Critical Care Bulletin: November 2021

 

A systematic review and meta-analysis of enrollment into ARDS and sepsis trials published between 2009 and 2019 in major journals

 

by Dustin C. Krutsinger, Kuldeep N. Yadav, Michael O. Harhay, Karsten Bartels and Katherine R. Courtright 

Critical Care volume 25, Article number: 392 (2021) 

 

Background

Enrollment problems are common among randomized controlled trials conducted in the ICU. However, little is known about actual trial enrollment rates and influential factors. We set out to determine the overall enrollment rate in recent randomized controlled trials (RCTs) of patients with acute respiratory distress syndrome (ARDS), acute lung injury (ALI), or sepsis, and which factors influenced enrollment rate.

Methods

We conducted a systematic review by searching Pubmed using predefined terms for ARDS/ALI and sepsis to identify individually RCTs published among the seven highest impact general medicine and seven highest impact critical care journals between 2009 and 2019. Cluster randomized trials were excluded. Data were extracted by two independent reviewers using an electronic database management system. We conducted a random-effects meta-analysis of the eligible trials for the primary outcome of enrollment rate by time and site.

Results

Out of 457 articles identified, 94 trials met inclusion criteria. Trials most commonly evaluated pharmaceutical interventions (53%), were non-industry funded (78%), and required prospective informed consent (81%). The overall mean enrollment rate was 0.83 (95% confidence interval: 0.57–1.21) participants per month per site. Enrollment in ARDS/ALI and sepsis trials were 0.48 (95% CI 0.32–0.70) and 0.98 (95% CI 0.62–1.56) respectively. The enrollment rate was significantly higher for single-center trials (4.86; 95% CI 2.49–9.51) than multicenter trials (0.52; 95% CI 0.41–0.66). Of the 36 trials that enrolled < 95% of the target sample size, 8 (22%) reported slow enrollment as the reason.

Conclusions

In this systematic review and meta-analysis, recent ARDS/ALI and sepsis clinical trials had an overall enrollment rate of less than 1 participant per site per month. Novel approaches to improve critical care trial enrollment efficiency are needed to facilitate the translation of best evidence into practice.

 

 

 

 

Metabolomic diferences between COVID-19 and H1N1 influenza induced ARDS

 

by Jose Angel Lorente, Nicolas Nin, Palmira Villa, Dovami Vasco, Ana B. Miguel-Coello, Ignacio Rodriguez, Raquel Herrero, Oscar Peñuelas, Jesús Ruiz-Cabello and Jose L. Izquierdo-Garcia 

 

Critical Care volume 25, Article number: 390 (2021) 

 

Background

Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by lung inflammation and pulmonary edema. Coronavirus disease 2019 (COVID-19) is associated with ARDS in the more severe cases. This study aimed to compare the specificity of the metabolic alterations induced by COVID-19 or Influenza A pneumonia (IAP) in ARDS.

Methods

Eighteen patients with ARDS due to COVID-19 and twenty patients with ARDS due to IAP, admitted to the intensive care unit. ARDS was defined as in the American-European Consensus Conference. As compared with patients with COVID-19, patients with IAP were younger and received more often noradrenaline to maintain a mean arterial pressure > 65 mm Hg. Serum samples were analyzed by Nuclear Magnetic Resonance Spectroscopy. Multivariate Statistical Analyses were used to identify metabolic differences between groups. Metabolic pathway analysis was performed to identify the most relevant pathways involved in ARDS development.

Results

ARDS due to COVID-19 or to IAP induces a different regulation of amino acids metabolism, lipid metabolism, glycolysis, and anaplerotic metabolism. COVID‐19 causes a significant energy supply deficit that induces supplementary energy-generating pathways. In contrast, IAP patients suffer more marked inflammatory and oxidative stress responses. The classificatory model discriminated against the cause of pneumonia with a success rate of 100%.

Conclusions

Our findings support the concept that ARDS is associated with a characteristic metabolomic profile that may discriminate patients with ARDS of different etiologies, being a potential biomarker for the diagnosis, prognosis, and management of this condition.

