Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained amp;gt;= 1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32-0.77); Pamp;lt;0.01], but no difference in complication rates [OR 1.02 (0.88-1.19); P = 0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62-0.92); Pamp;lt;0.01; I-2 = 87%] and reduced complication rates [OR 0.73 (0.61-0.88); Pamp;lt;0.01; I-2 = 89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.

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BackgroundThis Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research.MethodsThe RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities.ResultsData from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied.ConclusionThe RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.

We performed a systematic review to investigate the effects of vasopressor-induced hemodynamic changes in adults with shock. We applied a physiological approach using the interacting domains of intravascular volume, heart pump performance, and vascular resistance to structure the interpretation of responses to vasopressors. We hypothesized that incorporating changes in determinants of cardiac output and vascular resistance better reflect the vasopressor responsiveness beyond mean arterial pressure alone. We identified 28 studies including 678 subjects in Pubmed, EMBASE, and CENTRAL databases. All studies demonstrated significant increases in mean arterial pressure (MAP) and systemic vascular resistance during vasopressor infusion. The calculated mean systemic filling pressure analogue increased (16 +/- 3.3 mmHg to 18 +/- 3.4 mmHg; P = 0.02) by vasopressors with variable effects on central venous pressure and the pump efficiency of the heart leading to heterogenous changes in cardiac output. Changes in the pressure gradient for venous return and cardiac output, scaled by the change in MAP, were positively correlated (r (2) = 0.88, P < 0.001). Changes in the mean systemic filling pressure analogue and heart pump efficiency were negatively correlated (r (2) = 0.57, P < 0.001) while no correlation was found between changes in MAP and heart pump efficiency. We conclude that hemodynamic changes induced by vasopressor therapy are inadequately represented by the change in MAP alone despite its common use as a clinical endpoint. The more comprehensive analysis applied in this review illustrates how vasopressor administration may be optimized.

BackgroundWhen caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.MethodsWe distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.ResultsThe survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.ConclusionsThe responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.

Introduction: Assessing left ventricular (LV) systolic function in a rapid and reliable way can be challenging in the critically ill patient. The purpose of this study was to evaluate the feasibility and reliability of, as well as the association between, commonly used LV systolic parameters, by using serial transthoracic echocardiography (TTE). Methods: Fifty patients with shock and mechanical ventilation were included. TTE examinations were performed daily for a total of 7 days. Methods used to assess LV systolic function were visually estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method, mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging (TDIs), and velocity time integral in the left ventricular outflow tract (VTI). Results: EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%, 99%, 95% and 93%, respectively, of all possible examinations. The correlations between the Simpson and EBEF showed r values for all 7 days ranging from 0.79 to 0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed substantial variation over time, with the poorest results seen for TDIs and AVPDm. The repeatability was best for VTI (interobserver coefficient of variation (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm (5.3% and 4.4%, respectively), and worst for the Simpson method (8.2% and 10.6%, respectively). Conclusions: EBEF and AVPDm provided the best, and Simpson, the worst feasibility when assessing LV systolic function in a population of mechanically ventilated, hemodynamically unstable patients. Additionally, the Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LV ejection fraction in this category of patients. TDIs and AVPDm, as markers of longitudinal function of the LV, are not interchangeable with LV ejection fraction.

Background: Left ventricular (LV) dysfunction is well documented in the critically ill. We assessed 1-year mortality in relation to cardiac biomarkers and LV function parameters by echocardiography in patients with shock. Methods: A prospective, observational, cohort study of 49 patients. B-natriuretic peptide (BNP), high-sensitive troponin T (hsTNT) and transthoracic echocardiography (TTE) were assessed within 12 h of study inclusion. LV systolic function was measured by ejection fraction (LVEF), mean atrioventricular plane displacement (AVPDm), peak systolic tissue Doppler velocity imaging (TDIs) and velocity time integral in the LV outflow tract (LVOT VTI). LV diastolic function was evaluated by transmitral pulsed Doppler (E, A, E/A, E-deceleration time), tissue Doppler indices (e, a, E/e) and left atrial volume (La volume). APACHE II (Acute Physiology and Chronic Health Evaluation) and SOFA (Sequential Organ Failure Assessment) scores were calculated. Results: hsTNT was significantly higher in non-survivors than in survivors (60 [17.0-99.5] vs 168 [89.8-358] ng/l, p = 0.003). Other univariate predictors of mortality were APACHE II (p = 0.009), E/e (p = 0.023), SOFA (p = 0.024) and age (p = 0.031). Survivors and non-survivors did not differ regarding BNP (p = 0.26) or any LV systolic function parameter (LVEF p = 0.87, AVPDm p = 0.087, TDIs p = 0.93, LVOT VTI p = 0.18). Multivariable logistic regression analysis identified hsTNT (p = 0.010) as the only independent predictor of 1-year mortality; adjusted odds ratio 2.0 (95% CI 1.2-3.5). Conclusions: hsTNT was the only independent predictor of 1-year mortality in patients with shock. Neither BNP nor echocardiographic parameters had an independent prognostic value. Further studies are needed to establish the clinical significance of elevated hsTNT in patients in shock.

