Monitoring, management, and outcome of hypotension in Intensive Care Unit patients, an international survey of the European Society of Intensive Care Medicine.

INTRODUCTION: Hypotension in the ICU is common, yet management is challenging and variable. Insight in management by ICU physicians and nurses may improve patient care and guide future hypotension treatment trials and guidelines. METHODS: We conducted an international survey among ICU personnel to provide insight in monitoring, management, and perceived consequences of hypotension. RESULTS: Out of 1464 respondents, 1197 (81.7%) were included (928 physicians (77.5%) and 269 nurses (22.5%)). The majority indicated that hypotension is underdiagnosed (55.4%) and largely preventable (58.8%). Nurses are primarily in charge of monitoring changes in blood pressure, physicians are in charge of hypotension treatment. Balanced crystalloids, dobutamine, norepinephrine, and Trendelenburg position were the most frequently reported fluid, inotrope, vasopressor, and positional maneuver used to treat hypotension. Reported complications believed to be related to hypotension were AKI and myocardial injury. Most ICUs do not have a specific hypotension treatment guideline or protocol (70.6%), but the majority would like to have one in the future (58.1%). CONCLUSIONS: Both physicians and nurses report that hypotension in ICU patients is underdiagnosed, preventable, and believe that hypotension influences morbidity. Hypotension management is generally not protocolized, but the majority of respondents would like to have a specific hypotension management protocol.

Definition and incidence of hypotension in intensive care unit patients, an international survey of the European Society of Intensive Care Medicine.

INTRODUCTION: Although hypotension in ICU patients is associated with adverse outcome, currently used definitions are unknown and no universally accepted definition exists. METHODS: We conducted an international, peer-reviewed survey among ICU physicians and nurses to provide insight in currently used definitions, estimations of incidence, and duration of hypotension. RESULTS: Out of 1394 respondents (1055 physicians (76%) and 339 nurses (24%)), 1207 (82%) completed the questionnaire. In all patient categories, hypotension definitions were predominantly based on an absolute MAP of 65 mmHg, except for the neuro(trauma) category (75 mmHg, p < 0.001), without differences between answers from physicians and nurses. Hypotension incidence was estimated at 55%, and time per day spent in hypotension at 15%, both with nurses reporting higher percentages than physicians (estimated mean difference 5%, p = 0.01; and 4%, p < 0.001). CONCLUSIONS: An absolute MAP threshold of 65 mmHg is most frequently used to define hypotension in ICU patients. In neuro(trauma) patients a higher threshold was reported. The majority of ICU patients are estimated to endure hypotension during their ICU admission for a considerable amount of time, with nurses reporting a higher estimated incidence and time spent in hypotension than physicians.

Association of intraoperative hypotension with postoperative morbidity and mortality: systematic review and meta-analysis.

BACKGROUND: Intraoperative hypotension, with varying definitions in literature, may be associated with postoperative complications. The aim of this meta-analysis was to assess the association of intraoperative hypotension with postoperative morbidity and mortality. METHODS: MEDLINE, Embase and Cochrane databases were searched for studies published between January 1990 and August 2018. The primary endpoints were postoperative overall morbidity and mortality. Secondary endpoints were postoperative cardiac outcomes, acute kidney injury, stroke, delirium, surgical outcomes and combined outcomes. Subgroup analyses, sensitivity analyses and a meta-regression were performed to test the robustness of the results and to explore heterogeneity. RESULTS: The search identified 2931 studies, of which 29 were included in the meta-analysis, consisting of 130 862 patients. Intraoperative hypotension was associated with an increased risk of morbidity (odds ratio (OR) 2.08, 95 per cent confidence interval 1.56 to 2.77) and mortality (OR 1.94, 1.32 to 2.84). In the secondary analyses, intraoperative hypotension was associated with cardiac complications (OR 2.44, 1.52 to 3.93) and acute kidney injury (OR 2.69, 1.31 to 5.55). Overall heterogeneity was high, with an I2 value of 88 per cent. When hypotension severity, outcome severity and study population variables were added to the meta-regression, heterogeneity was reduced to 50 per cent. CONCLUSION: Intraoperative hypotension during non-cardiac surgery is associated with postoperative cardiac and renal morbidity, and mortality. A universally accepted standard definition of hypotension would facilitate further research into this topic.

