Cessation of screening for intestinal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae in a low-endemicity intensive care unit with universal contact precautions.

OBJECTIVES: The usefulness of screening for carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) with active surveillance cultures (ASC) remains equivocal in low-endemicity intensive care units (ICUs). Our primary objective was to appraise the impact of ceasing ASC on the incidence of ICU-acquired ESBL-E infections in an ICU with universal contact precautions (CP). Patient outcomes and carbapenem consumption were also investigated. METHODS: A single-ICU, retrospective, uncontrolled before-and-after study including all patients admitted for ≥3 days during two consecutive 1-year periods with and without ASC. RESULTS: A total of 524 and 545 patients were included during the ASC and the no-ASC periods, respectively. Twenty-eight patients (5.3%) from the ASC period were ESBL-E carriers. An ICU-acquired ESBL-E infection (median duration of risk exposure, 4 (range 2-9) days for both periods) occurred in 1.1% and 1.5% of patients admitted during the ASC and the no-ASC periods (p = 0.64), with no inter-period variation in incidence after adjustment on competing risks of death and ICU discharge (standardized hazard ratio (SHR) 2.32, 95% CI 0.80-6.73, p = 0.12). An admission during the no-ASC period exerted no independent impact on the hazards of ESBL-E infections (adjusted OR 1.16, 95% CI 0.38-3.50, p = 0.79), in-ICU death (SHR 1.22, 95% CI 0.93-1.59, p = 0.15) and extended length of stay (SHR for discharge 0.89, 95% CI 0.79-1.01, p = 0.08). Carbapenem exposure in patients without ESBL-E infection decreased between the ASC and no-ASC periods (75 versus 61 carbapenem-days per 1000 patient-days, p = 0.01). CONCLUSIONS: In a low-endemicity ICU with universal CP, the withdrawal of routine screening for ESBL-E carriage had no significant effect on the incidence of ICU-acquired ESBL-E infections and patient outcomes. Carbapenem consumption decreased in patients without ESBL-E infection.

Prognostic significance of central venous-to-arterial carbon dioxide difference during the first 24 hours of septic shock in patients with and without impaired cardiac function.

OBJECTIVE: To investigate the prognostic significance of central venous-to-arterial carbon dioxide difference (cv-art CO 2 gap) during septic shock in patients with and without impaired cardiac function. METHODS: We performed a prospective cohort study in 10 French intensive care units. Patients suffering from septic shock were assigned to the impaired cardiac function group ('cardiac group', n =123) if they had atrial fibrillation (AF) and/or left ventricular ejection fraction (LVEF) <50% at study entry and to the non-cardiac group ( n =240) otherwise. RESULTS: Central venous and arterial blood gases were sampled every 6 h during the first 24 h to calculate cv-art CO 2 gap. Patients in the cardiac group had a higher cv-art CO 2 gap [at study entry and 6 and 12 h (all P <0.02)] than the non-cardiac group. Patients in the cardiac group with a cv-art CO 2 gap >0.9 kPa at 12 h had a higher risk of day 28 mortality (hazard ratio=3.18; P =0.0049). Among the 59 patients in the cardiac group with mean arterial pressure (MAP) ≥65 mm Hg, central venous pressure (CVP) ≥8 mm Hg and central venous oxygen saturation (ScvO 2 ) ≥70% at 12 h, those with a high cv-art CO 2 gap (>0.9 kPa; n =19) had a higher day 28 mortality (37% vs. 13%; P =0.042). In the non-cardiac group, a high cv-art CO 2 gap was not linked to a higher risk of day 28 death, whatever the threshold value of the cv-art CO 2 gap. CONCLUSION: Patients with septic shock and with AF and/or low LVEF were more prone to a persistent high cv-art CO 2 gap, even when initial resuscitation succeeded in normalizing MAP, CVP, and ScvO 2 . In these patients, a persistent high cv-art CO 2 gap at 12 h was significantly associated with higher day 28 mortality.

