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).

Dye-free visualisation of intestinal perfusion using laser speckle contrast imaging in laparoscopic surgery: a prospective, observational multi-centre study.

INTRODUCTION: Intraoperative perfusion imaging may help the surgeon in creating the intestinal anastomoses in optimally perfused tissue. Laser speckle contrast imaging (LSCI) is such a perfusion visualisation technique that is characterized by dye-free, real-time and continuous imaging. Our aim is to validate the use of a novel, dye-free visualization tool to detect perfusion deficits using laparoscopic LSCI. METHODS: In this multi-centre study, a total of 64 patients were imaged using the laparoscopic laser speckle contrast imager. Post-operatively, surgeons were questioned if the additional visual feedback would have led to a change in clinical decision-making. RESULTS: This study suggests that the laparoscopic laser speckle contrast imager PerfusiX-Imaging is able to image colonic perfusion. All images were clear and easy to interpret for the surgeon. The device is non-disruptive of the surgical procedure with an average added surgical time of 2.5 min and no change in surgical equipment. The potential added clinical value is accentuated by the 17% of operating surgeons indicating a change in anastomosis location. Further assessment and analysis of both white light and PerfusiX perfusion images by non-involved, non-operating surgeons showed an overall agreement of 80%. CONCLUSION: PerfusiX-Imaging is a suitable laparoscopic perfusion imaging system for colon surgery that can visualize perfusion in real-time with no change in surgical equipment. The additional visual feedback could help guide the surgeons in placing the anastomosis at the most optimal site.

Experimental evaluation of laparoscopic laser speckle contrast imaging to visualize perfusion deficits during intestinal surgery.

BACKGROUND: Ischemia at the site of an intestinal anastomosis is one of the most important risk factors for anastomotic leakage (AL). Consequently, adequate intestinal microperfusion is essential for optimal tissue oxygenation and anastomotic healing. As visual inspection of tissue viability does not guarantee an adequate objective evaluation of intestinal microperfusion, surgeons are in dire need of supportive tools to decrease anastomotic leakage after colorectal surgery. METHODS: In this feasibility study, laparoscopic laser speckle contrast imaging (LSCI) was used to evaluate intestinal microperfusion in an experimental ischemic bowel loop model. Both large and small ischemic loops were created from the small intestine of a pig; each loop was divided into 5 regions of interest (ROI) with varying levels of ischemia. Speckle contrast and local capillary lactate (LCL) was measured in all ROIs. RESULTS: Both real-time visualization of intestinal microperfusion and induced perfusion deficits was achieved in all bowel loops. As a result, the emergence of regions of intestinal ischemia could be predicted directly after iatrogenic perfusion limitation, whereas without LSCI signs of decreased intestinal viability could only be seen after 30 minutes. Additionally, a significant relation was found between LCL and LSCI. CONCLUSION: In conclusion, LSCI can achieve real-time intraoperative visualization of intestinal microperfusion deficits, allowing for accurate prediction of long-term postoperative ischemic complications. With this revealing capacity, LSCI could potentially facilitate surgical decision-making when constructing intestinal anastomoses in order to mitigate ischemia-related complications such as AL.

The effect of protein provision and exercise therapy on patient-reported and clinical outcomes in intensive care unit survivors: A systematic review.

BACKGROUND: Intensive care unit (ICU) survivors deal with long-term health problems, which negatively affect their quality of life (QoL). Nutritional and exercise intervention could prevent the decline of muscle mass and physical functioning which occurs during critical illness. Despite the growing amount of research, robust evidence is lacking. METHODS: For this systematic review, Embase, PubMed and Cochrane Central Register of Controlled Trials databases were searched. The effect of protein provision (PP) or combined protein and exercise therapy (CPE) during or after ICU admission on QoL, physical functioning, muscle health, protein/energy intake and mortality was assessed compared to standard care. RESULTS: Four thousand nine hundred and fifty-seven records were identified. After screening, data were extracted for 15 articles (9 randomised controlled trials and 6 non-randomised studies). Two studies reported improvements in muscle mass, of which one found higher independency in activities of daily living. No significant effect was found on QoL. Overall, protein targets were seldom met and often below recommendations. CONCLUSION: Evidence for the effect of PP or CPE on patient-reported outcomes in ICU survivors is limited due to study heterogeneity and lack of high-quality studies. Future research and clinical practice should focus on adequate protein delivery with exercise interventions to improve long-term outcomes.

