Faculty Bibliography

BACKGROUND:Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. METHODS:From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. RESULTS:A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81-90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement). CONCLUSION/CONCLUSIONS:Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.

•COVID-19 infection is associated with a prothrombotic state•Point of care ultrasound (POCUS) provides prompt bedside diagnosis of covid-19 complications such as clot in transit•Bedside TEE guidance of mechanical CPR arm placement improves the efficiency of chest compressions.

A measurement is always afflicted with some degree of uncertainty. A correct understanding of the different types of uncertainty, their naming, and their definition is of crucial importance for an appropriate use of the measuring instruments. However, in perioperative and intensive care medicine, the metrological requirements for measuring instruments are poorly defined and often used spuriously. The correct use of metrological terms is also of crucial importance in validation studies. The European Union published a new directive on medical devices, mentioning that in the case of devices with a measuring function, the notified body is involved in all aspects relating to the conformity of the device with the metrological requirements. It is therefore the task of scientific societies to establish the standards in their area of expertise. After adopting the same understandings and definitions (part 1), the different procedures for the validation of major quality criteria of measuring devices must be consensually established. In this metrologic review (part 2), we review the terms and definitions of validation, some basic processes leading to the display of an indication from a physiologic signal, and procedures for the validation of measuring instrument properties, with specific focus on perioperative and intensive care medicine including appropriate examples.

Any measurement is always afflicted with some degree of uncertainty. A correct understanding of the different types of uncertainty, their naming, and their definition is of crucial importance for an appropriate use of measuring instruments. However, in perioperative and intensive care medicine, the metrological requirements for measuring instruments are poorly defined and often used spuriously. The correct use of metrological terms is also of crucial importance in validation studies. The European Union published a new directive on medical devices, mentioning that in the case of devices with a measuring function, the notified body is involved in all aspects relating to the conformity of the device with the metrological requirements. It is therefore the task of the scientific societies to establish the standards in their area of expertise. Adopting the same understandings and definitions among clinicians and scientists is obviously the first step. In this metrologic review (part 1), we list and explain the most important terms defined by the International Bureau of Weights and Measures regarding quantities and units, properties of measurements, devices for measurement, properties of measuring devices, and measurement standards, with specific examples from perioperative and intensive care medicine.

The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro and in vivo analyses, we report that Topoisomerase 1 (Top1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of Topotecan (TPT), a FDA-approved Top1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as four days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of Top1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing Top1 inhibitors for COVID-19 in humans.

Background: Transfusion practice on the intensive care unit (ICU) shifted from a liberal towards a more restrictive transfusion strategy during the last decades. However, current practice is still highly variable, as recently has been shown in non-bleeding critically ill patients. Bleeding patients are more complex and receive more and different blood products. Currently, no transfusion guideline for bleeding critically ill patients is available. Therefore, we hypothesized to find a great variety in transfusion practice in this patient population.
Aim(s): The aim of this survey was to study current transfusion practice in different bleeding subpopulations in the ICU and assess the availability and influence of transfusion guidelines.
Method(s): An online survey was performed among physicians working in the ICU only. The survey questioned transfusion practice in massively and non-massively bleeding ICU patients, including transfusion ratios of blood components and transfusion thresholds. Different relevant subpopulations were included. Also, the presence of transfusion guidelines was asked.
Result(s): A total of 611 physicians responded, of which 401 completed the survey, representing 64 countries. The majority of respondents work in high-income countries (72%) and 45% reports having a hospital wide transfusion protocol, 40% an ICU specific transfusion protocol, and 52% have a massive transfusion protocol available in their centre. In massively bleeding patients 67% of the respondents used conventional lab-based testing to guide their transfusion practice, 46% used fixed transfusion ratios and 41% used point of care visco-elastic tests. Of those who use fixed blood component ratio's, the 1:1:1 (red blood cell concentrates: plasma: platelet concentrates) was most commonly used (33%) followed by a 3:3:1 ratio (24%). In non-massively bleeding patients, different threshold were applied for different patient populations. In the general ICU population, a haemoglobin threshold of 7.0 [7.0-7.3] g/dl was used to transfuse red blood cells (RBCs). The highest variance in haemoglobin threshold was observed in patients treated with extracorporeal membrane oxygenation (ECMO) and in patients with haemorrhagic stroke or traumatic brain injury, with a haemoglobin threshold of 8.0 [7.0-9.0] g/dl each. In the general ICU population a platelet count threshold of 50 [26-50] x109 cells/l was applied. The highest threshold was observed in patients with haemorrhagic stroke or traumatic brain injury: 75 [50-100] cells/l. The presence of a hospital wide or an ICU specific transfusion guideline did not influence the applied transfusion thresholds in the non-massively bleeding patients. Summary/Conclusions: The majority of the respondents do not have an ICU specific transfusion guideline available in their centre. There is a high variance in the approach of both non-massive and massively bleeding ICU patients. In the general ICU population restrictive transfusion triggers are used. However, in ECMO and brain injury patients, physicians tend to transfuse more liberally

