Rhinovirus Detection in the Nasopharynx of Children Undergoing Cardiac Surgery Is Not Associated With Longer PICU Length of Stay: Results of the Impact of Rhinovirus Infection After Cardiac Surgery in Kids (RISK) Study.

OBJECTIVES: To determine whether children with asymptomatic carriage of rhinovirus in the nasopharynx before elective cardiac surgery have an increased risk of prolonged PICU length of stay. STUDY DESIGN: Prospective, single-center, blinded observational cohort study. SETTING: PICU in a tertiary hospital in The Netherlands. PATIENTS: Children under 12 years old undergoing elective cardiac surgery were enrolled in the study after informed consent of the parents/guardians. INTERVENTIONS: The parents/guardians filled out a questionnaire regarding respiratory symptoms. On the day of the operation, a nasopharyngeal swab was obtained. Clinical data were collected during PICU admission, and PICU/hospital length of stay were reported. If a patient was still intubated 3 days after operation, an additional nasopharyngeal swab was collected. Nasopharyngeal swabs were tested for rhinovirus and other respiratory viruses with polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Of the 163 included children, 74 (45%) tested rhinovirus positive. Rhinovirus-positive patients did not have a prolonged PICU length of stay (median 2 d each; p = 0.257). Rhinovirus-positive patients had a significantly shorter median hospital length of stay compared with rhinovirus-negative patients (8 vs 9 d, respectively; p = 0.006). Overall, 97 of the patients (60%) tested positive for one or more respiratory virus. Virus-positive patients had significantly shorter PICU and hospital length of stay, ventilatory support, and nonmechanical ventilation. Virus-negative patients had respiratory symptoms suspected for a respiratory infection more often. In 31% of the children, the parents reported mild upper respiratory complaints a day prior to the cardiac surgery, this was associated with postextubation stridor, but no other clinical outcome measures. CONCLUSIONS: Preoperative rhinovirus polymerase chain reaction positivity is not associated with prolonged PICU length of stay. Our findings do not support the use of routine polymerase chain reaction testing for respiratory viruses in asymptomatic children admitted for elective cardiac surgery.

Biventricular function in exercise during autonomic (thoracic epidural) block.

BACKGROUND: Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia (TEA) was previously shown to reduce right and left ventricular systolic function and effective pulmonary arterial elastance. At conditions of constant paced heart rate, cardiac output and systemic hemodynamics were unchanged. In this study, we further investigated the effect of cardiac sympathicolysis during physical stress and increased oxygen demand. METHODS: In a cross-over design, 12 patients scheduled to undergo thoracic surgery performed dynamic ergometric exercise tests with and without TEA. Hemodynamics were monitored and biventricular function was measured by transthoracic two-dimensional and M-mode echocardiography, pulsed wave Doppler and tissue Doppler imaging. RESULTS: TEA attenuated systolic RV function (TV S': - 21%, P < 0.001) and LV function (MV S': - 14%, P = 0.025), but biventricular diastolic function was not affected. HR (- 11%, P < 0.001), SVI (- 15%, P = 0.006), CI (- 21%, P < 0.001) and MAP (- 12%, P < 0.001) were decreased during TEA, but SVR was not affected. Exercise resulted in significant augmentation of systolic and diastolic biventricular function. During exercise HR, SVI, CI and MAP increased (respectively, + 86%, + 19%, + 124% and + 17%, all P < 0.001), whereas SVR decreased (- 49%, P < 0.001). No significant interactions between exercise and TEA were found, except for RPP (P = 0.024) and MV E DT (P = 0.035). CONCLUSION: Cardiac sympathetic blockade by TEA reduced LV and RV systolic function but did not significantly blunt exercise-induced increases in LV and RV function. These data indicate that additional mechanisms besides those controlled by the cardiac sympathetic nervous system are involved in the regulation of cardiac function during dynamic exercise. Trial registration Clinical trial registration: Nederlands Trial Register, NTR 4880 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4880 .

Respiratory Viruses in Invasively Ventilated Critically Ill Patients-A Prospective Multicenter Observational Study.

