Other bulletins in this series include:

Breast Surgery

Tuesday, 17 December 2019

The persistent potential of extracorporeal therapies in liver failure

Alshamsi and co-authors performed a systematic review and meta-analysis of randomized controlled trials (RCT) to examine the efficacy and safety of extracorporeal liver support (ECLS) in patients with liver failure [1]. ECLS can be divided into artificial (cell-free systems) and bioartificial liver support devices that incorporate hepatocytes in an artificial device. The authors identified 25 RCTs including 1796 patients, and used the GRADE approach to assess the certainty of evidence. Thirteen RCTs assessed patients with acute liver failure (ALF) and 13 RCTs investigated patients with acute-on-chronic liver failure (ACLF). Nineteen trials used artificial ECLS and five trials used bio-artificial ECLS. The authors observed a significant association of ECLS and reduction in mortality (RR 0.84, 95% CI 0.74–0.96, moderate certainty) and significant improvement in hepatic encephalopathy (RR 0.71, 95% CI 0.60–0.84, low certainty) in patients with ALF and ACLF. Subgroup analysis did not observe a difference of outcome using ECLS in patients with ALF and ACLF. Furthermore, kind of device, risk of bias and funding source did not reveal significant subgroup differences. Additional sensitivity analysis excluding four studies published in abstract form revealed similar results. The number needed to treat was 22 in patients with ALF and 16 in patients with ACLF. In summary, this systematic review and meta-analysis provides evidence that ECLS may reduce mortality in patients with ALF and ACLF. This effect was more prominent with artificial than with bio-artificial devices.

Epidemiology and prognosis of anti-infective therapy in the ICU setting during acute pancreatitis: a cohort study

by Philippe Montravers, Elie Kantor, Jean-Michel Constantin, Jean-Yves Lefrant, Thomas Lescot, Nicolas Nesseler, Catherine Paugam, Matthieu Jabaudon and Hervé Dupont

Critical Care volume 23, Article number: 393 (2019)

Recent international guidelines for acute pancreatitis (AP) recommend limiting anti-infective therapy (AIT) to cases of suspected necrotizing AP or nosocomial extrapancreatic infection. Limited data are available concerning empirical and documented AIT prescribing practices in patients admitted to the intensive care unit (ICU) for the management of AP.

Using a multicentre, retrospective (2009–2014), observational database of ICU patients admitted for AP, our primary objective was to assess the incidence of AIT prescribing practices during the first 30 days following admission. Secondary objectives were to assess the independent impact of centre characteristics on the incidence of AIT and to identify factors associated with crude hospital mortality in a logistic regression model.

In this cohort of 860 patients, 359 (42%) received AIT on admission. Before day 30, 340/359 (95%) AIT patients and 226/501 (45%) AIT-free patients on admission received additional AIT, mainly for intra-abdominal and lung infections. A large heterogeneity was observed between centres in terms of the incidence of infections, therapeutic management including AIT and prognosis. Administration of AIT on admission or until day 30 was not associated with an increased mortality rate. Patients receiving AIT on admission had increased rates of complications (septic shock, intra-abdominal and pulmonary infections), therapeutic (surgical, percutaneous, endoscopic) interventions and increased length of ICU stay compared to AIT-free patients. Patients receiving delayed AIT after admission and until day 30 had increased rates of complications (respiratory distress syndrome, intra-abdominal and pulmonary infections), therapeutic interventions and increased length of ICU stay compared to those receiving AIT on admission. Risk factors for hospital mortality assessed on admission were age (adjusted odds ratio [95% confidence interval] 1.03 [1.02–1.05]; p < 0.0001), Balthazar score E (2.26 [1.43–3.56]; p < 0.0001), oliguria/anuria (2.18 [1.82–4.33]; p < 0.0001), vasoactive support (2.83 [1.73–4.62]; p < 0.0001) and mechanical ventilation (1.90 [1.15–3.14]; p = 0.011), but not AIT (0.63 [0.40–1.01]; p = 0.057).

High proportions of ICU patients admitted for AP receive AIT, both on admission and during their ICU stay. A large heterogeneity was observed between centres in terms of incidence of infections, AIT prescribing practices, therapeutic management and outcome. AIT reflects the initial severity and complications of AP, but is not a risk factor for death.

“I had the feeling that I was trapped”: a bedside qualitative study of cognitive and affective attitudes toward noninvasive ventilation in patients with acute respiratory failure

by Marina Iosifyan, Matthieu Schmidt, Amélie Hurbault, Julien Mayaux, Christian Delafosse, Marina Mishenko, Nathalie Nion, Alexandre Demoule and Thomas Similowski

Annals of Intensive Care volume 9, Article number: 134 (2019)

Noninvasive ventilation (NIV) is the application of mechanical ventilation through a mask. It is used to treat certain forms of acute respiratory failure in intensive care units (ICU). NIV has clinical benefits but can be anxiogenic for the patients. This study aimed at describing cognitive and affective attitudes toward NIV among patients experiencing NIV for the first time in the context of an ICU stay.