Introduction: Decisions to withhold resuscitation in case of a circulatory arrest or in other life-threatening medical emergencies (do-not-resuscitate (DNR) decisions) are part of routine hospital practice.1 When properly executed, a DNR order is a useful method to ensure that preferences of a patients regarding CPR are honoured.2 However, the Intensive Care Unit (ICU) is an environment in which DNR decisions with patient involvement is almost always absent, as the majority of the ICU patients lack decision-making capacity.3 Advanced directives of patients are often not known. The number of patients with a malignancy admitted to the ICU has increased.4 Subsequently, DNR decisions in cancer patients admitted to the ICU may have to be made more frequently. Literature shows that stigma among health care providers concerning cancer patients do occur and that having a malignancy is associated with more DNR decisions made by the medical team.5 Objective: The aim was to provide an insight in DNR decisions in cancer patients admitted to the ICU.
Method(s): We conducted a retrospective observational cohort study. By using our hospital database, we identified patients with and without a malignancy, admitted to the ICU in 2017. A DNR order was defined as an instruction not to perform cardiopulmonary resuscitation in case of a cardiac arrest, or an instruction not to perform other life-saving treatments, such as tracheal intubation and mechanically ventilation in case of respiratory insufficiency. We used an univariate and multivariate logistic regression analysis to identify factors associated with DNR orders.
Result(s): Of the 2486 patients admitted during the study period, 470 were cancer patients (18.9%). A higher incidence of DNR decisions in cancer patients prior to ICU admission was seen compared to our general ICU population (8.5% vs. 3.8%, p-value<0.001). During ICU admission, a DNR decision was made in 8.9% of the cancer patients and in 8.6% of the patients without cancer (p-value 0.83). Age (OR 1.06, 95% CI 1.02-1.09, p-value 0.001), a haematological malignancy (OR 3.4, 95% CI 1.37-8.46, p-value 0.01), an unplanned ICU admission (OR 28.6, 95% CI 10.9-74.9, p-value <0.001), the SOFA score (OR 1.27, 95% CI 1.16-1.38, p-value <0.001) and sepsis (OR 12.8, 95% CI 6.39-25.6, p-value<0.001) were associated with a DNR order during ICU admission. However, in a multivariate binary logistic regression analysis, only age (OR 1.04, 95% CI 1.00-1.08, p-value 0.04) and SOFA score (OR 1.27, 95% CI 1.16-1.38, p-value <0.001) remained as predictor of a new DNR order during ICU admission. All the DNR decisions during ICU admission were made by the medical team, only 2 included patient's wishes as well (4.8%).
Conclusion(s): DNR decisions during ICU admission are generally made by the medical team and may not be determined by the presence of cancer, but by the severity of the critical illness and age. The presence of a malignancy was associated with a higher incidence of DNR decisions prior to the ICU admission

