Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: the CRYSTMAS study.

INTRODUCTION: Inadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients. METHODS: In order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a prospective, multicenter, active-controlled, double-blind, randomized study in intensive care units. RESULTS: 174 out of 196 patients reached HDS (88 and 86 patients for HES and NaCl, respectively). Significantly less HES was used to reach HDS vs. NaCl (1,379 ± 886 ml in the HES group and 1,709 ± 1,164 ml in the NaCl group (mean difference = -331 ± 1,033, 95% CI -640 to -21, P = 0.0185). Time to reach HDS was 11.8 10.1 hours vs. 14.3 ± 11.1 hours for HES and NaCl, respectively. Total quantity of study drug infused over four consecutive days, ICU and hospital LOS, and area under the curve of SOFA score were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients for HES and NaCl, respectively (P = 0.454). There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality, coagulation, or pruritus up to 90 days after treatment initiation. CONCLUSION: Significantly less volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups. CLINICALTRIALSGOV: NCT00464204.

"You helped me keep my head above water"-experience of bereavement research after loss of a loved one in the ICU: insights from the ARREVE study.

PURPOSE: Bereavement research has helped to improve end-of-life practices in the ICU. However, few studies have explored bereaved relatives experience of research participation in this context. We aimed to explore the experience of bereaved relatives' participation in the ARREVE study which included three telephone follow-up calls to complete several quantitative tools. METHODS: Volunteer relatives who participated in the 12-month follow-up call completed a questionnaire about research participation that included ten open-ended questions so that respondents could use their own words and thoughts. These open-ended questions were analyzed using qualitative analysis that examines themes within the data. RESULTS: 175/311 relatives completed the questionnaire. Three themes were derived from the thematic analysis: (1) struggling: reactivation of emotional distress associated with the ICU experience and the loss is frequent, specifically during the 1st follow-up call. (2) Resilience: as time goes by, research participation becomes increasingly positive. The calls are a help both in giving meaning to the relatives' experience and in accepting the loss. (3) Recognition: research calls can compensate for the absence of support during bereavement. CONCLUSION: Although some emotional difficulties must be acknowledged, bereavement research is overall associated with benefits, by facilitating emotional adjustments, meaning-making and resilience. Lack of support and social isolation during bereavement are frequent experiences, revealing that support strategies for bereaved relatives should be developed after the loss of a loved one in the ICU.

Continuous positive airway pressure vs. proportional assist ventilation for noninvasive ventilation in acute cardiogenic pulmonary edema.

OBJECTIVE: To compare continuous positive airway pressure (CPAP) and proportional assist ventilation (PAV) as modes of noninvasive ventilatory support in patients with severe cardiogenic pulmonary edema. DESIGN AND SETTING: A prospective multicenter randomized study in the medical ICUs of three teaching hospitals. PATIENTS: Thirty-six adult patients with cardiogenic pulmonary edema (CPA) with unresolving dyspnea, respiratory rate above 30/min and/or SpO2 above 90% with O2 higher than 10 l/min despite conventional therapy with furosemide and nitrates. INTERVENTIONS: Patients were randomized to undergo either CPAP (with PEEP 10 cmH2O) or PAV (with PEEP 5-6 cmH2O) noninvasive ventilation through a full face mask and the same ventilator. MEASUREMENTS AND RESULTS: The main outcome measure was the failure rate as defined by the onset of predefined intubation criteria, severe arrythmias or patient's refusal. On inclusion CPAP (n=19) and PAV (n=17) groups were similar with regard to age, sex ratio, type of heart disease, SAPS II, physiological parameters (mean arterial pressure, heart rate, blood gases), amount of infused nitrates and furosemide. Failure was observed in 7 (37%) CPAP and 7 (41%) PAV patients. Among these, 4 (21%) CPAP and 5 (29%) PAV patients required endotracheal intubation. Changes in physiological parameters were similar in the two groups. Myocardial infarction and ICU mortality rates were strictly similar in the two groups. CONCLUSIONS: In the present study PAV was not superior to CPAP for noninvasive ventilation in severe cardiogenic pulmonary edema with regard to either efficacy and tolerance.

Plethysmographic dynamic indices predict fluid responsiveness in septic ventilated patients.