Semi-structured interviews were conducted in 10 patients during their ICU stay and soon after their first NIV experience. None of the patients had ever received NIV previously. Evaluative assertion analysis and thematic analysis were used to investigate cognitive and affective attitudes toward NIV before, during, and after the first NIV experience, as well as patient attitudes toward caregivers and relatives.

Before their first NIV session, the cognitive attitudes of the patients were generally positive. They became less so and more ambiguous during and after NIV, as the patients discovered the actual barriers associated with NIV. Affective attitudes during NIV were more negative than affective attitudes before and after NIV, with reports of dyspnea, anxiety, fear, claustrophobic feelings, and reactivation of past traumatic experiences. The patients had more positive attitudes toward the presence of a caregiver during NIV, compared to the presence of a family member.

This study corroborates the possibly negative—or even traumatic—nature of the NIV experience, with emphasis on the role of affective attitudes. This is a rationale for evaluating the impact of NIV-targeted psychological interventions in ICU patients with acute respiratory failure.

How I search for a sepsis source

How I search for a sepsis source

Critical Care volume 23, Article number: 386 (2019) 

Identifying the infection source in a sepsis patient is important [1] as it allows for better antibiotic choices, recognizes the need for ancillary treatment, and identifies the need for source control interventions [23]. Searching for the source of infection cannot be disconnected from the other aspects of sepsis management [4]. We will start antibiotics based on local guidelines in parallel to the search for the infection source in these patients, but we adopt a watchful waiting strategy in doubtful cases without life-threatening organ failure [5]. (click the title for access to full content)

Early Palliative Care Consultation in the Medical ICU: A Cluster Randomized Crossover Trial

by Ma, Jessica; Chi, Stephen; Buettner, Benjamin; Pollard, Katherine; Muir, Monica; Kolekar, Charu; Al-Hammadi, Noor; Chen, Ling; Kollef, Marin; Dans, Maria

To assess the impact of early triggered palliative care consultation on the outcomes of high-risk ICU patients.

Design: Single-center cluster randomized crossover trial. Setting: Two medical ICUs at Barnes Jewish Hospital.

Patients: Patients (n = 199) admitted to the medical ICUs from August 2017 to May 2018 with a positive palliative care screen indicating high risk for morbidity or mortality. Interventions: The medical ICUs were randomized to intervention or usual care followed by washout and crossover, with independent assignment of patients to each ICU at admission. Intervention arm patients received a palliative care consultation from an interprofessional team led by board-certified palliative care providers within 48 hours of ICU admission.

 Measurements and Main Results: Ninety-seven patients (48.7%) were assigned to the intervention and 102 (51.3%) to usual care. Transition to do-not-resuscitate/do-not-intubate occurred earlier and significantly more often in the intervention group than the control group (50.5% vs 23.4%; p < 0.0001). The intervention group had significantly more transfers to hospice care (18.6% vs 4.9%; p < 0.01) with fewer ventilator days (median 4 vs 6 d; p < 0.05), tracheostomies performed (1% vs 7.8%; p < 0.05), and postdischarge emergency department visits and/or readmissions (17.3% vs 38.9%; p < 0.01). Although total operating cost was not significantly different, medical ICU (p < 0.01) and pharmacy (p < 0.05) operating costs were significantly lower in the intervention group. There was no significant difference in ICU length of stay (median 5 vs 5.5 d), hospital length of stay (median 10 vs 11 d), in-hospital mortality (22.6% vs 29.4%), or 30-day mortality between groups (35.1% vs 36.3%) (p > 0.05).

Conclusions: Early triggered palliative care consultation was associated with greater transition to do-not-resuscitate/do-not-intubate and to hospice care, as well as decreased ICU and post-ICU healthcare resource utilization. Our study suggests that routine palliative care consultation may positively impact the care of high risk, critically ill patients.

Estimated dead space fraction and the ventilatory ratio are associated with mortality in early ARDS

by Luis Morales-Quinteros, Marcus J. Schultz, Josep Bringué, Carolyn S. Calfee, Marta Camprubí, Olaf L. Cremer, Janneke Horn, Tom van der Poll, Pratik Sinha, Antonio Artigas and Lieuwe D. Bos

Annals of Intensive Care volume 9, Article number: 128 (2019)