Change in end-tidal carbon dioxide outperforms other surrogates for change in cardiac output during fluid challenge.

Background: During fluid challenge, volume expansion (VE)-induced increase in cardiac output (Δ VE CO) is seldom measured. Methods: In patients with shock undergoing strictly controlled mechanical ventilation and receiving VE, we assessed minimally invasive surrogates for Δ VE CO (by transthoracic echocardiography): fluid-induced increases in end-tidal carbon dioxide (Δ VE E'CO2 ); pulse (Δ VE PP), systolic (Δ VE SBP), and mean systemic blood pressure (Δ VE MBP); and femoral artery Doppler flow (Δ VE FemFlow). In the absence of arrhythmia, fluid-induced decrease in heart rate (Δ VE HR) and in pulse pressure respiratory variation (Δ VE PPV) were also evaluated. Areas under the receiver operating characteristic curves (AUC ROC s) reflect the ability to identify a response to VE (Δ VE CO ≥15%). Results: In 86 patients, Δ VE E'CO2 had an AUC ROC =0.82 [interquartile range 0.73-0.90], significantly higher than the AUC ROC for Δ VE PP, Δ VE SBP, Δ VE MBP, and Δ VE FemFlow (AUC ROC =0.61-0.65, all P <0.05). A value of Δ VE E'CO2 >1 mm Hg (>0.13 kPa) had good positive (5.0 [2.6-9.8]) and fair negative (0.29 [0.2-0.5]) likelihood ratios. The 16 patients with arrhythmia had similar relationships between Δ VE E'CO2 and Δ VE CO to patients with regular rhythm ( r 2 =0.23 in both subgroups). In 60 patients with no arrhythmia, Δ VE E'CO2 (AUC ROC =0.84 [0.72-0.92]) outperformed Δ VE HR (AUC ROC =0.52 [0.39-0.66], P <0.05) and tended to outperform Δ VE PPV (AUC ROC =0.73 [0.60-0.84], P =0.21). In the 45 patients with no arrhythmia and receiving ventilation with tidal volume <8 ml kg -1 , Δ VE E'CO2 performed better than Δ VE PPV, with AUC ROC =0.86 [0.72-0.95] vs 0.66 [0.49-0.80], P =0.02. Conclusions: Δ VE E'CO2 outperformed Δ VE PP, Δ VE SBP, Δ VE MBP, Δ VE FemFlow, and Δ VE HR and, during protective ventilation, arrhythmia, or both, it also outperformed Δ VE PPV. A value of Δ VE E'CO2 >1 mm Hg (>0.13 kPa) indicated a likely response to VE.

Predicting arterial blood gas and lactate from central venous blood analysis in critically ill patients: a multicentre, prospective, diagnostic accuracy study.

BACKGROUND: The estimation of arterial blood gas and lactate from central venous blood analysis and pulse oximetry [Formula: see text] readings has not yet been extensively validated. METHODS: In this multicentre, prospective study performed in 590 patients with acute circulatory failure, we measured blood gases and lactate in simultaneous central venous and arterial blood samples at 6 h intervals during the first 24 h after insertion of central venous and arterial catheters. The study population was randomly divided in a 2:1 ratio into model derivation and validation sets. We derived predictive models of arterial pH, carbon dioxide partial pressure, oxygen saturation, and lactate, using clinical characteristics, [Formula: see text], and central venous blood gas values as predictors, and then tested their performance in the validation set. RESULTS: In the validation set, the agreement intervals between predicted and actual values were -0.078/+0.084 units for arterial pH, -1.32/+1.36 kPa for arterial carbon dioxide partial pressure, -5.15/+4.47% for arterial oxygen saturation, and -1.07/+1.05 mmol litre(-1) for arterial lactate (i.e. around two times our predefined clinically tolerable intervals for all variables). This led to ∼5% (or less) of extreme-to-extreme misclassifications, thus giving our predictive models only marginal agreement. Thresholds of predicted variables (as determined from the derivation set) showed high predictive values (consistently >94%), to exclude abnormal arterial values in the validation set. CONCLUSIONS: Using clinical characteristics, [Formula: see text], and central venous blood analysis, we predicted arterial blood gas and lactate values with marginal accuracy in patients with circulatory failure. Further studies are required to establish whether the developed models can be used with acceptable safety.