Acetaminophen (paracetamol) is often used in critically ill patients with fever and pain; however, little is known about the effects of acetaminophen on cardiovascular function during systemic inflammation. Here, we investigated the effect of acetaminophen on changes in the systemic and pulmonary circulation induced by endotoxin (0.5 mu g/kg per hour) in anesthetized pigs. Endotoxin infusion led to a rapid increase in pulmonary artery pressure and pulmonary vascular resistance index. Acetaminophen delayed and attenuated this increase. Furthermore, acetaminophen reduced tachycardia and decreased stroke volume, accompanied by systemic inflammation, without affecting inflammatory parameters such as white blood cell count and TNF-alpha in blood. As a proof of concept, we injected a high dose of endotoxin (100 mu g), which induced rapid cardiovascular collapse in pigs. Pigs treated with acetaminophen survived with no obvious hemodynamic instability during the 50-min observation period. In conclusion, acetaminophen attenuates the effects of endotoxin on pulmonary circulation in anesthetized pigs. This may play a role in severe systemic inflammation.

Background Left ventricular longitudinal strain (LVLS) may be a sensitive indicator of left ventricular (LV) systolic function in patients with sepsis, but is dependent on high image quality and analysis software. Mitral annular plane systolic excursion (MAPSE) and the novel left ventricular longitudinal wall fractional shortening (LV-LWFS) are bedside echocardiographic indicators of LV systolic function that are less dependent on image quality. Both are sparsely investigated in the critically ill population, and may potentially be used as surrogates for LVLS. We assessed if LVLS may be predicted by LV-LWFS and MAPSE in patients with septic shock. We also assessed the repeatability and inter-rater agreement of LVLS, LV-LWFS and MAPSE measurements. Results 122 TTE studies from 3 echocardiographic data repositories of patients admitted to ICU with septic shock were retrospectively assessed, of which 73 were suitable for LVLS analysis using speckle tracking. The correlations between LVLS vs. LV-LWFS and LVLS vs. MAPSE were 0.89 (p < 0.001) and 0.81 (p < 0.001) with mean squared errors of 5.8% and 9.1%, respectively. Using the generated regression equation, LV-LWFS predicted LVLS with a high degree of accuracy and precision, with bias and limits of agreement of -0.044 +/- 4.7% and mean squared prediction error of 5.8%. Interobserver repeatability was good, with high intraclass correlation coefficients (0.96-0.97), small bias and tight limits of agreement (<= 4.1% for all analyses) between observers for all measurements. Conclusions LV-LWFS may be used to estimate LVLS in patients with septic shock. MAPSE also performed well, but was slightly inferior compared to LV-LWFS in estimating LVLS. Feasibility of MAPSE and LV-LWFS was excellent, as was interobserver repeatability.

BACKGROUNDIn recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery.AIMSThe aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery.METHODSThe guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies.RESULTSIn a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced.CONCLUSIONThe ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application.

BACKGROUND: Abnormal serum sodium concentrations are common in patients presenting for surgery. It remains unclear whether these abnormalities are independent risk factors for postoperative mortality.

METHODS: This is a secondary analysis of the European Surgical Outcome Study (EuSOS) that provided data describing 46 539 patients undergoing inpatient non-cardiac surgery. Patients were included in this study if they had a recorded value of preoperative serum sodium within the 28 days immediately before surgery. Data describing preoperative risk factors and serum sodium concentrations were analysed to investigate the relationship with in-hospital mortality using univariate and multivariate logistic regression techniques.

