Respiratory multiplex PCR and procalcitonin to reduce antibiotic exposure in severe SARS-CoV-2 pneumonia: a multicentre randomized controlled trial.

OBJECTIVES: We aimed at assessing the efficacy and safety on antibiotic exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in adult patients who were critically ill with laboratory-confirmed SARS-CoV-2 pneumonia. METHODS: This multicentre, parallel-group, open-label, randomized controlled trial enrolled patients admitted to 13 intensive care units (ICUs) in France. Patients were assigned (1:1) to the control strategy, in which antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first 7 days of randomization to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was >1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end point was antibiotic-free days at day 28. RESULTS: Between April 20th and November 23rd 2020, 194 patients were randomized, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial co-infection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference, -2.0, (95% CI, -10.6 to 6.6), p=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups. DISCUSSION: In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice.

Small, short-term, point-of-care creatinine changes as predictors of acute kidney injury in critically ill patients.

PURPOSE: To assess short-term creatinine changes as predictors of acute kidney injury (AKI) when used alone and in combination with AKI risk factors. METHODS: In this prospective cohort study, we identified all creatinine measurements from frequent point-of-care arterial blood gas measurements from ICU admission until AKI. We evaluated the predictive value of small changes between these creatinine measurements for AKI development, alone and with AKI risk factors. RESULTS: Of 377 patients with 3235 creatinine measurements, generating 15,075 creatinine change episodes, 215 (57%) patients developed AKI, and 68 (18%) developed stage 2 or 3 AKI. In isolation, a creatinine increase over 4.1-7.3 h had a 0.65 area under the curve for predicting stage 2 or 3 AKI within 3-37.7 h. Combining creatinine increases of ≥1 µmol/L/h (≥0.0113 mg/dL/h) over 4-5.8 h with three AKI risk factors (cardiac surgery, use of vasopressors, chronic liver disease) had 83% sensitivity, 79% specificity and 0.87 area under the curve for stage 2 or 3 AKI occurring 8.7-25.6 h later. CONCLUSION: In combination with key risk factors, frequent point-of-care creatinine assessment on arterial blood gases to detect small, short-term creatinine changes provides a robust, novel, low-cost, and rapid method for predicting AKI in critically ill patients.

Non-invasive quantification of acute macrophagic lung inflammation with [11C](R)-PK11195 using a three-tissue compartment kinetic model in experimental acute respiratory distress syndrome.

PURPOSE: Imaging of acute lung inflammation is pivotal to evaluate innovative ventilation strategies. We aimed to develop and validate a three-tissue compartment kinetic model (3TCM) of [11C](R)-PK11195 lung uptake in experimental acute respiratory distress syndrome (ARDS) to help quantify macrophagic inflammation, while accounting for the impact of its non-specific and irreversible uptake in lung tissues. MATERIAL AND METHODS: We analyzed the data of 38 positron emission tomography (PET) studies performed in 21 swine with or without experimental ARDS, receiving general anesthesia and mechanical ventilation. Model input function was a plasma, metabolite-corrected, image-derived input function measured in the main pulmonary artery. Regional lung analysis consisted in applying both the 3TCM and the two-tissue compartment model (2TCM); in each region, the best model was selected using a selection algorithm with a goodness-of-fit criterion. Regional best model binding potentials (BPND) were compared to lung macrophage presence, semi-quantified in pathology. RESULTS: The 3TCM was preferred in 142 lung regions (62%, 95% confidence interval: 56 to 69%). BPND determined by the 2TCM was significantly higher than the value computed with the 3TCM (overall median with interquartile range: 0.81 [0.44-1.33] vs. 0.60 [0.34-0.94], p < 0.02). Regional macrophage score was significantly associated with the best model BPND (p = 0.03). Regional BPND was significantly increased in the hyperinflated lung compartment, compared to the normally aerated one (median with interquartile range: 0.8 [0.6-1.7] vs. 0.6 [0.3-0.8], p = 0.03). CONCLUSION: To assess the intensity and spatial distribution of acute macrophagic lung inflammation in the context of experimental ARDS with mechanical ventilation, PET quantification of [11C](R)-PK11195 lung uptake was significantly improved in most lung regions using the 3TCM. This new methodology offers the opportunity to non-invasively evaluate innovative ventilatory strategies aiming at controlling acute lung inflammation.

The hemodynamic effects of warm versus room-temperature crystalloid fluid bolus therapy in post-cardiac surgery patients.

