Critical Care Bulletin - November 2022

 

Association between frailty, delirium, and mortality in older critically ill patients: a binational registry study

 

by Berhe W. Sahle, David Pilcher, Edward Litton, Richard Ofori-Asenso, Karlheinz Peter, James McFadyen and Tracey Bucknall 

 

Annals of Intensive Care volume 12, Article number: 108 (2022)

 

Background

Frailty and delirium are prevalent among older adults admitted to the intensive care unit (ICU) and associated with adverse outcomes; however, their relationships have not been extensively explored. This study examined the association between frailty and mortality and length of hospital stay (LOS) in ICU patients, and whether the associations are mediated or modified by an episode of delirium.

Methods

Retrospective analysis of data from the Australian New Zealand Intensive Care Society Adult Patient Database. A total of 149,320 patients aged 65 years or older admitted to 203 participating ICUs between 1 January 2017 and 31 December 2020 who had data for frailty and delirium were included in the analysis.

Results

A total of 41,719 (27.9%) older ICU patients were frail on admission, and 9,179 patients (6.1%) developed delirium during ICU admission. Frail patients had significantly higher odds of in-hospital mortality (OR: 2.15, 95% CI 2.05–2.25), episodes of delirium (OR: 1.86, 95% CI 1.77–1.95), and longer LOS (log-transformed mean difference (MD): 0.24, 95% CI 0.23–0.25). Acute delirium was associated with 32% increased odds of in-hospital mortality (OR: 1.32, 95% CI 1.23–1.43) and longer LOS (MD: 0.54, 95% CI 0.50–0.54). The odds ratios (95% CI) for in-hospital mortality were 1.37 (1.23–1.52), 2.14 (2.04–2.24) and 2.77 (2.51–3.05) for non-frail who developed delirium, frail without delirium, and frail and developed delirium during ICU admission, respectively. There was very small but statistically significant effect of frailty on in-hospital mortality (b for indirect effect: 0.00037, P < 0.001) and LOS (b for indirect effect: 0.019, P < 0.001) mediated through delirium.

Conclusion

Both frailty and delirium independently increase the risk of in-hospital mortality and LOS. Acute delirium is more common in frail patients; however, it does not mediate or modify a clinically meaningful amount of the association between frailty and in-hospital mortality and LOS.

 

High-flow nasal cannula versus non-invasive ventilation for acute hypercapnic respiratory failure in adults: a systematic review and meta-analysis of randomized trials

by N. Ovtcharenko, E. Ho, W. Alhazzani, A. Cortegiani, B. Ergan, R. Scala, G. Sotgiu, D. Chaudhuri, S. Oczkowski and K. Lewis 

Critical Care volume 26, Article number: 348 (2022)

Background

Non-invasive ventilation (NIV) with bi-level positive pressure ventilation is a first-line intervention for selected patients with acute hypercapnic respiratory failure. Compared to conventional oxygen therapy, NIV may reduce endotracheal intubation, death, and intensive care unit length of stay (LOS), but its use is often limited by patient tolerance and treatment failure. High-flow nasal cannula (HFNC) is a potential alternative treatment in this patient population and may be better tolerated.

Research question

For patients presenting with acute hypercapnic respiratory failure, is HFNC an effective alternative to NIV in reducing the need for intubation?

Methods

We searched EMBASE, MEDLINE, and the Cochrane library from database inception through to October 2021 for randomized clinical trials (RCT) of adults with acute hypercapnic respiratory failure assigned to receive HFNC or NIV. The Cochrane risk-of-bias tool for randomized trials was used to assess risk of bias. We calculated pooled relative risks (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with corresponding 95% confidence intervals (CI) using a random-effects model.

Results

We included eight RCTs (n = 528) in the final analysis. The use of HFNC compared to NIV did not reduce the risk of our primary outcome of mortality (RR 0.86, 95% CI 0.48–1.56, low certainty), or our secondary outcomes including endotracheal intubation (RR 0.80, 95% CI 0.46–1.39, low certainty), or hospital LOS (MD − 0.82 days, 95% CI − 1.83–0.20, high certainty). There was no difference in change in partial pressure of carbon dioxide between groups (MD − 1.87 mmHg, 95% CI − 5.34–1.60, moderate certainty).