OBJECTIVES: The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis. DESIGN: Prospective observational study. SETTING: Five ICUs in the Netherlands. PATIENTS: Between September 1, 2013, and April 30, 2014, 1,407 acutely admitted and invasively ventilated patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nasopharyngeal swabs and tracheobronchial aspirates were collected upon intubation and tested for 14 respiratory viruses. Out of 1,407 patients, 156 were admitted because of a severe acute respiratory infection and 1,251 for other reasons (non-severe acute respiratory infection). Respiratory viruses were detected in 28.8% of severe acute respiratory infection patients and 17.0% in non-severe acute respiratory infection (p < 0.001). In one third, viruses were exclusively detected in tracheobronchial aspirates. Rhinovirus and human metapneumovirus were more prevalent in severe acute respiratory infection patients (9.6% and 2.6% vs 4.5 and 0.2%; p = 0.006 and p < 0.001). In both groups, there were no associations between the presence of viruses and the number of ICU-free days at day 28, crude mortality, and mortality in multivariate regression analyses. CONCLUSIONS: Respiratory viruses are frequently detected in acutely admitted and invasively ventilated patients. Rhinovirus and human metapneumovirus are more frequently found in severe acute respiratory infection patients. Detection of respiratory viruses is not associated with worse clinically relevant outcomes in the studied cohort of patients.

Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial.

Importance: It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS). Objective: To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy. Design, Setting, and Participants: A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands. Interventions: Invasive ventilation using low tidal volumes (n = 477) or intermediate tidal volumes (n = 484). Main Outcomes and Measures: The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, or pneumothorax. Results: In total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. At day 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, -0.27 [95% CI, -1.74 to 1.19]; P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [-1.09 to 1.89]; P = .58) and hospital (median, 14 vs 15 days; -0.60 [-3.52 to 2.31]; P = .68) length of stay or 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and 90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24]; P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severe atelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55). Conclusions and Relevance: In patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02153294.

Thoracic Epidural Anesthesia Reduces Right Ventricular Systolic Function With Maintained Ventricular-Pulmonary Coupling.

BACKGROUND: Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia may affect right ventricular function and interfere with the coupling between right ventricular function and right ventricular afterload. Our main objectives were to study the effects of thoracic epidural anesthesia on right ventricular function and ventricular-pulmonary coupling. METHODS: In 10 patients scheduled for lung resection, right ventricular function and its response to increased afterload, induced by temporary, unilateral clamping of the pulmonary artery, was tested before and after induction of thoracic epidural anesthesia using combined pressure-conductance catheters. RESULTS: Thoracic epidural anesthesia resulted in a significant decrease in right ventricular contractility (ΔESV25: +25.5 mL, P=0.0003; ΔEes: -0.025 mm Hg/mL, P=0.04). Stroke work, dP/dtMAX, and ejection fraction showed a similar decrease in systolic function (all P<0.05). A concomitant decrease in effective arterial elastance (ΔEa: -0.094 mm Hg/mL, P=0.004) yielded unchanged ventricular-pulmonary coupling. Cardiac output, systemic vascular resistance, and mean arterial blood pressure were unchanged. Clamping of the pulmonary artery significantly increased afterload (ΔEa: +0.226 mm Hg/mL, P<0.001). In response, right ventricular contractility increased (ΔESV25: -26.6 mL, P=0.0002; ΔEes: +0.034 mm Hg/mL, P=0.008), but ventricular-pulmonary coupling decreased (Δ(Ees/Ea) = -0.153, P<0.0001). None of the measured indices showed significant interactive effects, indicating that the effects of increased afterload were the same before and after thoracic epidural anesthesia. CONCLUSIONS: Thoracic epidural anesthesia impairs right ventricular contractility but does not inhibit the native positive inotropic response of the right ventricle to increased afterload. Right ventricular-pulmonary arterial coupling was decreased with increased afterload but not affected by the induction of thoracic epidural anesthesia. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2844. Unique identifier: NTR2844.

Effectiveness and Clinical Outcomes of a Two-Step Implementation of Conservative Oxygenation Targets in Critically Ill Patients: A Before and After Trial.