RESULTS: Of 35 816 (77.0%) patients from the EuSOS database, 21 943 (61.3%) had normal values of serum sodium (138-142 mmol litre(-1)) before surgery, 8538 (23.8%) had hyponatraemia (serum sodium ≤137 mmol litre(-1)) and 5335 (14.9%) had hypernatraemia (serum sodium ≥143 mmol litre(-1)). After adjustment for potential confounding factors, moderate to severe hypernatraemia (serum sodium concentration ≥150 mmol litre(-1)) was independently associated with mortality [odds ratio 3.4 (95% confidence interval 2.0-6.0), P<0.0001]. Hyponatraemia was not associated with mortality.

CONCLUSIONS: Preoperative abnormalities in serum sodium concentrations are common, and hypernatraemia is associated with increased mortality after surgery. Abnormalities of serum sodium concentration may be an important biomarker of perioperative risk resulting from co-morbid disease.

Background

The growing awareness of transfusion-associated morbidity and mortality necessitates investigations into the underlying mechanisms. Small animals have been the dominant transfusion model but have associated limitations. This study aimed to develop a comprehensive large animal (ovine) model of transfusion encompassing: blood collection, processing and storage, compatibility testing right through to post-transfusion outcomes.

Materials and methods

Two units of blood were collected from each of 12 adult male Merino sheep and processed into 24 ovine-packed red blood cell (PRBC) units. Baseline haematological parameters of ovine blood and PRBC cells were analysed. Biochemical changes in ovine PRBCs were characterized during the 42-day storage period. Immunological compatibility of the blood was confirmed with sera from potential recipient sheep, using a saline and albumin agglutination cross-match. Following confirmation of compatibility, each recipient sheep (n = 12) was transfused with two units of ovine PRBC.

Results

Procedures for collecting, processing, cross-matching and transfusing ovine blood were established. Although ovine red blood cells are smaller and higher in number, their mean cell haemoglobin concentration is similar to human red blood cells. Ovine PRBC showed improved storage properties in saline–adenine–glucose–mannitol (SAG-M) compared with previous human PRBC studies. Seventy-six compatibility tests were performed and 17·1% were incompatible. Only cross-match compatible ovine PRBC were transfused and no adverse reactions were observed.

Conclusion

These findings demonstrate the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions.

Background

As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care.

Methods

We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries.

Results

A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2–7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries.

Conclusions

Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care.

Background

Assessing left ventricular (LV) dysfunction by echocardiography in ICU patients is common. The aim of this study was to investigate mitral annular plane systolic excursion (MAPSE) in critically ill patients with shock and its relation to LV systolic and diastolic function, myocardial injury and to outcome.

Methods

In a prospective, observational, cohort study we enrolled 50 patients with SIRS and shock despite fluid resuscitation. Transthoracic echocardiography (TTE) measuring LV function was performed within 12 hours after admission and daily for a 7-day observation period. TTE and laboratory measurements were related to 28-day mortality.

Results

MAPSE on day 1 correlated significantly with LV ejection fraction (LVEF), tissue Doppler indices of LV diastolic function (é, E/é) and high-sensitive troponin T (hsTNT) (p< 0.001, p= 0.039, p= 0.009, p= 0.003 respectively) whereas LVEF did not correlate significantly with any marker of LV diastolic function or myocardial injury. Compared to survivors, non-survivors had a significantly lower MAPSE (8 [IQR 7.5-11] versus 11 [IQR 8.9-13] mm; p= 0.028). Other univariate predictors were age (p=0.033), hsTNT (p=0.014) and Sequential Organ Failure Assessment (SOFA) scores (p=0.007). By multivariate analysis MAPSE (OR 0.6 (95% CI 0.5- 0.9), p= 0.015) and SOFA score (OR 1.6 (95% CI 1.1- 2.3), p= 0.018) were identified as independent predictors of mortality. Daily measurements showed that MAPSE, as sole echocardiographic marker, was significantly lower in most days in non-survivors (p<0.05 at day 1–2, 4–6).

Conclusions

MAPSE seemed to reflect LV systolic and diastolic function as well as myocardial injury in critically ill patients with shock. The combination of MAPSE and SOFA added to the predictive value for 28-day mortality.