Quantitative fluorescence-guided perfusion assessment of the gastric conduit to predict anastomotic complications after esophagectomy.

BACKGROUND: Fluorescence angiography (FA) assesses anastomotic perfusion during esophagectomy with gastric conduit reconstruction, but its interpretation is subjective. This study evaluated time to fluorescent enhancement in the gastric conduit, with the aim to determine a threshold to predict postoperative anastomotic complications. METHODS: In a prospective cohort study, all consecutive patients undergoing esophagectomy with gastric conduit reconstruction from July 2018 to October 2019 were included. FA was performed before anastomotic reconstruction following injection of indocyanine green (ICG). During FA, the following time points were recorded: ICG injection, first fluorescent enhancement in the lung, at the base of the gastric conduit, at the planned anastomotic site, and at ICG watershed or in the tip of the gastric conduit. Anastomotic complications including anastomotic leakage and clinically relevant strictures were documented. RESULTS: Eighty-four patients were included, the majority (67 out of 84, 80%) of which underwent an Ivor Lewis procedure. After a median follow-up of 297 days, anastomotic leakage was observed in 12 out of 84 (14.3%) and anastomotic stricture in 12 out of 82 (14.6%). Time between ICG injection and enhancement in the tip was predictive for anastomotic leakage (P = 0.174, area under the curve = 0.731), and a cut-off value of 98 seconds was derived (specificity: 98%). All times to enhancement at the planned anastomotic site and ICG watershed were significantly predictive for the occurrence of a stricture, however area under the curves were <0.7. CONCLUSIONS: The identified fluorescent threshold can be used for intraoperative decision making or to identify potentially high-risk patients for anastomotic leakage after esophagectomy with gastric conduit reconstruction.

The use of a machine-learning algorithm that predicts hypotension during surgery in combination with personalized treatment guidance: study protocol for a randomized clinical trial.

BACKGROUND: Intraoperative hypotension is associated with increased morbidity and mortality. Current treatment is mostly reactive. The Hypotension Prediction Index (HPI) algorithm is able to predict hypotension minutes before the blood pressure actually decreases. Internal and external validation of this algorithm has shown good sensitivity and specificity. We hypothesize that the use of this algorithm in combination with a personalized treatment protocol will reduce the time weighted average (TWA) in hypotension during surgery spent in hypotension intraoperatively. METHODS/DESIGN: We aim to include 100 adult patients undergoing non-cardiac surgery with an anticipated duration of more than 2 h, necessitating the use of an arterial line, and an intraoperatively targeted mean arterial pressure (MAP) of > 65 mmHg. This study is divided into two parts; in phase A baseline TWA data from 40 patients will be collected prospectively. A device (HemoSphere) with HPI software will be connected but fully covered. Phase B is designed as a single-center, randomized controlled trial were 60 patients will be randomized with computer-generated blocks of four, six or eight, with an allocation ratio of 1:1. In the intervention arm the HemoSphere with HPI will be used to guide treatment; in the control arm the HemoSphere with HPI software will be connected but fully covered. The primary outcome is the TWA in hypotension during surgery. DISCUSSION: The aim of this trial is to explore whether the use of a machine-learning algorithm intraoperatively can result in less hypotension. To test this, the treating anesthesiologist will need to change treatment behavior from reactive to proactive. TRIAL REGISTRATION: This trial has been registered with the NIH, U.S. National Library of Medicine at ClinicalTrials.gov, ID: NCT03376347 . The trial was submitted on 4 November 2017 and accepted for registration on 18 December 2017.

