrier, despite their near-normal and similar lung function test results. For both groups, exercise test results showed diminished but comparable exercise capacities, with similar alveolar-arterial oxygen gradients at peak exercise, and CT scans showed minor abnormal findings. HRQoL assessed by the 36-Item Short-Form Health Survey was poorer for both groups than for a sex- and age-matched general population group, but without between-group differences. ECLA and no-ECLA group patients, respectively, had symptoms of anxiety (50% and 56%) and depression (28% and 28%) and were at risk for posttraumatic stress disorder (41% and 44%). CONCLUSIONS: One year post-ICU discharge, a majority of survivors of A(H1N1)-associated ARDS had minor lung disabilities with diminished diffusion capacities across the blood-gas barrier, and most had psychologic impairment and poorer HRQoL than a sex- and age-matched general population group. ECLA and no-ECLA group patients had comparable outcomes. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01271842; URL: www.clinicaltrials.gov

Pragmatic approach to nutrition in the ICU: Expert opinion regarding which calorie protein target.

BACKGROUND & AIMS: Since the publications of the ESPEN guidelines on enteral and parenteral nutrition in ICU, numerous studies have added information to assist the nutritional management of critically ill patients regarding the recognition of the right population to feed, the energy-protein targeting, the route and the timing to start. METHODS: We reviewed and discussed the literature related to nutrition in the ICU from 2006 until October 2013. RESULTS: To identify safe, minimal and maximal amounts for the different nutrients and at the different stages of the acute illness is necessary. These amounts might be specific for different phases in the time course of the patient's illness. The best approach is to target the energy goal defined by indirect calorimetry. High protein intake (1.5 g/kg/d) is recommended during the early phase of the ICU stay, regardless of the simultaneous calorie intake. This recommendation can reduce catabolism. Later on, high protein intake remains recommended, likely combined with a sufficient amount of energy to avoid proteolysis. CONCLUSIONS: Pragmatic recommendations are proposed to practically optimize nutritional therapy based on recent publications. However, on some issues, there is insufficient evidence to make expert recommendations.

Discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus of the rat.

The aim of the present study was to characterize the discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the rat. In the absence of acoustic stimulation, two types of spontaneous discharge patterns were observed: units tended to fire in a bursting or in a nonbursting mode. The distribution of units in the DNLL based on spontaneous firing rate followed a rostrocaudal gradient: units with high spontaneous rates were most commonly located in the rostral part of the DNLL, whereas in the caudal part units had lower spontaneous discharge rates. The most common response pattern of DNLL units to 200 ms binaural noise bursts contained a prominent onset response followed by a lower but steady-state response and an inhibitory response in the early-off period. Thresholds of response to noise bursts were on average higher for DNLL units than for units recorded in the inferior colliculus under the same experimental conditions. The DNLL units were arranged according to a mediolateral sensitivity gradient with the lowest threshold units in the most lateral part of the nucleus. In the rat, as in other mammals, the most common DNLL binaural input type was an excitatory response to contralateral ear stimulation and inhibitory response to ipsilateral ear stimulation (EI type). Pure tone bursts were in general a more effective stimulus compared to noise bursts. Best frequency (BF) was established for 97 DNLL units and plotted according to their spatial location. The DNLL exhibits a loose tonotopic organization, where there is a concentric pattern with high BF units located in the most dorsal and ventral parts of the DNLL and lower BF units in the middle part of the nucleus.

Performance of an ICU ventilator and two turbin-based ventilators dedicated to non invasive ventilation (NIV) in simulated high inspiratory effort and rate: a NIV-bench-study.

