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…

Critical Care Bulletin: October 2021

 

Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial

Intensive Care Medicine Published: 05 October 2021

Purpose

Trials of tocilizumab in patients with severe COVID-19 pneumonia have demonstrated mixed results, and the role of tocilizumab in combination with other treatments is uncertain. Here we evaluated whether tocilizumab plus remdesivir provides greater benefit than remdesivir alone in patients with severe COVID-19 pneumonia.

Methods

This randomized, double-blind, placebo-controlled, multicenter trial included patients hospitalized with severe COVID-19 pneumonia requiring > 6 L/min supplemental oxygen. Patients were randomly assigned (2:1 ratio) to receive tocilizumab 8 mg/kg or placebo intravenously plus ≤ 10 days of remdesivir. The primary outcome was time from randomization to hospital discharge or “ready for discharge” (defined as category 1, assessed by the investigator on a 7-category ordinal scale of clinical status) to day 28. Patients were followed for 60 days.

Results

Among 649 enrolled patients, 434 were randomly assigned to tocilizumab plus remdesivir and 215 to placebo plus remdesivir. 566 patients (88.2%) received corticosteroids during the trial to day 28. Median time from randomization to hospital discharge or “ready for discharge” was 14 (95% CI 12–15) days with tocilizumab plus remdesivir and 14 (95% CI 11–16) days with placebo plus remdesivir [log-rank P = 0.74; Cox proportional hazards ratio 0.97 (95% CI 0.78–1.19)]. Serious adverse events occurred in 128 (29.8%) tocilizumab plus remdesivir and 72 (33.8%) placebo plus remdesivir patients; 78 (18.2%) and 42 (19.7%) patients, respectively, died by day 28.

Conclusions

Tocilizumab plus remdesivir did not shorten time to hospital discharge or “ready for discharge” to day 28 compared with placebo plus remdesivir in patients with severe COVID-19 pneumonia.

 

Effect of oral chlorhexidine de-adoption and implementation of an oral care bundle on mortality for mechanically ventilated patients in the intensive care unit (CHORAL): a multi-center stepped wedge cluster-randomized controlled trial

Intensive Care Medicine Published: 05 October 2021

Purpose

Oral chlorhexidine is used widely for mechanically ventilated patients to prevent pneumonia, but recent studies show an association with excess mortality. We examined whether de-adoption of chlorhexidine and parallel implementation of a standardized oral care bundle reduces intensive care unit (ICU) mortality in mechanically ventilated patients.

Methods

A stepped wedge cluster-randomized controlled trial with concurrent process evaluation in 6 ICUs in Toronto, Canada. Clusters were randomized to de-adopt chlorhexidine and implement a standardized oral care bundle at 2-month intervals. The primary outcome was ICU mortality. Secondary outcomes were time to infection-related ventilator-associated complications (IVACs), oral procedural pain and oral health dysfunction. An exploratory post hoc analysis examined time to extubation in survivors.

Results

A total of 3260 patients were enrolled; 1560 control, 1700 intervention. ICU mortality for the intervention and control periods were 399 (23.5%) and 330 (21.2%), respectively (adjusted odds ratio [aOR], 1.13; 95% confidence interval [CI] 0.82 to 1.54; P = 0.46). Time to IVACs (adjusted hazard ratio [aHR], 1.06; 95% CI 0.44 to 2.57; P = 0.90), time to extubation (aHR 1.03; 95% CI 0.85 to 1.23; P = 0.79) (survivors) and oral procedural pain (aOR, 0.62; 95% CI 0.34 to 1.10; P = 0.10) were similar between control and intervention periods. However, oral health dysfunction scores (− 0.96; 95% CI − 1.75 to − 0.17; P = 0.02) improved in the intervention period.

Conclusion

Among mechanically ventilated ICU patients, no benefit was observed for de-adoption of chlorhexidine and implementation of an oral care bundle on ICU mortality, IVACs, oral procedural pain, or time to extubation. The intervention may improve oral health.