Interpretation

The current body of evidence is limited in determining whether HFNC may be either superior, inferior, or equivalent to NIV for patients with acute hypercapnic respiratory failure given imprecision and study heterogeneity. Further studies are needed to better understand the effect of HFNC on this population.

 

 

 

 

Chest wall loading in the ICU: pushes, weights, and positions

 

by John Selickman and John J. Marini 

 

Annals of Intensive Care volume 12, Article number: 103 (2022)

 

Clinicians monitor mechanical ventilatory support using airway pressures—primarily the plateau and driving pressure, which are considered by many to determine the safety of the applied tidal volume. These airway pressures are influenced not only by the ventilator prescription, but also by the mechanical properties of the respiratory system, which consists of the series-coupled lung and chest wall. Actively limiting chest wall expansion through external compression of the rib cage or abdomen is seldom performed in the ICU. Recent literature describing the respiratory mechanics of patients with late-stage, unresolving, ARDS, however, has raised awareness of the potential diagnostic (and perhaps therapeutic) value of this unfamiliar and somewhat counterintuitive practice. In these patients, interventions that reduce resting lung volume, such as loading the chest wall through application of external weights or manual pressure, or placing the torso in a more horizontal position, have unexpectedly improved tidal compliance of the lung and integrated respiratory system by reducing previously undetected end-tidal hyperinflation. In this interpretive review, we first describe underappreciated lung and chest wall interactions that are clinically relevant to both normal individuals and to the acutely ill who receive ventilatory support. We then apply these physiologic principles, in addition to published clinical observation, to illustrate the utility of chest wall modification for the purposes of detecting end-tidal hyperinflation in everyday practice.

 

We wish you a smooth takeoff! Launching “Intensive Care Fundamentals”: an ESICM educational initiative for newcomers to intensive care unit

 

Editorial

 

Intensive Care Medicine Published: 07 November 2022

 

Only a few of us will ever forget that overwhelming feeling when we entered the intensive care unit (ICU) for the very first time as young doctors. Every year, more and more doctors come to the ICU for the first time, either at the start of their career in intensive care (in the countries where intensive care medicine (ICM) is a primary specialty) or as a part of the training in another baseline specialty. The educational needs of these doctors-in-training are similar across Europe, but their training is different. The early experience in ICU can determine a future career, including the decision to continue the specialist training in intensive care or to choose another specialty. Yet, only a minority of hospitals in Europe use standardised induction courses tailored to the educational needs of doctors on their first placement in ICU. A very similar situation exists for the growing number of advanced critical care practitioners. Non-specialised courses in intensive care exist and are very popular, such as the BASIC Course, which meets Australian and New Zealand College of Anaesthetists curriculum requirements. Not all aspects of international courses might be relevant for practitioners in Europe…

 

 

 

A genome-wide association study of survival in patients with sepsis

 

by Tamara Hernandez-Beeftink, Beatriz Guillen-Guio, Jose M. Lorenzo-Salazar, Almudena Corrales, Eva Suarez-Pajes, Rui Feng, Luis A. Rubio-Rodríguez, Megan L. Paynton, Raquel Cruz, M. Isabel García-Laorden, Miryam Prieto-González, Aurelio Rodríguez-Pérez, Demetrio Carriedo, Jesús Blanco, Alfonso Ambrós, Elena González-Higueras

 

Critical Care volume 26, Article number: 341 (2022)

 

Background

Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis.

Methods

This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10−8. Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants.

Findings

We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37–6.78], p = 4.92 × 10−8). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury.

Interpretation

We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.

 

 

How symptoms of prolonged grief disorder, posttraumatic stress disorder, and depression relate to each other for grieving ICU families during the first two years of bereavement

 

by Fur-Hsing Wen, Holly G. Prigerson, Wen-Chi Chou, Chung-Chi Huang, Tsung-Hui Hu, Ming Chu Chiang, Li-Pang Chuang and Siew Tzuh Tang 

 

Critical Care volume 26, Article number: 336 (2022) 

 

Background

Bereaved ICU family surrogates are at risk of comorbid prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depression. Knowledge about temporal relationships between PGD, PTSD, and depression is limited by a lack of relevant studies and diverse or inappropriate assessment time frames given the duration criterion for PGD. We aimed to determine the temporal reciprocal relationships between PGD, PTSD, and depressive symptoms among ICU decedents’ family surrogates during their first 2 bereavement years with an assessment time frame reflecting the PGD duration criterion.