Patient blood management in the cardiac surgical setting: An updated overview.

In cardiac surgical patients it is a complex challenge to find the ideal balance between anticoagulation and hemostasis. Preoperative anemia and perioperative higher transfusion rates are related to increased morbidity and mortality. Patient blood management (PBM) is an evidence based patient specific individualized protocol used in the perioperative setting in order to reduce perioperative bleeding and transfusion rates and to improve patient outcomes. The three pillars of PBM in cardiac surgery consist of optimization of preoperative erythropoiesis and hemostasis, minimizing blood loss, and improving patient specific physiological reserves. This narrative review focuses on the challenges with special emphasis on PBM in the preoperative phase and intraoperative transfusion management and hemostasis in cardiac surgery patients. It is a "must" that PBM is a collaborative effort between anesthesiologists, surgeons, perfusionists, intensivists and transfusion laboratory teams. This review represents an up to date overview over "PBM in cardiac surgery patients".

Effect of ephedrine on gastric conduit perfusion measured by laser speckle contrast imaging after esophagectomy: a prospective in vivo cohort study.

Compromised perfusion due to ligation of arteries and veins in esophagectomy with gastric tube reconstruction often (5-20%) results in necrosis and anastomotic leakage, which relate to high morbidity and mortality (3-4%). Ephedrine is used widely in anesthesia to treat intraoperative hypotension and may improve perfusion by the increase of cardiac output and mean arterial pressure (MAP). This study tests the effect of ephedrine on perfusion of the future anastomotic site of the gastric conduit, measured by laser speckle contrast imaging (LSCI). This prospective, observational, in vivo pilot study includes 26 patients undergoing esophagectomy with gastric tube reconstruction from October 2015 to June 2016 in the Academic Medical Center (Amsterdam). Perfusion of the gastric conduit was measured with LSCI directly after reconstruction and after an increase of MAP by ephedrine 5 mg. Perfusion was quantified in flux (laser speckle perfusion units, LSPU) in four perfusion locations, from good perfusion (base of the gastric tube) toward decreased perfusion (fundus). Intrapatient differences before and after ephedrine in terms flux were statistically tested for significance with a paired t-test. LSCI was feasible to image gastric microcirculation in all patients. Flux (LSPU) was significantly higher in the base of the gastric tube (791 ± 442) compared to the fundus (328 ± 187) (P < 0.001). After administration of ephedrine, flux increased significantly in the fundus (P < 0.05) measured intrapatients. Three patients developed anastomotic leakage. In these patients, the difference between measured flux in the fundus compared to the base of the gastric tube was high. This study presents the effect of ephedrine on perfusion of the gastric tissue measured with LSCI in terms of flux (LSPU) after esophagectomy with gastric tube reconstruction. We show a small but significant difference between flux measured before and after administration of ephedrine in the future anastomotic tissue (313 ± 178 vs. 397 ± 290). We also show a significant decrease of flux toward the fundus.

Optical techniques for perfusion monitoring of the gastric tube after esophagectomy: a review of technologies and thresholds.