Indirect indices for measuring impaired ventilation, such as the estimated dead space fraction and the ventilatory ratio, have been shown to be independently associated with an increased risk of mortality. This study aimed to compare various methods for dead space estimation and the ventilatory ratio in patients with acute respiratory distress syndrome (ARDS) and to determine their independent values for predicting death at day 30. The present study is a post hoc analysis of a prospective observational cohort study of ICUs of two tertiary care hospitals in the Netherlands.
Individual patient data from 940 ARDS patients were analyzed. Estimated dead space fraction and the ventilatory ratio at days 1 and 2 were significantly higher among non-survivors (p < 0.01). Dead space fraction calculation using the estimate from physiological variables [VD/VT phys] and the ventilatory ratio at day 2 showed independent association with mortality at 30 days (odds ratio 1.28 [95% CI 1.02–1.61], p < 0.03 and 1.20 [95% CI, 1.01–1.40], p < 0.03, respectively); whereas, the Harris–Benedict [VD/VT HB] and Penn State [VD/VT PS] estimations were not associated with mortality. The predicted validity of the estimated dead space fraction and the ventilatory ratio improved the baseline model based on PEEP, PaO2/FiO2, driving pressure and compliance of the respiratory system at day 2 (AUROCC 0.72 vs. 0.69, p < 0.05).
Estimated methods for dead space calculation and the ventilatory ratio during the early course of ARDS are associated with mortality at day 30 and add statistically significant but limited improvement in the predictive accuracy to indices of oxygenation and respiratory system mechanics at the second day of mechanical ventilation.

Respective contribution of intensive care unit-acquired limb muscle and severe diaphragm weakness on weaning outcome and mortality: a post hoc analysis of two cohorts

by Martin Dres, Boris Jung, Nicolas Molinari, Federico Manna, Bruno-Pierre Dubé, Gerald Chanques, Thomas Similowski, Samir Jaber and Alexandre Demoule

Critical Care volume 23, Article number: 370 (2019)

Intensive care unit (ICU)-acquired weakness (ICU-AW) and ICU-acquired diaphragm dysfunction (ICU-DD) occur frequently in mechanically ventilated (MV) patients. It is unknown whether they have different risk factors and different impacts on outcome. This study was designed to (1) describe the respective risk factors associated with ICU-AW and severe ICU-DD and (2) evaluate the respective impact of ICU-AW and severe ICU-DD on outcome.
Post hoc analysis of two prospective cohort studies conducted in two ICUs. In patients mechanically ventilated for at least 24 h undergoing a first spontaneous breathing trial, severe ICU-DD was defined as diaphragm twitch pressure < 7 cmH2O and ICU-AW was defined as Medical Research Council Score < 48.
One hundred sixteen patients were assessed. Factors independently associated with severe ICU-DD were age, longer duration of MV, and exposure to sufentanil, and those factors associated with ICU-AW were longer duration of MV and exposure to norepinephrine. Severe ICU-DD (OR 3.56, p = 0.008), but not ICU-AW, was independently associated with weaning failure (59%). ICU-AW (OR 4.30, p = 0.033), but not severe ICU-DD, was associated with ICU mortality. Weaning failure and mortality rate were higher in patients with both severe ICU-DD and ICU-AW (86% and 39%, respectively) than in patients with either severe ICU-DD (64% and 0%) or ICU-AW (63% and 13%).
Severe ICU-DD and ICU-AW have different risk factors and different impacts on weaning failure and mortality. The impact of the combination of ICU-DD and ICU-AW is more pronounced than their individual impact.

Derivation and validation of an easy-to-compute trauma score that improves prognostication of mortality or the Trauma Rating Index in Age, Glasgow Coma Scale, Respiratory rate and Systolic blood pressure (TRIAGES) score

by Atsushi Shiraishi, Yasuhiro Otomo, Shunsuke Yoshikawa, Koji Morishita, Ian Roberts and Hiroki Matsui 

Critical Care volume 23, Article number: 365 (2019)

Multiple trauma scores have been developed and validated, including the Revised Trauma Score (RTS) and the Mechanism, Glasgow Coma Scale, Age, and Arterial Pressure (MGAP) score. However, these scores are complex to calculate or have low prognostic abilities for trauma mortality. Therefore, we aimed to develop and validate a trauma score that is easier to calculate and more accurate than the RTS and the MGAP score.
The study was a retrospective prognostic study. Data from patients registered in the Japan Trauma Databank (JTDB) were dichotomized into derivation and validation cohorts. Patients’ data from the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage-2 (CRASH-2) trial were assigned to another validation cohort. We obtained age and physiological variables at baseline, created ordinal variables from continuous variables, and defined integer weighting coefficients. Score performance to predict all-cause in-hospital death was assessed using the area under the curve in receiver operating characteristics (AUROC) analyses.
Based on the JTDB derivation cohort (n = 99,867 with 12.5% mortality), the novel score ranged from 0 to 14 points, including 0–2 points for age, 0–6 points for the Glasgow Coma Scale, 0–4 points for systolic blood pressure, and 0–2 points for respiratory rate. The AUROC of the novel score was 0.932 for the JTDB validation cohort (n = 76,762 with 10.1% mortality) and 0.814 for the CRASH-2 cohort (n = 19,740 with 14.6% mortality), which was superior to RTS (0.907 and 0.808, respectively) and MGAP score (0.918 and 0.774, respectively) results.
We report an easy-to-use trauma score with better prognostication ability for in-hospital mortality compared to the RTS and MGAP score. Further studies to test clinical applicability of the novel score are warranted.