INTRODUCTION: The contribution of fluid temperature to the effect of crystalloid fluid bolus therapy (FBT) in post-cardiac surgery patients is unknown. We evaluated the hemodynamic effects of FBT with fluid warmed to 40°C (warm FBT) versus room-temperature fluid. METHODS: In this single centre prospective before-and-after study, we evaluated the effects of 500 ml of warm versus room-temperature compound sodium lactate administered over <30 minutes, in 50 cardiac surgery patients admitted to ICU. We recorded hemodynamics continuous before and for 30 minutes after the first FBT. We defined CI responsiveness (CI-R) as an CI increase >15% of baseline immediately after FBT and effect dissipation if the CI returned to <5% of baseline and MAP responsiveness as >10% increase and dissipation as return to <3 mmHg of baseline. RESULTS: Hypotension (56%) and low CI (40%) typically triggered FBT. Temperature decreased >0.3°C in 13 (52%) patients after room-temperature FBT versus 0 (0%) after warm FBT (p < 0.01). CI and MAP responsiveness was similar (16 [64%] versus 11 [44%], p = 0.15 and 15 [60%] versus 17 [68%], p = 0.77, respectively). Among CI responders, CI increased more with room-temperature FBT (+0.6 [IQR, 0.5-1.1] versus +0.5 [IQR, 0.4-0.6] L/min/m2, p = 0.01). However, dissipation was more common after room-temperature versus warm FBT (9/16 [56%] versus 1/11 [9%], p = 0.02). CONCLUSION: In postoperative cardiac surgery patients, warm FBT preserved core temperature and induced smaller but more sustained CI increases among responders. Fluid temperature appears to impact both core temperature and the duration of CI response.

Validation of a novel system to assess end-expiratory lung volume and alveolar recruitment in an ARDS model.

BACKGROUND: Personalizing mechanical ventilation requires the development of reliable bedside monitoring techniques. The multiple-breaths nitrogen washin-washout (MBNW) technique is currently available to measure end-expiratory lung volume (EELVMBNW), but the precision of the technique may be poor, with percentage errors ranging from 28 to 57%. The primary aim of the study was to evaluate the reliability of a novel MBNW bedside system using fast mainstream sensors to assess EELV in an experimental acute respiratory distress syndrome (ARDS) model, using computed tomography (CT) as the gold standard. The secondary aims of the study were: (1) to evaluate trending ability of the novel system to assess EELV; (2) to evaluate the reliability of estimated alveolar recruitment induced by positive end-expiratory pressure (PEEP) changes computed from EELVMBNW, using CT as the gold standard. RESULTS: Seven pigs were studied in 6 experimental conditions: at baseline, after experimental ARDS and during a decremental PEEP trial at PEEP 16, 12, 6 and 2 cmH2O. EELV was computed at each PEEP step by both the MBNW technique (EELVMBNW) and CT (EELVCT). Repeatability was assessed by performing replicate measurements. Alveolar recruitment between two consecutive PEEP levels after lung injury was measured with CT (VrecCT), and computed from EELV measurements (VrecMBNW) as ΔEELV minus the product of ΔPEEP by static compliance. EELVMBNW and EELVCT were significantly correlated (R2 = 0.97). An acceptable non-constant bias between methods was identified, slightly decreasing toward more negative values as EELV increased. The conversion equation between EELVMBNW and EELVCT was: EELVMBNW = 0.92 × EELVCT + 36. The 95% prediction interval of the bias amounted to ± 86 mL and the percentage error between both methods amounted to 13.7%. The median least significant change between repeated measurements amounted to 8% [CI95%: 4-10%]. EELVMBNW adequately tracked EELVCT changes over time (concordance rate amounting to 100% [CI95%: 87%-100%] and angular bias amounting to - 2° ± 10°). VrecMBNW and VrecCT were significantly correlated (R2 = 0.92). A non-constant bias between methods was identified, slightly increasing toward more positive values as Vrec increased. CONCLUSIONS: We report a new bedside MBNW technique that reliably assesses EELV in an experimental ARDS model with high precision and excellent trending ability.

A comparison of the hemodynamic effects of fluid bolus therapy with crystalloids vs. 4% albumin and vs. 20% albumin in patients after cardiac surgery.