Anastomotic leakage is one of the most severe complications after esophageal resection with gastric tube reconstruction. Impaired perfusion of the gastric fundus is seen as the main contributing factor for this complication. Optical modalities show potential in recognizing compromised perfusion in real time, when ischemia is still reversible. This review provides an overview of optical techniques with the aim to evaluate the (1) quantitative measurement of change in perfusion in gastric tube reconstruction and (2) to test which parameters are the most predictive for anastomotic leakage.A Pubmed, MEDLINE, and Embase search was performed and articles on laser Doppler flowmetry (LDF), near-infrared spectroscopy (NIRS), laser speckle contrast imaging (LSCI), fluorescence imaging (FI), sidestream darkfield microscopy (SDF), and optical coherence tomography (OCT) regarding blood flow in gastric tube surgery were reviewed. Two independent reviewers critically appraised articles and extracted the data: Primary outcome was quantitative measure of perfusion change; secondary outcome was successful prediction of necrosis or anastomotic leakage by measured perfusion parameters.Thirty-three articles (including 973 patients and 73 animals) were selected for data extraction, quality assessment, and risk of bias (QUADAS-2). LDF, NIRS, LSCI, and FI were investigated in gastric tube surgery; all had a medium level of evidence. IDEAL stage ranges from 1 to 3. Most articles were found on LDF (n = 12), which is able to measure perfusion in arbitrary perfusion units with a significant lower amount in tissue with necrosis development and on FI (n = 12). With FI blood flow routes could be observed and flow was qualitative evaluated in rapid, slow, or low flow. NIRS uses mucosal oxygen saturation and hemoglobin concentration as perfusion parameters. With LSCI, a decrease of perfusion units is observed toward the gastric fundus intraoperatively. The perfusion units (LDF, LSCI), although arbitrary and not absolute values, and low flow or length of demarcation to the anastomosis (FI) both seem predictive values for necrosis intraoperatively. SDF and OCT are able to measure microvascular flow, intraoperative prediction of necrosis is not yet described.Optical techniques aim to improve perfusion monitoring by real-time, high-resolution, and high-contrast measurements and could therefore be valuable in intraoperative perfusion mapping. LDF and LSCI use perfusion units, and are therefore subjective in interpretation. FI visualizes influx directly, but needs a quantitative parameter for interpretation during surgery.

Transfusion-associated circulatory overload: A survey among Dutch intensive care fellows.

OBJECTIVES: Transfusion-associated circulatory overload (TACO) is a severe pulmonary transfusion reaction and leading cause of transfusion-related morbidity and mortality in Europe. TACO is of particular importance in critically ill patients, since they often receive blood transfusions and have multiple risk factors for TACO. This study investigates transfusion practices in patients at risk of developing TACO, and furthermore knowledge concerning risk factors, diagnoses and treatment strategies among Dutch intensive care unit (ICU) fellows. MATERIAL AND METHODS: An unannounced paper-based survey was conducted among Dutch ICU fellows during an educational conference. The survey consisted of 16 multiple and open choice questions. RESULTS: Of all 65 Dutch ICU fellows 56.8% completed the survey; of respondents 88.9% identified the correct constellation of symptoms for TACO. In total, 29.7% of the respondents are aware they are obligated to report TACO cases to the blood bank. Major risk factors for TACO that respondents identified were reduced left ventricular function, infusion volume and infusion rate. In a non-emergency setting, 45.9% of fellows start red blood cell transfusion with 2 units or more. Transfusion rates exceeded national guidelines in 15.4% of fictitious cases. TACO is treated with furosemide by 94.5% of the fellows, however goals of the therapy varied greatly. CONCLUSION: Dutch ICU fellows are knowledgeable of TACO symptoms, risk factors and treatment, however knowledge on reporting and transfusion practice in the setting of at risk patients for TACO should be improved.

The effect of propofol on haemodynamics: cardiac output, venous return, mean systemic filling pressure, and vascular resistances.

BACKGROUND: Although arterial hypotension occurs frequently with propofol use in humans, its effects on intravascular volume and vascular capacitance are uncertain. We hypothesized that propofol decreases vascular capacitance and therefore decreases stressed volume. METHODS: Cardiac output (CO) was measured using Modelflow(®) in 17 adult subjects after upper abdominal surgery. Mean systemic filling pressure (MSFP) and vascular resistances were calculated using venous return curves constructed by measuring steady-state arterial and venous pressures and CO during inspiratory hold manoeuvres at increasing plateau pressures. Measurements were performed at three incremental levels of targeted blood propofol concentrations. RESULTS: Mean blood propofol concentrations for the three targeted levels were 3.0, 4.5, and 6.5 µg ml(-1). Mean arterial pressure, central venous pressure, MSFP, venous return pressure, Rv, systemic arterial resistance, and resistance of the systemic circulation decreased, stroke volume variation increased, and CO was not significantly different as propofol concentration increased. CONCLUSIONS: An increase in propofol concentration within the therapeutic range causes a decrease in vascular stressed volume without a change in CO. The absence of an effect of propofol on CO can be explained by the balance between the decrease in effective, or stressed, volume (as determined by MSFP), the decrease in resistance for venous return, and slightly improved heart function. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register: NTR2486.