 

Incidence, clinical characteristics, and outcome after unexpected cardiac arrest among critically ill adults with COVID-19: insight from the multicenter prospective ACICOVID-19 registry

 

by Jonathan Chelly, Gaetan Plantefève, Toufik Kamel, Cédric Bruel, Saad Nseir, Christopher Lai, Giulia Cirillo, Elena Skripkina, Sébastien Ehrminger, Fernando-Daniel Berdaguer-Ferrari, Julien Le Marec, Marine Paul, Aurélie Autret and Nicolas Deye

 

Annals of Intensive Care volume 11, Article number: 155 (2021)

 

Background

Initial reports have described the poor outcome of unexpected cardiac arrest (CA) in intensive care unit (ICU) among COVID-19 patients in China and the USA. However, there are scarce data on characteristics and outcomes of such CA patients in Europe.

Methods

Prospective registry in 35 French ICUs, including all in-ICU CA in COVID-19 adult patients with cardiopulmonary resuscitation (CPR) attempt. Favorable outcome was defined as modified Rankin scale ranging from 0 to 3 at day 90 after CA.

Results

Among the 2425 COVID-19 patients admitted to ICU from March to June 2020, 186 (8%) experienced in-ICU CA, of whom 146/186 (78%) received CPR. Among these 146 patients, 117 (80%) had sustained return of spontaneous circulation, 102 (70%) died in the ICU, including 48 dying within the first day after CA occurrence and 21 after withdrawal of life-sustaining therapy. Most of CA were non-shockable rhythm (90%). At CA occurrence, 132 patients (90%) were mechanically ventilated, 83 (57%) received vasopressors and 75 (51%) had almost three organ failures. Thirty patients (21%) had a favorable outcome. Sepsis-related organ failure assessment score > 9 before CA occurrence was the single parameter constantly associated with unfavorable outcome in multivariate analysis.

Conclusions

In-ICU CA incidence remains high among a large multicenter cohort of French critically ill adults with COVID-19. However, 21% of patients with CPR attempt remained alive at 3 months with good functional status. This contrasts with other recent reports showing poor outcome in such patients.

 

The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study

 

by Carol L. Hodgson, Alisa M. Higgins, Michael J. Bailey, Anne M. Mather, Lisa Beach, Rinaldo Bellomo, Bernie Bissett, Ianthe J. Boden, Scott Bradley, Aidan Burrell, D. James Cooper, Bentley J. Fulcher, Kimberley J. Haines, Jack Hopkins, Alice Y. M. Jones, Stuart Lane… 

 

Critical Care volume 25, Article number: 382 (2021) Published: 08 November 2021

Background

There are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months.

Methods

In a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM.

Results

Of 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51–70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06–13.77]; p < 0.001). Thirteen (11.4%) survivors had not returned to work due to poor health. There was a decrease in the EQ-5D-5LTM utility score (MD, − 0.19 [− 0.28 to − 0.10]; p < 0.001). At 6 months, 82 of 115 (71.3%) patients reported persistent symptoms. The independent predictors of death or new disability were higher severity of illness and increased frailty.

Conclusions

At six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning.

 

Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock: a systematic review and a component network meta-analysis

Tomoko Fujii, Georgia Salanti, Alessandro Belletti, Rinaldo Bellomo, Anitra Carr, Toshi A. Furukawa, Nora Luethi, Yan Luo, Alessandro Putzu, Chiara Sartini, Yasushi Tsujimoto, Andrew A. Udy, Fumitaka Yanase & Paul J. Young 

 

Intensive Care Medicine (2021) Published: 09 November 2021

 

