Variability of Microcirculatory Measurements in Critically Ill Patients.

INTRODUCTION: Monitoring the microcirculation may be helpful in guiding resuscitation in patients with circulatory shock. Sublingual side-stream dark field imaging cameras allow for noninvasive, bedside evaluation of the microcirculation, although their use in clinical practice has not yet been validated. The GlycoCheck system automatically analyzes images to determine glycocalyx thickness, red blood cell filling percentage, and vessel density. Although GlycoCheck has been used to study microcirculation in critically ill patients, little is known about the reproducibility of measurements in this population. MATERIALS AND METHODS: A total of 60 critically ill patients were studied. Three consecutive microcirculation measurements were performed with the GlycoCheck system in 40 of these patients by one of two experienced observers. Twenty patients were assessed by both observers. Intra- and interobserver variability were assessed using intraclass correlation coefficients (ICCs). RESULTS: ICCs of single measurements were poor for glycocalyx thickness and good for filling percentage and vessel density. Reproducibility could be substantially increased for all parameters when three consecutive measurements were performed and averaged. DISCUSSION: GlycoCheck can be used to study microcirculation. However, to obtain reliable results three consecutive measurements should be performed and averaged. The variation of the measurements currently hampers the clinical application in individual patients.

Early initiation of extracorporeal life support in refractory out-of-hospital cardiac arrest: Design and rationale of the INCEPTION trial.

Return of spontaneous circulation occurs in less than 10% of patients with cardiac arrest undergoing cardiopulmonary resuscitation (CPR) for more than 15 minutes. Studies suggest that extracorporeal life support during cardiopulmonary resuscitation (ECPR) improves survival rate in these patients. These studies, however, are hampered by their non-randomized, observational design and are mostly single-center. A multicenter, randomized controlled trial is urgently warranted to evaluate the effectiveness of ECPR. HYPOTHESIS: We hypothesize that early initiation of ECPR in refractory out-of-hospital cardiac arrest (OHCA) improves the survival rate with favorable neurological status. STUDY DESIGN: The INCEPTION trial is an investigator-initiated, prospective, multicenter trial that will randomly allocate 110 patients to either continued CPR or ECPR in a 1:1 ratio. Patients eligible for inclusion are adults (≤ 70 years) with witnessed OHCA presenting with an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT), who received bystander basic life support and who fail to achieve sustained return of spontaneous circulation within 15 minutes of cardiopulmonary resuscitation by emergency medical services. The primary endpoint of the study is 30-day survival rate with favorable neurological status, defined as 1 or 2 on the Cerebral Performance Category score. The secondary endpoints include 3, 6 and 12-month survival rate with favorable neurological status and the cost-effectiveness of ECPR compared to CCPR. SUMMARY: The INCEPTION trial aims to determine the clinical benefit for the use of ECPR in patients with refractory OHCA presenting with VF/VT. Additionally, the feasibility and cost-effectiveness of ECPR will be evaluated.

Clinical implementation of electric impedance tomography in the treatment of ARDS: a single centre experience.

To report on our clinical experience using EIT in individualized PEEP titration in ARDS. Using EIT assessment, we optimized PEEP settings in 39 ARDS patients. The EIT PEEP settings were compared with the physicians' PEEP settings and the PEEP settings according to the ARDS network. We defined a PEEP difference equal to or greater than 4 cm H2O as clinically relevant. Changes in lung compliance and PaO2/FiO2-ratio were compared in patients with EIT-based PEEP adjustments and in patients with unaltered PEEP. In 28% of the patients, the difference in EIT-based PEEP and physician-PEEP was clinically relevant; in 36%, EIT-based PEEP and physician-PEEP were equal. The EIT-based PEEP disagreed with the PEEP settings according to the ARDS network. Adjusting PEEP based upon EIT led to a rapid increase in lung compliance and PaO2/FiO2-ratio. However, this increase was also observed in the group where the PEEP difference was less than 4 cm H2O. We hypothesize that this can be attributed to the alveolar recruitment during the PEEP trial. EIT based individual PEEP setting appears to be a promising method to optimize PEEP in ARDS patients. The clinical impact, however, remains to be established.