Methods

This prospective, longitudinal, observational study examined PGD, PTSD, and depressive symptoms among 303 family surrogates of ICU decedents from two academic hospitals using 11 items of the Prolonged Grief Disorder-13, the Impact of Event Scale—Revised, and the depression subscale of the Hospital Anxiety and Depression Scale, respectively, at 6, 13, 18, and 24 months post-loss. Cross-lagged panel modeling was conducted: autoregressive coefficients indicate variable stability, and cross-lagged coefficients indicate the strength of reciprocal relationships among variables between time points.

Results

Symptoms (autoregressive coefficients) of PGD (0.570–0.673), PTSD (0.375–0.687), and depression (0.591–0.655) were stable over time. Cross-lagged standardized coefficients showed that depressive symptoms measured at 6 months post-loss predicted subsequent symptoms of PGD (0.146) and PTSD (0.208) at 13 months post-loss. PGD symptoms did not predict depressive symptoms. PTSD symptoms predicted subsequent depressive symptoms in the second bereavement year (0.175–0.278). PGD symptoms consistently predicted subsequent PTSD symptoms in the first 2 bereavement years (0.180–0.263), whereas PTSD symptoms predicted subsequent PGD symptoms in the second bereavement year only (0.190–0.214). PGD and PTSD symptoms are bidirectionally related in the second bereavement year.

Conclusions

PGD, PTSD, and depressive symptoms can persist for 2 bereavement years. Higher PGD symptoms at 6 months post-loss contributed to the exacerbation of PTSD symptoms over time, whereas long-lasting PTSD symptoms were associated with prolonged depression and PGD symptoms beyond the first bereavement year. Identification and alleviation of depression and PGD symptoms as early as 6 months post-loss enables bereaved surrogates to grieve effectively and avoid the evolution of those symptoms into long-lasting PGD, PTSD, and depression.

 

Association of early dexamethasone therapy with mortality in critically Ill COVID-19 patients: a French multicenter study

 

by Matthieu Raymond, Aurélie Le Thuaut, Pierre Asfar, Cédric Darreau, Florian Reizine, Gwenhaël Colin, Charly Dano, Julien Lorber, Baptiste Hourmant, Agathe Delbove, Aurélien Frérou, Jean Morin, Pierre Yves Egreteau, Philippe Seguin, Jean Reignier, Jean-Baptiste Lascarrou

 

Annals of Intensive Care volume 12, Article number: 102 (2022)

 

Background

Dexamethasone is recommended for COVID-19 patients who require oxygen therapy. However, its effectiveness in reducing mortality and intubation, and its safety, remain debated. We aimed to investigate whether dexamethasone reduces day-28 mortality in unselected patients with critical COVID-19.

Methods

We performed an observational cohort study in consecutive COVID-19 patients admitted to any of 13 French intensive care units (ICUs) in 2020. The primary objective was to determine whether early dexamethasone therapy was associated with day-28 mortality and the secondary objectives were to assess whether early dexamethasone decreased intubation requirements and to collect adverse events.

Results

Of 1058 included patients, 611 (57.75%) received early dexamethasone (early dexamethasone group), 358 (33.83%) did not receive any steroids (no steroids group), and 89 (8.41%) received late dexamethasone or other steroids. Day-28 mortality was similar between the early dexamethasone and the no steroids groups (15.06% and 14.25%, respectively; P = 0.59). Factors associated with day-28 mortality were older age (adjusted hazard ratio [aHR], 1.06; 1.04–1.09; P < 0.001), worse SOFA score (aHR, 1.13; 1.06–1.20; P < 0.001), and immunocompromised status (aHR, 1.59; 1.01–2.50; P = 0.043). Early dexamethasone was associated with fewer intubations (48.55% vs. 61.49%, P < 0.001) and more ventilator-free days by day 28 (22 [2–28] vs. 17 [1–28] days, P = 0.003), compared to no steroids. Ventilator-associated pneumonia (VAP) was more common with early dexamethasone (HR, 1.29 [1.01–1.63], P = 0.04) than with no steroids, whereas no differences were noted for bloodstream infection, fungal infection, or gastrointestinal bleeding.

