Conservative versus Liberal Oxygenation Targets in Intensive Care Unit Patients (ICONIC): A Randomized Clinical Trial.

Rationale: Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear. Objectives: This study aimed to determine whether a low-oxygenation strategy would lower 28-day mortality compared with a high-oxygenation strategy. Methods: This randomized multicenter trial included mechanically ventilated ICU patients with an expected ventilation duration of at least 24 hours. Patients were randomized 1:1 to a low-oxygenation (PaO2, 55-80 mm Hg; or oxygen saturation as measured by pulse oximetry, 91-94%) or high-oxygenation (PaO2, 110-150 mm Hg; or oxygen saturation as measured by pulse oximetry, 96-100%) target until ICU discharge or 28 days after randomization, whichever came first. The primary outcome was 28-day mortality. The study was stopped prematurely because of the COVID-19 pandemic when 664 of the planned 1,512 patients were included. Measurements and Main Results: Between November 2018 and November 2021, a total of 664 patients were included in the trial: 335 in the low-oxygenation group and 329 in the high-oxygenation group. The median achieved PaO2 was 75 mm Hg (interquartile range, 70-84) and 115 mm Hg (interquartile range, 100-129) in the low- and high-oxygenation groups, respectively. At Day 28, 129 (38.5%) and 114 (34.7%) patients had died in the low- and high-oxygenation groups, respectively (risk ratio, 1.11; 95% confidence interval, 0.9-1.4; P = 0.30). At least one serious adverse event was reported in 12 (3.6%) and 17 (5.2%) patients in the low- and high-oxygenation groups, respectively. Conclusions: Among mechanically ventilated ICU patients with an expected mechanical ventilation duration of at least 24 hours, using a low-oxygenation strategy did not result in a reduction of 28-day mortality compared with a high-oxygenation strategy. Clinical trial registered with the National Trial Register and the International Clinical Trials Registry Platform (NTR7376).

The right time to measure anti-Xa activity in critical illness: pharmacokinetics of therapeutic dose nadroparin.

Background: Peak anti-Xa activity of low-molecular-weight heparin nadroparin is measured 3 to 5 hours after subcutaneous injection. In critically ill patients, physiological changes and medical therapies may result in peak activities before or after this interval, possibly impacting dosing. Objectives: The primary objective was to determine the percentage of critically ill patients with adequately estimated peak activities drawn 3 to 5 hours after subcutaneous administration of a therapeutic dose of nadroparin. Adequate was defined as a peak activity of ≥80% of the actual peak anti-Xa activity. If ≥80% of patients had adequately estimated peak activities in the 3- to 5-hour interval, measurement in this interval was regarded as acceptable. The secondary objective was to determine the pharmacokinetic profile of nadroparin. Methods: In this single-center, prospective study, we evaluated anti-Xa activities in patients admitted to a general intensive care unit. After ≥4 equal doses of nadroparin, anti-Xa activity was measured according to a 12- to 24-hour sampling scheme. Results: In 25 patients, anti-Xa activities drawn between 3 and 5 hours after administration ranged 80% to 100% of the actual peak activity. Compared to the threshold level of an adequate estimation in at least 20 patients (≥80%), measuring anti-Xa activities in the 3- to 5-hour interval is an acceptable method (1-tailed binomial test; P < .02). We found a large interindividual variability for nadroparin exposure (mean ± SD area-under-the-curve0-12h, 10.3 ± 4.8 IU·h/mL) and delayed elimination (t1/2 range, 4.0-120.9 hours) despite adequate renal function. Conclusion: In critically ill patients, measuring anti-Xa activity in a 3- to 5-hour interval after subcutaneous injection of therapeutic nadroparin is an acceptable method to estimate the actual peak anti-Xa activity.

Impact of reduced antibiotic treatment duration on antimicrobial resistance in critically ill patients in the randomized controlled SAPS-trial.