A Novel and Generic Workflow of Indocyanine Green Perfusion Assessment Integrating Standardization and Quantification Toward Clinical Implementation.

OBJECTIVE: This study aims to generate a reproducible and generalizable Workflow model of ICG-angiography integrating Standardization and Quantification (WISQ) that can be applied uniformly within the surgical innovation realm independent of the user. SUMMARY BACKGROUND DATA: Tissue perfusion based on indocyanine green (ICG)-angiography is a rapidly growing application in surgical innovation. Interpretation of results has been subjective and error-prone due to the lack of a standardized and quantitative ICG-workflow and analytical methodology. There is a clinical need for a more generic, reproducible, and quantitative ICG perfusion model for objective assessment of tissue perfusion. METHODS: In this multicenter, proof-of-concept study, we present a generic and reproducible ICG-workflow integrating standardization and quantification for perfusion assessment. To evaluate our model's clinical feasibility and reproducibility, we assessed the viability of parathyroid glands after performing thyroidectomy. Biochemical hypoparathyroidism was used as the postoperative endpoint and its correlation with ICG quantification intraoperatively. Parathyroid gland is an ideal model as parathyroid function post-surgery is only affected by perfusion. RESULTS: We show that visual subjective interpretation of ICG-angiography by experienced surgeons on parathyroid perfusion cannot reliably predict organ function impairment postoperatively, emphasizing the importance of an ICG quantification model. WISQ was able to standardize and quantify ICG-angiography and provided a robust and reproducible perfusion curve analysis. A low ingress slope of the perfusion curve combined with a compromised egress slope was indicative for parathyroid organ dysfunction in 100% of the cases. CONCLUSION: WISQ needs prospective validation in larger series and may eventually support clinical decision-making to predict and prevent postoperative organ function impairment in a large and varied surgical population.

High Versus Normal Blood Pressure Targets in Relation to Right Ventricular Dysfunction After Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVE: Management of right ventricular (RV) dysfunction is challenging. Current practice predominantly is based on data from experimental and small uncontrolled studies and includes augmentation of blood pressure. However, whether such intervention is effective in the clinical setting of cardiac surgery is unknown. DESIGN: Randomized controlled trial. SETTING: Single-center study in a tertiary teaching hospital. PARTICIPANTS: The study comprised 78 patients equipped with a pulmonary artery catheter (PAC), classified according to PAC-derived RV ejection fraction (RVEF); 44 patients had an RVEF of <20%, and 34 patients had an RVEF between ≥20% and <30%. INTERVENTIONS: Patients randomly were assigned to either a normal target group (mean arterial pressure 65 mmHg) or a high target group [mean arterial pressure 85 mmHg]). The primary end- point was the change in RVEF over a one-hour study period. MEASUREMENTS AND MAIN RESULTS: There was no significant between-group difference in change of RVEF <20% (-1% [-3.3 to 1.8] in the normal-target group v 0.5% [-1 to 4] in the high-target group; p = 0.159). There was no significant between-group difference in change in RVEF 20%-to-30% (-1% [-3 to 0] in the normal-target group v 1% [-1 to 3] in the high-target group; p = 0.074). These results were in line with the simultaneous observation that echocardiographic variables of RV and left ventricular function also remained unaltered over time, irrespective of either baseline RVEF or treatment protocol. CONCLUSION: In a mixed cardiac surgery population with RV dysfunction, norepinephrine-mediated high blood pressure targets did not result in an increase in PAC-derived RVEF compared with normal blood pressure targets.

The Reduction in Right Ventricular Longitudinal Contraction Parameters Is Not Accompanied by a Reduction in General Right Ventricular Performance During Aortic Valve Replacement: An Explorative Study.