OBJECTIVES: In septic patients, reliable non-invasive predictors of fluid responsiveness are needed. We hypothesised that the respiratory changes in the amplitude of the plethysmographic pulse wave (DeltaP(PLET)) would allow the prediction of changes in cardiac index following volume administration in mechanically ventilated septic patients. DESIGN: Prospective clinical investigation. SETTING: An 11-bed hospital medical intensive care unit. PATIENTS: Twenty-three deeply sedated septic patients mechanically ventilated with tidal volume >or=8 ml/kg and equipped with an arterial catheter and a pulse oximetry plethysmographic sensor. INTERVENTIONS: Respiratory changes in pulse pressure (DeltaPP), DeltaP(PLET) and cardiac index (transthoracic Doppler echocardiography) were determined before and after volume infusion of colloids (8 ml/kg). MEASUREMENTS AND MAIN RESULTS: Twenty-eight volume challenges were performed in 23 patients. Before volume expansion, DeltaPP correlated with DeltaP(PLET) (r2 = 0.71, p<0.001). Changes in cardiac index after volume expansion significantly (p<0.001) correlated with baseline DeltaPP (r2 = 0.76) and DeltaP(PLET) (r2 = 0.50). The patients were defined as responders to fluid challenge when cardiac index increased by at least 15% after the fluid challenge. Such an event occurred 18 times. Before volume challenge, a DeltaPP value of 12% and a DeltaP(PLET) value of 14% allowed discrimination between responders and non-responders with sensitivity of 100% and 94% respectively and specificity of 70% and 80% respectively. Comparison of areas under the receiver operator characteristic curves showed that DeltaPP and DeltaP(PLET) predicted similarly fluid responsiveness. CONCLUSION: The present study found DeltaP(PLET) to be as accurate as DeltaPP for predicting fluid responsiveness in mechanically ventilated septic patients.

Correction to: Terminal weaning or immediate extubation for withdrawing mechanical ventilation in critically ill patients (the ARREVE observational study).

Correction to: Intensive Care Med (2017) DOI 10.1007/s00134-017-4891-0.

Terminal weaning or immediate extubation for withdrawing mechanical ventilation in critically ill patients (the ARREVE observational study).

PURPOSE: The relative merits of immediate extubation versus terminal weaning for mechanical ventilation withdrawal are controversial, particularly regarding the experience of patients and relatives. METHODS: This prospective observational multicentre study (ARREVE) was done in 43 French ICUs to compare terminal weaning and immediate extubation, as chosen by the ICU team. Terminal weaning was a gradual decrease in the amount of ventilatory assistance and immediate extubation was extubation without any previous decrease in ventilatory assistance. The primary outcome was posttraumatic stress symptoms (Impact of Event Scale Revised, IES-R) in relatives 3 months after the death. Secondary outcomes were complicated grief, anxiety, and depression symptoms in relatives; comfort of patients during the dying process; and job strain in staff. RESULTS: We enrolled 212 (85.5%) relatives of 248 patients with terminal weaning and 190 relatives (90.5%) of 210 patients with immediate extubation. Immediate extubation was associated with airway obstruction and a higher mean Behavioural Pain Scale score compared to terminal weaning. In relatives, IES-R scores after 3 months were not significantly different between groups (31.9 ± 18.1 versus 30.5 ± 16.2, respectively; adjusted difference, -1.9; 95% confidence interval, -5.9 to 2.1; p = 0.36); neither were there any differences in complicated grief, anxiety, or depression scores. Assistant nurses had lower job strain scores in the immediate extubation group. CONCLUSIONS: Compared to terminal weaning, immediate extubation was not associated with differences in psychological welfare of relatives when each method constituted standard practice in the ICU where it was applied. Patients had more airway obstruction and gasps with immediate extubation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01818895.

ICU physicians' and nurses' perceptions of terminal extubation and terminal weaning: a self-questionnaire study.