OBJECTIVES: Conservative oxygen therapy is aimed at the prevention of harm by iatrogenic hyperoxia while preserving adequate tissue oxygenation. Our aim was to study the effectiveness and clinical outcomes of a two-step implementation of conservative oxygenation targets in the ICU. DESIGN: This was a before and after stepwise implementation study of conservative oxygenation targets, between July 2011 and July 2014. The primary endpoint was the proportion of PaO2 values within the target range. Secondary outcomes included ventilator-free days at day 28, length of stay, and mortality. SETTING: Three closed-format ICUs in the Netherlands. PATIENTS: We analyzed data on 15,045 eligible admissions. INTERVENTIONS: The first implementation phase consisted of providing training and feedback on new guidelines instructing for explicit targets for arterial oxygen tension (PaO2, 55-86 mm Hg) and oxyhemoglobin saturation (SpO2, 92-95%). In the second phase, bedside clinicians were additionally assisted in guideline adherence by a computerized decision-support system. MEASUREMENTS AND MAIN RESULTS: The proportion of PaO2 in the target range increased from 47% at baseline to 63% in phase 1 and to 68% in phase 2 (p < 0.0001). Episodes of hyperoxia decreased (p < 0.0001), whereas hypoxic episodes remained unchanged (p = 0.06) during the study. Mechanical ventilation time was significantly lower (p < 0.01) during both study phases. After adjustment for potential confounders, ventilator-free days in phase 1 and phase 2 were higher than baseline: adjusted mean difference, 0.55 (95% CI, 0.25-0.84) and 0.48 (95% CI, 0.11-0.86), respectively. Adjusted ICU mortality and ICU-free days did not significantly differ between study phases. Hospital mortality decreased in reference to baseline: adjusted odds ratio, 0.84 (95% CI, 0.74-0.96) for phase 1 and 0.82 (95% CI, 0.69-0.96) for phase 2. CONCLUSIONS: Stepwise implementation of conservative oxygenation targets was feasible, effective, and seemed safe in critically ill patients. The implementation was associated with several changes in clinical outcomes, but the causal impact of conservative oxygenation is still to be determined.

Higher Tinzaparin Dosing Is Needed to Achieve Target Anti-Xa Levels in Pediatric Cardiac Intensive Care Patients.

OBJECTIVES: This study was conducted to evaluate tinzaparin dosing and therapeutic drug monitoring. DESIGN: Retrospective study. SETTING: Single tertiary-level PICU. PATIENTS: Tinzaparin doses and anti-Xa levels from all children admitted to a PICU (from October 1, 2010, to December 31, 2013) were retrospectively analyzed. Thirty-nine children, median age of 13 months (interquartile range, 73 mo), with 46 episodes of newly started therapeutic tinzaparin were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Local hospital policy is to determine the first anti-Xa level after 3-4 doses, 4 hours post dose, targeting 0.5-1.0 IU/mL for therapeutic dosing. First anti-Xa levels were determined after 3.8 (± 2.4; range, 1-14) doses and were below the target range in 37 of 46 episodes (76%) of tinzaparin use: mean, 0.30 (± 0.11) IU/mL. Tinzaparin was then increased by 23% (± 19) in 23 of 37 episodes (62%), and further anti-Xa levels were determined. In 14 episodes, further levels were not available because of cessation of tinzaparin therapy. Target anti-Xa levels, 0.69 (± 0.24) IU/mL, were eventually reached in the PICU in 22 patients after a mean of 8.8 (± 7.3) doses. In the entire cohort, the dose required to achieve target anti-Xa levels was significantly higher (+51 [± 62] U/kg; p = 0.003) than the recommended starting dose. CONCLUSIONS: Target anti-Xa levels were reached with tinzaparin dosing in PICU patients after more than 8 doses, warranting further dose-effect research. Especially in the younger age group, substantially higher dose requirements than proposed in the internationally used guidelines are required. With the results of our study, we suggest a different therapeutic drug monitoring approach than that currently used.

Cardiac output response to norepinephrine in postoperative cardiac surgery patients: interpretation with venous return and cardiac function curves.

OBJECTIVE: We studied the variable effects of norepinephrine infusion on cardiac output in postoperative cardiac surgical patients in whom norepinephrine increased mean arterial pressure. We hypothesized that the directional change in cardiac output would be determined by baseline cardiac function, as quantified by stroke volume variation, and the subsequent changes in mean systemic filling pressure and vasomotor tone. DESIGN: Intervention study. SETTING: ICU of a university hospital. PATIENTS: Sixteen mechanically ventilated postoperative cardiac surgery patients. INTERVENTIONS: Inspiratory holds were performed at baseline-1, during increased norepinephrine infusion, and baseline-2 conditions. MEASUREMENTS AND MAIN RESULTS: We measured mean arterial pressure, heart rate, central venous pressure, cardiac output, stroke volume variation and, with use of inspiratory hold maneuvers, mean systemic filling pressure, then calculated resistance for venous return and systemic vascular resistance. Increasing norepinephrine by 0.04 ± 0.02 µg·kg·min increased mean arterial pressure 20 mm Hg in all patients. Cardiac output decreased in ten and increased in six patients. In all patients mean systemic filling pressure, systemic vascular resistance and resistance for venous return increased and stroke volume variation decreased. Resistance for venous return and systemic vascular resistance increased more (p = 0.019 and p = 0.002) in the patients with a cardiac output decrease. Heart rate decreased in the patients with a cardiac output decrease (p = 0.002) and was unchanged in the patients with a cardiac output increase. Baseline stroke volume variation was higher in those in whom cardiac output increased (14.4 ± 4.2% vs. 9.1 ± 2.4%, p = 0.012). Stroke volume variation >8.7% predicted the increase in cardiac output to norepinephrine (area under the receiver operating characteristic curve 0.900). CONCLUSIONS: The change in cardiac output induced by norepinephrine is determined by the balance of volume recruitment (increase in mean systemic filling pressure), change in resistance for venous return, and baseline heart function. Furthermore, the response of cardiac output on norepinephrine can be predicted by baseline stroke volume variation.