OBJECTIVE: The aim of the present study was to identify whether the decrease of longitudinal parameters after cardiothoracic surgery (ie, tricuspid annular systolic plane excursion [TAPSE] and systolic excursion velocity [S']) is accompanied by a reduction in global right ventricular (RV) performance. DESIGN: Prospective, observational study. SETTING: Single-center explorative study in a tertiary teaching hospital. PARTICIPANTS: The study comprised 20 patients who underwent aortic valve replacement with or without coronary artery bypass grafting. INTERVENTIONS: During cardiac surgery, simultaneous measurements of RV function were performed with a pulmonary artery catheter and transesophageal echocardiography. MEASUREMENTS AND MAIN RESULTS: TAPSE and S' were reduced significantly directly after surgery compared with the time before surgery (TAPSE from 20.8 [16.6-23.4] mm to 9.1 [5.6-15.5] mm; p < 0.001 and S' from 8.7 [7.9-10.7] cm/s to 7.2 [5.7-8.6] cm/s; p = 0.041). However, the reduction in TAPSE and S' was not accompanied by a reduction in RV performance, as assessed with the TEE-derived myocardial performance index (MPI) and pulmonary artery catheter-derived RV ejection fraction (RVEF). Both remained statistically unaltered before and after the procedure (MPI from 0.52 [0.43-0.58] to 0.50 [0.42-0.88]; p = 0.278 and RVEF from 27% [22%-32%] to 26% [22%-28%]; p = 0.294). CONCLUSIONS: In the direct postoperative phase, the reduction of echocardiographic parameters of longitudinal RV contractility (TAPSE and S') were not accompanied by a reduction in global RV performance, expressed as MPI and RVEF. Solely relying on a single RV parameter as a marker for global RV performance may not be adequate to assess the complex adaptation of the right ventricle to aortic valve replacement.

Alterations of retinal vessels in patients with sepsis.

To compare the retinal vasculature of septic patients with age-matched healthy volunteers. This is a single-centre prospective observational study from January 2018 to May 2019 in a third-level ICU. We performed a single fundus imaging using a hand-held digital fundus camera in patients with sepsis or septic shock (n = 40) during the first 24 h after ICU admission and compared these data with age-matched healthy controls (n  =  20). Semi-automated image analysis was performed. The average retinal arteriolar and venular caliber were calculated and summarized as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Arteriole:venular ratio (AVR) was defined as the ratio of CRAE:CRVE. The vascular length density of segmented retinal vessels was = defined as the skeletonized vessel area/total area × 100%. Median CRAE of septic patients was significantly higher in comparison to healthy controls (165[149-187] vs. 146[142-158] µm, p = 0.002). However, median CRVE and AVR of septic patients did not differ with healthy controls (247[223-282] vs. 244[215-272], p = 0.396 and 0.64[0.58-0.74] vs. 0.61[0.55-0.68], p = 0.145) respectively. Patients with sepsis showed a significant decrease in retinal vascular length density compared with healthy subjects (p < 0.001). Retinal observation using a hand-held fundus imaging device showed signs of arteriolar vasodilation with decreased vascular density in septic patients in comparison to healthy controls.

Differences in capillary recruitment between cardiac surgery and septic patients after fluid resuscitation.

BACKGROUND: Clinical evaluation of the effects of fluid therapy remains cumbersome and strategies are based on the assumption that normalization of macrohemodynamic variables will result in parallel improvement in organ perfusion. Recently, we and others suggested the use of direct in-vivo observation of the microcirculation to evaluate the effects of fluid therapy. METHODS: A single-centre observational study, using in-vivo microscopy to assess total vessel density (TVD) in two subsets of ICU patients. RESULTS: After fluid resuscitation TVD showed no difference between sepsis patients (N = 47) and cardiac surgery patients (N = 52): 18.4[16.8-20.8] vs 18.7[16.8-20.9] mm/mm2, p = 0.59. In cardiac surgery patients there was a significant correlation between the amount of fluids administered and TVD, with an optimum in the third quartile. However, such correlation was absent in septic patients. CONCLUSIONS: TVD after fluid administration is not different between 2 subtypes of intensive care patients. However, only in septic patients we observed a lack of coherence between the amount of fluids administered and TVD. Further research is needed to determine if TVD may serve as potential endpoint for fluid administration.