PURPOSE: Terminal extubation (TE) and terminal weaning (TW) are the methods available for withdrawing mechanical ventilation. Perceptions of TE and TW by intensive care unit (ICU) staff may influence bedside practices and the feasibility of studies comparing these methods. METHODS: From January to June 2013, 5 nurses and 5 physicians in each of 46 (out of 70, 65.7 %) French ICUs completed an anonymous self-questionnaire. Clusters of staff members defined by perceptions of TE and TW were identified by exploratory analysis. Denominators for computing percentages were total numbers of responses to each item; cases with missing data were excluded for the relevant item. RESULTS: Of the 451 (98 %) participants (225 nurses and 226 physicians), 37 (8.4 %) had never or almost never performed TW and 138 (31.3 %) had never or almost never performed TE. A moral difference between TW and TE was perceived by 205 (45.8 %) participants. The exploratory analysis identified three clusters defined by personal beliefs about TW and TE: 21.2 % of participants preferred TW, 18.1 % preferred TE, and 60.7 % had no preference. A preference for TW seemed chiefly related to unfavorable perceptions or insufficient knowledge of TE. Staff members who preferred TE and those with no preference perceived TE as providing a more natural dying process with less ambiguity. CONCLUSION: Nearly two-fifths of ICU nurses and physicians in participating ICUs preferred TW or TE. This finding suggests both a need for shared decision-making and training before performing TE or TW and a high risk of poor compliance with randomly allocated TW or TE.

Pulse Wave Transit Time Measurements of Cardiac Output in Septic Shock Patients: A Comparison of the Estimated Continuous Cardiac Output System with Transthoracic Echocardiography.

BACKGROUND: We determined reliability of cardiac output (CO) measured by pulse wave transit time cardiac output system (esCCO system; COesCCO) vs transthoracic echocardiography (COTTE) in mechanically ventilated patients in the early phase of septic shock. A secondary objective was to assess ability of esCCO to detect change in CO after fluid infusion. METHODS: Mechanically ventilated patients admitted to the ICU, aged >18 years, in sinus rhythm, in the early phase of septic shock were prospectively included. We performed fluid infusion of 500 ml of crystalloid solution over 20 minutes and recorded CO by EsCCO and TTE immediately before (T0) and 5 minutes after (T1) fluid administration. Patients were divided into 2 groups (responders and non-responders) according to a threshold of 15% increase in COTTE in response to volume expansion. RESULTS: In total, 25 patients were included, average 64±15 years, 15 (60%) were men. Average SAPSII and SOFA scores were 55±21.3 and 13±2, respectively. ICU mortality was 36%. Mean cardiac output at T0 was 5.8±1.35 L/min by esCCO and 5.27±1.17 L/min by COTTE. At T1, respective values were 6.63 ± 1.57 L/min for esCCO and 6.10±1.29 L/min for COTTE. Overall, 12 patients were classified as responders, 13 as non-responders by the reference method. A threshold of 11% increase in COesCCO was found to discriminate responders from non-responders with a sensitivity of 83% (95% CI, 0.52-0.98) and a specificity of 77% (95% CI, 0.46-0.95). CONCLUSION: We show strong correlation esCCO and echocardiography for measuring CO, and change in CO after fluid infusion in ICU patients.

The respiratory variation in inferior vena cava diameter as a guide to fluid therapy.

OBJECTIVE: To investigate whether the respiratory variation in inferior vena cava diameter (DeltaD(IVC)) could be related to fluid responsiveness in mechanically ventilated patients. DESIGN: Prospective clinical study. SETTING: Medical ICU of a non-university hospital. PATIENTS: Mechanically ventilated patients with septic shock (n=39). INTERVENTIONS: Volume loading with 8 mL/kg of 6% hydroxyethylstarch over 20 min. MEASUREMENTS AND RESULTS: Cardiac output and DeltaD(IVC) were assessed by echography before and immediately after the standardized volume load. Volume loading induced an increase in cardiac output from 5.7+/-2.0 to 6.4+/-1.9 L/min (P<0.001) and a decrease in DeltaD(IVC) from 13.8+/-13.6 vs 5.2+/-5.8% (P<0.001). Sixteen patients responded to volume loading by an increase in cardiac output > or =15% (responders). Before volume loading, the DeltaD(IVC) was greater in responders than in non-responders (25+/-15 vs 6+/-4%, P<0.001), closely correlated with the increase in cardiac output (r=0.82, P<0.001), and a 12% DeltaD(IVC) cut-off value allowed identification of responders with positive and negative predictive values of 93% and 92%, respectively. CONCLUSION: Analysis of DeltaD(IVC) is a simple and non-invasive method to detect fluid responsiveness in mechanically ventilated patients with septic shock.