Comparing hemodynamic effects with three different measurement devices, of two methods of external leg compression versus passive leg raising in patients after cardiac surgery.

External leg compression (ELC) may increase cardiac output (CO) in fluid-responsive patients like passive leg raising (PLR). We compared the hemodynamic effects of two methods of ELC and PLR measured by thermodilution (COtd), pressure curve analysis Modelflow™ (COmf) and ultra-sound HemoSonic™ (COhs), to evaluate the method with the greatest hemodynamic effect and the most accurate less invasive method to measure that effect. We compared hemodynamic effects of two different ELC methods (circular, A (n = 16), vs. wide, B (n = 13), bandages inflated to 30 cm H2O for 15 min) with PLR prior to each ELC method, in 29 post-operative cardiac surgical patients. Hemodynamic responses were measured with COtd, COmf and COhs. PLR A increased COtd from 6.1 ± 1.7 to 6.3 ± 1.8 L·min(-1) (P = 0.016), and increased COhs from 4.9 ± 1.5 to 5.3 ± 1.6 L·min(-1) (P = 0.001), but did not increase COmf. ELC A increased COtd from 6.4 ± 1.8 to 6.7 ± 1.9 L·min(-1) (P = 0.001) and COmf from 6.9 ± 1.7 to 7.1 ± 1.8 L·min(-1) (P = 0.021), but did not increase COhs. ELC A increased COtd and COmf as in PLR A. PLR B increased COtd from 5.4 ± 1.3 to 5.8 ± 1.4 L·min(-1) (P < 0.001), and COhs from 5.0 ± 1.0 to 5.4 ± 1.0 L·min(-1) (P = 0.013), but not COmf. ELC B increased COtd from 5.2 ± 1.2 to 5.4 ± 1.1 L·min(-1) (P = 0.003), but less than during PLR B (P = 0.012), while COmf and COhs did not change. Bland-Altman and polar plots showed lower limits of agreement with changes in COtd for COmf than for COhs. The circular leg compression increases CO more than bandage compression, and is able to increase CO as in PLR. The less invasive Modelflow™ can detect these changes reasonably well.

Determination of vascular waterfall phenomenon by bedside measurement of mean systemic filling pressure and critical closing pressure in the intensive care unit.

BACKGROUND: Mean systemic filling pressure (Pmsf) can be determined at the bedside by measuring central venous pressure (Pcv) and cardiac output (CO) during inspiratory hold maneuvers. Critical closing pressure (Pcc) can be determined using the same method measuring arterial pressure (Pa) and CO. If Pcc > Pmsf, there is then a vascular waterfall. In this study, we assessed the existence of a waterfall and its implications for the calculation of vascular resistances by determining Pmsf and Pcc at the bedside. METHODS: In 10 mechanically ventilated postcardiac surgery patients, inspiratory hold maneuvers were performed, transiently increasing Pcv and decreasing Pa and CO to 4 different steady-state levels. For each patient, values of Pcv and CO were plotted in a venous return curve to determine Pmsf. Similarly, Pcc was determined with a ventricular output curve plotted for Pa and CO. Measurements were performed in each patient before and after volume expansion with 0.5 L colloid, and vascular resistances were calculated. RESULTS: For every patient, the relationship between the 4 measurements of Pcv and CO and of Pa and CO was linear. Baseline Pmsf was 18.7 ± 4.0 mm Hg (mean ± SD) and differed significantly from Pcc 45.5 ± 11.1 mm Hg (P < 0.0001). The difference of Pcc and Pmsf was 26.8 ± 10.7 mm Hg, indicating the presence of a systemic vascular waterfall. Volume expansion increased Pmsf (26.3 ± 3.2 mm Hg), Pcc (51.5 ± 9.0 mm Hg), and CO (5.5 ± 1.8 to 6.8 ± 1.8 L · min(-1)). Arterial (upstream of Pcc) and venous (downstream of Pmsf) vascular resistance were 8.27 ± 4.45 and 2.75 ± 1.23 mm Hg · min · L(-1); the sum of both (11.01 mm Hg · min · L(-1)) was significantly different from total systemic vascular resistance (16.56 ± 8.57 mm Hg · min · L(-1); P = 0.005). Arterial resistance was related to total resistance. CONCLUSIONS: Vascular pressure gradients in cardiac surgery patients suggest the presence of a vascular waterfall phenomenon, which is not affected by CO. Thus, measures of total systemic vascular resistance may become irrelevant in assessing systemic vasomotor tone.