Pharmacokinetics of high-dose nebulized amikacin in ventilated critically ill patients.

BACKGROUND: Antibiotic nebulization theoretically allows the delivery of high doses to the lungs together with limited systemic exposure and toxicity. This study aimed to describe amikacin pharmacokinetics, and especially its absorption, in patients treated with high-dose nebulized amikacin. PATIENTS AND METHODS: Twenty critically ill patients experiencing ventilator-associated pneumonia received a 20 mg/kg infusion of amikacin, followed by either three other infusions or three nebulizations of 60 mg/kg amikacin. An extensive sampling regimen allowed measurement of amikacin serum concentrations at 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 24 h after each administration. Amikacin pharmacokinetics was studied by population compartmental modelling. RESULTS: Amikacin pharmacokinetics was best described using a two-compartment structural model with first-order distribution and elimination, in which lung absorption was described using a transit model. Estimated means (interindividual variability) of the main parameters were: bioavailability F = 2.65% (22.1%); transit compartments n = 1.58 (fixed); transit constant ktr = 1.38 h-1 (33.4%); central volume Vc = 10.2 L (10.5%); and elimination constant k10 = 0.488 h-1 (35.8%). The addition of interoccasion variability on F (44.0%) and k10 (41.7%) allowed the description of intraindividual variability of bioavailability and elimination. Amikacin clearance was positively correlated with baseline creatinine clearance. CONCLUSIONS: Our pharmacokinetic model provided an accurate description of amikacin concentrations following nebulization. There was wide interindividual and interoccasion variability in the absorption and elimination of amikacin. Nevertheless, systemic exposure after nebulization was always much lower than after infusion, an observation suggesting that nebulized high doses are safe in this regard and may be used to treat ventilator-associated pneumonia.

Blood pressure monitoring during arrhythmia: agreement between automated brachial cuff and intra-arterial measurements.

BACKGROUND: Since arrhythmia induces irregular pulse waves, it is widely considered to cause flawed oscillometric brachial cuff measurements of blood pressure (BP). However, strong data are lacking. We assessed whether the agreement of oscillometric measurements with intra-arterial measurements is worse during arrhythmia than during regular rhythm. METHODS: Among patients of three intensive care units (ICUs), a prospective comparison of three pairs of intra-arterial and oscillometric BP readings was performed among patients with arrhythmia and an arterial line already present. After each inclusion in the arrhythmia group, one patient with regular rhythm was included as a control. International Organization for Standardization (ISO) standard validation required a mean bias <5 (sd 8) mm Hg. RESULTS: In 135 patients with arrhythmia, the agreement between oscillometric and intra-arterial measurements of systolic, diastolic and mean BP was similar to that observed in 136 patients with regular rhythm: for mean BP, similar mean bias [-0.1 (sd 5.2) and 1.9 (sd 5.9) mm Hg]. In both groups, the ISO standard was satisfied for mean and diastolic BP, but not for systolic BP (sd >10 mm Hg) in our ICU population. The ability of oscillometry to detect hypotension (systolic BP <90 mm Hg or mean BP <65 mm Hg), response to therapy (>10% increase in mean BP after cardiovascular intervention) and hypertension (systolic BP >140 mm Hg) was good and similar during arrhythmia and regular rhythm (respective areas under the receiver operating characteristic curves ranging from 0.89 to 0.96, arrhythmia vs regular rhythm between-group comparisons all associated with P>0.3). CONCLUSIONS: Contrary to widespread belief, arrhythmia did not cause flawed automated brachial cuff measurements.