BACKGROUND: Crystalloids, 4% albumin and 20% albumin are used for fluid bolus therapy (FBT) in patients after cardiac surgery. However, their detailed early (30 min) hemodynamic effects remain unstudied. METHODS: In a comparative prospective observational trial of 120 ventilated, we studied post cardiac surgery patients who received crystalloid 500 ml FBT, 4% albumin 500 ml FBT or 20% albumin 100 ml FBT (40 per group). We recorded second-by-second hemodynamic parameters and 15-minutely cardiac index (CI) data before and for 30 min after FBT. We compared the crystalloid group (reference) vs. the 4% albumin group, and vs. the 20% albumin group. RESULTS: Immediately after FBT, the mean (standard deviation) CI increase was 0.4 (0.4) L/min/m2 with crystalloids, 0.4 (0.5) L/min/m2 with 4% albumin and 0.3 (0.4) L/min/m2 with 20% albumin, despite the much smaller FBT volume with 20% albumin. Mean arterial pressure (MAP) increase was 11 (10), 12 (9) and 9 (6) mm Hg, respectively. There was no group effect or interaction for changes in CI. However, there were time-group interactions for MAP changes such that crystalloid FBT had faster MAP reduction than 4% (p<0.001) or 20% albumin (p < 0.001). Moreover, patients treated with crystalloid FBT showed a faster decline in central venous pressure, perfusion pressure than the two groups. Finally, 20% albumin attenuated the fall in temperature induced by FBT. CONCLUSION: In postoperative cardiac surgery patients, after a similar initial CI and MAP response, the MAP effect of crystalloid FBT dissipates faster than that of 4% or 20% albumin FBT. These findings can be used to inform clinical practice.

Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI): a pilot randomized controlled feasibility trial.

PURPOSE: We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation. METHODS: This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization. RESULTS: Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm. CONCLUSIONS: In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified.

Comparison of the Hemodynamic and Temperature Effects of a 500-mL Bolus of 4% Albumin at Room Versus Body Temperature in Cardiac Surgery Patients.

OBJECTIVE: To compare the hemodynamic effect of room temperature (cold) 4% albumin fluid bolus therapy (FBT) with body temperature (warm) albumin FBT. DESIGN: Prospective, before-after trial. SETTING: A tertiary intensive care unit (ICU). PARTICIPANTS: Sixty ventilated, post-cardiac surgery patients prescribed with 4% albumin FBT. INTERVENTION: Cold or warm 4% albumin 500 ml FBT. MEASUREMENTS AND MAIN RESULTS: We recorded hemodynamic parameters before and for 30 minutes after FBT. Cardiac index (CI) and mean arterial pressure (MAP) responses were defined by a CI increase >15% and a MAP increase >10%, respectively. Immediately after FBT, median [interquartile range] core temperature changed by -0.3 [-0.4; -0.3] °C with cold albumin vs. 0.0 [0.0; 0.1]°C with warm albumin (P<0.001). The median CI increase was 0.3 [0.0; 0.5] L/min/m2 with 14 CI-responders (47%) in both groups (P>0.99). The median immediate MAP increase was 9 [3; 15] mmHg with cold albumin vs. 11 [5; 13] mmHg with warm albumin (P=0.79), with a MAP-response in 16 vs. 17 patients (P=0.99). There was an interaction between group and time for MAP (P=0.002), mean pulmonary artery pressure (PAP) (P=0.002) and core temperature (P<0.001). In the cold albumin group, after the initial response, MAP and mean PAP decreased more slowly than with warm albumin and, after the initial fall, core temperature increased toward baseline. CONCLUSION: In postoperative cardiac surgery patients, warm albumin FBT prevents the decrease in core temperature and, after an initial similar increase, is associated with a faster return of MAP and mean PAP toward baseline.

Temperature and haemodynamic effects of a 100 mL bolus of 20% albumin at room versus body temperature in cardiac surgery patients.

Objective: To study the temperature and haemodynamic effects of room versus body temperature 20% albumin fluid bolus therapy (FBT). Design: Single-centre, prospective, before-after trial. Setting: A tertiary intensive care unit (ICU) in Australia. Participants: Sixty ventilated post-cardiac surgery patients. Intervention: Room versus body temperature 100 mL 20% albumin FBT. Main outcome measures: We recorded haemodynamic data from FBT start to 30 minutes after FBT. The cardiac index (CI) response was defined by a CI increase > 15%, and the mean arterial pressure (MAP) response was defined by a MAP increase > 10%. Outcomes: Immediately after FBT, median blood temperature decreased by -0.1°C (interquartile range [IQR], -0.1 to 0.0°C) with room temperature albumin versus 0.0°C (IQR, -0.1 to 0.0°C) with body temperature albumin (P < 0.001). The CI or MAP responses were similar. There was, however, a time and study group interaction for blood temperature (P < 0.001) for absolute and relative changes. In addition, mean pulmonary arterial pressure (PAP) (P = 0.002) increased more with body temperature albumin and remained higher for most of the observation period. Conclusion: Compared with room temperature albumin FBT, body temperature 20% albumin FBT prevents FBT-associated blood temperature fall and increases mean PAP. However, CI and MAP changes were the similar between the two groups, implying that fluid temperature has limited haemodynamic effects in these patients.