 

High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial

Intensive Care Medicine Published: 03 October 2021

 

Purpose

This study aimed at evaluating the efficacy and safety of high-dose (> 0.2 L/kg of treated plasma per day) coupled plasma filtration-adsorption (CPFA) in treating patients with septic shock.

Methods

Multicentre, randomised, adaptive trial, performed in 12 Italian intensive care units (ICUs). Patients aged 14 or more, admitted to the ICU with septic shock, or had developed it during the stay were eligible. The final outcome was mortality at discharge from the last hospital at which the patient received care.

Results

Between May 2015, and October 2017, 115 patients were randomised. The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%, p = 0.35). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards (p = 0.100). An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure (p = 0.025); a dose–response relationship was observed between treated plasma volume and mortality (p = 0.010).

Conclusion

The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock. The harmful effect, if present, was particularly marked in the early phase of septic shock. Patients not requiring renal replacement therapy seemed most exposed to the possible harm, with evidence of a dose–response effect. Until the mechanisms behind these results are fully understood, the use of CPFA for the treatment of patients with septic shock is not recommended.

 

Long-term survival of mechanically ventilated patients with severe COVID-19: an observational cohort study

 

by Oscar Peñuelas, Laura del Campo-Albendea, Amanda Lesmes González de Aledo, José Manuel Añón, Carmen Rodríguez-Solís, Jordi Mancebo, Paula Vera, Daniel Ballesteros, Jorge Jiménez, Emilio Maseda, Juan Carlos Figueira, Nieves Franco, Ángela Algaba, Juan Pablo Avilés, Ricardo Díaz, Beatriz Abad…

 

Annals of Intensive Care volume 11, Article number: 143 Published: 02 October 2021

Background

Information is lacking regarding long-term survival and predictive factors for mortality in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) and undergoing invasive mechanical ventilation. We aimed to estimate 180-day mortality of patients with COVID-19 requiring invasive ventilation, and to develop a predictive model for long-term mortality.

Methods

Retrospective, multicentre, national cohort study between March 8 and April 30, 2020 in 16 intensive care units (ICU) in Spain. Participants were consecutive adults who received invasive mechanical ventilation for COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected in positive testing of a nasopharyngeal sample and confirmed by real time reverse-transcriptase polymerase chain reaction (rt-PCR). The primary outcomes was 180-day survival after hospital admission. Secondary outcomes were length of ICU and hospital stay, and ICU and in-hospital mortality. A predictive model was developed to estimate the probability of 180-day mortality.

Results

868 patients were included (median age, 64 years [interquartile range [IQR], 56–71 years]; 72% male). Severity at ICU admission, estimated by SAPS3, was 56 points [IQR 50–63]. Prior to intubation, 26% received some type of noninvasive respiratory support. The unadjusted overall 180-day survival rates was 59% (95% CI 56–62%). The predictive factors measured during ICU stay, and associated with 180-day mortality were: age [Odds Ratio [OR] per 1-year increase 1.051, 95% CI 1.033–1.068)), SAPS3 (OR per 1-point increase 1.027, 95% CI 1.011–1.044), diabetes (OR 1.546, 95% CI 1.085–2.204), neutrophils to lymphocytes ratio (OR per 1-unit increase 1.008, 95% CI 1.001–1.016), failed attempt of noninvasive positive pressure ventilation prior to orotracheal intubation (OR 1.878 (95% CI 1.124–3.140), use of selective digestive decontamination strategy during ICU stay (OR 0.590 (95% CI 0.358–0.972) and administration of low dosage of corticosteroids (methylprednisolone 1 mg/kg) (OR 2.042 (95% CI 1.205–3.460).

Conclusion

The long-term survival of mechanically ventilated patients with severe COVID-19 reaches more than 50% and may help to provide individualized risk stratification and potential treatments.