The safety and efficacy of irreversible electroporation for the ablation of prostate cancer: a multicentre prospective human in vivo pilot study protocol.

INTRODUCTION: Current surgical and ablative treatment options for prostate cancer have a relatively high incidence of side effects, which may diminish the quality of life. The side effects are a consequence of procedure-related damage of the blood vessels, bowel, urethra or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective in destroying tumour cells and harbours the advantage of sparing surrounding tissue and vital structures. The aim of the study is to evaluate the safety and efficacy and to acquire data on patient experience of minimally invasive, transperineally image-guided IRE for the focal ablation of prostate cancer. METHODS AND ANALYSIS: In this multicentre pilot study, 16 patients with prostate cancer who are scheduled for a radical prostatectomy will undergo an IRE procedure, approximately 30 days prior to the radical prostatectomy. Data as adverse events, side effects, functional outcomes, pain and quality of life will be collected and patients will be controlled at 1 and 2 weeks post-IRE, 1 day preprostatectomy and postprostatectomy. Prior to the IRE procedure and the radical prostatectomy, all patients will undergo a multiparametric MRI and contrast-enhanced ultrasound of the prostate. The efficacy of ablation will be determined by whole mount histopathological examination, which will be correlated with the imaging of the ablation zone. ETHICS AND DISSEMINATION: The protocol is approved by the ethics committee at the coordinating centre (Academic Medical Center (AMC) Amsterdam) and by the local Institutional Review Board at the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. CONCLUSIONS: This pilot study will determine the safety and efficacy of IRE in the prostate. It will show the radiological and histopathological effects of IRE ablations and it will provide data to construct an accurate treatment planning tool for IRE in prostate tissue. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov database: NCT01790451.

Positive end-expiratory pressure following coronary artery bypass grafting.

BACKGROUND: Cardiac surgery-related pulmonary complications include alterations in lung mechanics and anomalies in gas exchange. Higher levels of positive end-expiratory pressure (PEEP) have been suggested to benefit cardiac surgical patients. We compared respiratory compliance, arterial oxygenation and time till tracheal extubation in 2 cohorts of patients weaned from mechanical ventilation with different levels of PEEP after elective and uncomplicated coronary artery bypass grafting (CABG). We hypothesized that higher PEEP levels improve pulmonary compliance and gas exchange in the first hours of weaning from mechanical ventilation, but not to shorten time till tracheal extubation. METHODS: Secondary retrospective analysis of 2 randomized controlled trials: in the first trial patients were weaned with PEEP levels of 10 cmH2O for the first 4 hours followed by PEEP levels of 5 cmH2O until tracheal extubation (high PEEP, HP); and the second trial patients were weaned with PEEP levels of 5 cmH2O during the entire weaning phase (low PEEP, LP). The primary endpoint was pulmonary compliance. Secondary endpoints included arterial oxygenation, duration of mechanical ventilation and postoperative pulmonary complications. RESULTS: The analysis included 121 patients; 60 HP patients and 61 LP patients. Baseline characteristics were similar. Compared to LP patients, HP patients had a better pulmonary compliance, 47.2±14.1 versus 42.7±10.2 ml/cmH2O (P<0.05), and higher levels of PaO2, 18.5±6.6 (138.75±49.5) versus 16.7±5.4 (125.25±40.5) kPa (mmHg) (P<0.05). Patients in the HP group were less frequent in need of supplementary oxygen after ICU discharge. These differences remained present during the entire weaning phase, even after reduction of PEEP. However, HP patients had a longer time till tracheal extubation, 16.9±6.1 versus 10.5±5.0 hours (P<0.001). HP patients had longer durations of postoperative infusion of propofol, 4.9 (2.6-7.4) versus 3.5 (1.8-5.8) hours (P<0.05). There were no differences in use of inotropes. Cumulative fluid balances were slightly higher in HP patients. CONCLUSION: Use of higher PEEP levels after elective uncomplicated CABG improves pulmonary compliance and oxygenation but seems to be associated with a delay in tracheal extubation.