QUIT EMR trial: a prospective, observational, multicentre study to evaluate quality and 24†hours post-transport morbidity of interhospital transportation of critically ill patients: study protocol.

INTRODUCTION: It is widely accepted that transportation of critically ill patients is high risk. Unfortunately, however, there are currently no evidence-based criteria with which to determine the quality of various interhospital transport systems and their impact on the outcomes for patients. We aim to rectify this by assessing 2 scores which were developed in our hospital in a prospective, observational study. Primarily, we will be examining the Quality of interhospital critical care transportation in the Euregion Meuse-Rhine (QUIT EMR) score, which focuses on the quality of the transport system, and secondarily the SEMROS (Simplified EMR outcome score) which detects changes in the patient's clinical condition in the 24 hours following their transportation. METHODS AND ANALYSIS: A web-based application will be used to document around 150 pretransport, intratransport and post-transport items of each patient case.To be included, patients must be at least 18-years of age and should have been supervised by a physician during an interhospital transport which was started in the study region.The quality of the QUIT EMR score will be assessed by comparing 3 predefined levels of transport facilities: the high, medium and low standards. Subsequently, SEMROS will be used to determine the effect of transport quality on the morbidity 24 hours after transportation.It is estimated that there will be roughly 3000 appropriate cases suitable for inclusion in this study per year. Cases shall be collected from 1 April 2015 until 31 December 2017. ETHICS AND DISSEMINATION: This trial was approved by the Ethics committees of the university hospitals of Maastricht (Netherlands) and Aachen (Germany). The study results will be published in a peer reviewed journal. Results of this study will determine if a prospective randomised trial involving patients of various categories being randomly assigned to different levels of transportation system shall be conducted. TRIAL REGISTRATION NUMBER: NTR4937.

Stenotrophomonas maltophilia ventilator-associated pneumonia. A retrospective matched case-control study.

BACKGROUND: Stenotrophomonas maltophilia is increasingly identified in critically ill patients, but it is considered a pathogen with limited pathogenicity and it is therefore infrequently targeted. This study explores whether S. maltophilia may cause ventilator-associated pneumonia (VAP) and whether it affects intensive care unit (ICU) mortality and 28-day mortality when compared to VAP caused by other Gram-negative bacilli. METHODS: Retrospective analysis of a 19-year prospectively collected database. Stenotrophomonas maltophilia as a cause was considered in VAP-suspected cases when S. maltophilia growth of ≥10(4) cfu/ml was detected in bronchoalveolar lavage fluid analysis. Cases were matched on hospital, gender, age and acute physiology and chronic health evaluation II score in a 1:3 ratio with controls from the same database suffering from VAP caused by other Gram-negative bacilli. RESULTS: Eight cases met the inclusion criteria, of which three were labelled as 'probable' SM-VAP and three as 'possible' SM-VAP. These six patients constitute 1.8% of all VAPs in the studied period. No significant differences in baseline characteristics and duration of mechanical ventilation (p = 0.68), length of stay in the ICU (p = 0.55) and hospital (p = 0.84) between cases and controls were identified between cases and controls. Intensive care unit mortality odds ratio was 1.7 (p = 0.55; 95% CI 0.3-10.5) and 28-day mortality odds ratio was 1.4 (p = 0.70; 95% CI 0.2-9.1). CONCLUSIONS: Stenotrophomonas maltophilia is a possible, yet infrequent cause of VAP. No outcome differences were found when compared to matched VAP caused by other Gram-negative bacilli.

Ventilator-associated Pneumonia caused by commensal oropharyngeal Flora; [corrected] a retrospective Analysis of a prospectively collected Database.