 

 

Prone Positioning of Nonintubated Patients With Coronavirus Disease 2019—A Systematic Review and Meta-Analysis

 

by Ponnapa Reddy, Mallikarjuna; Subramaniam, Ashwin; Afroz, Afsana; Billah, Baki; Lim, Zheng Jie; Zubarev, Alexandr; Blecher, Gabriel; Tiruvoipati, Ravindranath; Ramanathan, Kollengode; Wong, Suei Nee; Brodie, Daniel; Fan, Eddy; Shekar, Kiran 

 

Critical Care Medicine: October 2021 - Volume 49 - Issue 10 - p e1001-e1014

 

OBJECTIVES: 

Several studies have reported prone positioning of nonintubated patients with coronavirus diseases 2019–related hypoxemic respiratory failure. This systematic review and meta-analysis evaluated the impact of prone positioning on oxygenation and clinical outcomes.

DESIGN AND SETTING: 

We searched PubMed, Embase, and the coronavirus diseases 2019 living systematic review from December 1, 2019, to November 9, 2020.

SUBJECTS AND INTERVENTION: 

Studies reporting prone positioning in hypoxemic, nonintubated adult patients with coronavirus diseases 2019 were included.

MEASUREMENTS AND MAIN RESULTS: 

Data on prone positioning location (ICU vs non-ICU), prone positioning dose (total minutes/d), frequency (sessions/d), respiratory supports during prone positioning, relative changes in oxygenation variables (peripheral oxygen saturation, Pao2, and ratio of Pao2 to the Fio2), respiratory rate pre and post prone positioning, intubation rate, and mortality were extracted. Twenty-five observational studies reporting prone positioning in 758 patients were included. There was substantial heterogeneity in prone positioning location, dose and frequency, and respiratory supports provided. Significant improvements were seen in ratio of Pao2 to the Fio2 (mean difference, 39; 95% CI, 25–54), Pao2 (mean difference, 20 mm Hg; 95% CI, 14–25), and peripheral oxygen saturation (mean difference, 4.74%; 95% CI, 3–6%). Respiratory rate decreased post prone positioning (mean difference, –3.2 breaths/min; 95% CI, –4.6 to –1.9). Intubation and mortality rates were 24% (95% CI, 17–32%) and 13% (95% CI, 6–19%), respectively. There was no difference in intubation rate in those receiving prone positioning within and outside ICU (32% [69/214] vs 33% [107/320]; p = 0.84). No major adverse events were recorded in small subset of studies that reported them.

CONCLUSIONS: 

Despite the significant variability in frequency and duration of prone positioning and respiratory supports applied, prone positioning was associated with improvement in oxygenation variables without any reported serious adverse events. The results are limited by a lack of controls and adjustments for confounders. Whether this improvement in oxygenation results in meaningful patient-centered outcomes such as reduced intubation or mortality rates requires testing in well-designed randomized clinical trials.

 

Oral health care for the critically ill: a narrative review

by Lewis Winning, Fionnuala T. Lundy, Bronagh Blackwood, Daniel F. McAuley and Ikhlas El Karim 

Critical Care volume 25, Article number: 353, Published: 01 October 2021

Background

The link between oral bacteria and respiratory infections is well documented. Dental plaque has the potential to be colonized by respiratory pathogens and this, together with microaspiration of oral bacteria, can lead to pneumonia particularly in the elderly and critically ill. The provision of adequate oral care is therefore essential for the maintenance of good oral health and the prevention of respiratory complications.

Main body

Numerous oral care practices are utilised for intubated patients, with a clear lack of consensus on the best approach for oral care. This narrative review aims to explore the oral-lung connection and discuss in detail current oral care practices to identify shortcomings and offer suggestions for future research. The importance of adequate oral care has been recognised in guideline interventions for the prevention of pneumonia, but practices differ and controversy exists particularly regarding the use of chlorhexidine. The oral health assessment is also an important but often overlooked element of oral care that needs to be considered. Oral care plans should ideally be implemented on the basis of an individual oral health assessment. An oral health assessment prior to provision of oral care should identify patient needs and facilitate targeted oral care interventions.