INTRODUCTION. The role of turbine-based NIV ventilators (TBV) versus ICU ventilators with NIV mode activated (ICUV) to deliver NIV in case of severe respiratory failure remains debated. OBJECTIVES. To compare the response time and pressurization capacity of TBV and ICUV during simulated NIV with normal and increased respiratory demand, in condition of normal and obstructive respiratory mechanics. METHODS. In a two-chamber lung model, a ventilator simulated normal (P0.1 = 2 mbar, respiratory rate RR = 15/min) or increased (P0.1 = 6 mbar, RR = 25/min) respiratory demand. NIV was simulated by connecting the lung model (compliance 100 ml/mbar; resistance 5 or 20 l/mbar) to a dummy head equipped with a naso-buccal mask. Connections allowed intentional leaks (29 ± 5 % of insufflated volume). Ventilators to test: Servo-i (Maquet), V60 and Vision (Philips Respironics) were connected via a standard circuit to the mask. Applied pressure support levels (PSL) were 7 mbar for normal and 14 mbar for increased demand. Airway pressure and flow were measured in the ventilator circuit and in the simulated airway. Ventilator performance was assessed by determining trigger delay (Td, ms), pressure time product at 300 ms (PTP300, mbar s) and inspiratory tidal volume (VT, ml) and compared by three-way ANOVA for the effect of inspiratory effort, resistance and the ventilator. Differences between ventilators for each condition were tested by oneway ANOVA and contrast (JMP 8.0.1, p\0.05). RESULTS. Inspiratory demand and resistance had a significant effect throughout all comparisons. Ventilator data figure in Table 1 (normal demand) and 2 (increased demand): (a) different from Servo-i, (b) different from V60.CONCLUSION. In this NIV bench study, with leaks, trigger delay was shorter for TBV with normal respiratory demand. By contrast, it was shorter for ICUV when respiratory demand was high. ICUV afforded better pressurization (PTP 300) with increased demand and PSL, particularly with increased resistance. TBV provided a higher inspiratory VT (i.e., downstream from the leaks) with normal demand, and a significantly (although minimally) lower VT with increased demand and PSL.

Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients.

BACKGROUND AND AIMS: Critically ill patients with complicated evolution are frequently hypermetabolic, catabolic, and at risk of underfeeding. The study aimed at assessing the relationship between energy balance and outcome in critically ill patients. METHODS: Prospective observational study conducted in consecutive patients staying > or = 5 days in the surgical ICU of a University hospital. Demographic data, time to feeding, route, energy delivery, and outcome were recorded. Energy balance was calculated as energy delivery minus target. Data in means+/-SD, linear regressions between energy balance and outcome variables. RESULTS: Forty eight patients aged 57+/-16 years were investigated; complete data are available in 669 days. Mechanical ventilation lasted 11+/-8 days, ICU stay 15+/-9 was days, and 30-days mortality was 38%. Time to feeding was 3.1+/-2.2 days. Enteral nutrition was the most frequent route with 433 days. Mean daily energy delivery was 1090+/-930 kcal. Combining enteral and parenteral nutrition achieved highest energy delivery. Cumulated energy balance was between -12,600+/-10,520 kcal, and correlated with complications (P < 0.001), already after 1 week. CONCLUSION: Negative energy balances were correlated with increasing number of complications, particularly infections. Energy debt appears as a promising tool for nutritional follow-up, which should be further tested. Delaying initiation of nutritional support exposes the patients to energy deficits that cannot be compensated later on.

Clinical characteristics and outcome of patients admitted to a medico- surgical ICU requiring non invasive ventilation (NIV) for hypercapnic respiratory failure

Introduction Because it decreases intubation rate and mortality, NIV has become first-line treatment in case of hypercapnic acute respiratory failure (HARF). Whether this approach is equally successful for all categories of HARF patients is however debated. We assessed if any clinical characteristics of HARF patients were associated with NIV intensity, success, and outcome, in order to identify prognostic factors. Methods Retrospective analysis of the clinical database (clinical information system and MDSi) of patients consecutively admitted to our medico-surgical ICU, presenting with HARF (defined as PaCO2 > 50 mmHg), and receiving NIV between May 2008 and December 2010. Demographic data, medical diagnoses (including documented chronic lung disease), reason for ICU hospitalization, recent surgical interventions, SAPS II and McCabe scores were extracted from the database. Total duration of NIV and the need for tracheal intubation during the 5 days following the first hypercapnia documentation, as well as ICU, hospital and one year mortality were recorded. Results are reported as median [IQR]. Comparisons were carried out with Chi2 or Kruskal-Wallis tests, p<0.05 (*). Results Two hundred and twenty patients were included. NIV successful patients received 16 [9-31] hours of NIV for up to 5 days. Fifty patients (22.7%) were intubated 11 [2-34] hours after HARF occurence, after having receiving 10 [5-21] hours of NIV. Intubation was correlated with increased ICU (18% vs. 6%, p<0.05) and hospital (42% vs. 31%, p>0.05) mortality. SAPS II score was related to increasing ICU (51 [29-74] vs. 23 [12-41]%, p<0.05), hospital (37% [20-59] vs 20% [12-37], p<0.05) and one year mortality (35% vs 20%, p<0.05). Surgical patients were less frequent among hospital fatalities (28.8% vs. 46.3%, p<0.05, RR 0.8 [0-6-0.9]). Nineteen patients (8.6%) died in the ICU, 73 (33.2%) during their hospital stay and 108 (49.1%) were dead one year after HARF. Conclusion The practice to start NIV in all suitable patients suffering from HARF is appropriate. NIV can safely and appropriately be used in patients suffering from HARF from an origin different from COPD exacerbation. Beside usual predictors of severity such as severity score (SAPS II) appear to be associated with increased mortality. Although ICU mortality was low in our patients, hospital and one year mortality were substantial. Surgical patients, although undergoing a similar ICU course, had a better hospital and one year outcome.