There is a need for large trials that test the clinical effectiveness of interventions in the field of perioperative medicine. Clinical outcome measures used in such trials must be robust, clearly defined and patient-relevant. Our objective was to develop standards for the use of clinical outcome measures to strengthen the methodological quality of perioperative medicine research. A literature search was conducted using PubMed and opinion leaders worldwide were invited to nominate papers that they believed the group should consider. The full texts of relevant articles were reviewed by the taskforce members and then discussed to reach a consensus on the required standards. The report was then circulated to opinion leaders for comment and review. This report describes definitions for 22 individual adverse events with a system of severity grading for each. In addition, four composite outcome measures were identified, which were designed to evaluate postoperative outcomes. The group also agreed on standards for four outcome measures for the evaluation of healthcare resource use and quality of life. Guidance for use of these outcome measures is provided, with particular emphasis on appropriate duration of follow-up. This report provides clearly defined and patient-relevant outcome measures for large clinical trials in perioperative medicine. These outcome measures may also be of use in clinical audit. This report is intended to complement and not replace other related work to improve assessment of clinical outcomes following specific surgical procedures.

Purpose of reviewThe aim of this study was to illustrate the varying roles of echocardiography in all phases of shock ranging from a rapid, diagnostic tool at the bedside, to a tool for monitoring the adequacy and effects of shock treatment and finally for identification of patients suitable for de-escalation of therapy.Recent findingsEchocardiography has become an indispensable tool for establishing diagnosis in patients with shock. It is also important for assessing the adequacy of treatment such as fluid resuscitation, vasopressors and inotropes by providing integrated information on cardiac contractility and systemic flow conditions, particularly when used in conjunction with other methods of advanced haemodynamic monitoring. Apart from a traditional, diagnostic role, it may be used as an advanced, albeit intermittent, monitoring tool. Examples include the assessment of heart-lung interactions in mechanically ventilated patients, fluid responsiveness, vasopressor adequacy, preload dependence in ventilator-induced pulmonary oedema and indications for and monitoring during extracorporeal life support. Emerging studies also illustrate the role of echocardiography in de-escalation of shock treatment.This study provides the reader with a structured review on the uses of echocardiography in all phases of shock treatment.

BACKGROUND Mortality among patients admitted to intensive care units (ICUs) with COVID-19 is unclear due to variable follow-up periods. Few nationwide data are available to compare risk factors, treatment and outcomes of COVID-19 patients after ICU admission. OBJECTIVE To evaluate baseline characteristics, treatments and 30-day outcomes of patients admitted to Swedish ICUs with COVID-19. DESIGN Registry-based cohort study with prospective data collection. SETTING Admissions to Swedish ICUs from 6 March to 6 May 2020 with laboratory confirmed COVID-19 disease. PARTICIPANTS Adult patients admitted to Swedish ICUs. EXPOSURES Baseline characteristics, intensive care treatments and organ failures. MAIN OUTCOMES AND MEASURES The primary outcome was 30-day all-cause mortality. A multivariable model was used to determine the independent association between potential predictor variables and death. RESULTS We identified 1563 patients with complete 30-day follow-up. The 30-day all-cause mortality was 26.7%. Median age was 61 [52 to 69], Simplified Acute Physiology Score III (SAPS III) was 53 [46 to 59] and 62.5% had at least one comorbidity. Median PaO2/FiO(2) on admission was 97.5 [75.0 to 140.6] mmHg, 74.7% suffered from moderate-to-severe acute respiratory failure. Age, male sex [adjusted odds ratio (aOR) 1.5 (1.1 to 2.2)], SAPS III score [aOR 1.3 (1.2 to 1.4)], severe respiratory failure [aOR 3.0 (2.0 to 4.7)], specific COVID-19 pharmacotherapy [aOR 1.4 (1.0 to 1.9)] and continuous renal replacement therapy [aOR 2.1 (1.5 to 3.0)] were associated with increased mortality. Except for chronic lung disease, the presence of comorbidities was not independently associated with mortality. CONCLUSIONS Thirty-day mortality rate in COVID-19 patients admitted to Swedish ICUs is generally lower than previously reported despite a severe degree of hypoxaemia on admission. Mortality was driven by age, baseline disease severity, the presence and degree of organ failure, rather than pre-existing comorbidities.