Conclusions

Early dexamethasone in critically ill COVID-19 patients was not associated with lower day-28 mortality. However, early dexamethasone was associated with lower intubation needs and more ventilator-free days by day 28. In patients treated with invasive mechanical ventilation, early dexamethasone was associated with a higher risk of VAP.

 

Extracorporeal versus conventional cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: a secondary analysis of the Prague OHCA trial

by Daniel Rob, Jana Smalcova, Ondrej Smid, Ales Kral, Tomas Kovarnik, David Zemanek, Petra Kavalkova, Michal Huptych, Arnost Komarek, Ondrej Franek, Stepan Havranek, Ales Linhart and Jan Belohlavek 

Critical Care volume 26, Article number: 330 (2022)

Background

Survival rates in refractory out-of-hospital cardiac arrest (OHCA) remain low with conventional advanced cardiac life support (ACLS). Extracorporeal life support (ECLS) implantation during ongoing resuscitation, a method called extracorporeal cardiopulmonary resuscitation (ECPR), may increase survival. This study examined whether ECPR is associated with improved outcomes.

Methods

Prague OHCA trial enrolled adults with a witnessed refractory OHCA of presumed cardiac origin. In this secondary analysis, the effect of ECPR on 180-day survival using Kaplan–Meier estimates and Cox proportional hazard model was examined.

Results

Among 256 patients (median age 58 years, 83% male) with median duration of resuscitation 52.5 min (36.5–68), 83 (32%) patients achieved prehospital ROSC during ongoing conventional ACLS prehospitally, 81 (32%) patients did not achieve prehospital ROSC with prolonged conventional ACLS, and 92 (36%) patients did not achieve prehospital ROSC and received ECPR. The overall 180-day survival was 51/83 (61.5%) in patients with prehospital ROSC, 1/81 (1.2%) in patients without prehospital ROSC treated with conventional ACLS and 22/92 (23.9%) in patients without prehospital ROSC treated with ECPR (log-rank p < 0.001). After adjustment for covariates (age, sex, initial rhythm, prehospital ROSC status, time of emergency medical service arrival, resuscitation time, place of cardiac arrest, percutaneous coronary intervention status), ECPR was associated with a lower risk of 180-day death (HR 0.21, 95% CI 0.14–0.31; P < 0.001).

Conclusions

In this secondary analysis of the randomized refractory OHCA trial, ECPR was associated with improved 180-day survival in patients without prehospital ROSC.

 

Chest dual-energy CT to assess the effects of steroids on lung function in severe COVID-19 patients

 

by Gaetano Perchiazzi, Aleksandra Larina, Tomas Hansen, Robert Frithiof, Michael Hultström, Miklos Lipcsey and Mariangela Pellegrini

 

Critical Care volume 26, Article number: 328 (2022)

 

Background

Steroids have been shown to reduce inflammation, hypoxic pulmonary vasoconstriction (HPV) and lung edema. Based on evidence from clinical trials, steroids are widely used in severe COVID-19. However, the effects of steroids on pulmonary gas volume and blood volume in this group of patients are unexplored.

Objective

Profiting by dual-energy computed tomography (DECT), we investigated the relationship between the use of steroids in COVID-19 and distribution of blood volume as an index of impaired HPV. We also investigated whether the use of steroids influences lung weight, as index of lung edema, and how it affects gas distribution.

Methods

Severe COVID-19 patients included in a single-center prospective observational study at the intensive care unit at Uppsala University Hospital who had undergone DECT were enrolled in the current study. Patients’ cohort was divided into two groups depending on the administration of steroids. From each patient’s DECT, 20 gas volume maps and the corresponding 20 blood volume maps, evenly distributed along the cranial–caudal axis, were analyzed. As a proxy for HPV, pulmonary blood volume distribution was analyzed in both the whole lung and the hypoinflated areas. Total lung weight, index of lung edema, was estimated.