Intestinal Mucosal and Serosal Microcirculation at the Planned Anastomosis during Abdominal Surgery.

INTRODUCTION: Intestinal blood flow is often named as a key factor in the pathophysiology of anastomotic leakage. The distribution between mucosal and serosal microperfusion during surgery remains to be elucidated. OBJECTIVE: The aim of this study was to assess if the mucosal microcirculation of the intestine is more vulnerable to a surgical hit than the serosal microcirculation during surgery. METHODS: In an observational cohort study (n = 9 patients), the microcirculation of the bowel serosa and mucosa was visualized with incident dark-field imaging during surgery. At the planned anastomosis, the following microcirculatory parameters were determined: microvascular flow index (MFI), percentage of perfused vessels (PPV), perfused vessel density (PVD), and total vessel density (TVD). Data are presented as median (interquartile range [IQR]). RESULTS: Perfusion parameters and vessel density were significantly higher for the mucosa than the serosal microcirculation at the planned site for anastomosis or stoma. Mucosal MFI was 3.00 (IQR 3.00-3.00) compared to a serosal MFI of 2.75 (IQR 2.21-2.94), p = 0.03. The PPV was 99% (IQR 98-100) versus 92% (IQR 66-94), p = 0.01. The TVD was 16.77 mm/mm2 (IQR 13.04-18.01) versus 10.42 mm/mm2 (IQR 9.36-11.81), p = 0.01, and the PVD was 15.44 mm/mm2 (IQR 13.04-17.78) versus 9.02 mm/mm2 (IQR 6.43-9.43), p = 0.01. CONCLUSIONS: The mucosal microcirculation was preserved, while lower perfusion of the serosa was found at the planned anastomosis or stoma during surgery. Further research is needed to link our observations to the clinically relevant endpoint of anastomotic leakage.

Alterations of conjunctival glycocalyx and microcirculation in non-septic critically ill patients.

As of now the relationship between glycocalyx degradation and microcirculatory perfusion abnormalities in non-septic critical ill patients is unclear. In addition, conjunctival sidestream dark field-imaging for the purpose of glycocalyx thickness estimation has never been performed. We aimed to investigate whether changes in glycocalyx thickness in non-septic patients are associated with microcirculatory alterations in conjunctival and sublingual mucosa. In this single-centre prospective observational study, using techniques for direct in-vivo observation of the microcirculation, we performed a single measurement of microcirculatory perfusion parameters and visualized glycocalyx thickness in both ocular conjunctiva and sublingual mucosa in mixed cardio surgical (n = 18) and neurocritical patients (n = 27) and compared these data with age-matched healthy controls (n = 20). In addition we measured systemic syndecan-1 levels. In the sublingual and conjunctival region we observed a significant increase of the perfused boundary region (PBR) in both neuro-critical and cardiac surgical ICU patients, compared to controls. There was a significant increase of syndecan-1 in ICU patients comparing with controls and in cardiac patients comparing with neurological (120.0[71.0-189.6] vs. 18.0[7.2-40.7], p < 0.05). We detected a weak correlation between syndecan-1 and sublingual PBR but no correlations between global glycocalyx damage and conjuctival glycocalyx thickness. We found significantly lower perfused vessel density (PVD) of small vessels in sublingual mucosa in patients after cardiac surgery in comparison with healthy subjects. In neuro-critical, but not cardiac surgery patients conjunctival TVD and PVD of small vessels were found to be significantly lower in comparison with controls.

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis.

BACKGROUND: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. METHODS: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. RESULTS: In 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). CONCLUSIONS: In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010.

Ultrafiltration rate is an important determinant of microcirculatory alterations during chronic renal replacement therapy.