BACKGROUND: The significance of commensal oropharyngeal flora (COF) as a potential cause of ventilator-associated pneumonia (VAP) is scarcely investigated and consequently unknown. Therefore, the aim of this study was to explore whether COF may cause VAP. METHODS: Retrospective clinical, microbiological and radiographic analysis of all prospectively collected suspected VAP cases in which bronchoalveolar lavage fluid exclusively yielded ≥ 10(4) cfu/ml COF during a 9.5-year period. Characteristics of 899 recent intensive care unit (ICU) admissions were used as a reference population. RESULTS: Out of the prospectively collected database containing 159 VAP cases, 23 patients were included. In these patients, VAP developed after a median of 8 days of mechanical ventilation. The patients faced a prolonged total ICU length of stay (35 days [P < .001]), hospital length of stay (45 days [P = .001]), and a trend to higher mortality (39 % vs. 26 %, [P = .158]; standardized mortality ratio 1.26 vs. 0.77, [P = .137]) compared to the reference population. After clinical, microbiological and radiographic analysis, COF was the most likely cause of respiratory deterioration in 15 patients (9.4 % of all VAP cases) and a possible cause in 2 patients. CONCLUSION: Commensal oropharyngeal flora appears to be a potential cause of VAP in limited numbers of ICU patients as is probably associated with an increased length of stay in both ICU and hospital. As COF-VAP develops late in the course of ICU admission, it is possibly associated with the immunocompromised status of ICU patients.

Ventilator-associated pneumonia rates after introducing selective digestive tract decontamination.

The incidence of ventilator-associated pneumonia (VAP) before and after the introduction of selective oral decontamination (SOD) only and selective digestive tract decontamination (SDD) in a general intensive care population was examined. SOD as standard of care was introduced in December 2010 and SDD, including SOD, in January 2012 for all patients with an expected length of intensive care unit (ICU) stay of at least 48 h. The diagnosis of VAP was based on clinical criteria and quantitative cultures of bronchoalveolar lavage fluid. A total of 4945 mechanically ventilated patients accounting for 37 554 ventilator days in the period from 2005 to 2013 were analyzed. The incidence of VAP per 1000 ventilator days declined significantly from 4.38 ± 1.64 before to 1.64 ± 0.43 after introduction of SOD/SDD (p = 0.007). Implementation of SOD/SDD as standard of care in ICUs may thus be effective in preventing VAP.

Short-term outcomes and mortality after interhospital intensive care transportation: an observational prospective cohort study of 368 consecutive transports with a mobile intensive care unit.

OBJECTIVES: To evaluate short-term outcomes and mortality after interhospital transportation of intensive care patients performed by a mobile intensive care unit (MICU). SETTING: This study was performed in the tertiary care process of interhospital transportation using the local MICU system in the South East of the Netherlands. PARTICIPANTS: Between March 2009 and December 2011, all transports of adult patients being performed by the local MICU centre have been documented; data on 42 variables, including a 24 h follow-up Sequential Organ Failure Assessment (SOFA) score of 368 consecutive interhospital transports of intensive care patients, were recorded. In 24 cases, the follow-up SOFA score was missing, so 344 data sets were included. INTERVENTIONS: No interventions have been done. PRIMARY/SECONDARY OUTCOME MEASURES: Primary outcome measures were the mean SOFA score before and 24 h after transport, and the 24 h post-transport mortality. Moreover, the differences between the groups of 24 h post-transport survivors and non-survivors have been analysed. RESULTS: The mean SOFA score before transport was 8.8 for the whole population and 8.6 for those patients who were alive 24 h after transport, with a mean SOFA score of 8.4 after transport. The adverse events rate was 6.4%. Fourteen patients (4.1%) died within 24 h after transport. Patients in this group had a higher SOFA score, lower pH, higher age and more additional medical support devices than those patients in the survivor group. CONCLUSIONS: The non-significant decrease in the post-transport SOFA score and the lack of an association between transport and 24 h post-transport mortality indicates that in the study setting, interhospital transportation of intensive care patients performed by a MICU system was not associated with a clinically relevant deterioration of the patient.

Endotracheal aspirate and bronchoalveolar lavage fluid analysis: interchangeable diagnostic modalities in suspected ventilator-associated pneumonia?