Arm occlusion pressure is a useful predictor of an increase in cardiac output after fluid loading following cardiac surgery.

BACKGROUND AND OBJECTIVE: In pharmacological research, arm occlusion pressure is used to study haemodynamic effects of drugs. However, arm occlusion pressure might be an indicator of static filling pressure of the arm. We hypothesised that arm occlusion pressure can be used to predict fluid loading responsiveness. METHODS: Twenty-four patients who underwent cardiac surgery were studied during their first 2 h in the ICU. The lungs were ventilated mechanically and left ventricular function was supported as necessary. Arm occlusion pressure was defined as the radial artery pressure after occluding arterial flow for 35 s by a blood pressure cuff inflated to 50 mmHg above SBP. The cuff was positioned around the arm in which a radial artery catheter had been inserted. Measurements were performed before (baseline) and after fluid loading (500 ml hydroxyethyl starch 6%). Patients whose cardiac output increased by at least 10% were defined as responders. RESULTS: In responders (n = 17), arm occlusion pressure, mean arterial pressure and central venous pressure increased and stroke volume variation and pulse pressure variation decreased. In non-responders (n = 7), arm occlusion pressure and central venous pressure increased, and pulse pressure variation decreased. Mean arterial pressure, stroke volume variation and heart rate did not change significantly. The area under the curve to predict fluid loading responsiveness for arm occlusion pressure was 0.786 (95% confidence interval 0.567-1.000), at a cut-off of 21.9 mmHg, with sensitivity of 71% and specificity of 88% in predicting fluid loading responsiveness. Prediction of responders with baseline arm occlusion pressure was as good as baseline stroke volume variation and pulse pressure variation. CONCLUSION: Arm occlusion pressure was a good predictor of fluid loading responsiveness in our group of cardiac surgery patients and offers clinical advantages over stroke volume variation and pulse pressure variation.

Defining human mean circulatory filling pressure in the intensive care unit.

Potentially, mean circulatory filling pressure (Pmcf) could aid hemodynamic management in patients admitted to the intensive care unit (ICU). However, data regarding the normal range for Pmcf do not exist challenging its clinical use. We aimed to define the range for Pmcf for ICU patients and also calculated in what percentage of cases equilibrium between arterial blood pressure (ABP) and central venous pressure (CVP) was reached. In patients in whom no equilibrium was reached, we corrected for arterial-to-venous compliance differences. Finally, we studied the influence of patient characteristics on Pmcf. We hypothesized fluid balance, the use of vasoactive medication, being on mechanical ventilation, and the level of positive end-expiratory pressure would be positively associated with Pmcf. We retrospectively studied a cohort of 311 patients that had cardiac arrest in ICU while having active recording of ABP and CVP 1 min after death. Median Pmcf was 15 mmHg [interquartile range (IQR) 12-18]. ABP and CVP reached an equilibrium state in 52% of the cases. Correction for arterial-to-venous compliances differences resulted in a maximum alteration of 1.3 mmHg in Pmcf. Fluid balance over the last 24 h, the use of vasoactive medication, and being on mechanical ventilation were associated with a higher Pmcf. Median Pmcf was 15 mmHg (IQR 12-18). When ABP remained higher than CVP, correction for arterial-to-venous compliance differences did not result in a clinically relevant alteration of Pmcf. Pmcf was affected by factors known to alter vasomotor tone and effective circulating blood volume.NEW & NOTEWORTHY In a cohort of 311 intensive care unit (ICU) patients, median mean circulatory filling pressure (Pmcf) measured after cardiac arrest was 15 mmHg (interquartile range 12-18). In 48% of cases, arterial blood pressure remained higher than central venous pressure, but correction for arterial-to-venous compliance differences did not result in clinically relevant alterations of Pmcf. Fluid balance, use of vasopressors or inotropes, and being on mechanical ventilation were associated with a higher Pmcf.