BACKGROUND: Hemodialysis (HD) with ultrafiltration (UF) in chronic renal replacement therapy is associated with hemodynamic instability, morbidity and mortality. Sublingual Sidestream Dark Field (SDF) imaging during HD revealed reductions in microcirculatory blood flow (MFI). This study aims to determine underlying mechanisms. METHODS: The study was performed in the Medical Centre Leeuwarden and the Lithuanian University of Health Sciences. Patients underwent 4-h HD session with linear UF. Nine patients were subject to combinations of HD and UF: 4 h of HD followed by 1 h isolated UF and 4 h HD with blood-volume-monitoring based UF. Primary endpoint: difference in MFI before and after intervention. During all sessions monitoring included blood pressure, heartrate and SDF-imaging. TRIAL REGISTRATION NUMBER: NCT01396980. RESULTS: Baseline characteristics were not different between the two centres as within the HD/UF modalities. MFI was not different before and after HD with UF. Total UF did not differ between modalities. Median MFI decreased significantly during isolated UF [2.8 (2.5-2.9) to 2.5 (2.2-2.8), p = 0.03]. Baseline MFI of each UF session was correlated with MFI after the intervention (r s = 0.52, p = 0.006). CONCLUSION: During HD with UF or isolated HD we observed no changes in MFI. This indicates that non-flow mediated mechanisms are of unimportance. During isolated UF we observed a reduction in MFI in conjunction with a negative intravascular fluid balance. The correlation between MFI before and after intervention suggests that volume status at baseline is a factor in microvascular alterations. In conclusion we observed a significant decrease of sublingual MFI, related to UF rate during chronic renal replacement therapy.

Right Ventricular Function After Cardiac Surgery Is a Strong Independent Predictor for Long-Term Mortality.

OBJECTIVE: To establish the all-cause mortality of right ventricular dysfunction after cardiac surgery in a heterogeneous group of cardiac surgery patients. DESIGN: Retrospective analysis of a heterogeneous group of 1,109 cardiac surgery patients in a 4-year period. SETTING: Single-center study in a tertiary teaching hospital. PARTICIPANTS: One thousand one hundred nine cardiac surgery patients. By protocol, patients were monitored with a pulmonary artery catheter, enabling continuous right ventricular ejection fraction (RVEF) measurements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements were performed once per minute for the first 24 postoperative hours and expressed as average over the complete period. Primary outcome was 2-year all-cause mortality. RVEF was categorized into 3 subgroups: <20%, 20-30%, and >30%. Median follow-up time was 739 days. Two-year mortality was significantly different across groups: 4.1% for patients with RVEF >30%, 8.2% in the group with RVEF 20-30%, and 16.7% for patients with RVEF <20%, p < 0.001. Additional risk factors for a poor RVEF were age, body weight, New York Heart Association class, chronic obstructive pulmonary disease, poor left ventricular function, and higher risk scores (Acute Physiology and Chronic Health Evaluation and European System for Cardiac Operative Risk Evaluation). In a multivariate analysis, RVEF as a continuous variable was associated independently with the primary outcome (odds ratio 0.95 confidence interval 0.91-0.99, p = 0.011.) Odds ratios for RVEF <20% were 1.88 (confidence interval 1.18-3.00, p = 0.008). CONCLUSIONS: Right ventricular function is associated independently with 2-year all-cause mortality in a heterogenic cardiac surgery population.

Conjunctival microcirculatory blood flow is altered but not abolished in brain dead patients: a prospective observational study.

BACKGROUND: The conjunctival microcirculation has potential as a window to cerebral perfusion due to related blood supply, close anatomical proximity and easy accessibility for microcirculatory imaging technique, such as sidestream dark field (SDF) imaging. Our study aims to evaluate conjunctival and sublingual microcirculation in brain dead patients and to compare it with healthy volunteers in two diametrically opposed conditions: full stop versus normal arterial blood supply to the brain. METHODS: In a prospective observational study we analyzed conjunctival and sublingual microcirculation using SDF imaging in brain dead patients after reaching systemic hemodynamic targets to optimize perfusion of donor organs, and in healthy volunteers. All brain death diagnoses were confirmed by cerebral angiography. Microcirculatory images were obtained and analyzed using standardized published recommendations. Study registered at ClinicalTrials.gov, number NCT02483273. RESULTS: Eleven brain dead patients and eleven apparently healthy controls were enrolled in the study. Microvascular flow index (MFI) of small vessels was significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (2.7 [2.4-2.9] vs. 3.0 [2.9-3.0], p = 0.01) and in sublingual mucosa (2.8 [2.6-2.9] vs. 3.0 [2.9-3.0], p = 0.02). Total vessel density (TVD) and perfused vessel density (PVD) of small vessels were significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (10.2 [6.6-14.8] vs. 18.0 [18.0-25.4] mm/mm(2), p = 0.001 and 5.0 [3.5-7.3] vs. 10.9 [10.9-13.5] 1/mm, p = 0.001), but not in sublingual mucosa. CONCLUSION: In comparison to healthy controls brain dead patients had a significant reduction in conjunctival microvascular blood flow and density. However, the presence of conjunctival flow in case general cerebral flow is completely absent makes it impossible to use the conjunctival microcirculation as a substitute for brain flow, and further research should focus on the link between the ocular microcirculation, intracranial pressure and alternative ocular circulation.