Neonatal and adult ICU ventilators to provide ventilation in neonates, infants, and children: a bench model study.

BACKGROUND: Using a bench test model, we investigated the hypothesis that neonatal and/or adult ventilators equipped with neonatal/pediatric modes currently do not reliably administer pressure support (PS) in neonatal or pediatric patient groups in either the absence or presence of air leaks. METHODS: PS was evaluated in 4 neonatal and 6 adult ventilators using a bench model to evaluate triggering, pressurization, and cycling in both the absence and presence of leaks. Delivered tidal volumes were also assessed. Three patients were simulated: a preterm infant (resistance 100 cm H2O/L/s, compliance 2 mL/cm H2O, inspiratory time of the patient [TI] 400 ms, inspiratory effort 1 and 2 cm H2O), a full-term infant (resistance 50 cm H2O/L/s, compliance 5 mL/cm H2O, TI 500 ms, inspiratory effort 2 and 4 cm H2O), and a child (resistance 30 cm H2O/L/s, compliance 10 mL/cm H2O, TI 600 ms, inspiratory effort 5 and 10 cm H2O). Two PS levels were tested (10 and 15 cm H2O) with and without leaks and with and without the leak compensation algorithm activated. RESULTS: Without leaks, only 2 neonatal ventilators and one adult ventilator had trigger delays under a given predefined acceptable limit (1/8 TI). Pressurization showed high variability between ventilators. Most ventilators showed TI in excess high enough to seriously impair patient-ventilator synchronization (> 50% of the TI of the subject). In some ventilators, leaks led to autotriggering and impairment of ventilation performance, but the influence of leaks was generally lower in neonatal ventilators. When a noninvasive ventilation algorithm was available, this was partially corrected. In general, tidal volume was calculated too low by the ventilators in the presence of leaks; the noninvasive ventilation algorithm was able to correct this difference in only 2 adult ventilators. CONCLUSIONS: No ventilator performed equally well under all tested conditions for all explored parameters. However, neonatal ventilators tended to perform better in the presence of leaks. These findings emphasize the need to improve algorithms for assisted ventilation modes to better deal with situations of high airway resistance, low pulmonary compliance, and the presence of leaks.

Increased blood glucose variability during therapeutic hypothermia and neurological recovery after cardiac arrest