Plethysmographic variation index predicts fluid responsiveness in ventilated patients in the early phase of septic shock in the emergency department: a pilot study.

PURPOSE: Feasibility study examining whether plethysmographic variability index (PVI) can predict fluid responsiveness in mechanically ventilated patients in the early phase of septic shock in the emergency department. MATERIALS AND METHODS: Monocentric, prospective, observational study that included 31 mechanically ventilated and sedated patients with septic shock in whom volume expansion was planned. The patients were equipped with a pulse oximeter that automatically calculated and displayed PVI. The intervention consisted in infusing 8 mL/kg of hydroxylethyl starch over a 20-minute period. Before and after intervention, we recorded PVI and measured the aortic velocity-time integral (VTIao) using transthoracic echocardiography. Responders were defined as patients who increased their VTIao by 15% or higher after fluid infusion. RESULTS: Sixteen patients were classified as responders, and 15 as nonresponders. Mean PVI values before intervention were significantly higher in responders vs nonresponders (30%±9% vs 8%±5%, P<.001). Plethysmographic variability index values before intervention were correlated with percent changes in VTIao induced by intervention (R2=0.67; P<.001). A PVI threshold value of 19% discriminates responders from nonresponders with a sensitivity of 94% and a specificity of 87% (area under the curve, 0.97; P<.001). CONCLUSION: Our study suggests that PVI is a feasible and interesting method to predict fluid responsiveness in early phase septic shock patients in the emergency department.

Procalcitonin levels to guide antibiotic therapy in adults with non-microbiologically proven apparent severe sepsis: a randomised controlled trial.

OBJECTIVE: Some patients with the phenotype of severe sepsis may have no overt source of infection or identified pathogen. We investigated whether a procalcitonin-based algorithm influenced antibiotic use in patients with non-microbiologically proven apparent severe sepsis. DESIGN: This multicentre, randomised, controlled, single-blind trial was performed in two parallel groups. SETTING: Eight intensive care units in France. PARTICIPANTS: Adults with the phenotype of severe sepsis and no overt source of infection, negative microbial cultures from multiple matrices and no antibiotic exposure shortly before intensive care unit admission. INTERVENTION: The initiation and duration of antibiotic therapy was based on procalcitonin levels in the experimental arm and on the intensive care unit physicians' clinical judgement without reference to procalcitonin values in the control arm. MAIN OUTCOME MEASURE: The primary outcome was the proportion of patients on antibiotics on day 5 postrandomisation. RESULTS: Over a 3-year period, 62/1250 screened patients were eligible for the study, of whom 31 were randomised to each arm; 4 later withdrew their consent. At day 5, 18/27 (67%) survivors were on antibiotics in the experimental arm, versus 21/26 (81%) controls (p=0.24; relative risk=0.83, 95% CI: 0.60 to 1.14). Only 8/58 patients (13%) had baseline procalcitonin <0.25 µg/l; in these patients, physician complied poorly with the algorithm. CONCLUSIONS: In intensive care unit patients with the phenotype of severe sepsis or septic shock and without an overt source of infection or a known pathogen, the current study was unable to confirm that a procalcitonin-based algorithm may influence antibiotic exposure. However, the premature termination of the trial may not allow definitive conclusions.

Clinical relevance of echocardiography in acute severe dyspnea.

BACKGROUND: The aim of this study was to assess the most relevant echocardiographic parameter for the clinical diagnosis of acute dyspnea due to left-heart dysfunction. METHODS: Transthoracic echocardiography was performed in 88 patients in sinus rhythm admitted for respiratory distress. Two experts determined the cause of dyspnea as cardiogenic (26 patients) or noncardiogenic (62 patients). RESULTS: The feasibility was 100% for the E/A ratio and the E/E deceleration time (EDT) ratio but 97%, 89%, and 85% for the E/Ea ratio, left ventricular ejection fraction (LVEF), and the E/propagation velocity (Vp) ratio, respectively. The area under the receiver operating characteristic curve for E/EDT (0.947 +/- 0.035) was statistically significantly greater than that for E/A (0.753 +/- 0.068) (P = .004). The areas under the curves for all other parameters were not statistically significantly different. In the subpopulation of patients with LVEFs > 45%, the area under the curve for LVEF was significantly smaller than those for E/Ea, E/EDT, and E/Vp. CONCLUSION: E/EDT, E/Ea, and E/Vp appear equally useful to distinguish acute dyspnea due to left-heart dysfunction from that of pulmonary origin. However, E/EDT and E/Ea can be considered the best indices with regard to feasibility.

