Faculty Bibliography

INTRODUCTION/BACKGROUND:Post-extubation dysphagia is commonly observed in ICU patients and associated with increased aspiration rates, delayed resumption of oral intake/ malnutrition, prolonged ICU and hospital length of stay, decreased quality of life, and increased mortality. Conventional therapeutic approaches are limited. Pharyngeal electrical stimulation (PES) was previously shown to improve swallowing function and airway safety in severely dysphagic tracheostomised stroke patients. METHODS:In a multi-center, single-blind, 1:1 randomized controlled study, up to 400 (360 evaluable) mixed emergency adult ICU patients with recent extubation following mechanical ventilation and confirmed oropharyngeal dysphagia will be enrolled at investigational academic ICUs. Primary objective is to evaluate the effectiveness of PES in reducing the severity of unsafe swallows. Patients will be randomized to receive PES (or sham) treatment on 3 consecutive days in addition to best supportive care. Primary endpoint is a composite of 2 endpoints with hierarchy based on clinical priorities: DISCUSSION:: This study will evaluate the effects of PES on swallowing safety in critically ill ICU patients post mechanical ventilation with oropharyngeal dysphagia.

Rationale: A recent randomized controlled trial showed that a peripheral perfusion-guided resuscitation strategy was associated with lower mortality and less organ dysfunction when compared with lactate-guided resuscitation strategy in patients with septic shock, but the difference in the primary outcome, 28-day mortality, did not reach the proposed statistical significance threshold (P = 0.06). We tested different analytic methods to aid in the interpretation of these results.Objectives: To reassess the results of the ANDROMEDA-SHOCK trial using both Bayesian and frequentist frameworks.Methods: All patients recruited in ANDROMEDA-SHOCK were included. Both a post hoc Bayesian analysis and a mixed logistic regression analysis were performed. The Bayesian analysis included four different priors (optimistic, neutral, null, and pessimistic) for mortality endpoints. The probability of having a Sequential Organ Failure Assessment in the lowest quartile at 72 hours was assessed using Bayesian networks.Measurements and Main Results: In the Bayesian analysis, the posterior probability that a peripheral perfusion-targeted resuscitation strategy is superior to lactate-targeted resuscitation at 28 days was above 90% for all priors; the probability of benefit at 90 days was above 90% for all but the pessimistic prior. Using an optimistic prior, posterior median odds ratios were 0.61 (95% credible interval, 0.41-0.90) and 0.68 (95% credible interval, 0.47-1.01) for 28-day and 90-day mortality, respectively. The comparable frequentist odds ratios for 28-day and 90-day mortality were 0.61 (95% confidence interval [CI], 0.38-0.92) and 0.70 (95% CI, 0.45-1.08), respectively. The odds that that patients in the peripheral perfusion-targeted resuscitation arm had Sequential Organ Failure Assessment scores in the lower quartile at 72 hours was 1.55 (95% CI, 1.02-2.37).Conclusions: Peripheral perfusion-targeted resuscitation may result in lower mortality and faster resolution of organ dysfunction when compared with a lactate-targeted resuscitation strategy.

BACKGROUND:Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock. METHODS:A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h. RESULTS:Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0-510] vs. 1500[650-2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500-1900] vs. 2600[1600-3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h. CONCLUSION:A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.

There is a tight relationship between lactate levels (and its changes over time) with morbidity and mortality and the presence of tissue hypoxia/hypoperfusion in both models of shock and clinical studies. These findings have placed lactate in the center of guiding resuscitation in patients with increased lactate levels. However, given the complex metabolism and clearance of lactate, especially in sepsis, the actual use of lactate is more complex than suggested by some guidelines. By using other markers of tissue hypoperfusion together with lactate levels provides a more solid framework to guide the initial hours of resuscitation.

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

Although the definition of septic shock is straightforward, the physiological response to inadequate hemodynamics in patients with septic shock is variable. Therefore, the clinical recognition is limited not only by the patient's response but also by the clinical parameters we can use at the bedside. In this short overview we will argue that the state of the peripheral perfusion can help to identify and to treat patients with septic shock.

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

BACKGROUND:Anaemia and coagulopathy are common issues in critically ill patients. Transfusion can be lifesaving, however, is associated with potential life threatening adverse events. As an international transfusion guideline for this specific patient population is lacking, we hypothesize that a high heterogeneity in transfusion practices exists. In this pilot-study we assessed transfusion practice in a university hospital in the Netherlands and tested the feasibility of this protocol for an international multi-centre study. METHODS:A prospective single centre cohort study was conducted. For seven days all consecutive non-readmitted patients to the adult Intensive Care Unit (ICU) were included and followed for 28 days. Patients were prospectively followed until ICU discharge or up to day 28. Patient outcome data was collected at day 28. Workload for this study protocol was scored in hours and missing data. RESULTS:In total, 48 patients were included, needed in total three hours patient to include and collect all data, with 1.6% missing data showing the feasibility of the data acquisition. Six (12.5%) patients received red blood cells (RBCs), three patients (6.3%) received platelet concentrates, and two (4.2%) patients received plasma units. In total eight (16.7%) patients were transfused with one or more blood products. Median pre- and post-transfusion haemoglobin (Hb) levels were 7.6 (6.7-7.7) g/dL and 8.1 (7.6-8.7) g/dL, respectively. CONCLUSION/CONCLUSIONS:In this pilot-study we proved the feasibility of our protocol and observed in this small population a restrictive transfusion practice for all blood products.