Introduction: The number of patients with a malignancy who require intensive care treatment has increased (1). Historically, patients with cancer were generally considered ineligible for intensive care treatment due to the unfavourable outcome (2, 3). Although Intensive Care Unit (ICU) survival of cancer patients has improved (4), literature suggest that healthcare professionals display implicit 'cognitive biases' towards cancer patients (5), potentially influencing (admission) decisions of (ICU) physicians.
Objective(s): The aim was to assess the mortality of critically ill patients with a current diagnosis of malignancy or a malignancy in their medical history admitted unplanned to the ICU, compared to a general unplanned ICU population.
Method(s): We conducted a retrospective observational, single centre cohort study. The study population was defined as all patients with an active malignancy or a malignancy in their medical history admitted unplanned to our ICU during 1 year (January 1, 2017 to December 31, 2017). Complete remission (CR) was defined as no detectable malignancy and was determined by using the electronic database.We used an univariate and multivariate binary logistic regression analysis to identify factors independently associated with hospital mortality.
Result(s): During the study period, 2486 patients were admitted to our ICU, of which 702 patients (28.2%) with an active malignancy or a malignancy in the medical history. Two hundred and twenty-one (221) were admitted in an unplanned setting. Slightly more than half of the patients was admitted with an active malignancy (122, 55.2%). Hospital mortality was 43% (n=95). Compared to our general ICU population, a significant difference was seen (29.6% vs 43%, p-value <0.001). The ICU- and 30-day mortality were 29.9% (n=66) and 43.9% (n=97). The ICU mortality of our study population showed no statistically significant difference compared to our general ICU population (29.9% vs. 23.8%, p-value 0.08. Only SOFA score (OR 1.15, 95% CI 1.05-1.26, p-value 0.003) and gender (OR 1.94, 95% CI 1.01-3.73, p-value<0.05) were independently associated with mortality. The malignancy type (solid or hematologic malignancy) and status (active, CR<1 year or CR>1 year) were not associated with hospital mortality.
Conclusion(s): The majority of the patients in our study population survived the ICU admission. Therefore, the potential stigma and the biases concerning patients with a malignancy are not generally justified

Despite the high number of intensive care beds in German hospitals compared to other European countries, intensive care medical shortages are common in daily clinical practice. This is due to a hardly established cross-departmental discharge and transfer management with missing objective discharge criteria, lack of personnel and bed closures. Aboveaverage lengths of stays and increased readmission rates to the intensive care unit also indicate an inefficient use of resources in German hospitals. Against this background, a systematic literature search was carried out on the current state of research on discharge criteria from the intensive care unit and transfer processes to follow-up wards. Between 1983 and 2020, 1,917 sources were found, 286 were selected as full text, 104 of which were considered relevant and used as the basis for this work. Approaches, such as a root cause analy- sis of bottleneck situations including the entire hospital system with its interdependent admission, transfer and discharge processes, and the use of electronic decision support in conjunction with standardised discharge criteria can improve the use of existing intensive care capacities and lead to safer and better patient flow. For better use of resources, the therapeutic outcome must be viewed along the entire clinical pathway in order to care for the right patient at the right place and at the right time. A standardised care transition management using objective discharge criteria could help to include the various stakeholders in the discharge decision and patient-transfer process to reflect patient-, caregiver-, process, and institution-specific factors, and ultimately to manage, proactively and efficiently, the available intensive care resources. Decision support in the discharge process using self-learning systems based on available data from patient data management systems is forward-looking, but must be validated more widely in clinical practice.
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BACKGROUND:Persistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. Therefore, pursuing lactate normalization may lead to the risk of fluid overload. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. We designed the present randomized controlled trial to address the impact of a CRT-targeted (CRT-T) vs. a lactate-targeted (LAC-T) fluid resuscitation strategy on fluid balances within 24 h of septic shock diagnosis. In addition, we compared the effects of both strategies on organ dysfunction, regional and microcirculatory flow, and tissue hypoxia surrogates. RESULTS:content difference ratio; and lactate/pyruvate ratio. There was no difference between CRT-T vs. LAC-T in 6 h-fluid boluses (875 [375-2625] vs. 1500 [1000-2000], p = 0.3), or balances (982[249-2833] vs. 15,800 [740-6587, p = 0.2]). CRT-T was associated with a higher achievement of the predefined perfusion target (62 vs. 24, p = 0.03). No significant differences in perfusion-related variables or hypoxia surrogates were observed. CONCLUSIONS:CRT-targeted fluid resuscitation was not superior to a lactate-targeted one on fluid administration or balances. However, it was associated with comparable effects on regional and microcirculatory flow parameters and hypoxia surrogates, and a faster achievement of the predefined resuscitation target. Our data suggest that stopping fluids in patients with CRT ≤ 3 s appears as safe in terms of tissue perfusion. Clinical Trials: ClinicalTrials.gov Identifier: NCT03762005 (Retrospectively registered on December 3rd 2018).