Prolonged postoperative cerebral oxygen desaturation after cardiac surgery: A prospective observational study.

BACKGROUND: Near-infrared spectroscopy (NIRS) is used routinely to monitor cerebral tissue oxygen saturation (SctO2) during cardiopulmonary bypass (CPB) but is rarely employed outside the operating room. Previous studies indicate that patients are at risk of postoperative cerebral oxygen desaturation after cardiac surgery. OBJECTIVES: We aimed to assess perioperative and postoperative changes in NIRS-derived SctO2 in cardiac surgery patients. DESIGN: Prospective observational study. SETTING: The study was conducted in a tertiary referral university hospital in Australia from December 2017 to December 2018. PATIENTS: We studied 34 adult patients (70.6% men) undergoing cardiac surgery requiring CPB and a reference group of 36 patients undergoing non-cardiac surgical procedures under general anaesthesia. MAIN OUTCOME MEASURES: We measured SctO2 at baseline, during and after surgery, and then once daily until hospital discharge, for a maximum of 7 days. We used multivariate linear mixed-effects modelling to adjust for all relevant imbalances between the two groups. RESULTS: In the cardiac surgery group, SctO2 was 63.7% [95% confidence interval (CI), 62.0 to 65.5] at baseline and 61.0% (95% CI, 59.1 to 62.9, P = 0.01) on arrival in the ICU. From day 2 to day 7 after cardiac surgery, SctO2 progressively declined. At hospital discharge, SctO2 was significantly lower than baseline, at 53.5% (95% CI, 51.8 to 55.2, P < 0.001). In the reference group, postoperative SctO2 was not significantly different from baseline. On multivariable analysis, cardiac surgery, peripheral vascular disease and time since the operation were associated with greater cerebral desaturation, whereas higher haemoglobin concentrations were associated with slightly better cerebral oxygenation. CONCLUSION: After cardiac surgery on CPB, but not after non-cardiac surgery, most patients experience prolonged cerebral desaturation. Such postoperative desaturation remained unresolved 7 days after surgery. The underlying mechanisms and time to resolution of such cerebral desaturations require further investigation.

Quantitative-analysis of computed tomography in COVID-19 and non COVID-19 ARDS patients: A case-control study.

PURPOSE: The aim of this study was to assess whether the computed tomography (CT) features of COVID-19 (COVID+) ARDS differ from those of non-COVID-19 (COVID-) ARDS patients. MATERIALS AND METHODS: The study is a single-center prospective observational study performed on adults with ARDS onset ≤72 h and a PaO2/FiO2 ≤ 200 mmHg. CT scans were acquired at PEEP set using a PEEP-FiO2 table with VT adjusted to 6 ml/kg predicted body weight. RESULTS: 22 patients were included, of whom 13 presented with COVID-19 ARDS. Lung weight was significantly higher in COVID- patients, but all COVID+ patients presented supranormal lung weight values. Noninflated lung tissue was significantly higher in COVID- patients (36 ± 14% vs. 26 ± 15% of total lung weight at end-expiration, p < 0.01). Tidal recruitment was significantly higher in COVID- patients (20 ± 12 vs. 9 ± 11% of VT, p < 0.05). Lung density histograms of 5 COVID+ patients with high elastance (type H) were similar to those of COVID- patients, while those of the 8 COVID+ patients with normal elastance (type L) displayed higher aerated lung fraction.

Continuous Magnesium Infusion to Prevent Atrial Fibrillation After Cardiac Surgery: A Sequential Matched Case-Controlled Pilot Study.