Background: In the previously reported SAPS trial (https://clinicaltrials.gov/ct2/show/NCT01139489), procalcitonin-guidance safely reduced the duration of antibiotic treatment in critically ill patients. We assessed the impact of shorter antibiotic treatment on antimicrobial resistance development in SAPS patients. Materials and methods: Cultures were assessed for the presence of multi-drug resistant (MDR) or highly resistant organisms (HRMO) and compared between PCT-guided and control patients. Baseline isolates from 30 days before to 5 days after randomization were compared with those from 5 to 30 days post-randomization. The primary endpoint was the incidence of new MDR/HRMO positive patients. Results: In total, 8,113 cultures with 96,515 antibiotic test results were evaluated for 439 and 482 patients randomized to the PCT and control groups, respectively. Disease severity at admission was similar for both groups. Median (IQR) durations of the first course of antibiotics were 6 days (4-10) and 7 days (5-11), respectively (p = 0.0001). Antibiotic-free days were 7 days (IQR 0-14) and 6 days (0-13; p = 0.05). Of all isolates assessed, 13% were MDR/HRMO positive and at baseline 186 (20%) patients were MDR/HMRO-positive. The incidence of new MDR/HRMO was 39 (8.9%) and 45 (9.3%) in PCT and control patients, respectively (p = 0.82). The time courses for MDR/HRMO development were also similar for both groups (p = 0.33). Conclusions: In the 921 randomized patients studied, the small but statistically significant reduction in antibiotic treatment in the PCT-group did not translate into a detectable change in antimicrobial resistance. Studies with larger differences in antibiotic treatment duration, larger study populations or populations with higher MDR/HRMO incidences might detect such differences.

Ventilation practices in burn patients-an international prospective observational cohort study.

BACKGROUND: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28). METHODS: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V T) was defined as V T ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma. RESULTS: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures <30 cmH2O. CONCLUSION: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V T was not associated with a reduction in VFD-28. TRIAL REGISTRATION: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014.

Implementation and evaluation of a nurse-centered computerized potassium regulation protocol in the intensive care unit--a before and after analysis.

BACKGROUND: Potassium disorders can cause major complications and must be avoided in critically ill patients. Regulation of potassium in the intensive care unit (ICU) requires potassium administration with frequent blood potassium measurements and subsequent adjustments of the amount of potassium administrated. The use of a potassium replacement protocol can improve potassium regulation. For safety and efficiency, computerized protocols appear to be superior over paper protocols. The aim of this study was to evaluate if a computerized potassium regulation protocol in the ICU improved potassium regulation. METHODS: In our surgical ICU (12 beds) and cardiothoracic ICU (14 beds) at a tertiary academic center, we implemented a nurse-centered computerized potassium protocol integrated with the pre-existent glucose control program called GRIP (Glucose Regulation in Intensive Care patients). Before implementation of the computerized protocol, potassium replacement was physician-driven. Potassium was delivered continuously either by central venous catheter or by gastric, duodenal or jejunal tube. After every potassium measurement, nurses received a recommendation for the potassium administration rate and the time to the next measurement. In this before-after study we evaluated potassium regulation with GRIP. The attitude of the nursing staff towards potassium regulation with computer support was measured with questionnaires. RESULTS: The patient cohort consisted of 775 patients before and 1435 after the implementation of computerized potassium control. The number of patients with hypokalemia (<3.5 mmol/L) and hyperkalemia (>5.0 mmol/L) were recorded, as well as the time course of potassium levels after ICU admission. The incidence of hypokalemia and hyperkalemia was calculated. Median potassium-levels were similar in both study periods, but the level of potassium control improved: the incidence of hypokalemia decreased from 2.4% to 1.7% (P < 0.001) and hyperkalemia from 7.4% to 4.8% (P < 0.001). Nurses indicated that they considered computerized potassium control an improvement over previous practice. CONCLUSIONS: Computerized potassium control, integrated with the nurse-centered GRIP program for glucose regulation, is effective and reduces the prevalence of hypo- and hyperkalemia in the ICU compared with physician-driven potassium regulation.

Changes in ventilator settings and ventilation-induced lung injury in burn patients-A systematic review.