INTRODUCTION. Recent studies suggest that increased blood glucose variability (BGV) is associated with ICU mortality1. Hypothermia is known to induce insulin resistance, thus potentially increasing BGV. No studies however have examined the effect of therapeutic hypothermia (TH) on insulin requirements and BGV. OBJECTIVES. To examine the effect of TH on BGV and its relationship to outcome in patients with coma after cardiac arrest (CA). METHODS. We prospectively studied 132 consecutive comatose CA patients treated with TH (target core temp 33_C for 24 h, using surface cooling). All patients were treated with intravenous insulin (blood glucose target 6-8 mM), according to a written algorithm, with nurse-driven adjustment of insulin dose. For each patient, standard deviation of repeated blood glucose samples was used to calculate BGV. Two time-points, comparable in duration, were studied: TH (stable maintenance phase, i.e. 6-24 h, core temp ± 33_C) vs. Normothermia (NT, i.e. after rewarming, stable normothermic phase, core temp ± 37_C). Mortality and neurological recovery (Glasgow-Pittsburgh Cerebral Performance Categories, CPC, dichotomized as good = CPC 1-2 vs. poor = CPC 3-5) were assessed at hospital discharge. Statistical analysis was performed with ANOVA for repeated measures. RESULTS. Compared to NT, TH was associated with increased intravenous insulin dose (0.8 ± 1.1 vs. 1.6 ± 2 U/h, P\0.0001), higher mean (6.9 ± 1.3 vs. 7.7 ± 1.8 mM, P\0.0001) and maximum (9.1 ± 3.7 vs. 10.9 ± 3.6 mM, P\0.0001) blood glucose, and increased BGV (1.3 ± 1.2 vs. 1.7 ± 1.1 mM, P = 0.004). Increased BGV was strongly associated with mortality (2.5 ± 1.5 mM in non-survivors vs. 1.6 ± 1 mM in survivors, P\0.001) and worse outcome (2.3 ± 1.4 mM in patients with poor vs. 1.5 ± 0.8 mM in those with good neurological recovery, P\0.0001). CONCLUSIONS. Therapeutic hypothermia is associated with increased insulin requirements and higher blood glucose variability,which in turn correlateswithworse prognosis in patientswith post- CA coma. Strategies aimed to maintain stable glycemic profile and avoid blood glucose variability might contribute to optimize the management of TH and may translate into better outcome.

Antifungals in the ICU.

PURPOSE OF REVIEW: Invasive fungal infections remain a serious complication for critically ill ICU patients. The aim of this article is to review recent efficacy data of newer antifungal agents for the treatment of invasive candidiasis. The influence that recent epidemiological trends, advances in diagnostic testing, and risk prediction methods exert on the optimization of antifungal therapy for critically ill ICU patients will also be reviewed. RECENT FINDINGS: Recent clinical trials have documented the clinical efficacy of the echinocandins and the newer triazoles for the management of invasive candidiasis. Thus far, resistance to echinocandins remains rare. Changes in the epidemiology of Candida spp. causing invasive candidiasis, such as an increasing relative proportion of non-albicans Candida spp., have not been universally reported, although they have important implications for the use of fluconazole as first-line therapy for invasive candidiasis. Efforts to improve the timeliness and accuracy of laboratory diagnostic techniques and clinical prediction models to allow early and accurately targeted antifungal intervention strategies continue. SUMMARY: Echinocandins, given their clinical efficacy, spectrum of activity, and favourable pharmacological properties, are likely to replace fluconazole as initial antifungal agents of choice among critically ill ICU patients. The optimization of patient outcomes will require more accurately targeted early antifungal intervention strategies based upon sensitive and specific biological and clinical markers of risk.

Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries.

With advances in the effectiveness of treatment and disease management, the contribution of chronic comorbid diseases (comorbidities) found within the Charlson comorbidity index to mortality is likely to have changed since development of the index in 1984. The authors reevaluated the Charlson index and reassigned weights to each condition by identifying and following patients to observe mortality within 1 year after hospital discharge. They applied the updated index and weights to hospital discharge data from 6 countries and tested for their ability to predict in-hospital mortality. Compared with the original Charlson weights, weights generated from the Calgary, Alberta, Canada, data (2004) were 0 for 5 comorbidities, decreased for 3 comorbidities, increased for 4 comorbidities, and did not change for 5 comorbidities. The C statistics for discriminating in-hospital mortality between the new score generated from the 12 comorbidities and the Charlson score were 0.825 (new) and 0.808 (old), respectively, in Australian data (2008), 0.828 and 0.825 in Canadian data (2008), 0.878 and 0.882 in French data (2004), 0.727 and 0.723 in Japanese data (2008), 0.831 and 0.836 in New Zealand data (2008), and 0.869 and 0.876 in Swiss data (2008). The updated index of 12 comorbidities showed good-to-excellent discrimination in predicting in-hospital mortality in data from 6 countries and may be more appropriate for use with more recent administrative data.