Beta-blockers doubled risk of hospitalization from COPD exacerbations (BLOCK-COPD)

PulmCCM - November 17, 2019

Beta-blockers have generally been considered safe and beneficial for patients with COPD, but a new randomized trial calls that assumption into doubt. The use of oral beta blockers without a cardiac indication appeared to double the risk of hospitalization for people experiencing a COPD exacerbation.

Authors randomized 532 patients with moderate or severe COPD with an exacerbation within the past year to receive either extended release metoprolol or placebo. Patients were not already taking beta blockers and had not had myocardial infarctions or other cardiac indications for beta blocker use. The trial was called BLOCK-COPD and was published in the New England Journal of Medicine.

Promoting Family Engagement in the ICU: Experience From a National Collaborative of 63 ICUs*

by Kleinpell, Ruth; Zimmerman, Jerry; Vermoch, Kathleen L.; Harmon, Lori A.; Vondracek, Hugh; Hamilton, Rebekah; Hanson, Bruce; Hwang, David Y.

Objectives: As part of an improvement program targeting ICU, a national collaborative was launched to help hospitals implement patient- and family-centered care engagement initiatives.
Design: Ten-month quality improvement collaborative.
Setting: Guided by a national patient and family advisory group, participating teams implemented an individual project including open visitation; integrating families on rounds; establishing a patient and family advisory committee; using patient and family diaries, among others.
Subjects: Sixty-three adult and PICU teams from both academic and community hospitals in 34 states participated. Interventions: Monthly team calls, quarterly webinars, newsletters, an online eCommunity, and team reporting assignments were used to facilitate project implementation.
Measurements and Main Results: The Family Satisfaction with Care in the ICU 24 was used to assess family satisfaction. Clinician perceptions were assessed with the Institute for Patient- and Family-Centered Care Self-Assessment Inventory. Thematic analysis was used to explore narrative data captured from team reports of project barriers, facilitators, and the experience of participating in the collaborative. A total of 2,530 family member and 3,999 clinician surveys were completed. Postimplementation, family members reported statistically significant increases in overall family satisfaction, satisfaction with decision-making, and satisfaction with quality of care (Family Satisfaction with Care in the ICU mean score change range 0.83–1.24; p ≤ 0.027). Clinicians reported that opportunities for families to participate as members of the care team increased. Major barriers included lack of buy-in and ability to promote change in the clinical setting, managing the workload of implementation, and funding to support initiatives.
Conclusions: A national collaborative format was useful to assist ICU teams to implement patient- and family-engagement initiatives. Enlisting stakeholder support, engaging unit-based champions, and highlighting benefits of family engagement can help ICU teams to promote family member involvement and engagement.

Which Multicenter Randomized Controlled Trials in Critical Care Medicine Have Shown Reduced Mortality? A Systematic Review

by Santacruz, Carlos A.; Pereira, Adriano J.; Celis, Edgar; Vincent, Jean-Louis 

Objectives: To determine which multicenter randomized controlled trials in critically ill patients have shown that the study intervention was associated with a statistically significant reduction in mortality. Our analysis provides an update to a report published 10 years ago.
Data Sources: MEDLINE database and PubMed interface from inception until April 30, 2019.
Study Selection: All adult multicenter randomized controlled trials that evaluated the effects of any intervention or monitoring system in critically ill patients and reported mortality as a primary or secondary outcome were included.
Data Extraction: Numbers of centers and patients, type of intervention, reported mortality outcome, and rate and level of significance were extracted into predefined tables. Included randomized controlled trials were classified as reporting reduced, increased, or no effect of the intervention on mortality. Methodologic quality of trials was evaluated using the updated Consolidated Standards of Reporting Trials statement.
Data Synthesis: A total of 212 trials met the inclusion criteria: 27 (13%) reported a significant reduction in mortality, 16 (7%) an increase in mortality, and 170 (80%) no difference in mortality (one study was reported in 2 groups). Of the 27 trials reporting reduced mortality, six had assessed interventions likely to decrease ventilator-induced lung injury, including low tidal volume, prone position, and neuromuscular blockers, demonstrating the negative effects of mechanical ventilation strategies or improved process of care rather than positive effects of new therapies. Seven of the 27 trials reported beneficial effects of noninvasive ventilation. Results from some positive randomized controlled trials, for example, studies of recombinant activated protein C, talactoferrin, interleukin-1 receptor antagonist in sepsis, and muscle relaxants in severe acute respiratory distress syndrome were not replicated in subsequent randomized controlled trials. Other interventions, for example, gastric tonometry, have been abandoned.
Conclusions: A systematic literature search provided no conclusive evidence of any pharmacologic intervention that has consistently reduced mortality in critically ill patients. Strategies associated with improved or noninvasive mechanical ventilation were associated with reduced mortality.