OBJECTIVE: Ventilation strategies aiming at prevention of ventilator-induced lung injury (VILI), including low tidal volumes (VT) and use of positive end-expiratory pressures (PEEP) are increasingly used in critically ill patients. It is uncertain whether ventilation practices changed in a similar way in burn patients. Our objective was to describe applied ventilator settings and their relation to development of VILI in burn patients. DATA SOURCES: Systematic search of the literature in PubMed and EMBASE using MeSH, EMTREE terms and keywords referring to burn or inhalation injury and mechanical ventilation. STUDY SELECTION: Studies reporting ventilator settings in adult or pediatric burn or inhalation injury patients receiving mechanical ventilation during the ICU stay. DATA EXTRACTION: Two authors independently screened abstracts of identified studies for eligibility and performed data extraction. DATA SYNTHESIS: The search identified 35 eligible studies. VT declined from 14 ml/kg in studies performed before to around 8 ml/kg predicted body weight in studies performed after 2006. Low-PEEP levels (<10 cmH2O) were reported in 70% of studies, with no changes over time. Peak inspiratory pressure (PIP) values above 35 cmH2O were frequently reported. Nevertheless, 75% of the studies conducted in the last decade used limited maximum airway pressures (≤35 cmH2O) compared to 45% of studies conducted prior to 2006. Occurrence of barotrauma, reported in 45% of the studies, ranged from 0 to 29%, and was more frequent in patients ventilated with higher compared to lower airway pressures. CONCLUSION: This systematic review shows noticeable trends of ventilatory management in burn patients that mirrors those in critically ill non-burn patients. Variability in available ventilator data precluded us from drawing firm conclusions on the association between ventilator settings and the occurrence of VILI in burn patients.

Nebulized Heparin in Burn Patients with Inhalation Trauma-Safety and Feasibility.

BACKGROUND: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin. METHODS: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility. RESULTS: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations. CONCLUSION: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients.

Computer-assisted glucose control in critically ill patients.

OBJECTIVE: Intensive insulin therapy is associated with the risk of hypoglycemia and increased costs of material and personnel. We therefore evaluated the safety and efficiency of a computer-assisted glucose control protocol in a large population of critically ill patients. DESIGN AND SETTING: Observational cohort study in three intensive care units (32 beds) in a 1,300-bed university teaching hospital. PATIENTS: All 2,800 patients admitted to the surgical, neurosurgical, and cardiothoracic units; the study period started at each ICU after implementation of Glucose Regulation for Intensive Care Patients (GRIP), a freely available computer-assisted glucose control protocol. MEASUREMENTS AND RESULTS: We analysed compliance in relation to recommended insulin pump rates and glucose measurement frequency. Patients were on GRIP-ordered pump rates 97% of time. Median measurement time was 5min late (IQR 20min early to 34 min late). Hypoglycemia was uncommon (7% of patients for mild hypoglycemia, < 3.5mmol/l; 0.86% for severe hypoglycemia, < 2.2 mmol/l). Our predefined target range (4.0-7.5 mmol/l) was reached after a median of 5.6 h (IQR 0.2-11.8) and maintained for 89% (70-100%) of the remaining stay at the ICU. The number of measurements needed was 5.9 (4.8-7.3) per patient per day. In-hospital mortality was 10.1%. CONCLUSIONS: Our computer-assisted glucose control protocol provides safe and efficient glucose regulation in routine intensive care practice. A low rate of hypoglycemic episodes was achieved with a considerably lower number of glucose measurements than used in most other schemes.

The impact of a reduced dose of dexamethasone on glucose control after coronary artery bypass surgery.

BACKGROUND: Intensive insulin therapy to maintain normoglycemia after cardiac surgery reduces morbidity and mortality. We investigated the magnitude and duration of hyperglycemia caused by dexamethasone administered after cardiopulmonary bypass. METHODS: A single-center before-after cohort study was performed. All consecutive patients undergoing coronary artery bypass grafting with cardiopulmonary bypass during a 6-month period were included. Insulin administration was guided by a sliding scale protocol. Halfway the observation period, the dexamethasone protocol was changed. The single dose (1D) group received a pre-operative dose of dexamethasone of 1 mg/kg. The double dose group (2D) received an additional dose of 0.5 mg/kg of dexamethasone post-operatively at ICU admission. RESULTS: We included 116 patients in the 1D group and 158 patients in the 2D group. There were no significant baseline differences between the groups. Median Euroscore was 5. In univariable analysis, the glucose level was different between groups 1D and 2D at 4, 6, 9, 12 and 24 hours after ICU admission (all p < 0.001). Insulin infusion was higher in the 1D group. Corrected for insulin dose in multivariable linear analysis, the difference in glucose between the 1D and 2D groups was 1.5 mmol/L (95% confidence interval 1.0-2.0, p < 0.001) 12 hours after ICU admission. CONCLUSION: Dexamethasone exerts a hyperglycemic effect in cardiac surgery patients. Patients receiving high-dose corticosteroid therapy should be monitored and treated more intensively for hyperglycemic episodes.