We aimed to compare the effects of vitamin C, glucocorticoids, vitamin B1, combinations of these drugs, and placebo or usual care on longer-term mortality in adults with sepsis or septic shock. MEDLINE, Embase, CENTRAL, ClinicalTrials.gov and WHO-ICTRP were searched. The final search was carried out on September 3rd, 2021. Multiple reviewers independently selected randomized controlled trials (RCTs) comparing very-high-dose vitamin C (≥ 12 g/day), high-dose vitamin C (< 12, ≥ 6 g/day), vitamin C (< 6 g/day), glucocorticoid (< 400 mg/day of hydrocortisone), vitamin B1, combinations of these drugs, and placebo/usual care. We performed random-effects network meta-analysis and, where applicable, a random-effects component network meta-analysis. We used the Confidence in Network Meta-Analysis framework to assess the degree of treatment effect certainty. The primary outcome was longer-term mortality (90-days to 1-year). Secondary outcomes were severity of organ dysfunction over 72 h, time to cessation of vasopressor therapy, and length of stay in intensive care unit (ICU). Forty-three RCTs (10,257 patients) were eligible. There were no significant differences in longer-term mortality between treatments and placebo/usual care or between treatments (10 RCTs, 7,096 patients, moderate to very-low-certainty). We did not find any evidence that vitamin C or B1 affect organ dysfunction or ICU length of stay. Adding glucocorticoid to other treatments shortened duration of vasopressor therapy (incremental mean difference, − 29.8 h [95% CI − 44.1 to − 15.5]) and ICU stay (incremental mean difference, − 1.3 days [95% CI − 2.2 to − 0.3]). Metabolic resuscitation with vitamin C, glucocorticoids, vitamin B1, or combinations of these drugs was not significantly associated with a decrease in longer-term mortality.

 

Cardiac injury in COVID-19

Julie Helms, Alain Combes &  Nadia Aissaoui 

Intensive Care Medicine (2021) Published: 02 November 2021

Patients with coronavirus disease 2019 (COVID-19) can present with a large panel of cardiac manifestations, including myocardial infarction with (type 1) or without (type 2) obstructive coronary artery disease, arterial or venous thromboembolic disease, pericarditis and myocarditis, arrhythmias, acute heart failure, shock or cardiac arrest. The most frequent cardiac abnormality reported in COVID-19 is acute cardiac injury (ACI), defined by cardiac troponin elevation > 99th percentile. ACI occurred in as many as 50% and 21% of critically ill and hospitalized COVID-19 patients, respectively, rates which were higher than in severe diseases caused by other respiratory viruses. COVID-19 patients with ACI were older (median age 70 years), had increased markers of systemic inflammation, more frequent malignant arrhythmias, shock and need for intensive care unit (ICU) care and higher mortality rates, with myocardial injury being the second cause of death after respiratory failure. Furthermore, compared to a pre-COVID-19 population, COVID-19 patients with type 1 myocardial infarction had prolonged symptom-to-admission times, more frequent cardiogenic shock and higher mortality. It should also be emphasized that COVID-19 patients had frequent cardiovascular comorbidities such as hypertension, obesity, metabolic syndrome and pre-existing coronary artery disease that may have precipitated cardiac complications…

 

Separation from mechanical ventilation and survival after spinal cord injury: a systematic review and meta-analysis

 

by Annia F. Schreiber, Jacopo Garlasco, Fernando Vieira, Yie Hui Lau, Dekel Stavi, David Lightfoot, Andrea Rigamonti, Karen Burns, Jan O. Friedrich, Jeffrey M. Singh and Laurent J. Brochard

 

Annals of Intensive Care volume 11, Article number: 149 (2021)

 

Background

Prolonged need for mechanical ventilation greatly impacts life expectancy of patients after spinal cord injury (SCI). Weaning outcomes have never been systematically assessed. In this systematic review and meta-analysis, we aimed to investigate the probability of weaning success, duration of mechanical ventilation, mortality, and their predictors in mechanically ventilated patients with SCI.

Methods

We searched six databases from inception until August 2021 for randomized-controlled trials and observational studies enrolling adult patients (≥ 16 years) with SCI from any cause requiring mechanical ventilation. Titles and abstracts were screened independently by two reviewers. Full texts of the identified articles were then assessed for eligibility. Data were extracted independently and in duplicate by pairs of authors, using a standardized data collection form. Synthetic results are reported as meta-analytic means and proportions, based on random effects models.