Tuesday, 22 October 2019

2019 IDSA Guidelines for Community Acquired Pneumonia in Adults: To HCAP, we just say fare thee well

by Jon-Emile S. Kenny 

New guidelines from the American Thoracic Society/Infectious Disease Society of America


The last American Thoracic Society/Infectious Disease Society of America [ATS/IDSA] guidelines on community acquired pneumonia [CAP] were published in 2007; it seems hard to remember the world at that time – free from the tweeting of medical information, free from the tweeting of world leaders.  Is 2019 better for everyone?  Worse?  For some?

The 2019 inception of the ATS/IDSA guidelines for CAP reserves a more pragmatic approach than its screed-like predecessor – clearly defining 16 high-yield clinical questions and answering them under the direction of the PICO framework.  Critically, the current recommendations make clear that:

This guideline focuses on patients in the United States who have not recently completed foreign travel…. on adults who do not have an immunocompromising condition, such as inherited or acquired immune deficiency or drug-induced neutropenia, including patients actively receiving cancer chemotherapy, patients infected with HIV with suppressed CD4 counts, and solid organ or bone marrow transplant recipients.”

Accordingly, and as mentioned in the 2016 update on hospital-acquired and ventilator-associated pneumonia, guidelines remain guidelines.  They are not sacrosanct; they needn’t be followed without falter in all patients, always; clinical judgement and individual patient characteristics are also guiding principles.  In my humble opinion, the only deontological imperative is that you are informed and the current IDSA CAP guidelines are an excellent fund of rational, practical information.

RBC Transfusion Strategies in the ICU: A Concise Review

by Cable, Casey A.; Razavi, Seyed Amirhossein; Roback, John D.; Murphy, David J. 

Objectives: To critically assess available high-level clinical studies regarding RBC transfusion strategies, with a focus on hemoglobin transfusion thresholds in the ICU.
Data Sources: Source data were obtained from a PubMed literature review.
Study Selection: English language studies addressing RBC transfusions in the ICU with a focus on the most recent relevant studies.
Data Extraction: Relevant studies were reviewed and the following aspects of each study were identified, abstracted, and analyzed: study design, methods, results, and implications for critical care practice.
Data Synthesis: Approximately 30–50% of ICU patients receive a transfusion during their hospitalization with anemia being the indication for 75% of transfusions. A significant body of clinical research evidence supports using a restrictive transfusion strategy (e.g., hemoglobin threshold < 7 g/dL) compared with a more liberal approach (e.g., hemoglobin threshold < 10 g/dL). A restrictive strategy (hemoglobin < 7 g/dL) is recommended in patients with sepsis and gastrointestinal bleeds. A slightly higher restrictive threshold is recommended in cardiac surgery (hemoglobin < 7.5 g/dL) and stable cardiovascular disease (hemoglobin < 8 g/dL). Although restrictive strategies are generally supported in hematologic malignancies, acute neurologic injury, and burns, more definitive studies are needed, including acute coronary syndrome. Massive transfusion protocols are the mainstay of treatment for hemorrhagic shock; however, the exact RBC to fresh frozen plasma ratio is still unclear. There are also emerging complimentary practices including nontransfusion strategies to avoid and treat anemia and the reemergence of whole blood transfusion.
Conclusions: The current literature supports the use of restrictive transfusion strategies in the majority of critically ill populations. Continued studies of optimal transfusion strategies in various patient populations, coupled with the integration of novel complementary ICU practices, will continue to enhance our ability to treat critically ill patients.

Impact of natural light exposure on delirium burden in adult patients receiving invasive mechanical ventilation in the ICU: a prospective study

by Roland Smonig, Eric Magalhaes, Lila Bouadma, Olivier Andremont, Etienne de Montmollin, Fatiah Essardy, Bruno Mourvillier, Jordane Lebut, Claire Dupuis, Mathilde Neuville, Mathilde Lermuzeaux, Jean-François Timsit and Romain Sonneville

Annals of Intensive Care volume 9, Article number: 120 (2019)

To determine whether potential exposure to natural light via windows is associated with reduced delirium burden in critically ill patients admitted to the ICU in a single room.
Prospective single-center study.
Medical ICU of a university hospital, Paris, France.
Adult patients receiving invasive mechanical ventilation.
Consecutive patients admitted to a single room with (LIGHT group) or without (DARK group) exposure to natural light via windows were evaluated for delirium. The primary endpoint was the incidence of delirium. Main secondary endpoints included incidence of severe agitation intervened with antipsychotics and incidence of hallucinations.
A total of 195 patients were included (LIGHT group: n = 110; DARK group: n = 85). The incidence of delirium was similar in the LIGHT group and the DARK group (64% vs. 71%; relative risk (RR) 0.89, 95% CI 0.73–1.09). Compared with the DARK group, patients from the LIGHT group were less likely to be intervened with antipsychotics for agitation episodes (13% vs. 25%; RR 0.52, 95% CI 0.27–0.98) and had less frequent hallucinations (11% vs. 22%; RR 0.49, 95% CI 0.24–0.98). In multivariate logistic regression analysis, natural light exposure was independently associated with a reduced risk of agitation episodes intervened with antipsychotics (adjusted odds ratio = 0.39; 95% CI 0.17–0.88).
Admission to a single room with potential exposure to natural light via windows was not associated with reduced delirium burden, as compared to admission to a single room without windows. However, natural light exposure was associated with a reduced risk of agitation episodes and hallucinations.