Fluid Resuscitation in Septic Patients Improves Systolic but not Diastolic Middle Cerebral Artery Flow Velocity.

To investigate the effects of fluid resuscitation on cerebral hemodynamics in sepsis, the following set of transcranial Doppler (TCD) parameters was used: maximal change in flow velocity (FV) during stroke onset (acc), maximal FV during first (sys1) or second (sys2) phase of systole and mean diastolic FV (dias@560). We aim to evaluate changes in cerebral hemodynamics that result from (i) sepsis and (ii) adequate fluid resuscitation in critically ill septic patients. In the majority of 16 septic patients sys2 was initially absent but reappeared during the period of fluid resuscitation; whereas sys2 absence was never seen in healthy controls. Second, adequate fluid resuscitation resulted in a significant increase of the systolic FV components (acc, sys1, sys2 and systolic blood pressure); whereas the diastolic components (dias@560 and diastolic blood pressure) remained unchanged. Sys2 absence and reappearance in sepsis suggests that TCD could become a non-invasive alternative for hemodynamic monitoring.

Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial.

BACKGROUND: In critically ill patients, antibiotic therapy is of great importance but long duration of treatment is associated with the development of antimicrobial resistance. Procalcitonin is a marker used to guide antibacterial therapy and reduce its duration, but data about safety of this reduction are scarce. We assessed the efficacy and safety of procalcitonin-guided antibiotic treatment in patients in intensive care units (ICUs) in a health-care system with a comparatively low use of antibiotics. METHODS: We did a prospective, multicentre, randomised, controlled, open-label intervention trial in 15 hospitals in the Netherlands. Critically ill patients aged at least 18 years, admitted to the ICU, and who received their first dose of antibiotics no longer than 24 h before inclusion in the study for an assumed or proven infection were eligible to participate. Patients who received antibiotics for presumed infection were randomly assigned (1:1), using a computer-generated list, and stratified (according to treatment centre, whether infection was acquired before or during ICU stay, and dependent on severity of infection [ie, sepsis, severe sepsis, or septic shock]) to receive either procalcitonin-guided or standard-of-care antibiotic discontinuation. Both patients and investigators were aware of group assignment. In the procalcitonin-guided group, a non-binding advice to discontinue antibiotics was provided if procalcitonin concentration had decreased by 80% or more of its peak value or to 0·5 µg/L or lower. In the standard-of-care group, patients were treated according to local antibiotic protocols. Primary endpoints were antibiotic daily defined doses and duration of antibiotic treatment. All analyses were done by intention to treat. Mortality analyses were completed for all patients (intention to treat) and for patients in whom antibiotics were stopped while being on the ICU (per-protocol analysis). Safety endpoints were reinstitution of antibiotics and recurrent inflammation measured by C-reactive protein concentrations and they were measured in the population adhering to the stopping rules (per-protocol analysis). The study is registered with ClinicalTrials.gov, number NCT01139489, and was completed in August, 2014. FINDINGS: Between Sept 18, 2009, and July 1, 2013, 1575 of the 4507 patients assessed for eligibility were randomly assigned to the procalcitonin-guided group (761) or to standard-of-care (785). In 538 patients (71%) in the procalcitonin-guided group antibiotics were discontinued in the ICU. Median consumption of antibiotics was 7·5 daily defined doses (IQR 4·0-12·7) in the procalcitonin-guided group versus 9·3 daily defined doses (5·0-16·6) in the standard-of-care group (between-group absolute difference 2·69, 95% CI 1·26-4·12, p<0·0001). Median duration of treatment was 5 days (3-9) in the procalcitonin-guided group and 7 days (4-11) in the standard-of-care group (between-group absolute difference 1·22, 0·65-1·78, p<0·0001). Mortality at 28 days was 149 (20%) of 761 patients in the procalcitonin-guided group and 196 (25%) of 785 patients in the standard-of-care group (between-group absolute difference 5·4%, 95% CI 1·2-9·5, p=0·0122) according to the intention-to-treat analysis, and 107 (20%) of 538 patients in the procalcitonin-guided group versus 121 (27%) of 457 patients in the standard-of-care group (between-group absolute difference 6·6%, 1·3-11·9, p=0·0154) in the per-protocol analysis. 1-year mortality in the per-protocol analysis was 191 (36%) of 538 patients in the procalcitonin-guided and 196 (43%) of 457 patients in the standard-of-care groups (between-group absolute difference 7·4, 1·3-13·8, p=0·0188). INTERPRETATION: Procalcitonin guidance stimulates reduction of duration of treatment and daily defined doses in critically ill patients with a presumed bacterial infection. This reduction was associated with a significant decrease in mortality. Procalcitonin concentrations might help physicians in deciding whether or not the presumed infection is truly bacterial, leading to more adequate diagnosis and treatment, the cornerstones of antibiotic stewardship. FUNDING: Thermo Fisher Scientific.