OBJECTIVE: The authors aimed to test whether a bolus of magnesium followed by continuous intravenous infusion might prevent the development of atrial fibrillation (AF) after cardiac surgery. DESIGN: Sequential, matched, case-controlled pilot study. SETTING: Tertiary university hospital. PARTICIPANTS: Matched cohort of 99 patients before and intervention cohort of 99 consecutive patients after the introduction of a continuous magnesium infusion protocol. INTERVENTIONS: The magnesium infusion protocol consisted of a 10 mmol loading dose of magnesium sulphate followed by a continuous infusion of 3 mmol/h over a maximum duration of 96 hours or until intensive care unit discharge. MEASUREMENTS AND MAIN RESULTS: The study groups were balanced except for a lower cardiac index in the intervention cohort. The mean duration of magnesium infusion was 27.93 hours (95% confidence interval [CI]: 24.10-31.76 hours). The intervention group had greater serum peak magnesium levels: 1.72 mmol/L ± 0.34 on day 1, 1.32 ± 0.36 on day 2 versus 1.01 ± 1.14 and 0.97 ± 0.13, respectively, in the control group (p < 0.01). Atrial fibrillation occurred in 25 patients (25.3%) in the intervention group and 40 patients (40.4%) in the control group (odds ratio 0.49, 95% CI, 0.27-0.92; p = 0.023). On a multivariate Cox proportional hazards model, the hazard ratio for the development of AF was significantly less in the intervention group (hazard ratio 0.45, 95% CI, 0.26-0.77; p = 0.004). CONCLUSION: The magnesium delivery strategy was associated with a decreased incidence of postoperative AF in cardiac surgery patients. These findings provide a rationale and preliminary data for the design of future randomized controlled trials.

Haemodynamic effect of a 20% albumin fluid bolus in post-cardiac surgery patients.

OBJECTIVE: To study the cardiovascular effect over 30 minutes following the end of fluid bolus therapy (FBT) with 20% albumin in patients after cardiac surgery. DESIGN: Prospective observational study. SETTING: Intensive care unit of a tertiary university-affiliated hospital. PARTICIPANTS: Twenty post-cardiac surgery mechanically ventilated patients with a clinical decision to administer FBT. INTERVENTION: FBT with a 100 mL bolus of 20% albumin. MAIN OUTCOME MEASURES: Cardiac index (CI) response was defined by a ≥ 15% increase, while mean arterial pressure (MAP) response was defined by a ≥ 10% increase. RESULTS: The most common indication for FBT was hypotension (40%). Median duration of infusion was 7 minutes (interquartile range [IQR], 3-9 min). At the end of FBT, five patients (25%) showed a CI response, which increased to almost half in the following 30 minutes and dissipated in one patient. MAP response occurred in 11 patients (55%) and dissipated in five patients (45%) by a median of 6 minutes (IQR, 6-10 min). CI and MAP responses coexisted in four patients (20%). An intrabolus MAP response occurred in 17 patients (85%) but dissipated in 11 patients (65%) within a median of 7 minutes (IQR, 2-11 min). On regression analysis, faster fluid bolus administration predicted MAP increase at the end of the bolus. CONCLUSION: In post-cardiac surgery patients, CI response to 20% albumin FBT was not congruous with MAP response over 30 minutes. Although hypotension was the main indication for FBT and a MAP response occurred in most of patients, such response was maximal during the bolus, dissipated in a few minutes, and was dissociated from the CI response.

A Pilot, Double-Blind, Randomized, Controlled Trial of High-Dose Intravenous Vitamin C for Vasoplegia After Cardiac Surgery.

OBJECTIVE: To conduct a pilot feasibility and physiologic efficacy study of high-dose vitamin C in patients with vasoplegia after cardiac surgery. DESIGN: Prospective, double-blind, randomized, controlled trial. SETTING: Two tertiary intensive care units (ICUs). PARTICIPANTS: Post-cardiac surgery patients with vasoplegia. INTERVENTIONS: The authors randomly assigned the patients to receive either high-dose intravenous vitamin C (1,500 mg every 6 hours) or placebo. The primary outcome was time from randomization to resolution of vasoplegia. Secondary outcomes included total norepinephrine equivalent dose in the first 2 days, ICU length of stay, ICU mortality, and in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: The authors studied 50 patients (25 patients in each arms). The mean (standard deviation) time to resolution of vasoplegia was 27.0 (16.5) hours in the vitamin C group versus 34.7 (41.1) hours in the placebo group (mean decrease with vitamin C of 7.7 hours, 95% confidence interval -10.5 to 25.9, p = 0.40). The median (interquartile range) norepinephrine equivalent dose in the first 2 days was 64.9 (23.5-236.5) µg/kg versus 47.4 (21.4-265.9) µg/kg in the vitamin C and placebo group (p = 0.75). The median duration of ICU admission was similar (1.4 [0.5-2.5] days and 1.5 [0.5-3.3] days in the vitamin C and placebo group; p = 0.36). Only 1 patient, in the vitamin C arm, died. CONCLUSION: In patients with post-cardiac surgery vasoplegia, high-dose vitamin C infusion was feasible, appeared safe, and, within the limitations of a pilot study, did not achieve statistically faster resolution of vasoplegia.