An evaluation of a new single-use flexible bronchoscope with a large suction channel: reliability of bronchoalveolar lavage in ventilated piglets and initial clinical experience.

A single-use flexible bronchoscope with a large suction channel has become available recently and we have evaluated this innovative device. Firstly, bronchoalveolar lavage was performed and quantified in ventilated piglets. Next, the bronchoscope was evaluated in three intensive care units and a satisfaction questionnaire was carried out. Sixteen bronchoalveolar lavages were performed in piglets with a recovery rate of 83 (79-86 [72-89])% of the instilled volume. Quality and performance of all devices tested was identical. The medical satisfaction questionnaire was as follows: 'acceptable' to 'very good' for quality of aspiration, manoeuvrability and quality of vision; 'very good' to 'perfect' for setting up and insertion. This encouraging preliminary evaluation demonstrates the effectiveness of this new single-use device, which may obviate the need for disinfection procedures and, thereby, eradicate a potential vector of patient cross-contamination.

Brachial cuff measurements of blood pressure during passive leg raising for fluid responsiveness prediction.

OBJECTIVE: The passive leg raising maneuver (PLR) for fluid responsiveness testing relies on cardiac output (CO) measurements or invasive measurements of arterial pressure (AP) whereas the initial hemodynamic management during shock is often based solely on brachial cuff measurements. We assessed PLR-induced changes in noninvasive oscillometric readings to predict fluid responsiveness. STUDY DESIGN: Multicentre interventional study. PATIENTS AND METHODS: In ICU sedated patients with circulatory failure, AP (invasive and noninvasive readings) and CO measurements were performed before, during PLR (trunk supine, not modified) and after 500-mL volume expansion. Areas under the ROC curves (AUC) were determined for fluid responsiveness (>10% volume expansion-induced increase in CO) prediction. RESULTS: In 112 patients (19% with arrhythmia), changes in noninvasive systolic AP during PLR (noninvasiveΔ(PLR)SAP) only predicted fluid responsiveness (cutoff 17%, n=21, positive likelihood ratio [LR] of 26 [18-38]), not unresponsiveness. If PLR-induced change in central venous pressure (CVP) was at least of 2 mm Hg (n=60), suggesting that PLR succeeded in altering cardiac preload, noninvasiveΔ(PLR)SAP performance was good: AUC of 0.94 [0.85-0.98], positive and negative LRs of 5.7 [4.6-6.8] and 0.07 [0.009-0.5], respectively, for a cutoff of 9%. Of note, invasive AP-derived indices did not outperform noninvasiveΔ(PLR)SAP. CONCLUSION: Regardless of CVP (i.e., during "blind PLR"), noninvasiveΔ(PLR)SAP more than 17% reliably identified fluid responders. During "CVP-guided PLR", in case of sufficient change in CVP, noninvasiveΔ(PLR)SAP performed better (cutoff of 9%). These findings, in sedated patients who had already undergone volume expansion and/or catecholamines, have to be verified during the early phase of circulatory failure (before an arterial line and/or a CO measuring device is placed).

Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study.