Survival benefit of cardiopulmonary bypass support in bilateral lung transplantation for emphysema patients.

BACKGROUND: This study is designed to examine a possible association of cardiopulmonary bypass (CPB) support and outcome of lung transplantation in a well-balanced group of emphysema patients. METHODS: We performed a retrospective analysis of 62 consecutive primary bilateral lung transplantations for emphysema. Risk factors for their possible association with patient survival were analyzed by multivariate logistic regression. RESULTS: The use of CPB support was associated with improved survival (odds ratio=0.25; P=0.038). The actuarial survival at 1 year was 97% for patients treated with CPB and 77% for patients treated without CPB support. In 28 patients (45%), 2 human leukocyte antigen (HLA)-DR mismatches between donor and recipient occurred, whereas 34 patients had 0 or 1 HLA-DR mismatches. The use of CPB support in the group with two HLA-DR mismatches was associated with improved survival (odds ratio=0.06; P=0.020). This association was not present in the group with 0 or 1 HLA-DR mismatches. CONCLUSIONS: These results demonstrate a significant survival benefit of CPB support during bilateral lung transplantation in emphysema patients. The difference in survival benefit of CPB support between the patients with 0 or 1 HLA-DR mismatches and the patients with 2 HLA-DR mismatches indicates that the immunosuppressive effect of CPB support might be responsible for this survival benefit. The underlying immunological mechanism might be important in the future treatment of organ transplantation.

Patient recollection of airway suctioning in the ICU: routine versus a minimally invasive procedure.

OBJECTIVE: Many patients have an unpleasant recollection of routine endotracheal suctioning after discharge from the Intensive Care Unit (ICU). We hypothesized that through minimally invasive airway suctioning discomfort and stress may be prevented, resulting in less recollection. DESIGN: A prospective randomized clinical trial. SETTING: Two ICUs at the University Hospital of Groningen, the Netherlands. PATIENTS AND PARTICIPANTS: Adult patients with an intubation period exceeding 24 h were included. INTERVENTIONS: Patients received either routine endotracheal suctioning (RES) or minimally invasive airway suctioning (MIAS) during the duration of intubation. MEASUREMENTS AND RESULTS: Within 3 days after ICU discharge all patients were interviewed, regarding recollection and discomfort of suctioning. The level of discomfort was quantified on a visual analogue scale (VAS). We analyzed data from 208 patients (RES: n=113, and MIAS: n=95). A significantly lower prevalence of recollection of airway suctioning was found in the MIAS group (20%) compared to the RES group (41%) (P-value =0.001). No significant difference in level of discomfort was found between the RES and the MIAS group (P-value =0.136). CONCLUSIONS: Minimally invasive airway suctioning results in a lower prevalence of recollection of airway suction than in RES, but not in discomfort.

Endotracheal suctioning versus minimally invasive airway suctioning in intubated patients: a prospective randomised controlled trial.