Haemodynamic response to fluid boluses in children after cardiac surgery: a technical report.

OBJECTIVE: To describe the haemodynamic response to fluid boluses (FB) in children after cardiac surgery. DESIGN: A prospective observational pilot study. SETTING: Single-centre, paediatric cardiac intensive care unit. PARTICIPANTS: Children after cardiac surgery. INTERVENTIONS: FB of 0.9% saline, 4% albumin or modified ultrafiltrate blood administered in less than 30 minutes. MAIN OUTCOME MEASURES: Heart rate, arterial blood pressure, central venous pressure, oesophageal temperature, and end-tidal carbon dioxide were measured continuously and reported minutely from 5 minutes before and 30 minutes after FB. A mean arterial pressure (MAP)-responsive episode was defined as a 10% increase in MAP from baseline. RESULTS: There were 21 FB recorded in 9 patients. Most patients (n = 8) weighed ≤ 6 kg, and three had univentricular circulation. Fourteen FB (67%) were 4% albumin and 15 (71%) were ≤ 7.5 mL/kg. There were nine MAP-responsive episodes (43%). Episodes of MAP responsiveness had a median MAP increment from baseline of 5 mmHg (interquartile range [IQR], 5-7) and 5 mmHg (IQR, 2-17) at 15 minutes and 30 minutes, respectively, significantly higher when compared with non-responsive episodes (median, 1 mmHg [IQR, -2 to 3]; and median, -1 mmHg [IQR, -3 to 1]; P < 0.01). In MAP-responsive episodes, median time to response was 6 minutes (IQR, 3-12) and seven episodes (78%) dissipated at a median of 2 minutes after response (IQR, 1-8). MAP response was not associated with fluid volume nor fluid composition. CONCLUSION: In this study, the haemodynamic response to FB in children is infrequent and unsustained. Larger studies are required to demonstrate the pattern of haemodynamic response of FB in critically ill children.

Change in cardiac output during Trendelenburg maneuver is a reliable predictor of fluid responsiveness in patients with acute respiratory distress syndrome in the prone position under protective ventilation.

BACKGROUND: Predicting fluid responsiveness may help to avoid unnecessary fluid administration during acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the diagnostic performance of the following methods to predict fluid responsiveness in ARDS patients under protective ventilation in the prone position: cardiac index variation during a Trendelenburg maneuver, cardiac index variation during an end-expiratory occlusion test, and both pulse pressure variation and change in pulse pressure variation from baseline during a tidal volume challenge by increasing tidal volume (VT) to 8 ml.kg-1. METHODS: This study is a prospective single-center study, performed in a medical intensive care unit, on ARDS patients with acute circulatory failure in the prone position. Patients were studied at baseline, during a 1-min shift to the Trendelenburg position, during a 15-s end-expiratory occlusion, during a 1-min increase in VT to 8 ml.kg-1, and after fluid administration. Fluid responsiveness was deemed present if cardiac index assessed by transpulmonary thermodilution increased by at least 15% after fluid administration. RESULTS: There were 33 patients included, among whom 14 (42%) exhibited cardiac arrhythmia at baseline and 15 (45%) were deemed fluid-responsive. The area under the receiver operating characteristic (ROC) curve of the pulse contour-derived cardiac index change during the Trendelenburg maneuver and the end-expiratory occlusion test were 0.90 (95% CI, 0.80-1.00) and 0.65 (95% CI, 0.46-0.84), respectively. An increase in cardiac index ≥ 8% during the Trendelenburg maneuver enabled diagnosis of fluid responsiveness with sensitivity of 87% (95% CI, 67-100), and specificity of 89% (95% CI, 72-100). The area under the ROC curve of pulse pressure variation and change in pulse pressure variation during the tidal volume challenge were 0.52 (95% CI, 0.24-0.80) and 0.59 (95% CI, 0.31-0.88), respectively. CONCLUSIONS: Change in cardiac index during a Trendelenburg maneuver is a reliable test to predict fluid responsiveness in ARDS patients in the prone position, while neither change in cardiac index during end-expiratory occlusion, nor pulse pressure variation during a VT challenge reached acceptable predictive performance to predict fluid responsiveness in this setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01965574 . Registered on 16 October 2013. The trial was registered 6 days after inclusion of the first patient.