Authoritative guidelines state that the diagnosis of ventilator-associated pneumonia (VAP) can be established using either endotracheal aspirate (ETA) or bronchoalveolar lavage fluid (BALF) analysis, thereby suggesting that their results are considered to be in accordance. Therefore, the results of ETA Gram staining and semiquantitative cultures were compared to the results from a paired ETA-BALF analysis. Different thresholds for the positivity of ETAs were assessed. This was a prospective study of all patients who underwent bronchoalveolar lavage for suspected VAP in a 27-bed university intensive care unit during an 8-year period. VAP was diagnosed when ≥ 2% of the BALF cells contained intracellular organisms and/or when BALF quantitative culture revealed ≥ 10(4) CFU/ml of potentially pathogenic microorganisms. ETA Gram staining and semiquantitative cultures were compared to the results from paired BALF analysis by Cohen's kappa coefficients. VAP was suspected in 311 patients and diagnosed in 122 (39%) patients. In 288 (93%) patients, the results from the ETA analysis were available for comparison. Depending on the threshold used and the diagnostic modality, VAP incidences varied from 15% to 68%. For the diagnosis of VAP, the most accurate threshold for positivity of ETA semiquantitative cultures was moderate or heavy growth, whereas the optimal threshold for BALF Gram staining was ≥ 1 microorganisms per high power field. The Cohen's kappa coefficients were 0.22, 0.31, and 0.60 for ETA and paired BALF Gram stains, cultures, and BALF Gram stains, respectively. Since the ETA and BALF Gram stains and cultures agreed only fairly, they are probably not interchangeable for diagnosing VAP.

Surveillance cultures in intensive care units: a nationwide survey on current practice providing future perspectives.

PURPOSE: To explore the extent of surveillance culture (SC) implementation underlying motives for obtaining SC and decision making based on the results. MATERIALS AND METHODS: A questionnaire was distributed to Heads of Department (HODs) and microbiologists within all intensive care departments in the Netherlands. RESULTS: Response was provided by 75 (79%) of 95 HODs and 38 (64%) of 59 laboratories allied to an intensive care unit (ICU). Surveillance cultures were routinely obtained according to 55 (73%) of 75 HODs and 33 (87%) of 38 microbiologists. Surveillance cultures were obtained in more than 80% of higher-level ICUs and in 58% of lower-level ICUs (P < .05). Surveillance cultures were obtained twice weekly (88%) and sampled from trachea (87%), pharynx (74%), and rectum (68%). Thirty (58%) of 52 HODs obtained SC to optimize individual patient treatment. On suspicion of infection from an unknown source, microorganisms identified by SC were targeted according to 87%. One third of HODs targeted microorganisms identified by SC in the case of an infection not at the location where the SC was obtained. This was significantly more often than microbiologists in case of no infection (P = .02) or infection of unknown origin (P < .05). CONCLUSIONS: Surveillance culture implementation is common in Dutch ICUs to optimize individual patients' treatment. Consensus is lacking on how to deal with SC results when the focus of infection is not at the sampled site.

Cardiac output measurement by bioimpedance and noninvasive pulse contour analysis compared with the continuous pulmonary artery thermodilution technique.

OBJECTIVE: The aim of the present study was to compare 2 noninvasive cardiac output measurement methods with the continuous cardiac output thermodilution (CCO-TD) method. DESIGN: A single-center prospective design. SETTING: A university hospital. PARTICIPANTS: Fifty-three consecutive patients scheduled for elective, non-emergent cardiac surgery. INTERVENTIONS: With each participant the cardiac output was measured using 3 methods: CCO-TD, the Endotracheal Cardiac Output Monitor (ECOM), and the Nexfin monitor. MEASUREMENTS AND MAIN RESULTS: Measurements were performed simultaneously at 7 time points: After induction, before cardiopulmonary bypass, after cardiopulmonary bypass, after protamine, after arrival in the intensive care unit, and before extubation on postoperative day 1. Statistical analysis was performed using Pearson's correlation, Bland-Altman, percent error, and polar plots. Compared to CCO-TD, ECOM showed significant correlation of R0.619 with a bias of -0.13 L/min (95% confidence interval -2.19-1.93 L/min), a percent error of 40%, and trending ability of 87% and 97% within 0.5 L/min and 1.0 L/min, respectively. The Nexfin monitor showed significant correlation of R0.535 with a bias of-0.35 L/min (95% confidence interval-3.36-2.66 L/min), a percent error of 58% and trending ability of 84% and 97% were within 0.5 L/min and 1.0 L/min limits of agreement. CONCLUSIONS: Neither the ECOM nor the Nexfin had the ability to replace the thermodilution-based continuous cardiac output monitor. The ECOM did not have acceptable accuracy or trending ability and only could be utilized for intubated patients. The Nexfin lacked reliability and trending ability. Also, the Nexfin did not provide consistent results.