Assessing fluid responses after coronary surgery: role of mathematical coupling of global end-diastolic volume to cardiac output measured by transpulmonary thermodilution.

BACKGROUND: Mathematical coupling may explain in part why cardiac filling volumes obtained by transpulmonary thermodilution may better predict and monitor responses of cardiac output to fluid loading than pressures obtained by pulmonary artery catheters (PACs). METHODS: Eleven consecutive patients with hypovolaemia after coronary surgery and a PAC, allowing central venous pressure (CVP) and continuous cardiac index (CCIp) measurements, received a femoral artery catheter for transpulmonary thermodilution measurements of global end-diastolic blood volume index (GEDVI) and cardiac index (CItp). One to five colloid fluid-loading steps of 250 ml were done in each patient (n = 48 total). RESULTS: Fluid responses were predicted and monitored similarly by CItp and CCIp, whereas CItp and CCIp correlated at r = 0.70 (P < 0.001) with a bias of 0.40 l min(-1) m(-2). Changes in volumes (and not in CVP) related to changes in CItp and not in CCIp. Changes in CVP and GEDVI similarly related to changes in CItp, after exclusion of two patients with greatest CItp outliers (as compared to CCIp). Changes in GEDVI correlated better to changes in CItp when derived from the same thermodilution curve than to changes in CItp of unrelated curves and changes in CCIp. CONCLUSIONS: After coronary surgery, fluid responses can be similarly assessed by intermittent transpulmonary and continuous pulmonary thermodilution methods, in spite of overestimation of CCIp by CItp. Filling pressures are poor monitors of fluid responses and superiority of GEDVI can be caused, at least in part, by mathematical coupling when cardiac volume and output are derived from the same thermodilution curve.

Perioperative proADM-change is associated with the development of acute respiratory distress syndrome in critically ill cardiac surgery patients: a prospective cohort study.

Aim: Biomarkers of acute respiratory distress syndrome (ARDS) after cardiac-surgery may help risk-stratification and management. Preoperative single-value proADM increases predictive capacity of scoring-system EuroSCORE. To include the impact of surgery, we aim to assess the predictive value of the perioperative proADM-change on development of ARDS in 40 cardiac-surgery patients. Materials & methods: ProADM was measured in nine sequential blood samples. The Berlin definition of ARDS was used. For data-analyses, a multivariate model of EuroSCORE and perioperative proADM-change, linear mixed models and logistic regression were used. Results: Perioperative proADM-change was associated with ARDS after cardiac-surgery, and it was superior to EuroSCORE. A perioperative proADM-change >1.5 nmol/l could predict ARDS. Conclusion: Predicting post-surgery ARDS with perioperative proADM-change enables clinicians to intensify lung-protective interventions and individualized fluid therapy to minimize secondary injury.

Vasoresponsiveness in patients with heart failure (VASOR): protocol for a prospective observational study.

BACKGROUND: Vasoplegia is a severe complication which may occur after cardiac surgery, particularly in patients with heart failure. It is a result of activation of vasodilator pathways, inactivation of vasoconstrictor pathways and the resistance to vasopressors. However, the precise etiology remains unclear. The aim of the Vasoresponsiveness in patients with heart failure (VASOR) study is to objectify and characterize the altered vasoresponsiveness in patients with heart failure, before, during and after heart failure surgery and to identify the etiological factors involved. METHODS: This is a prospective, observational study conducted at Leiden University Medical Center. Patients with and patients without heart failure undergoing cardiac surgery on cardiopulmonary bypass are enrolled. The study is divided in two inclusion phases. During phase 1, 18 patients with and 18 patients without heart failure are enrolled. The vascular reactivity in response to a vasoconstrictor (phenylephrine) and a vasodilator (nitroglycerin) is assessed in vivo on different timepoints. The response to phenylephrine is assessed on t1 (before induction), t2 (before induction, after start of cardiotropic drugs and/or vasopressors), t3 (after induction), t4 (15 min after cessation of cardiopulmonary bypass) and t5 (1 day post-operatively). The response to nitroglycerin is assessed on t1 and t5. Furthermore, a sample of pre-pericardial fat tissue, containing resistance arteries, is collected intraoperatively. The ex vivo vascular reactivity is assessed by constructing concentrations response curves to various vasoactive substances using isolated resistance arteries. Next, expression of signaling proteins and receptors is assessed using immunohistochemistry and mRNA analysis. Furthermore, the groups are compared with respect to levels of organic compounds that can influence the cardiovascular system (e.g. copeptin, (nor)epinephrine, ANP, BNP, NTproBNP, angiotensin II, cortisol, aldosterone, renin and VMA levels). During inclusion phase 2, only the ex vivo vascular reactivity test is performed in patients with (N = 12) and without heart failure (N = 12). DISCUSSION: Understanding the difference in vascular responsiveness between patients with and without heart failure in detail, might yield therapeutic options or development of preventive strategies for vasoplegia, leading to safer surgical interventions and improvement in outcome. TRIAL REGISTRATION: The Netherlands Trial Register (NTR), NTR5647. Registered 26 January 2016.