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Background We sought to provide a description of surge response strategies and characteristics, clinical management and outcomes of patients with severe COVID-19 in the intensive care unit (ICU) during the first wave of the pandemic in Denmark, Finland, Iceland, Norway and Sweden. Methods Representatives from the national ICU registries for each of the five countries provided clinical data and a description of the strategies to allocate ICU resources and increase the ICU capacity during the pandemic. All adult patients admitted to the ICU for COVID-19 disease during the first wave of COVID-19 were included. The clinical characteristics, ICU management and outcomes of individual countries were described with descriptive statistics. Results Most countries more than doubled their ICU capacity during the pandemic. For patients positive for SARS-CoV-2, the ratio of requiring ICU admission for COVID-19 varied substantially (1.6%-6.7%). Apart from age (proportion of patients aged 65 years or over between 29% and 62%), baseline characteristics, chronic comorbidity burden and acute presentations of COVID-19 disease were similar among the five countries. While utilization of invasive mechanical ventilation was high (59%-85%) in all countries, the proportion of patients receiving renal replacement therapy (7%-26%) and various experimental therapies for COVID-19 disease varied substantially (e.g. use of hydroxychloroquine 0%-85%). Crude ICU mortality ranged from 11% to 33%. Conclusion There was substantial variability in the critical care response in Nordic ICUs to the first wave of COVID-19 pandemic, including usage of experimental medications. While ICU mortality was low in all countries, the observed variability warrants further attention.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the ISTH guidelines for antithrombotic treatment in COVID-19. This evidence-based guideline serves as a useful decision aid for Nordic anaesthesiologists caring for patients with COVID-19.

Purpose of review Acute myocardial injury occurs commonly during perioperative care. There is still considerable confusion regarding its diagnosis and definition, and a lack of consensus on who and how to screen, exacerbated by a lack of studies addressing how to manage patients with detected myocardial injury. Recent findings Far from a benign biochemical anomaly, myocardial injury occurring perioperatively is largely a silent disease and is not necessarily because of ischaemia. Preoperative, postoperative, and perioperative changes in cardiac troponins (cTns) are independently associated with increased mortality and adverse cardiovascular outcomes. Routine screening with cTns is required for reliable detection of myocardial injury. Measurement of changes (from preoperative to postoperative) will detect acute events as well as identify patients with chronic troponin increases. This review aims to bring together current literature regarding myocardial injury that is detected perioperatively, identifies knowledge gaps for future research and provides suggestions for management.

Background: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality. Methods: Prospective, observational, cohort study in patients &gt;= 50 yr of age undergoing elective major noncardiac surgery at seven hospitals in Sweden. The exposures were hs-cTnT measured before and days 0-3 after surgery. Two previously published thresholds for myocardial injury and two thresholds identified using receiver operating characteristic analyses were evaluated using multivariable logistic regression models and externally validated. The weighted comparison net benefit method was applied to determine the additional value of hs-cTnT thresholds when compared with the Revised Cardiac Risk Index (RCRI). The primary outcome was a composite of 30-day all-cause mortality and MACCE. Results: We included 1291 patients between April 2017 and December 2020. The primary outcome occurred in 124 patients (9.6%). Perioperative increase in hs-cTnT &gt;= 14 ng L-1 above preoperative values provided statistically optimal model performance and was associated with the highest risk for the primary outcome (adjusted odds ratio 2.9, 95% confidence interval 1.8-4.7). Validation in an independent, external cohort confirmed these findings. A net benefit over RCRI was demonstrated across a range of clinical thresholds. Conclusions: Perioperative increases in hsTnT &gt;= 14 ng L-1 above baseline values identifies acute perioperative myocardial injury and provides a net prognostic benefit when added to RCRI for the identification of patients at high risk of death and MACCE.

The Scandinavian Society of Anaesthesiology and Intensive Care Medicine Clinical Practice Committee endorses the recent DASAIM/DSIT guideline for prevention of rhabdomyolysis-induced acute kidney injury. However, we emphasize the low quality of evidence with only weak recommendations for all interventions, highlighting that further research is very likely to have an important impact on the confidence in the estimate of effect and is likely to change the estimates.

The right ventricle (RV) has historically been given less importance than the left. There are important anatomical differences, including several intracardiac structures that may complicate echocardiographic assessments. The right heart is sensitive to changes in pressure and its function is affected by common interventions in critical care such as fluid loading and positive pressure ventilation. Right and left ventricular functions are inextricably linked, and both systolic and diastolic ventricular interdependence occur. The echocardiographic examination of the RV includes an assessment of size and dimensions, systolic and diastolic function, estimation of intracardiac and pulmonary pressures. These should be interpreted in the context of the clinical interventions that the patient was subjected to at the time of imaging, as well as left ventricular function. RV failure is associated with poorer outcomes in several disease states including congestive cardiac failure and acute myocardial infarction. In critically ill patients, acute respiratory distress syndrome (ARDS) has significant implications for right heart function, where there is a necessary balance between respiratory mechanics and haemodynamics.