Pre-ejection period variations predict the fluid responsiveness of septic ventilated patients.

OBJECTIVES: In septic patients with acute circulatory failure, reliable predictors of fluid responsiveness are needed at the bedside. We hypothesized that the respiratory change in pre-ejection period (DeltaPEP) would allow the prediction of changes in cardiac index following volume administration in mechanically ventilated septic patients. DESIGN: Prospective clinical investigation. SETTING: A ten-bed hospital intensive care unit. PATIENTS: Patients admitted after septic shock equipped with an arterial catheter. INTERVENTIONS: Pre-ejection period (PEP)--defined as the time interval between the beginning of the R wave on the electrocardiogram and the upstroke of the radial arterial pressure curve (PEPKT) or the pulse plethysmographic waveforms (PEPPLET)--and cardiac index (transthoracic echocardiography-Doppler) were determined before and after volume infusion of colloid (8 mL x kg). DeltaPEP (%) was defined as the difference between expiratory and inspiratory PEP divided by the mean of expiratory and inspiratory values. Respiratory changes in pulse pressure (DeltaPP) was also measured. MEASUREMENTS AND MAIN RESULTS: : Twenty-two volume challenges were done in 20 deeply sedated patients. DeltaPEPKT, DeltaPEPPLET, and DeltaPP (measured in all patients) before volume expansion were correlated with cardiac index change after fluid challenge (r = .73, r = .67, and r = .70, respectively, p < .0001). Patients with a cardiac index increase induced by volume expansion > or = 15% and <15% were classified as responders and nonresponders, respectively. Receiver operating characteristic curves showed that the threshold DeltaPP value of 17% allowed discrimination between responder/nonresponder patients with a sensitivity of 85% and a specificity of 100%. For both DeltaPEPKT and DeltaPEPPLET, the best threshold value was 4% with a sensitivity-specificity of 92%-89% and 100%-67%, respectively. CONCLUSIONS: The present study found DeltaPEPKT and DeltaPEPPLET to be as accurate as DeltaPP in the prediction of fluid responsiveness in mechanically ventilated septic patients.

Half the family members of intensive care unit patients do not want to share in the decision-making process: a study in 78 French intensive care units.

OBJECTIVE: To evaluate the opinions of intensive care unit staff and family members about family participation in decisions about patients in intensive care units in France, a country where the approach of physicians to patients and families has been described as paternalistic. DESIGN: Prospective multiple-center survey of intensive care unit staff and family members. SETTING: Seventy-eight intensive care units in university-affiliated hospitals in France. PATIENTS: We studied 357 consecutive patients hospitalized in the 78 intensive care units and included in the study starting on May 1, 2001, with five patients included per intensive care unit. INTERVENTIONS: We recorded opinions and experience about family participation in medical decision making. Comprehension, satisfaction, and Hospital Anxiety and Depression Scale scores were determined in family members. MEASUREMENTS AND MAIN RESULTS: Poor comprehension was noted in 35% of family members. Satisfaction was good but anxiety was noted in 73% and depression in 35% of family members. Among intensive care unit staff members, 91% of physicians and 83% of nonphysicians believed that participation in decision making should be offered to families; however, only 39% had actually involved family members in decisions. A desire to share in decision making was expressed by only 47% of family members. Only 15% of family members actually shared in decision making. Effectiveness of information influenced this desire. CONCLUSION: Intensive care unit staff should seek to determine how much autonomy families want. Staff members must strive to identify practical and psychological obstacles that may limit their ability to promote autonomy. Finally, they must develop interventions and attitudes capable of empowering families.