Results

Thirty-nine studies (14,637 patients, mean age 43) were selected. Cervical lesions were predominant (12,717 patients had cervical lesions only, 1843 in association with other levels’ lesions). Twenty-five studies were conducted in intensive care units (ICUs), 14 in rehabilitative settings.

In ICU, the mean time from injury to hospitalization was 8 h [95% CI 7–9], mean duration of mechanical ventilation 27 days [20–34], probability of weaning success 63% [45–78] and mortality 8% [5–11]. Patients hospitalized in rehabilitation centres had a greater number of high-level lesions (C3 or above), were at 40 days [29–51] from injury and were ventilated for a mean of 97 days [65–128]; 82% [70–90] of them were successfully weaned, while mortality was 1% [0–19].

Conclusions

Although our study highlights the lack of uniform definition of weaning success, of clear factors associated with weaning outcomes, and of high-level evidence to guide optimal weaning in patients with SCI, it shows that around two-thirds of mechanically ventilated patients can be weaned in ICU after SCI. A substantial gain in weaning success can be obtained during rehabilitation, with additional duration of stay but minimal increase in mortality. The study is registered with PROSPERO (CRD42020156788).

 

The effect of opioids on gastrointestinal function in the ICU

 

by Yun Yan, Yu Chen and Xijing Zhang 

 

Critical Care volume 25, Article number: 370 (2021)

 

Gastrointestinal (GI) dysfunction is common in the critical care setting and is highly associated with clinical outcomes. Opioids increase the risk for GI dysfunction and are frequently prescribed to reduce pain in critically ill patients. However, the role of opioids in GI function remains uncertain in the ICU. This review aims to describe the effect of opioids on GI motility, their potential risk of increasing infection and the treatment of GI dysmotility with opioid antagonists in the ICU setting…

 

Fever and hypothermia represent two populations of sepsis patients and are associated with outside temperature

 

by Daniel O. Thomas-Rüddel, Peter Hoffmann, Daniel Schwarzkopf, Christian Scheer, Friedhelm Bach, Marcus Komann, Herwig Gerlach, Manfred Weiss, Matthias Lindner, Hendrik Rüddel, Philipp Simon, Sven-Olaf Kuhn, Reinhard Wetzker, Michael Bauer, Konrad Reinhart and Frank Bloos 

 

Critical Care volume 25, Article number: 368 (2021) 

 

Background

Fever and hypothermia have been observed in septic patients. Their influence on prognosis is subject to ongoing debates.

Methods

We did a secondary analysis of a large clinical dataset from a quality improvement trial. A binary logistic regression model was calculated to assess the association of the thermal response with outcome and a multinomial regression model to assess factors associated with fever or hypothermia.

Results

With 6542 analyzable cases we observed a bimodal temperature response characterized by fever or hypothermia, normothermia was rare. Hypothermia and high fever were both associated with higher lactate values. Hypothermia was associated with higher mortality, but this association was reduced after adjustment for other risk factors. Age, community-acquired sepsis, lower BMI and lower outside temperatures were associated with hypothermia while bacteremia and higher procalcitonin values were associated with high fever.

Conclusions

Septic patients show either a hypothermic or a fever response. Whether hypothermia is a maladaptive response, as indicated by the higher mortality in hypothermic patients, or an adaptive response in patients with limited metabolic reserves under colder environmental conditions, remains an open question.

 

Refractory ineffective triggering during pressure support ventilation: effect of proportional assist ventilation with load-adjustable gain factors

 

by Anne-Fleur Haudebourg, Tommaso Maraffi, Samuel Tuffet, François Perier, Nicolas de Prost, Keyvan Razazi, Armand Mekontso Dessap and Guillaume Carteaux 

 

Annals of Intensive Care volume 11, Article number: 147 (2021) 

Background

Ineffective triggering is frequent during pressure support ventilation (PSV) and may persist despite ventilator adjustment, leading to refractory asynchrony. We aimed to assess the effect of proportional assist ventilation with load-adjustable gain factors (PAV+) on the occurrence of refractory ineffective triggering.