Hemodynamic effects of short-term hyperoxia after coronary artery bypass grafting.

BACKGROUND: Although oxygen is generally administered in a liberal manner in the perioperative setting, the effects of oxygen administration on dynamic cardiovascular parameters, filling status and cerebral perfusion have not been fully unraveled. Our aim was to study the acute hemodynamic and microcirculatory changes before, during and after arterial hyperoxia in mechanically ventilated patients after coronary artery bypass grafting (CABG) surgery. METHODS: This was a single-center physiological study in a tertiary care ICU in the Netherlands. Twenty-two patients scheduled for ICU admission after elective CABG were enrolled in the study between September 2014 and September 2015. In the ICU, patients were exposed to a fraction of inspired oxygen (FiO2) of 90% allowing a 15-min wash-in period. Various hemodynamic parameters were measured using direct pressure signals and continuous arterial waveform analysis at three sequential time points: before, during and after hyperoxia. RESULTS: During a 15-min exposure to a fraction of inspired oxygen (FiO2) of 90%, the partial pressure of arterial oxygen (PaO2) and arterial oxygen saturation (SaO2) were significantly higher. The systemic resistance increased (P < 0.0001), without altering the heart rate. Stroke volume variation and pulse pressure variation decreased slightly. The cardiac output did not significantly decrease (P = 0.08). Mean systemic filling pressure and arterial critical closing pressure increased (P < 0.01whereas the percentage of perfused microcirculatory vessels decreased (P < 0.01). Other microcirculatory parameters and cerebral blood flow velocity showed only slight changes. CONCLUSIONS: We found that short-term hyperoxia affects hemodynamics in ICU patients after CABG. This was translated in several changes in central circulatory variables, but had only slight effects on cardiac output, cerebral blood flow and the microcirculation. Clinical trial registration Netherlands Trial Register: NTR5064.

PReVENT--protective ventilation in patients without ARDS at start of ventilation: study protocol for a randomized controlled trial.

BACKGROUND: It is uncertain whether lung-protective mechanical ventilation using low tidal volumes should be used in all critically ill patients, irrespective of the presence of the acute respiratory distress syndrome (ARDS). A low tidal volume strategy includes use of higher respiratory rates, which could be associated with increased sedation needs, a higher incidence of delirium, and an increased risk of patient-ventilator asynchrony and ICU-acquired weakness. Another alleged side-effect of low tidal volume ventilation is the risk of atelectasis. All of these could offset the beneficial effects of low tidal volume ventilation as found in patients with ARDS. METHODS/DESIGN: PReVENT is a national multicenter randomized controlled trial in invasively ventilated ICU patients without ARDS with an anticipated duration of ventilation of longer than 24 hours in 5 ICUs in The Netherlands. Consecutive patients are randomly assigned to a low tidal volume strategy using tidal volumes from 4 to 6 ml/kg predicted body weight (PBW) or a high tidal volume ventilation strategy using tidal volumes from 8 to 10 ml/kg PBW. The primary endpoint is the number of ventilator-free days and alive at day 28. Secondary endpoints include ICU and hospital length of stay (LOS), ICU and hospital mortality, the incidence of pulmonary complications, including ARDS, pneumonia, atelectasis, and pneumothorax, the cumulative use and duration of sedatives and neuromuscular blocking agents, incidence of ICU delirium, and the need for decreasing of instrumental dead space. DISCUSSION: PReVENT is the first randomized controlled trial comparing a low tidal volume strategy with a high tidal volume strategy, in patients without ARDS at onset of ventilation, that recruits a sufficient number of patients to test the hypothesis that a low tidal volume strategy benefits patients without ARDS with regard to a clinically relevant endpoint. TRIAL REGISTRATION: The trial is registered at www.clinicaltrials.gov under reference number NCT02153294 on 23 May 2014.