Emergency Department to ICU Time Is Associated With Hospital Mortality: A Registry Analysis of 14,788 Patients From Six University Hospitals in The Netherlands*

Groenland, Carline N. L.; Termorshuizen, Fabian; Rietdijk, Wim J. R.; van den Brule, Judith; Dongelmans, Dave A.; de Jonge, Evert; de Lange, Dylan W.; de Smet, Anne Marie G. A.; de Keizer, Nicolette F.; Weigel, Joachim D.; Jewbali, Lucia S. D.; Boersma, Eric; den Uil, Corstiaan A.

Objectives: Prolonged emergency department to ICU waiting time may delay intensive care treatment, which could negatively affect patient outcomes. The aim of this study was to investigate whether emergency department to ICU time is associated with hospital mortality.
Design, Setting, and Patients: We conducted a retrospective observational cohort study using data from the Dutch quality registry National Intensive Care Evaluation. Adult patients admitted to the ICU directly from the emergency department in six university hospitals, between 2009 and 2016, were included. Using a logistic regression model, we investigated the crude and adjusted (for disease severity; Acute Physiology and Chronic Health Evaluation IV probability) odds ratios of emergency department to ICU time on mortality. In addition, we assessed whether the Acute Physiology and Chronic Health Evaluation IV probability modified the effect of emergency department to ICU time on mortality. Secondary outcomes were ICU, 30-day, and 90-day mortality.
Interventions: None.
Measurements and Main Results: A total of 14,788 patients were included. The median emergency department to ICU time was 2.0 hours (interquartile range, 1.3–3.3 hr). Emergency department to ICU time was correlated to adjusted hospital mortality (p < 0.002), in particular in patients with the highest Acute Physiology and Chronic Health Evaluation IV probability and long emergency department to ICU time quintiles: odds ratio, 1.29; 95% CI, 1.02–1.64 (2.4–3.7 hr) and odds ratio, 1.54; 95% CI, 1.11–2.14 (> 3.7 hr), both compared with the reference category (< 1.2 hr). For 30-day and 90-day mortality, we found similar results. However, emergency department to ICU time was not correlated to adjusted ICU mortality (p = 0.20).
Conclusions: Prolonged emergency department to ICU time (> 2.4 hr) is associated with increased hospital mortality after ICU admission, mainly driven by patients who had a higher Acute Physiology and Chronic Health Evaluation IV probability. We hereby provide evidence that rapid admission of the most critically ill patients to the ICU might reduce hospital mortality.

A Machine Learning Algorithm to Predict Severe Sepsis and Septic Shock: Development, Implementation, and Impact on Clinical Practice*

by Giannini, Heather M.; Ginestra, Jennifer C.; Chivers, Corey; Draugelis, Michael; Hanish, Asaf; Schweickert, William D.; Fuchs, Barry D.; Meadows, Laurie; Lynch, Michael; Donnelly, Patrick J.; Pavan, Kimberly; Fishman, Neil O.; Hanson, C. William III; Umscheid, Craig A

Objectives: Develop and implement a machine learning algorithm to predict severe sepsis and septic shock and evaluate the impact on clinical practice and patient outcomes.
Design: Retrospective cohort for algorithm derivation and validation, pre-post impact evaluation. Setting: Tertiary teaching hospital system in Philadelphia, PA.
Patients: All non-ICU admissions; algorithm derivation July 2011 to June 2014 (n = 162,212); algorithm validation October to December 2015 (n = 10,448); silent versus alert comparison January 2016 to February 2017 (silent n = 22,280; alert n = 32,184).
Interventions: A random-forest classifier, derived and validated using electronic health record data, was deployed both silently and later with an alert to notify clinical teams of sepsis prediction. Measurement and Main Result: Patients identified for training the algorithm were required to have International Classification of Diseases, 9th Edition codes for severe sepsis or septic shock and a positive blood culture during their hospital encounter with either a lactate greater than 2.2 mmol/L or a systolic blood pressure less than 90 mm Hg. The algorithm demonstrated a sensitivity of 26% and specificity of 98%, with a positive predictive value of 29% and positive likelihood ratio of 13. The alert resulted in a small statistically significant increase in lactate testing and IV fluid administration. There was no significant difference in mortality, discharge disposition, or transfer to ICU, although there was a reduction in time-to-ICU transfer.
Conclusions: Our machine learning algorithm can predict, with low sensitivity but high specificity, the impending occurrence of severe sepsis and septic shock. Algorithm-generated predictive alerts modestly impacted clinical measures. Next steps include describing clinical perception of this tool and optimizing algorithm design and delivery.