STUDY OBJECTIVE: Endotracheal suctioning in intubated patients is routinely applied in most ICUs but may have negative side effects. We hypothesised that on-demand minimally invasive suctioning would have fewer side effects than routine deep endotracheal suctioning, and would be comparable in duration of intubation, length of stay in the ICU, and ICU mortality. DESIGN: Randomised prospective clinical trial. SETTING: In two ICUs at University Hospital Groningen, the Netherlands. PATIENTS: Three hundred and eighty-three patients requiring endotracheal intubation for more than 24 h. INTERVENTIONS: Routine endotracheal suctioning (n=197) using a 49-cm suction catheter was compared with on-demand minimally invasive airway suctioning (n=186) using a suction catheter only 29 cm long. MEASUREMENTS AND RESULTS: No differences were found between the routine endotracheal suctioning group and the minimally invasive airway suctioning group in duration of intubation [median (range) 4 (1-75) versus 5 (1-101) days], ICU-stay [median (range) 8 (1-133) versus 7 (1-221) days], ICU mortality (15% versus 17%), and incidence of pulmonary infections (14% versus 13%). Suction-related adverse events occurred more frequently with RES interventions than with MIAS interventions; decreased saturation: 2.7% versus 2.0% (P=0.010); increased systolic blood pressure 24.5% versus 16.8% (P<0.001); increased pulse pressure rate 1.4% versus 0.9% (P=0.007); blood in mucus 3.3% versus 0.9% (P<0.001). CONCLUSIONS: This study demonstrated that minimally invasive airway suctioning in intubated ICU-patients had fewer side effects than routine deep endotracheal suctioning, without being inferior in terms of duration on intubation, length of stay, and mortality.

Discomfort and factual recollection in intensive care unit patients.

INTRODUCTION: A stay in the intensive care unit (ICU), although potentially life-saving, may cause considerable discomfort to patients. However, retrospective assessment of discomfort is difficult because recollection of stressful events may be impaired by sedation and severe illness during the ICU stay. This study addresses the following questions. What is the incidence of discomfort reported by patients recently discharged from an ICU? What were the sources of discomfort reported? What was the degree of factual recollection during patients' stay in the ICU? Finally, was discomfort reported more often in patients with good factual recollection? METHODS: All ICU patients older than 18 years who had needed prolonged (>24 hour) admission with tracheal intubation and mechanical ventilation were consecutively included. Within three days after discharge from the ICU, a structured, in-person interview was conducted with each individual patient. All patients were asked to complete a questionnaire consisting of 14 questions specifically concerning the environment of the ICU they had stayed in. Furthermore, they were asked whether they remembered any discomfort during their stay; if they did then they were asked to specify which sources of discomfort they could recall. A reference group of surgical ward patients, matched by sex and age to the ICU group, was studied to validate the questionnaire. RESULTS: A total of 125 patients discharged from the ICU were included in this study. Data for 123 ICU patients and 48 surgical ward patients were analyzed. The prevalence of recollection of any type of discomfort in the ICU patients was 54% (n = 66). These 66 patients were asked to identify the sources of discomfort, and presence of an endotracheal tube, hallucinations and medical activities were identified as such sources. The median (min-max) score for factual recollection in the ICU patients was 15 (0-28). The median (min-max) score for factual recollection in the reference group was 25 (19-28). Analysis revealed that discomfort was positively related to factual recollection (odds ratio 1.1; P < 0.001), especially discomfort caused by the presence of an endotracheal tube, medical activities and noise. Hallucinations were reported more often with increasing age. Pain as a source of discomfort was predominantly reported by younger patients. CONCLUSION: Among postdischarge ICU patients, 54% recalled discomfort. However, memory was often impaired: the median factual recollection score of ICU patients was significantly lower than that of matched control patients. The presence of an endotracheal tube, hallucinations and medical activities were most frequently reported as sources of discomfort. Patients with a higher factual recollection score were at greater risk for remembering the stressful presence of an endotracheal tube, medical activities and noise. Younger patients were more likely to report pain as a source of discomfort.

HEPBURN - investigating the efficacy and safety of nebulized heparin versus placebo in burn patients with inhalation trauma: study protocol for a multi-center randomized controlled trial.