Conclusion

Oral health is an important consideration in the management of the critically ill. Studies have suggested benefit in the reduction of respiratory complication such as Ventilator Associated Pneumonia associated with effective oral health care practices. However, at present there is no consensus as to the best way of providing optimal oral health care in the critically ill. Further research is needed to standardise oral health assessment and care practices to enable development of evidenced based personalised oral care for the critically ill.

Individualised versus conventional glucose control in critically-ill patients: the CONTROLING study—a randomized clinical trial

Intensive Care Medicine Published: 29 September 2021

 

Purpose

Hyperglycaemia is an adaptive response to stress commonly observed in critical illness. Its management remains debated in the intensive care unit (ICU). Individualising hyperglycaemia management, by targeting the patient’s pre-admission usual glycaemia, could improve outcome.

Methods

In a multicentre, randomized, double-blind, parallel-group study, critically-ill adults were considered for inclusion. Patients underwent until ICU discharge either individualised glucose control by targeting the pre-admission usual glycaemia using the glycated haemoglobin A1c level at ICU admission (IC group), or conventional glucose control by maintaining glycaemia below 180 mg/dL (CC group). A non-commercial web application of a dynamic sliding-scale insulin protocol gave to nurses all instructions for glucose control in both groups. The primary outcome was death within 90 days.

Results

Owing to a low likelihood of benefit and evidence of the possibility of harm related to hypoglycaemia, the study was stopped early. 2075 patients were randomized; 1917 received the intervention, 942 in the IC group and 975 in the CC group. Although both groups showed significant differences in terms of glycaemic control, survival probability at 90-day was not significantly different (IC group: 67.2%, 95% CI [64.2%; 70.3%]; CC group: 69.6%, 95% CI [66.7%; 72.5%]). Severe hypoglycaemia (below 40 mg/dL) occurred in 3.9% of patients in the IC group and in 2.5% of patients in the CC group (p = 0.09). A post hoc analysis showed for non-diabetic patients a higher risk of 90-day mortality in the IC group compared to the CC group (HR 1.3, 95% CI [1.05; 1.59], p = 0.018).

Conclusion

Targeting an ICU patient’s pre-admission usual glycaemia using a dynamic sliding-scale insulin protocol did not demonstrate a survival benefit compared to maintaining glycaemia below 180 mg/dL.

 

The impact of wearable continuous vital sign monitoring on deterioration detection and clinical outcomes in hospitalised patients: a systematic review and meta-analysis

 

by Carlos Areia, Christopher Biggs, Mauro Santos, Neal Thurley, Stephen Gerry, Lionel Tarassenko, Peter Watkinson and Sarah Vollam 

 

Critical Care volume 25, Article number: 351; Published: 28 September 2021

 

Background

Timely recognition of the deteriorating inpatient remains challenging. Wearable monitoring systems (WMS) may augment current monitoring practices. However, there are many barriers to implementation in the hospital environment, and evidence describing the clinical impact of WMS on deterioration detection and patient outcome remains unclear.

Objective

To assess the impact of vital-sign monitoring on detection of deterioration and related clinical outcomes in hospitalised patients using WMS, in comparison with standard care.

Methods

A systematic search was conducted in August 2020 using MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, CENTRAL, Health Technology Assessment databases and grey literature. Studies comparing the use of WMS against standard care for deterioration detection and related clinical outcomes in hospitalised patients were included. Deterioration related outcomes (primary) included unplanned intensive care admissions, rapid response team or cardiac arrest activation, total and major complications rate. Other clinical outcomes (secondary) included in-hospital mortality and hospital length of stay. Exploratory outcomes included alerting system parameters and clinical trial registry information.