Major asthma guideline update: ICS-LABA as-needed replaces albuterol

In their first major update in 30 years, newly published asthma guidelines recommend significant changes to the way physicians treat millions of patients diagnosed with asthma. The Global Initiative for Asthma (GINA) now advises that, in general:  Most people with asthma can now be prescribed just one inhaler: an inhaled corticosteroid-and-long-acting beta agonist (ICS-LABA) combination [... read more]

Physiological effects of high-flow oxygen in tracheostomized patients

by Daniele Natalini, Domenico L. Grieco, Maria Teresa Santantonio, Lucrezia Mincione, Flavia Toni, Gian Marco Anzellotti, Davide Eleuteri, Pierluigi Di Giannatale, Massimo Antonelli and Salvatore Maurizio Maggiore

Annals of Intensive Care volume 9, Article number: 114 (2019)

High-flow oxygen therapy via nasal cannula (HFOTNASAL) increases airway pressure, ameliorates oxygenation and reduces work of breathing. High-flow oxygen can be delivered through tracheostomy (HFOTTRACHEAL), but its physiological effects have not been systematically described. We conducted a cross-over study to elucidate the effects of increasing flow rates of HFOTTRACHEAL on gas exchange, respiratory rate and endotracheal pressure and to compare lower airway pressure produced by HFOTNASAL and HFOTTRACHEAL.
Twenty-six tracheostomized patients underwent standard oxygen therapy through a conventional heat and moisture exchanger, and then HFOTTRACHEAL through a heated humidifier, with gas flow set at 10, 30 and 50 L/min. Each step lasted 30 min; gas flow sequence during HFOTTRACHEAL was randomized. In five patients, measurements were repeated during HFOTTRACHEAL before tracheostomy decannulation and immediately after during HFOTNASAL. In each step, arterial blood gases, respiratory rate, and tracheal pressure were measured.
During HFOTTRACHEAL, PaO2/FiO2 ratio and tracheal expiratory pressure slightly increased proportionally to gas flow. The mean [95% confidence interval] expiratory pressure raise induced by 10-L/min increase in flow was 0.2 [0.1–0.2] cmH2O (ρ = 0.77, p < 0.001). Compared to standard oxygen, HFOTTRACHEAL limited the negative inspiratory swing in tracheal pressure; at 50 L/min, but not with other settings, HFOTTRACHEAL increased mean tracheal expiratory pressure by (mean difference [95% CI]) 0.4 [0.3–0.6] cmH2O, peak tracheal expiratory pressure by 0.4 [0.2–0.6] cmH2O, improved PaO2/FiO2 ratio by 40 [8–71] mmHg, and reduced respiratory rate by 1.9 [0.3–3.6] breaths/min without PaCO2 changes. As compared to HFOTTRACHEAL, HFOTNASAL produced higher tracheal mean and peak expiratory pressure (at 50 L/min, mean difference [95% CI]: 3 [1–5] cmH2O and 4 [1–7] cmH2O, respectively).
As compared to standard oxygen, 50 L/min of HFOTTRACHEAL are needed to improve oxygenation, reduce respiratory rate and provide small degree of positive airway expiratory pressure, which, however, is significantly lower than the one produced by HFOTNASAL.

Extracorporeal liver support in patients with liver failure: a systematic review and meta-analysis of randomized trials

Alshamsi, F., Alshammari, K., Belley-Cote, E. et al. Intensive Care Med (2019).

First online: 07.10.2019

Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure.
We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence.
We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain.

ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.

Lactated Ringer’s Versus 4% Albumin on Lactated Ringer’s in Early Sepsis Therapy in Cancer Patients: A Pilot Single-Center Randomized Trial

by Park, Clarice Hyesuk Lee; de Almeida, Juliano Pinheiro; de Oliveira, Gisele Queiroz; Rizk, Stéphanie Itala; Fukushima, Julia Tizue; Nakamura, Rosana Ely; Mourão, Matheus Moraes; Galas, Filomena Regina Barbosa Gomes; Abdala, Edson; Pinheiro Freire, Maristela; Kalil Filho, Roberto; Costa Auler, Jose Otavio Jr; Nardelli, Pasquale; Martin, Greg S.; Landoni, Giovanni; Hajjar, Ludhmila Abrahao