PURPOSE: To determine whether procalcitonin (PCT) levels could help discriminate isolated viral from mixed (bacterial and viral) pneumonia in patients admitted to the intensive care unit (ICU) during the A/H1N1v2009 influenza pandemic. METHODS: A retrospective observational study was performed in 23 French ICUs during the 2009 H1N1 pandemic. Levels of PCT at admission were compared between patients with confirmed influenzae A pneumonia associated or not associated with a bacterial co-infection. RESULTS: Of 103 patients with confirmed A/H1N1 infection and not having received prior antibiotics, 48 (46.6%; 95% CI 37-56%) had a documented bacterial co-infection, mostly caused by Streptococcus pneumoniae (54%) or Staphylococcus aureus (31%). Fifty-two patients had PCT measured on admission, including 19 (37%) having bacterial co-infection. Median (range 25-75%) values of PCT were significantly higher in patients with bacterial co-infection: 29.5 (3.9-45.3) versus 0.5 (0.12-2) µg/l (P < 0.01). For a cut-off of 0.8 µg/l or more, the sensitivity and specificity of PCT for distinguishing isolated viral from mixed pneumonia were 91 and 68%, respectively. Alveolar condensation combined with a PCT level of 0.8 µg/l or more was strongly associated with bacterial co-infection (OR 12.9, 95% CI 3.2-51.5; P < 0.001). CONCLUSIONS: PCT may help discriminate viral from mixed pneumonia during the influenza season. Levels of PCT less than 0.8 µg/l combined with clinical judgment suggest that bacterial infection is unlikely.

Mortality rate attributable to ventilator-associated nosocomial pneumonia in an adult intensive care unit: a prospective case-control study.

OBJECTIVE: To evaluate the mortality rate attributable to nosocomial ventilator-associated pneumonia in an intensive care unit. DESIGN: Prospective, matched, risk-adjusted cohort study. SETTING: A 18-bed adult medical-surgical intensive care unit in a 1,100-bed regional and teaching hospital in France. PATIENTS: From January 1, 1996, to April 30, 1999, 135 patients who developed nosocomial pneumonia were matched with 135 control patients without nosocomial pneumonia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nosocomial pneumonia was identified on the basis of results of distal bronchial samples. The matching process was conducted according to the following primary criteria: cause of admission, indication for ventilatory support, immunologic status, cardiac status, probability of death (+/-5%), Glasgow Coma Scale score (+/-2 points), age (+/-7 yrs), and duration of exposure to risk. When possible, case and control patients were matched according to five secondary criteria: respiratory and alcoholism status before admission, diagnosis categories, surgical procedure or not, and gender. The mortality rates were compared between case and control patients by using the Kaplan-Meier estimate and the log-rank test. The influence of nosocomial pneumonia on mortality rate then was tested by adjusting for the secondary criteria and other possible confounding factors by using the Cox proportional-hazards model. The matching process was successful for 1,080 of 1,080 primary criteria. The crude intensive care unit mortality rate was higher in patients with nosocomial pneumonia than in control patients (41 vs. 14%; p <.0001). In actuarial survival analysis, the probability of intensive care unit death was higher in the case patients (odds ratio = 2.7, 95% confidence interval = 1.8-3.1, p =.028). After adjustment, the occurrence of nosocomial pneumonia remained an independent risk factor of death (odds ratio = 2.1, 95% confidence interval = 1.2-3.6, p =.008). Nosocomial pneumonia attributable to multiresistant microorganisms was significantly associated with death (odds ratio = 2.6, 95% confidence interval = 1.1-5.8, p =.02). The length of intensive care unit stay was higher in case than in control patients (31 +/- 19 vs. 26 +/- 17 days, p <.0001). CONCLUSIONS: Nosocomial pneumonia is independently associated with death in the intensive care unit. In addition, it increases the length of intensive care unit stay.

Estimating cardiac filling pressure in mechanically ventilated patients with hyperinflation.