Results

Sixty patients were analyzed, whereof 43 received steroids. Patients not exposed to steroids showed a more extensive non-perfused area (19% vs 13%, p < 0.01) and less homogeneous pulmonary blood volume of hypoinflated areas (kurtosis: 1.91 vs 2.69, p < 0.01), suggesting a preserved HPV compared to patients treated with steroids. Moreover, patients exposed to steroids showed a significantly lower lung weight (953 gr vs 1140 gr, p = 0.01). A reduction in alveolar–arterial difference of oxygen followed the treatment with steroids (322 ± 106 mmHg at admission vs 267 ± 99 mmHg at DECT, p = 0.04).

Conclusions

The use of steroids might cause impaired HPV and might reduce lung edema in severe COVID-19. This is consistent with previous findings in other diseases. Moreover, a reduced lung weight, as index of decreased lung edema, and a more homogeneous distribution of gas within the lung were shown in patients treated with steroids.

 

 

 

 

 

 

 

 

Virtual and augmented reality in critical care medicine: the patient’s, clinician’s, and researcher’s perspective

 

by Raphael Romano Bruno, Georg Wolff, Bernhard Wernly, Maryna Masyuk, Kerstin Piayda, Susannah Leaver, Ralf Erkens, Daniel Oehler, Shazia Afzal, Houtan Heidari, Malte Kelm and Christian Jung 

 

Critical Care volume 26, Article number: 326 (2022)

 

Virtual reality (VR) and augmented reality (AR) are aspiring, new technologies with increasing use in critical care medicine. While VR fully immerses the user into a virtual three-dimensional space, AR adds overlaid virtual elements into a real-world environment. VR and AR offer great potential to improve critical care medicine for patients, relatives and health care providers. VR may help to ameliorate anxiety, stress, fear, and pain for the patient. It may assist patients in mobilisation and rehabilitation and can improve communication between all those involved in the patient’s care. AR can be an effective tool to support continuous education of intensive care medicine providers, and may complement traditional learning methods to acquire key practical competences such as central venous line placement, cardiopulmonary resuscitation, extracorporeal membrane oxygenation device management or endotracheal intubation. Currently, technical, human, and ethical challenges remain. The adaptation and integration of VR/AR modalities into useful clinical applications that can be used routinely on the ICU is challenging. Users may experience unwanted side effects (so-called “cybersickness”) during VR/AR sessions, which may limit its applicability. Furthermore, critically ill patients are one of the most vulnerable patient groups and warrant special ethical considerations if new technologies are to be introduced into their daily care. To date, most studies involving AR/VR in critical care medicine provide only a low level of evidence due to their research design. Here we summarise background information, current developments, and key considerations that should be taken into account for future scientific investigations in this field.

 

Comparison of continuous versus intermittent enteral feeding in critically ill patients: a systematic review and meta-analysis

 

by Aaron J. Heffernan, C. Talekar, M. Henain, L. Purcell, M. Palmer and H. White 

 

Critical Care volume 26, Article number: 325 (2022) 

 

Background

The enteral route is commonly utilised to support the nutritional requirements of critically ill patients. However, there is paucity of data guiding clinicians regarding the appropriate method of delivering the prescribed dose. Continuous enteral feeding is commonly used; however, a bolus or intermittent method of administration may provide several advantages such as minimising interruptions. The purpose of this meta-analysis is to compare a continuous versus an intermittent or bolus enteral nutrition administration method.

Methods

A systematic review and meta-analysis were performed with studies identified from the PubMed, EMBASE, Cochrane Library and Web of Science databases. Studies were included if they compared a continuous with either an intermittent or bolus administration method of enteral nutrition in adult patients admitted to the intensive care unit. Study quality was assessed using the PEDro and Newcastle–Ottawa scoring systems. Review Manager was used for performing the random-effects meta-analysis on the outcomes of mortality, constipation, diarrhoea, increased gastric residuals, pneumonia, and bacterial colonisation.

Results

A total of 5546 articles were identified, and 133 were included for full text review. Fourteen were included in the final analysis. There was an increased risk of constipation with patients receiving continuous enteral nutrition (relative risk 2.24, 95% confidence interval 1.01–4.97, p = 0.05). No difference was identified in other outcome measures. No appreciable bias was identified.

Conclusion

The current meta-analysis has not identified any clinically relevant difference in most outcome measures relevant to the care of critically ill patients. However, there is a paucity of high-quality randomised controlled clinical trials to guide this decision. Therefore, clinicians may consider either dosing regimen in the context of the patient’s care requirements.