The main objective of this chapter is to obtain an understanding of the interaction between pain, sedation, and delirium. Specifically, the reader should be able to identify the unique challenges for their management taking into account that the very old are a particularly vulnerable group with often conflicting treatment priorities. This chapter will discuss implications for short- and long-term ICU outcomes including mortality, time on mechanical ventilation, and increased ICU and hospital lengths of stay, as well long-term cognitive impairment. Finally, the reader should be able to formulate a plan for sedation, pain, and delirium management for the very old ICU patient using ABCDEF principles.

Failure or dysfunction of the cardiovascular system is the defining feature of septic shock. While there is now evidence for the central role of the heart in the pathophysiology of septic shock, it is important to remember that it is only one component of the cardiovascular system. Thus, it is often impossible to distinguish between the direct effects of sepsis on the heart and its responses to other changes in the cardiovascular system. Systolic, diastolic, left, and right heart functions are variably affected and are not mutually exclusive. They may be associated with rises in cardiac troponins and may be associated with underlying cardiovascular disease. Current evidence suggests left ventricular systolic dysfunction (assessed as reduced ejection fraction) is not associated with increased mortality, while diastolic dysfunction seems to be more predictive. Right heart failure occurs commonly, even with lung-protective ventilation strategies. Echocardiography is currently the only bedside technique providing comprehensive information regarding heart function during sepsis. In combination with information obtained with pulmonary arterial catheterization, it may be used to monitor the effects of fluid loading, mechanical ventilation, and vasopressor/inotropic therapy in the patient with septic shock. Future areas of research include (1) the development of a universal definition for septic cardiomyopathy; (2) investigating methods for distinguishing sepsis-specific changes from underlying disease; (3) investigating the relationship between cardiac biomarkers and echocardiographic changes; (4) investigating new echocardiographic markers of systolic and diastolic function; (5) integration of lung-protective mechanical ventilation and haemodynamic management strategies guided by echocardiographic findings.

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Myocardial injury is now an acknowledged complication in patients undergoing noncardiac surgery. Heterogeneity in the definitions of myocardial injury contributes to difficulty in evaluating the value of cardiac troponins (cTns) measurement in perioperative care. Pre-, post-, and peri-operatively increased cTns are encompassed by the umbrella term myocardial injury and are likely to reflect different pathophysiological mechanisms. Increased cTns are independently associated with cardiovascular and non-cardiovascular complications, poor short-term and long-term cardiovascular outcomes, and increased mortality. Preoperative measurement of cTns aids preoperative risk stratification beyond the Revised Cardiac Risk Index. Systematic measurement detects acute perioperative increases and allows early identification of acute myocardial injury. Common definitions and standards for reporting are a prerequisite for designing impactful future trials and perioperative management strategies.

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SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1-6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1-2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2-3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9-3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality (5.4 (95%CI 4.3-6.7)). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.

Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, &gt;= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score &gt;= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P&lt;0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)

In critically ill patients, fluid infusion is aimed at increasing cardiac output and tissue perfusion. However, it may contribute to fluid overload which may be harmful. Thus, volume status, risks and potential efficacy of fluid administration and/or removal should be carefully evaluated, and monitoring techniques help for this purpose. Central venous pressure is a marker of right ventricular preload. Very low values indicate hypovolemia, while extremely high values suggest fluid harmfulness. The pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile and is particularly useful for indicating the risk of pulmonary oedema through the pulmonary artery occlusion pressure. Besides cardiac output and preload, transpulmonary thermodilution measures extravascular lung water, which reflects the extent of lung flooding and assesses the risk of fluid infusion. Echocardiography estimates the volume status through intravascular volumes and pressures. Finally, lung ultrasound estimates lung edema. Guided by these variables, the decision to infuse fluid should first consider specific triggers, such as signs of tissue hypoperfusion. Second, benefits and risks of fluid infusion should be weighted. Thereafter, fluid responsiveness should be assessed. Monitoring techniques help for this purpose, especially by providing real time and precise measurements of cardiac output. When decided, fluid resuscitation should be performed through fluid challenges, the effects of which should be assessed through critical endpoints including cardiac output. This comprehensive evaluation of the risk, benefits and efficacy of fluid infusion helps to individualize fluid management, which should be preferred over a fixed restrictive or liberal strategy.