Plasma glutamine levels in patients after non-elective or elective ICU admission: an observational study.

BACKGROUND: A low plasma glutamine level at the time of acute admission to the intensive care unit (ICU) is an independent predictor of an unfavourable outcome in critically ill patients. The primary objective of this study was to determine whether there are differences in plasma glutamine levels upon non-elective or elective ICU admission. The secondary objective was to compare glutamine levels over time, and to determine correlations between glutamine levels and the severity of illness and presence of infection in ICU patients. METHODS: We performed a single-centre observational study in a closed-format, 22-bed, mixed ICU. Plasma glutamine levels were measured at admission and every morning at 6.00 a.m. during the ICU stay. We aimed to include at least 80 patients per group. The study was approved by the local Medical Ethics Committee. RESULTS: In 88 patients after elective surgery, the median plasma glutamine level at admission was significantly higher compared with that in 90 non-elective patients (0.43 mmol/l [0.33-0.55 mmol/l] versus 0.25 mmol/l [0.09-0.37 mmol/l], P = 0.001). During the ICU stay, plasma glutamine levels remained significantly higher in elective patients than in non-elective patients. There was a significant correlation between the APACHE IV score and glutamine levels (R = 0.52, P < 0.001). Moreover, backward linear regression analysis showed that this correlation was independently associated with the APACHE IV score and the presence of infection, but not with the type of admission. CONCLUSIONS: Plasma glutamine levels are significantly lower after non-elective admission compared with elective admission to the ICU. A considerable amount of elective and non-elective patients have decreased plasma glutamine levels, but this is not independently associated with the type of admission. In contrast to previous studies, we found that plasma glutamine levels were determined by the severity of illness and the presence of an infection. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02310035.

International study on microcirculatory shock occurrence in acutely ill patients.

OBJECTIVES: Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. The prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and its predictive value in an integrative model of macro- and microcirculatory variables. DESIGN: Multicenter observational point prevalence study. SETTING: The Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide. PATIENTS: A heterogeneous ICU population consisting of 501 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, hemodynamic, and laboratory data were collected in all ICU patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging was performed to determine the prevalence of an abnormal capillary microvascular flow index (< 2.6) and its additional value in predicting hospital mortality. In 501 patients with a median Acute Physiology and Chronic Health Evaluation II score of 15 (10-21), a Sequential Organ Failure Assessment score of 5 (2-8), and a hospital mortality of 28.4%, 17% exhibited an abnormal capillary microvascular flow index. Tachycardia (heart rate > 90 beats/min) (odds ratio, 2.71; 95% CI, 1.67-4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963-0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11-3.07; p = 0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28-3.62; p = 0.004) were independent risk factors for hospital mortality, but not abnormal microvascular flow index. In reference to microvascular flow index, a significant interaction was observed with tachycardia. In patients with tachycardia, the presence of an abnormal microvascular flow index was an independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95% CI, 1.30-8.06; p = 0.011). This was not true for nontachycardic patients nor for the total group of patients. CONCLUSIONS: In a heterogeneous ICU population, an abnormal microvascular flow index was present in 17% of patients. This was not associated with mortality. However, in patients with tachycardia, an abnormal microvascular flow index was independently associated with an increased risk of hospital death.