Design

Observational assessment followed by prospective cross-over physiological study.

Setting

Academic medical ICU.

Patients

Ineffective triggering was detected during PSV by a twice-daily inspection of the ventilator’s screen. The impact of pressure support level (PSL) adjustments on the occurrence of asynchrony was recorded. Patients experiencing refractory ineffective triggering, defined as persisting asynchrony at the lowest tolerated PSL, were included in the physiological study.

Interventions

Physiological study: Flow, airway, and esophageal pressures were continuously recorded during 10 min under PSV with the lowest tolerated PSL, and then under PAV+ with the gain adjusted to target a muscle pressure between 5 and 10 cmH2O.

Measurements

Primary endpoint was the comparison of asynchrony index between PSV and PAV+ after PSL and gain adjustments.

Results

Among 36 patients identified having ineffective triggering under PSV, 21 (58%) exhibited refractory ineffective triggering. The lowest tolerated PSL was higher in patients with refractory asynchrony as compared to patients with non-refractory ineffective triggering. Twelve out of the 21 patients with refractory ineffective triggering were included in the physiological study. The median lowest tolerated PSL was 17 cmH2O [12–18] with a PEEP of 7 cmH2O [5–8] and FiO2 of 40% [39–42]. The median gain during PAV+ was 73% [65–80]. The asynchrony index was significantly lower during PAV+ than PSV (2.7% [1.0–5.4] vs. 22.7% [10.3–40.1], p < 0.001) and consistently decreased in every patient with PAV+. Esophageal pressure–time product (PTPes) did not significantly differ between the two modes (107 cmH2O/s/min [79–131] under PSV vs. 149 cmH2O/s/min [129–170] under PAV+, p = 0.092), but the proportion of PTPes lost in ineffective triggering was significantly lower with PAV+ (2 cmH2O/s/min [1–6] vs. 8 cmH2O/s/min [3–30], p = 0.012).

Conclusions

Among patients with ineffective triggering under PSV, PSL adjustment failed to eliminate asynchrony in 58% of them (21 of 36 patients). In these patients with refractory ineffective triggering, switching from PSV to PAV+ significantly reduced or even suppressed the incidence of asynchrony.

 

Trends in 28-Day Mortality of Critical Care Patients With Coronavirus Disease 2019 in the United Kingdom: A National Cohort Study, March 2020 to January 2021*

 

by Dennis, John M.; McGovern, Andrew P.; Thomas, Nicholas J.; Wilde, Harrison; Vollmer, Sebastian J.; Mateen, Bilal A. 

 

Critical Care Medicine: November 2021 - Volume 49 - Issue 11 - p 1895-1900

 

OBJECTIVES: 

To determine whether the previously described trend of improving mortality in people with coronavirus disease 2019 in critical care during the first wave was maintained, plateaued, or reversed during the second wave in United Kingdom, when B117 became the dominant strain.

DESIGN: 

National retrospective cohort study.

SETTING: 

All English hospital trusts (i.e., groups of hospitals functioning as single operational units), reporting critical care admissions (high dependency unit and ICU) to the Coronavirus Disease 2019 Hospitalization in England Surveillance System.

PATIENTS: 

A total of 49,862 (34,336 high dependency unit and 15,526 ICU) patients admitted between March 1, 2020, and January 31, 2021 (inclusive).

INTERVENTIONS: 

Not applicable.