Although guidelines provide excellent expert guidance for managing patients with septic shock, they leave room for personalization according to patients condition. Hemodynamic monitoring depends on the evolution phase: salvage, optimization, stabilization, and de-escalation. Initially during the salvage phase, monitoring to identify shock etiology and severity should include arterial pressure and lactate measurements together with clinical examination, particularly skin mottling and capillary refill time. Low diastolic blood pressure may trigger vasopressor initiation. At this stage, echocardiography may be useful to identify significant cardiac dysfunction. During the optimization phase, echocardiographic monitoring should be pursued and completed by the assessment of tissue perfusion through central or mixed-venous oxygen saturation, lactate, and carbon dioxide veno-arterial gradient. Transpulmonary thermodilution and the pulmonary artery catheter should be considered in the most severe patients. Fluid therapy also depends on shock phases. While administered liberally during the resuscitation phase, fluid responsiveness should be assessed during the optimization phase. During stabilization, fluid infusion should be minimized. In the de-escalation phase, safe fluid withdrawal could be achieved by ensuring tissue perfusion is preserved. Norepinephrine is recommended as first-line vasopressor therapy, while vasopressin may be preferred in some patients. Essential questions remain regarding optimal vasopressor selection, combination therapy, and the most effective and safest escalation. Serum renin and the angiotensin I/II ratio may identify patients who benefit most from angiotensin II. The optimal therapeutic strategy for shock requiring high-dose vasopressors is scant. In all cases, vasopressor therapy should be individualized, based on clinical evaluation and blood flow measurements to avoid excessive vasoconstriction. Inotropes should be considered in patients with decreased cardiac contractility associated with impaired tissue perfusion. Based on pharmacologic properties, we suggest as the first test a limited dose of dobutamine, to add enoximone or milrinone in the second line and substitute or add levosimendan if inefficient. Regarding adjunctive therapies, while hydrocortisone is nowadays advised in patients receiving high doses of vasopressors, patients responding to corticosteroids may be identified in the future by the analysis of selected cytokines or specific transcriptomic endotypes. To conclude, although some general rules apply for shock management, a personalized approach should be considered for hemodynamic monitoring and support.

Background: While frailty is a known predictor of adverse outcomes in older patients, its effect in younger populations is unknown. This prospective observational study was conducted in a tertiary-level mixed ICU to assess the impact of frailty on long-term survival in intensive care patients of different ages. Methods: Data on premorbid frailty (Clinical Frailty Score; CFS), severity of illness (the Simplified Acute Physiology Score, third version; SAPS3), limitations of care and outcome were collected in 817 adult ICU patients. Hazard ratios (HR) for death within 180 days after ICU admission were calculated. Unadjusted and adjusted analyses were used to evaluate the association of frailty with outcome in different age groups. Results: Patients were classified into predefined age groups (18-49 years (n = 241), 50-64 (n = 188), 65-79 (n = 311) and 80 years or older (n = 77)). The proportion of frail (CFS &gt;= 5) patients was 41% (n = 333) in the overall population and increased with each age strata (n = 46 (19%) vs. n = 67 (36%) vs. n = 174 (56%) vs. n = 46 (60%), P &lt; 0.05). Frail patients had higher SAPS3, more treatment restrictions and higher ICU mortality. Frailty was associated with an increased risk of 180-day mortality in all age groups (HR 5.7 (95% CI 2.8-11.4), P &lt; 0.05; 8.0 (4.0-16.2), P &lt; 0.05; 4.1 (2.2-6.6), P &lt; 0.05; 2.4 (1.1-5.0), P = 0.02). The effect remained significant after adjustment for SAPS3, comorbidity and limitations of treatment only in patients aged 50-64 (2.1 (1.1-3.1), P &lt; 0.05). Conclusions: Premorbid frailty is common in ICU patients of all ages and was found in 55% of patients aged under 64 years. Frailty was independently associated with mortality only among middle-aged patients, where the risk of death was increased twofold. Our study supports the use of frailty assessment in identifying younger ICU patients at a higher risk of death.