Accuracy of end-tidal CO2 capnometers in post-cardiac surgery patients during controlled mechanical ventilation.

BACKGROUND: The determination of end-tidal carbon dioxide (etCO2) is very helpful in cardiac resuscitation for confirmation and monitoring of endotracheal tube placement and as an indicator of return of circulation and effectiveness of chest compressions. There is now also widespread use of capnometry on-site at emergency and trauma fields. OBJECTIVE: We studied the accuracy and correlation of three capnometers (EMMA, Medtronic, and Evita) with partial pressure of arterial CO2 (PaCO2) measurements. METHODS: The three capnometers were placed in-line in the ventilator tubing of the patient. Forty sedated and mechanically ventilated post-cardiac surgery patients were studied. Twenty consecutive etCO2 values were collected simultaneously from all three monitors while drawing an arterial blood sample. Paired sample t-test and Pearson correlation were used to compare the capnometers and their correlation with PaCO2. RESULTS: The correlation of etCO2 measurements between all three capnometers was good (Emma vs. Evita: 0.874, Emma vs. Medtronic: 0.949, Evita vs. Medtronic: 0.878). The correlation of PaCO2 with the Evita is the lowest (0.671) as compared to the EMMA (0.693) and the Medtronic (0.727). The lowest dispersion of the difference between etCO2 and PaCO2 was seen in EMMA (3.30), the highest in Evita (3.98). CONCLUSIONS: A good correlation between etCO2 and PaCO2 was shown with the three capnometers in the present study. However, etCO2 measurements were not valid to estimate PaCO2 in these patients. Therefore, capnometry cannot be used to replace serial blood gas analyses completely, but may be a good cardiopulmonary trend monitor and alerting system in catastrophic events.

Impaired skeletal muscle substrate oxidation in glucose-intolerant men improves after weight loss.

OBJECTIVE: An impaired fatty acid handling in skeletal muscle may be involved in the development of insulin resistance and diabetes mellitus type 2 (DM2). We investigated muscle fatty acid metabolism in glucose-intolerant men (impaired glucose tolerance (IGT)), a prediabetic state, relative to BMI-matched control men (normal glucose tolerance (NGT)) during fasting and after a meal, because most people in the western society are in the fed state most of the day. METHODS AND PROCEDURES: Skeletal muscle free fatty acid (FFA) uptake and oxidation were studied using the stable isotope tracer [2,2-(2)H]-palmitate and muscle indirect calorimetry in the forearm model during fasting and after a mixed meal (33 energy % (E%) carbohydrates, 61 E% fat). Intramyocellular triglycerides (IMTGs) were monitored with 1H-magnetic resonance spectroscopy. IGT men were re-examined after weight loss (-15% of body weight (BW)). RESULTS: The postprandial increase in forearm muscle respiratory quotient (RQ) was blunted in IGT compared to NGT, but improved after weight loss. Weight loss also improved fasting-fat oxidation and tended to decrease IMTGs (P=0.08). No differences were found in fasting and postprandial forearm muscle fatty acid uptake between NGT and IGT, or in IGT before and after weight loss. DISCUSSION: The ability to switch from fat oxidation to carbohydrate oxidation after a meal is already impaired in the prediabetic state, suggesting this may be an early factor in the development toward DM2. This impaired ability to regulate fat oxidation during fasting and after a meal (impaired metabolic flexibility) can be (partly) reversed by weight loss.