MEASUREMENTS AND MAIN RESULTS: 

The primary outcome was inhospital 28-day mortality by calendar month of admission, from March 2020 to January 2021. Unadjusted mortality was estimated, and Cox proportional hazard models were used to estimate adjusted mortality, controlling for age, sex, ethnicity, major comorbidities, social deprivation, geographic location, and operational strain (using bed occupancy as a proxy). Mortality fell to trough levels in June 2020 (ICU: 22.5% [95% CI, 18.2–27.4], high dependency unit: 8.0% [95% CI, 6.4–9.6]) but then subsequently increased up to January 2021: (ICU: 30.6% [95% CI, 29.0–32.2] and high dependency unit, 16.2% [95% CI, 15.3–17.1]). Comparing patients admitted during June–September 2020 with those admitted during December 2020–January 2021, the adjusted mortality was 59% (CI range, 39–82) higher in high dependency unit and 88% (CI range, 62–118) higher in ICU for the later period. This increased mortality was seen in all subgroups including those under 65.

CONCLUSIONS: 

There was a marked deterioration in outcomes for patients admitted to critical care at the peak of the second wave of coronavirus disease 2019 in United Kingdom (December 2020–January 2021), compared with the post-first-wave period (June 2020–September 2020). The deterioration was independent of recorded patient characteristics and occupancy levels. Further research is required to determine to what extent this deterioration reflects the impact of the B117 variant of concern.

 

Effects of high flow nasal cannula on the coordination between swallowing and breathing in postextubation patients, a randomized crossover study

 

by Pornpan Rattanajiajaroen and Napplika Kongpolprom 

 

Critical Care volume 25, Article number: 365 (2021)

 

Background

Timing of swallows in relation to respiratory phases is associated with aspiration events. Oxygen therapy possibly affects the timing of swallows, which may alter airway protective mechanisms.

Objectives

To compare the coordination between swallowing and respiration during water infusion in post-extubation patients using high flow nasal oxygen (HFNO) with the coordination in those using low flow nasal oxygen (LFNO).

Methods

We conducted a randomized controlled crossover study in post-extubation patients. The patients extubated within 48 h were randomly assigned to two groups, namely, HFNO and LFNO. The eligible patients in each group received either HFNO with fraction of inspired oxygen (FiO2) 0.35, flow 50 L per minute (LPM), and temperature 34 °C or LFNO 5 LPM for 5 min. The coordination between swallowing and respiration was observed during continuous infusion of 10-ml water one minute three times. Respiratory phases and swallowing were monitored using electrocardiogram (EKG)-derived respiratory signals and submental electromyography (EMG), respectively. The swallowing frequency and timing of swallows in relation to respiratory phases were recorded. The coordination between swallowing and respiration was classified into 4 patterns, namely I, E, I-E, and E-I swallows. (I; inspiration and E; expiration) Subsequently, after a 5-min washout period, the patients were switched to the other type of oxygen therapy using the same procedure. The Wilcoxon Signed-Rank Test was used for statistical analysis.

Results

A total of 22 patients with a mean age of 56 years were enrolled in the study. The major indication for invasive mechanical ventilation was pneumonia with a median duration of endotracheal intubation of 2.5 days. The median total swallowing numbers (three minutes) were 18.5 times in the HFNO period and 21 times in the LFNO period (p = NS). The most common swallowing pattern was E-swallow. The patients using HFNO had higher numbers of E-swallow pattern (74.3% in HFNO vs 67.6% in LFNO; p = 0.048) and lower numbers of I-swallow pattern (14.3% in HFNO vs 23.1% in LFNO; p = 0.044). The numbers of other swallowing patterns were not different between the 2 groups.

Conclusions

Compared with LFNO, HFNO significantly increased the E-swallow and decreased the I-swallow in post-extubation patients. The findings indicated that HFNO might reduce a risk of aspiration during the post-extubation period.

 

 

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021

Critical Care Medicine: November 2021 - Volume 49 - Issue 11 - p e1063-e1143

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection (1). Sepsis and septic shock are major healthcare problems, impacting millions of people around the world each year and killing between one in three and one in six of those it affects (2–4). Early identification and appropriate management in the initial hours after the development of sepsis improve outcomes.

The recommendations in this document are intended to provide guidance for the clinician caring for adult patients with sepsis or septic shock in the hospital setting. Recommendations from these guidelines cannot replace the clinician’s decision-making capability when presented with a unique patient’s clinical variables. These guidelines are intended to reflect best practice…