OBJECTIVE: When positive end-expiratory pressure (PEEP) is applied, the intracavitary left ventricular end-diastolic pressure (LVEDP) exceeds the LV filling pressure because pericardial pressure exceeds 0 at end-expiration. Under those conditions, the LV filling pressure is itself better reflected by the transmural LVEDP (tLVEDP) (LVEDP minus pericardial pressure). By extension, end-expiratory pulmonary artery occlusion pressure (eePAOP), as an estimate of end-expiratory LVEDP, overestimates LV filling pressure when pericardial pressure is >0, because it occurs when PEEP is present. We hypothesized that LV filling pressure could be measured from eePAOP by also knowing the proportional transmission of alveolar pressure to pulmonary vessels calculated as index of transmission = (end-inspiratory PAOP--eePAOP)/(plateau pressure--total PEEP). We calculated transmural pulmonary artery occlusion pressure (tPAOP) with this equation: tPAOP = eePAOP--(index of transmission x total PEEP). We compared tPAOP with airway disconnection nadir PAOP measured during rapid airway disconnection in subjects undergoing PEEP with and without evidence of dynamic pulmonary hyperinflation. DESIGN: Prospective study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: We studied 107 patients mechanically ventilated with PEEP for acute respiratory failure. Patients without dynamic pulmonary hyperinflation (group A; n = 58) were analyzed separately from patients with dynamic pulmonary hyperinflation (group B; n = 49). INTERVENTION: Transient airway disconnection. MEASUREMENTS AND MAIN RESULTS: In group A, tPAOP (8.5+/-6.0 mm Hg) and nadir PAOP (8.6+/-6.0 mm Hg) did not differ from each other but were lower than eePAOP (12.4+/-5.6 mm Hg; p < .05). The agreement between tPAOP and nadir PAOP was good (bias, 0.15 mm Hg; limits of agreement, -1.5-1.8 mm Hg). In group B, tPAOP (9.7+/-5.4 mm Hg) was lower than both nadir PAOP and eePAOP (12.1+/-5.4 and 13.9+/-5.2 mm Hg, respectively; p < .05 for both comparisons). The agreement between tPAOP and nadir PAOP was poor (bias, 2.3 mm Hg; limits of agreement, -0.2-4.8 mm Hg). CONCLUSIONS: Indexing the transmission of proportional alveolar pressure to PAOP in the estimation of LV filling pressure is equivalent to the nadir method in patients without dynamic pulmonary hyperinflation and may be more reliable than the nadir PAOP method in patients with dynamic pulmonary hyperinflation.

Unplanned extubations in the adult intensive care unit: a prospective multicenter study. Association des Réanimateurs du Centre-Ouest.

The predisposing factors and complications of unplanned extubation (UEX) in mechanically ventilated adult patients are not well recognized. We designed a prospective multicenter observational study to identify risk factors and describe the complications of UEX. We followed 426 ventilated patients over a 2-mo period. Clinical characteristics such as diagnosis on admission and reasons for ventilation were used to classify the patients. The presence or absence of potential risk factors was daily noted, including the types of ventilators, tracheal tubes, tube fixations, ventilatory support modes, route for intubation, and the use of intravenous sedation. Circumstances and complications of UEX were prospectively recorded. Forty-six (10.8%) patients experienced at least one episode of UEX. Ten UEX occurred during nursing procedures. At the moment of UEX, 61% of patients were agitated. The rates of mortality, laryngeal complications, nosocomial pneumonia after extubation, and the length of mechanical ventilation were similar in UEX and non-UEX patients. Patients were more often reintubated after UEX (28 of 46) than after planned extubation (28 of 284). All the non-reintubated UEX patients survived. One death occurred as a direct consequence of UEX. By use of multivariate analysis, we identified four factors contributing to UEX: chronic respiratory failure, endotracheal tube fixation with only thin adhesive tape, orotracheal intubation, and the lack of intravenous sedation. Considering these factors, we hypothesized that simple measures should be adopted to minimize the incidence of UEX and its related complications: more vigilance during procedures at patients' bedsides, adequate sedation of agitated patients, strong fixation of the tracheal tube, particular attention paid to orally intubated patients, and daily reassessment of the possibility of weaning from the ventilator.

Efficacy of epinephrine therapy in shock complicating pulmonary embolism.

A case of shock and pulmonary embolism in a 57-year-old woman is described in which hemodynamics were unresponsive both to usual therapy (volume loading, dobutamine, thrombolysis) and then to norepinephrine. Epinephrine proved to be effective, above all by strong beta 1-inotropic effect.