Results

Of 8706 citations, 10 studies with different designs met the inclusion criteria, of which 7 were included in the meta-analyses. Overall study quality was moderate. The meta-analysis indicated that the WMS, when compared with standard care, was not associated with significant reductions in intensive care transfers (risk ratio, RR 0.87; 95% confidence interval, CI 0.66–1.15), rapid response or cardiac arrest team activation (RR 0.84; 95% CI 0.69–1.01), total (RR 0.77; 95% CI 0.44–1.32) and major (RR 0.55; 95% CI 0.24–1.30) complications prevalence. There was also no statistically significant association with reduced mortality (RR 0.48; 95% CI 0.18–1.29) and hospital length of stay (mean difference, MD − 0.09; 95% CI − 0.43 to 0.44).

Conclusion

This systematic review indicates that there is no current evidence that implementation of WMS impacts early deterioration detection and associated clinical outcomes, as differing design/quality of available studies and diversity of outcome measures make it difficult to reach a definite conclusion. Our narrative findings suggested that alarms should be adjusted to minimise false alarms and promote rapid clinical action in response to deterioration.

 

Effectiveness of anisodamine for the treatment of critically ill patients with septic shock: a multicentre randomized controlled trial

 

by Yuetian Yu, Cheng Zhu, Yucai Hong, Lin Chen, Zhiping Huang, Jiancang Zhou, Xin Tian, Dadong Liu, Bo Ren, Cao Zhang, Caibao Hu, Xinan Wang, Rui Yin, Yuan Gao and Zhongheng Zhang 

 

Critical Care volume 25, Article number: 349; Published: 27 September 2021

 

Background

Septic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. There is currently no specific agent for treating septic shock. Anisodamine is an agent extracted from traditional Chinese medicine with potent anti-inflammatory effects. However, its clinical effectiveness remains largely unknown.

Methods

In a multicentre, open-label trial, we randomly assigned adults with septic shock to receive either usual care or anisodamine (0.1–0.5 mg per kilogram of body weight per hour), with the anisodamine doses adjusted by clinicians in accordance with the patients’ shock status. The primary end point was death on hospital discharge. The secondary end points were ventilator-free days at 28 days, vasopressor-free days at 28 days, serum lactate and sequential organ failure assessment (SOFA) score from days 0 to 6. The differences in the primary and secondary outcomes were compared between the treatment and usual care groups with the χ2 test, Student’s t test or rank-sum test, as appropriate. The false discovery rate was controlled for multiple testing.

Results

Of the 469 patients screened, 355 were assigned to receive the trial drug and were included in the analyses—181 patients received anisodamine, and 174 were in the usual care group. We found no difference between the usual care and anisodamine groups in hospital mortality (36% vs. 30%; p = 0.348), or ventilator-free days (median [Q1, Q3], 24.4 [5.9, 28] vs. 26.0 [8.5, 28]; p = 0.411). The serum lactate levels were significantly lower in the treated group than in the usual care group after day 3. Patients in the treated group were less likely to receive vasopressors than those in the usual care group (OR [95% CI] 0.84 [0.50, 0.93] for day 5 and 0.66 [0.37, 0.95] for day 6).

Conclusions

There is no evidence that anisodamine can reduce hospital mortality among critically ill adults with septic shock treated in the intensive care unit.

 

Restricted visitation policies in acute care settings during the COVID-19 pandemic: a scoping review

by Stephana J. Moss, Karla D. Krewulak, Henry T. Stelfox, Sofia B. Ahmed, Melanie C. Anglin, Sean M. Bagshaw, Karen E. A. Burns, Deborah J. Cook, Christopher J. Doig, Alison Fox-Robichaud, Robert Fowler, Laura Hernández, Michelle E. Kho, Maia Kredentser, Kira Makuk, Srinivas Murthy… 

Critical Care volume 25, Article number: 347; Published: 25 September 2021

Background

Restricted visitation policies in acute care settings because of the COVID-19 pandemic have negative consequences. The objective of this scoping review is to identify impacts of restricted visitation policies in acute care settings, and describe perspectives and mitigation approaches among patients, families, and healthcare professionals.