BACKGROUND: Pulmonary coagulopathy is a hallmark of lung injury following inhalation trauma. Locally applied heparin attenuates lung injury in animal models of smoke inhalation. Whether local treatment with heparin benefits patients with inhalation trauma is uncertain. The present trial aims at comparing a strategy using frequent nebulizations of heparin with standard care in intubated and ventilated burn patients with bronchoscopically confirmed inhalation trauma. METHODS: The Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized HEParin versus Placebo in BURN Patients with Inhalation Trauma (HEPBURN) is an international multi-center, double-blind, placebo-controlled, two-arm study. One hundred and sixteen intubated and ventilated burn patients with confirmed inhalation trauma are randomized to nebulizations of heparin (the nebulized heparin strategy) or nebulizations of normal saline (the control strategy) every four hours for 14 days or until extubation, whichever comes first. The primary endpoint is the number of ventilator-free days, defined as days alive and breathing without assistance during the first 28 days, if the period of unassisted breathing lasts for at least 24 consecutive hours. DISCUSSION: As far as the authors know, HEPBURN is the first randomized, placebo-controlled trial, powered to investigate whether local treatment with heparin shortens duration of ventilation of intubated and ventilated burn patients with inhalation trauma. TRIAL REGISTRATION: NCT01773083 (http://www.clinicaltrials.gov), registered on 16 January 2013.Recruiting. Randomisation commenced on 1 January 2014.

Systemic VEGF levels after coronary artery bypass graft surgery reflects the extent of inflammatory response.

BACKGROUND: Circulating vascular endothelial growth factor (VEGF) was studied as a substitute endpoint for treatment response after VEGF plasmid therapy. The effect of coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB) on systemic VEGF levels are however largely unknown, therefore, we studied the effect of this procedure to measure VEGF levels after surgery alone. METHODS: Fourteen patients requiring CABG were included. VEGF165 levels, ischemic markers, and hematology were measured before, directly after six days after surgery. RESULTS: VEGF165 in serum and whole blood levels were increased up to six days after CABG, respectively 249.6+/-50.4 to 451.7+/-56.4 (day 6) and 581.9+/-105.1 to 783.4+/-97.7 (day six). There was a close correlation of circulating VEGF165 with leukocyte counts and platelets and not with ischemic markers. CONCLUSION: Following surgery and in case of activated leukocyte and platelet counts care must be taken in the interpretation of systemic VEGF165 levels.

To ventilate or not after minimally invasive direct coronary artery bypass surgery: the role of epidural anesthesia.

OBJECTIVE: To evaluate the effect of immediate postoperative extubation and postoperative ventilation after minimally invasive direct coronary artery bypass (MIDCAB) surgery and to assess the role of epidural anesthesia. DESIGN: Randomized prospective study. SETTING: University hospital, single institution. PARTICIPANTS: Patients (n = 90) scheduled for elective MIDCAB surgery. INTERVENTIONS: Patients were divided into 3 groups: 30 patients had general anesthesia and were extubated immediately after surgery (extubated group), 30 patients had a thoracic epidural and general anesthesia and were extubated immediately after surgery (epidural group), and 30 patients had general anesthesia and were ventilated after surgery (intubated group). MEASUREMENTS AND MAIN RESULTS: With a similar cardiac index and less vasoactive medication, mean arterial blood pressure (77 plus minus 8 mmHg [mean plus minus SD]) and heart rate (76 plus minus 10 beats/min) in the epidural group were lower on the first postoperative day than in the intubated group (83 plus minus 10 mmHg and 81 plus minus 13 beats/min) and the extubated group (86 plus minus 10 mmHg and 83 plus minus 13) (p = 0.01 and p = 0.09). Oxygenation on the first postoperative day was better in the epidural group than in the intubated group (14.8 plus minus 3.8 kPa v 12.6 plus minus 3.2 kPa; p = 0.05). The epidural group and the extubated group had a transient respiratory acidosis postoperatively. Pain score in the epidural group was lower on the first postoperative day than in the extubated group with general anesthesia (3.0 plus minus 1.6 visual analog scale v 4.6 plus minus 1.8 visual analog scale; p = 0.01). Hospital stay was shorter in the epidural group than in the ventilated group (5.9 plus minus 2.4 days v 8.1 plus minus 5.3 days; p = 0.05) CONCLUSION: Immediate postoperative extubation in patients with thoracic epidural anesthesia and supplemental general anesthesia provides the most favorable clinical circumstances after MIDCAB surgery.