'Sepsis-related anemia' is absent at hospital presentation; a retrospective cohort analysis.

BACKGROUND: Anemia is a common feature during sepsis that occurs due to iatrogenic blood loss, depression of serum iron levels and erythropoietin production, and a decreased lifespan of erythrocytes. However, these mechanisms are unlikely to play a role in anemia at the start of sepsis. Moreover, sequestration of fluids, renal failure and increase of intravascular space may additionally influence the change in hemoglobin concentration during intravenous fluid administration in the acute phase of sepsis. METHODS: In this retrospective study, patients who were admitted acutely to the Intensive Care Unit (ICU) were included. Patients who fulfilled the international criteria for severe sepsis or septic shock were included in the sepsis group (S-group). The remaining patients were allocated to the control group (C-group). Laboratory data from blood samples taken at first presentation to the hospital and at admission to the ICU, the amount of intravenous fluid administration and length of stay in the emergency department were collected and tested for significant differences between groups. RESULTS: The difference in hemoglobin concentration between the S-group (n = 296) and C-group (n = 320) at first presentation in hospital was not significant (8.8 ± 1.2 versus 8.9 ± 1.2 mmol/l, respectively, p = 0.07). The reduction in hemoglobin concentration from the first presentation at the emergency department to ICU admission was significantly greater in the S-group compared to the C-group (1 [0.5-1.7] versus 0.5 [0.1-1.1] mmol/l, (p < 0.001)). Spearman rho correlation coefficients between the reduction in hemoglobin concentration and the amount of intravenous fluids administered or the creatinine level in the emergency department were significant (0.3 and 0.4, respectively, p < 0.001). In a multivariate regression analysis, creatinine, the amount of fluid administration and the presence of sepsis remained independently associated. CONCLUSIONS: Prior to in-hospital intravenous fluid administration, there is no significant difference in hemoglobin concentration between acute septic patients and acutely ill controls. Within several hours after hospital admission, there is a significant reduction in hemoglobin concentration, not only associated with the amount of intravenous fluids administered and the creatinine level, but also independently with sepsis itself.

Nonelective surgery at night and in-hospital mortality: Prospective observational data from the European Surgical Outcomes Study.

BACKGROUND: Evidence suggests that sleep deprivation associated with night-time working may adversely affect performance resulting in a reduction in the safety of surgery and anaesthesia. OBJECTIVE: Our primary objective was to evaluate an association between nonelective night-time surgery and in-hospital mortality. We hypothesised that urgent surgery performed during the night was associated with higher in-hospital mortality and also an increase in the duration of hospital stay and the number of admissions to critical care. DESIGN: A prospective cohort study. This is a secondary analysis of a large database related to perioperative care and outcome (European Surgical Outcome Study). SETTING: Four hundred and ninety-eight hospitals in 28 European countries. PATIENTS: Men and women older than 16 years who underwent nonelective, noncardiac surgery were included according to time of the procedure. INTERVENTION: None. MAIN OUTCOME MEASURES: Primary outcome was in-hospital mortality; the secondary outcome was the duration of hospital stay and critical care admission. RESULTS: Eleven thousand two hundred and ninety patients undergoing urgent surgery were included in the analysis with 636 in-hospital deaths (5.6%). Crude mortality odds ratios (ORs) increased sequentially from daytime [426 deaths (5.3%)] to evening [150 deaths (6.0%), OR 1.14; 95% confidence interval 0.94 to 1.38] to night-time [60 deaths (8.3%), OR 1.62; 95% confidence interval 1.22 to 2.14]. Following adjustment for confounding factors, surgery during the evening (OR 1.09; 95% confidence interval 0.91 to 1.31) and night (OR 1.20; 95% confidence interval 0.9 to 1.6) was not associated with an increased risk of postoperative death. Admittance rate to an ICU increased sequentially from daytime [891 (11.1%)], to evening [347 (13.8%)] to night time [149 (20.6%)]. CONCLUSION: In patients undergoing nonelective urgent noncardiac surgery, in-hospital mortality was associated with well known risk factors related to patients and surgery, but we did not identify any relationship with the time of day at which the procedure was performed. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01203605.