Methods

We searched Medline, Embase, PsycINFO, Healthstar, CINAHL, Cochrane Central Register of Controlled Trials on January 01/2021, unrestricted, for published primary research records reporting any study design. We included secondary (e.g., reviews) and non-research records (e.g., commentaries), and performed manual searches in web-based resources. We excluded records that did not report primary data. Two reviewers independently abstracted data in duplicate.

Results

Of 7810 citations, we included 155 records. Sixty-six records (43%) were primary research; 29 (44%) case reports or case series, and 26 (39%) cohort studies; 21 (14%) were literature reviews and 8 (5%) were expert recommendations; 54 (35%) were commentary, editorial, or opinion pieces. Restricted visitation policies impacted coping and daily function (n = 31, 20%) and mental health outcomes (n = 29, 19%) of patients, families, and healthcare professionals. Participants described a need for coping and support (n = 107, 69%), connection and communication (n = 107, 69%), and awareness of state of well-being (n = 101, 65%). Eighty-seven approaches to mitigate impact of restricted visitation were identified, targeting families (n = 61, 70%), patients (n = 51, 59%), and healthcare professionals (n = 40, 46%).

Conclusions

Patients, families, and healthcare professionals were impacted by restricted visitation polices in acute care settings during COVID-19. The consequences of this approach on patients and families are understudied and warrant evaluation of approaches to mitigate their impact. Future pandemic policy development should include the perspectives of patients, families, and healthcare professionals.

 

 

 

 

 

 

Coronavirus Disease 2019 Policy Restricting Family Presence May Have Delayed End-of-Life Decisions for Critically Ill Patients

 

by Azad, Tej D.; Al-Kawaz, Mais N.; Turnbull, Alison E.; Rivera-Lara, Lucia 

 

Critical Care Medicine: October 2021 - Volume 49 - Issue 10 - p e1037-e1039

 

OBJECTIVES: 

To determine if a restrictive visitor policy inadvertently lengthened the decision-making process for dying inpatients without coronavirus disease 2019.

DESIGN: 

Regression discontinuity and time-to-event analysis.

SETTING: 

Two large academic hospitals in a unified health system.

PATIENTS OR SUBJECTS: 

Adult decedents who received greater than or equal to 1 day of ICU care during their terminal admission over a 12-month period.

INTERVENTIONS: 

Implementation of a visit restriction policy.

MEASUREMENTS AND MAIN RESULTS: 

We identified 940 adult decedents without coronavirus disease 2019 during the study period. For these patients, ICU length of stay was 0.8 days longer following policy implementation, although this effect was not statistically significant (95% CI, –2.3 to 3.8; p = 0.63). After excluding patients admitted before the policy but who died after implementation, we observed that ICU length of stay was 2.9 days longer post-policy (95% CI, 0.27–5.6; p = 0.03). A time-to-event analysis revealed that admission after policy implementation was associated with a significantly longer time to first do not resuscitate/do not intubate/comfort care order (adjusted hazard ratio, 2.2; 95% CI, 1.6–3.1; p < 0.0001).

CONCLUSIONS: 

Policies restricting family presence may lead to longer ICU stays and delay decisions to limit treatment prior to death. Further policy evaluation and programs enabling access to family-centered care and palliative care during the ongoing coronavirus disease 2019 pandemic are imperative.