The purpose of this update of the European Society of Anaesthesiology (ESA) guidelines on the pre-operative evaluation of the adult undergoing noncardiac surgery is to present recommendations based on the available relevant clinical evidence. Well performed randomised studies on the topic are limited and therefore many recommendations rely to a large extent on expert opinion and may need to be adapted specifically to the healthcare systems of individual countries. This article aims to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthesiologists all over Europe to integrate - wherever possible - this knowledge into daily patient care. The Guidelines Committee of the ESA formed a task force comprising members of the previous task force, members of ESA scientific subcommittees and an open call for volunteers was made to all individual active members of the ESA and national societies. Electronic databases were searched from July 2010 (end of the literature search of the previous ESA guidelines on pre-operative evaluation) to May 2016 without language restrictions. A total of 34066 abtracts were screened from which 2536 were included for further analysis. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the level of evidence and to grade recommendations. The final draft guideline was posted on the ESA website for 4 weeks and the link was sent to all ESA members, individual or national (thus including most European national anaesthesia societies). Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

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Nebulised antibiotics are frequently used for the prevention or treatment of ventilator-associated pneumonia. Many factors may influence pulmonary drug concentrations with inaccurate dosing schedules potentially leading to therapeutic failure and/or the emergence of antibiotic resistance. We describe a research pathway for studying the pharmacokinetics of a nebulised antibiotic during mechanical ventilation using in vitro methods and ovine models, using tobramycin as the study antibiotic.

Editors PerspectiveWhat We Already Know about This Topic For most bacterial pneumonia, the lung interstitium is considered to be the site of infection, and adequate antibiotic concentrations are important for drug effect Despite systemic antibiotic therapy, therapeutic failure is common, perhaps due to poor lung penetration, and resulting low interstitial space fluid antibiotic concentrations Increasing systemic antibiotic doses in order to increase interstitial space fluid antibiotic concentrations could lead to toxicities such as nephrotoxicity What This Article Tells Us That Is New In a mechanically ventilated healthy large animal model, nebulized tobramycin produced higher peak lung interstitial space fluid concentrations, as well as higher initial epithelial lining fluid concentrations, with lower plasma concentrations than were observed after intravenous administration due to more extensive lung penetration Background: Nebulized antibiotics may be used to treat ventilator-associated pneumonia. In previous pharmacokinetic studies, lung interstitial space fluid concentrations have never been reported. The aim of the study was to compare intravenous and nebulized tobramycin concentrations in the lung interstitial space fluid, epithelial lining fluid, and plasma in mechanically ventilated sheep with healthy lungs. Methods: Ten anesthetized and mechanically ventilated healthy ewes underwent surgical insertion of microdialysis catheters in upper and lower lobes of both lungs and the jugular vein. Five ewes were given intravenous tobramycin 400 mg, and five were given nebulized tobramycin 400 mg. Microdialysis samples were collected every 20 min for 8 h. Bronchoalveolar lavage was performed at 1 and 6 h. Results: The peak lung interstitial space fluid concentrations were lower with intravenous tobramycin 20.2 mg/l (interquartile range, 12 mg/l, 26.2 mg/l) versus the nebulized route 48.3 mg/l (interquartile range, 8.7 mg/l, 513 mg/l), P = 0.002. For nebulized tobramycin, the median epithelial lining fluid concentrations were higher than the interstitial space fluid concentrations at 1 h (1,637; interquartile range, 650, 1,781, vs. 16 mg/l, interquartile range, 7, 86, P amp;lt; 0.001) and 6 h (48, interquartile range, 17, 93, vs. 4 mg/l, interquartile range, 2, 9, P amp;lt; 0.001). For intravenous tobramycin, the median epithelial lining fluid concentrations were lower than the interstitial space fluid concentrations at 1 h (0.19, interquartile range, 0.11, 0.31, vs. 18.5 mg/l, interquartile range, 9.8, 23.4, P amp;lt; 0.001) and 6 h (0.34, interquartile range, 0.2, 0.48, vs. 3.2 mg/l, interquartile range, 0.9, 4.4, P amp;lt; 0.001). Conclusions: Compared with intravenous tobramycin, nebulized tobramycin achieved higher lung interstitial fluid and epithelial lining fluid concentrations without increasing systemic concentrations.

Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20µg/mL and flow rate of 1.0µL/min had the best recovery. A concentration of 5.0µg/mL and flow rate of 1.0µL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.