The effects of esmolol and dexmedetomidine on myocardial oxygen consumption during sympathetic stimulation in dogs.

OBJECTIVE: The purpose of this study was to compare the potential of the beta(1)-adrenergic receptor blocker esmolol and the alpha(2)-adrenergic receptor agonist dexmedetomidine to suppress the cardiovascular and neuroendocrine response to a sympathetic stimulus. DESIGN: Experimental study. SETTING: Laboratory of university. PARTICIPANTS: Eleven anesthetized dogs. INTERVENTIONS: Catheters for arterial and coronary venous blood sampling and calculation of myocardial oxygen consumption were inserted. Pressure sensors were placed in the aorta, left ventricle, and a carotid artery. Flow probes were placed around the aortic root and around the left anterior descending coronary artery. Esmolol was infused (loading dose of 1 mg/kg, infusion of 0.3 mg/kg/h), and the adequacy of beta-blockade was checked. Thirty minutes after stopping esmolol, dexmedetomidine infusion was started (loading dose of 1 microg/kg, infusion of 1.5 microg/kg/min). Occlusion of both carotid arteries was used as a sympathetic stimulus before and during infusion of esmolol and before and during infusion of dexmedetomidine. MEASUREMENTS AND MAIN RESULTS: The variables were measured just before and during sympathetic stimulation, and changes were calculated. Both drugs suppressed the increase in dPdT(max). Dexmedetomidine suppressed the increase in plasma norepinephrine and the increase in systemic vascular resistance (dexmedetomidine 4% +/- 4% and esmolol 25% +/- 19% increase, p = 0.02). Esmolol attenuated the heart rate response (esmolol 2% +/- 2% and dexmedetomidine 20% +/- 18% increase, p = 0.02). However, dexmedetomidine decreased baseline heart rate more than esmolol; therefore, the absolute maximal heart rate during sympathetic stimulation was lower in the presence of dexmedetomidine (dexmedetomidine 119 +/- 14 and esmolol 141 +/- 15 beats/min, p = 0.01). Neither drug suppressed the increase in myocardial oxygen consumption. CONCLUSIONS: Both esmolol and dexmedetomidine have the potential to suppress some of the cardiovascular and neuroendocrine changes to a sympathetic stimulus but neither drug abolished the increase in myocardial oxygen consumption.

Postprandial interleukin-6 release from skeletal muscle in men with impaired glucose tolerance can be reduced by weight loss.

CONTEXT: Obesity and type 2 diabetes mellitus are associated with increased levels of IL-6, a marker of inflammation. OBJECTIVE: This study addressed the question of whether IL-6 was released from skeletal muscle after a high-fat meal in men with impaired glucose tolerance (IGT), a prediabetic state, and whether IL-6 release could be reduced by weight loss. DESIGN: Skeletal muscle metabolism was studied in men with IGT (n = 11) and compared with men with normal glucose tolerance (NGT, n = 9), matched for body mass index and age. IL-6 flux over skeletal muscle was measured with the forearm model. Eight IGT men were willing to participate in a 12-wk weight loss program and were tested again. RESULTS: IL-6, but not C-reactive protein or TNF-alpha receptor 1 and 2, was released by skeletal muscle. Muscle IL-6 release was higher in IGT than in NGT during fasting (IGT = 2.26 +/- 1.89 vs. NGT = 0.87 +/- 0.48 fmol x 100 ml tissue(-1) x min(-1), P = 0.04) and after a meal (mean area under the curve per minute: IGT = 3.48 +/- 2.63 vs. NGT = 1.37 +/- 0.75 fmol x 100 ml tissue(-1) x min(-1); P = 0.03). In the IGT men, body weight loss resulted in a decrease of postprandial IL-6 release from skeletal muscle (-52%; P = 0.04), reaching levels of the obese, NGT controls. CONCLUSION: The present data suggest that a high-fat meal can evoke IL-6 release from muscle and that the IL-6 release is a consequence rather than a cause of the obese, insulin-resistant, and/or IGT state.