The persistent potential of extracorporeal therapies in liver failure

The persistent potential of extracorporeal therapies in liver failure

Valentin Fuhrmann, Michael Bauer & Alexander Wilmer 

Intensive Care Medicine (2019)

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

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)

Background:

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.

Methods:

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.

Results:

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).

Conclusions:

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

“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)

Background:

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.

Methods:

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.

Results:

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.

Conclusion:

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

Jan J. De Waele & Yasser Sakr 

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 [2, 3]. 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

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

Critical Care Medicine: December 2019 - Volume 47 - Issue 12 - p 1707-1715

Objectives:

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

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)

Background:

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.

Results:

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).

Conclusions:

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

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)

Background:

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.

Methods:

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.

Results:

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%).

Conclusion:

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

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)

Background:

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.

Methods:

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.

Results:

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.

Conclusions:

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)

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*

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.

Critical Care Medicine: December 2019 - Volume 47 - Issue 12 - p 1692-1698

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

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 

Critical Care Medicine: December 2019 - Volume 47 - Issue 12 - p 1680-1691

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.