Objective: To investigate the effects of the administration of 4% albumin on lactated Ringer’s, when compared with lactated Ringer’s alone, in the early phase of sepsis in cancer patients.
Design: Single-center, randomized, double-blind, controlled-parallel trial.
Setting: A tertiary care university cancer hospital.
Patients: Cancer patients with severe sepsis or septic shock. Interventions: Between October 2014 and December 2016, patients were randomly assigned to receive either bolus of albumin in a lactated Ringer’s solution or lactated Ringer’s solution alone during the first 6 hours of fluid resuscitation after intensive care medicine (ICU) admission. Primary outcome was defined as death from any cause at 7 days. Secondary outcomes were defined as death from any cause within 28 days, change in Sequence Organ Failure Assessment scores from baseline to day 7, days alive and free of mechanical ventilation, days alive and free of vasopressor, renal replacement therapy during ICU stay, and length of ICU and hospital stay.
Measurements and Main Results: A total of 360 patients were enrolled in the trial. At 7 days, 46 of 180 patients (26%) died in the albumin group and 40 of 180 (22%) died in the lactated Ringer’s group (p = 0.5). At 28 days, 96 of 180 patients (53%) died in the albumin group and 83 of 180 (46%) died in the lactated Ringer’s group (p = 0.2). No significant differences in secondary outcomes were observed.
Conclusions: Adding albumin to early standard resuscitation with lactated Ringer’s in cancer patients with sepsis did not improve 7-day survival.

Early prediction of noninvasive ventilation failure in COPD patients: derivation, internal validation, and external validation of a simple risk score

by Jun Duan, Shengyu Wang, Ping Liu, Xiaoli Han, Yao Tian, Fan Gao, Jing Zhou, Junhuan Mou, Qian Qin, Jingrong Yu, Linfu Bai, Lintong Zhou and Rui Zhang

Annals of Intensive Care volume 9, Article number: 108 (2019)

Early identification of noninvasive ventilation (NIV) failure is a promising strategy for reducing mortality in chronic obstructive pulmonary disease (COPD) patients. However, a risk-scoring system is lacking.
To develop a scale to predict NIV failure, 500 COPD patients were enrolled in a derivation cohort. Heart rate, acidosis (assessed by pH), consciousness (assessed by Glasgow coma score), oxygenation, and respiratory rate (HACOR) were entered into the scoring system. Another two groups of 323 and 395 patients were enrolled to internally and externally validate the scale, respectively. NIV failure was defined as intubation or death during NIV.
Using HACOR score collected at 1–2 h of NIV to predict NIV failure, the area under the receiver operating characteristic curves (AUC) was 0.90, 0.89, and 0.71 for the derivation, internal-validation, and external-validation cohorts, respectively. For the prediction of early NIV failure in these three cohorts, the AUC was 0.91, 0.96, and 0.83, respectively. In all patients with HACOR score > 5, the NIV failure rate was 50.2%. In these patients, early intubation (< 48 h) was associated with decreased hospital mortality (unadjusted odds ratio = 0.15, 95% confidence interval 0.05–0.39, p < 0.01).
HACOR scores exhibited good predictive power for NIV failure in COPD patients, particularly for the prediction of early NIV failure (< 48 h). In high-risk patients, early intubation was associated with decreased hospital mortality.

Randomized Clinical Trial of an ICU Recovery Pilot Program for Survivors of Critical Illness*

Bloom, Sarah L.; Stollings, Joanna L.; Kirkpatrick, Olivia; Wang, Li; Byrne, Daniel W.; Sevin, Carla M.; Semler, Matthew W.

Objectives: To examine the effect of an interdisciplinary ICU recovery program on process measures and clinical outcomes.
Design: A prospective, single-center, randomized pilot trial.
Setting: Academic, tertiary-care medical center.
Patients: Adult patients admitted to the medical ICU for at least 48 hours with a predicted risk of 30-day same-hospital readmission of at least 15%.
Interventions: Patients randomized to the ICU recovery program group were offered a structured 10-intervention program, including an inpatient visit by a nurse practitioner, an informational pamphlet, a 24 hours a day, 7 days a week phone number for the recovery team, and an outpatient ICU recovery clinic visit with a critical care physician, nurse practitioner, pharmacist, psychologist, and case manager. For patients randomized to the usual care group, all aspects of care were determined by treating clinicians.
Measurements and Main Results: Among the primary analysis of enrolled patients who survived to hospital discharge, patients randomized to the ICU recovery program (n = 111) and usual care (n = 121) were similar at baseline. Patients in the ICU recovery program group received a median of two interventions compared with one intervention in the usual care group (p < 0.001). A total of 16 patients (14.4%) in the ICU recovery program group and 26 patients (21.5%) in the usual care group were readmitted to the study hospital within 30 days of discharge (p = 0.16). For these patients, the median time to readmission was 21.5 days (interquartile range, 11.5–26.2 d) in the ICU recovery program group and 7 days (interquartile range, 4–21.2 d) in the usual care group (p = 0.03). Four patients (3.6%) in the ICU recovery program and 14 patients (11.6%) in the usual care group were readmitted within 7 days of hospital discharge (p = 0.02). The composite outcome of death or readmission within 30 days of hospital discharge occurred in 20 patients (18%) in the ICU recovery program group and 36 patients (29.8%) in usual care group (p = 0.04).
Conclusions: This randomized pilot trial found that a multidisciplinary ICU recovery program could deliver more interventions for post ICU recovery than usual care. The finding of longer time-to-readmission with an ICU recovery program should be examined in future trials.