Evaluation of a bedside device to assess the activated partial thromboplastin time for heparin monitoring in infants.

To determine the relationship between the activated partial thromboplastin time (aPTT) measured with a standard laboratory assay and the aPTT measured with a bedside device in infants on heparin therapy after cardiothoracic surgery. Twenty infants aged below 1 year who were on heparin therapy were included. Exclusion criteria were prematurity, dysmaturity and the use of anticoagulants other than heparin. Nineteen samples were obtained from four adults in intensive care who were on heparin. The aPTT values were analyzed with the Coaguchek Pro/DM bedside device (aPTTbed) and compared with the aPTT values obtained from the laboratory Electra 1800C coagulation analyzer (aPTTlab). Correlation analysis was performed by linear regression. The agreement was calculated using Bland-Altman analysis. The correlation coefficient of samples obtained from infants was lower (r = 0.48) compared with samples from adults (r = 0.85). A substantial positive bias (27 s) and scatter [95% confidence interval (CI) -11; +65 s) was found. The bias showed a genuine trend to increase at higher aPTT values (r = 0.90; P < 0.001). The bedside device overestimates the aPTT in infants treated with heparin. The disagreement between the bedside device and laboratory increases at higher aPTTs. Bedside devices should not be used to monitor heparin therapy in infants in intensive care.

Estimation of mean systemic filling pressure in postoperative cardiac surgery patients with three methods.

PURPOSE: To assess the level of agreement between different bedside estimates of effective circulating blood volume-mean systemic filling pressure (Pmsf), arm equilibrium pressure (Parm) and model analog (Pmsa)-in ICU patients. METHODS: Eleven mechanically ventilated postoperative cardiac surgery patients were studied. Sequential measures were made in the supine position, rotating the bed to a 30° head-up tilt and after fluid loading (500 ml colloid). During each condition four inspiratory hold maneuvers were done to determine Pmsf; arm stop-flow was created by inflating a cuff around the upper arm for 30 s to measure Parm, and Pmsa was estimated from a Guytonian model of the systemic circulation. RESULTS: Mean Pmsf, Parm and Pmsa across all three states were 20.9 ± 5.6, 19.8 ± 5.7 and 14.9 ± 4.0 mmHg, respectively. Bland-Altman analysis for the difference between Parm and Pmsf showed a non-significant bias of -1.0 ± 3.08 mmHg (p = 0.062), a coefficient of variation (COV) of 15 %, and limits of agreement (LOA) of -7.3 and 5.2 mmHg. For the difference between Pmsf and Pmsa we found a bias of -6.0 ± 3.1 mmHg (p < 0.001), COV 17 % and LOA -12.4 and 0.3 mmHg. Changes in Pmsf and Parm and in Pmsf and Pmsa were directionally concordant in response to head-up tilt and volume loading. CONCLUSIONS: Parm and Pmsf are interchangeable in mechanically ventilated postoperative cardiac surgery patients. Changes in effective circulatory volume are tracked well by changes in Parm and Pmsa.

Transpulmonary versus continuous thermodilution cardiac output after valvular and coronary artery surgery.

Residual left-sided valvular insufficiencies after valvular surgery may confound transpulmonary thermodilution cardiac output (COtp). We compared the technique with the continuous right-sided thermodilution technique (CCO) after valvular surgery (n=8) and coronary artery surgery (n=8). Patients with pulmonary and femoral artery catheters in the intensive care unit (ICU) were included. After valvular surgery, there was minimal aortic insufficiency in four patients and minimal to moderate mitral valve insufficiency in six. Five fluid loading steps (250 ml) were done in each patient. CCO and COtp were measured prior to and 15 min after each step. The cardiac output was lower after valvular than coronary artery surgery but responses to fluid loading steps were similar among surgery types and techniques. After valvular and coronary artery surgery, cardiac output was lower prior to responses than in non-responses to fluids, by either technique. After valvular surgery, COtp and CCO correlated (r=0.64, P<0.001, n=48) but fluid-induced changes did not. After coronary artery surgery, COtp and CCO correlated (r=0.81, P<0.001) and changes also did (r=0.55, P<0.001). At fluid-induced CCO increases <20%, the r for changes in cardiac output measured by both techniques was similar after valvular and coronary artery surgery. Thus, COtp and CCO were of similar value in predicting and monitoring fluid responses after both surgery types. This argues against left-sided valvular insufficiencies confounding COtp.