Early predictability of the need for tracheotomy after admission to ICU: an observational study.

BACKGROUND: The goal of this study was to explore the ability of professional judgment to predict the need for tracheotomy early among intensive care unit (ICU) patients. METHODS: Prospective study using daily questionnaires among ICU physicians in a mixed medical-surgical ICU. The prediction of tracheotomy was by a visual analogue scale (VAS, from 1 to 10, with 1 representing 'absolutely no need for tracheotomy' and 10 representing 'pertinent need for tracheotomy') during ICU stay until tracheal extubation or tracheotomy. For the purpose of this study, a VAS score ≥ 8 was considered a positive prediction for tracheotomy. RESULTS: A total of 476 questionnaires were retrieved for 75 patients (6.4 ± 5.2 questionnaires per patient), of which 11 patients finally proceeded with a tracheostomy. At first assessment (mean of 2.4 ± 0.8 days after ICU admittance), ICU physicians predicted the need for tracheotomy 3.0 (2.0-6.0) higher VAS points for patients who were finally tracheotomized (P<0.01). Patients with a positive prediction had a 5.4 (1.2-24.1) higher chance of receiving tracheotomy (P=0.03). Considering the median VAS score over a maximum of 10 days before tracheotomy, ICU physicians scored tracheotomized patients significantly higher from day 8 onwards. When comparing ICU physicians, fellows and residents separately, only staff physicians scored a significant difference in the VAS score (P<0.05). CONCLUSION: ICU physicians are able to differentiate between patients in need for tracheotomy from those who do not, within 2 days from admittance. The closer the time to the actual intervention, the better the physicians are able to predict this decision.

Tracheostomy: current practice on timing, correction of coagulation disorders and peri-operative management - a postal survey in the Netherlands.

BACKGROUND: Several factors may delay tracheostomy. As many critically ill patients either suffer from coagulation abnormalities or are being treated with anticoagulants, fear of bleeding complications during the procedure may also delay tracheostomy. It is unknown whether such (usually mild) coagulation abnormalities are corrected first and to what extent. The purpose of this study was to ascertain current practice of tracheostomy in the Netherlands with regard to timing, pre-operative correction of coagulation disorders and peri-/intra-operative measures. METHODS: In October 2005, a questionnaire was sent to the medical directors of all non-pediatric ICUs with >/=5 beds suitable for mechanical ventilation in the Netherlands. RESULTS: A response was obtained from 44 (64%) out of 69 ICUs included in the survey. Seventy-five percent of patients receive tracheostomy within 2 days after the decision to proceed with a tracheostomy. Reasons indicated as frequent causes for delay were most often logistical factors. A heterogeneous attitude exists regarding values of coagulation parameters acceptable to perform tracheostomy. Fifty percent of the respondents have no guideline on correction of coagulation disorders or anticoagulant therapy before tracheostomy. Antimicrobial prophylaxis is almost never administered before tracheostomy. Forty-eight percent mentioned always using endoscopic guidance and 66% of ICUs only perform chest radiography on indication. CONCLUSIONS: There is a high variation in peri- and intra-operative practice of tracheostomy in the Netherlands. Especially on the subject of coagulation and tracheostomy there are different opinions and protocols are often lacking.