 

Early versus late awake prone positioning in non-intubated patients with COVID-19

 

by Ramandeep Kaur, David L. Vines, Sara Mirza, Ahmad Elshafei, Julie A. Jackson, Lauren J. Harnois, Tyler Weiss, J. Brady Scott, Matthew W. Trump, Idrees Mogri, Flor Cerda, Amnah A. Alolaiwat, Amanda R. Miller, Andrew M. Klein, Trevor W. Oetting, Lindsey Morris… 

 

Critical Care volume 25, Article number: 340 Published: 17 September 2021

 

Background

Awake prone positioning (APP) is widely used in the management of patients with coronavirus disease (COVID-19). The primary objective of this study was to compare the outcome of COVID-19 patients who received early versus late APP.

Methods

Post hoc analysis of data collected for a randomized controlled trial (ClinicalTrials.gov NCT04325906). Adult patients with acute hypoxemic respiratory failure secondary to COVID-19 who received APP for at least one hour were included. Early prone positioning was defined as APP initiated within 24 h of high-flow nasal cannula (HFNC) start. Primary outcomes were 28-day mortality and intubation rate.

Results

We included 125 patients (79 male) with a mean age of 62 years. Of them, 92 (73.6%) received early APP and 33 (26.4%) received late APP. Median time from HFNC initiation to APP was 2.25 (0.8–12.82) vs 36.35 (30.2–75.23) hours in the early and late APP group (p < 0.0001), respectively. Average APP duration was 5.07 (2.0–9.05) and 3.0 (1.09–5.64) hours per day in early and late APP group (p < 0.0001), respectively. The early APP group had lower mortality compared to the late APP group (26% vs 45%, p = 0.039), but no difference was found in intubation rate. Advanced age (OR 1.12 [95% CI 1.0–1.95], p = 0.001), intubation (OR 10.65 [95% CI 2.77–40.91], p = 0.001), longer time to initiate APP (OR 1.02 [95% CI 1.0–1.04], p = 0.047) and hydrocortisone use (OR 6.2 [95% CI 1.23–31.1], p = 0.027) were associated with increased mortality.

Conclusions

Early initiation (< 24 h of HFNC use) of APP in acute hypoxemic respiratory failure secondary to COVID-19 improves 28-day survival.

 

Comparison of Bivalirudin Versus Heparin for Maintenance Systemic Anticoagulation During Adult and Pediatric Extracorporeal Membrane Oxygenation

 

Seelhammer, Troy G.; Bohman, John K.; Schulte, Phillip J.; Hanson, Andrew C.; Aganga, Devon O.

Critical Care Medicine: September 2021 - Volume 49 - Issue 9 - p 1481-1492

OBJECTIVES: 

To provide a comparative analysis of conventional heparin-versus bivalirudin-based systemic anticoagulation in adult and pediatric patients supported on extracorporeal membrane oxygenation.

DESIGN: 

Retrospective chart review study of adult and pediatric patients receiving extracorporeal membrane oxygenation from January 1, 2014, to October 1, 2019.

SETTING: 

A large, high-volume tertiary referral adult and pediatric extracorporeal membrane oxygenation center.

PATIENTS: 

Four hundred twenty-four individuals requiring extracorporeal membrane oxygenation support and systemically anticoagulated with either unfractionated heparin (223 adult and 65 pediatric patients) or bivalirudin (110 adult and 24 pediatric patients) were included.

INTERVENTIONS: 

None.

MEASUREMENTS AND MAIN RESULTS: 

Digital data abstraction was used to retrospectively collect patient details. The majority of both groups were cannulated centrally (67%), and the extracorporeal membrane oxygenation type was predominantly venoarterial (84%). The adult bivalirudin group had a greater occurrence of heparin-induced thrombocytopenia (12% vs 1%; p < 0.01) and was more likely to require postcardiotomy extracorporeal membrane oxygenation (36% vs 55%; p < 0.01). There were no statistical differences between the groups in regards to age, sex, and extracorporeal membrane oxygenation initiation location. The main finding was a reduced mortality in the adult bivalirudin group (odds ratio, 0.39; p < 0.01), whereas no difference was noted in the pediatric group. A significant reduction in the composite transfusion requirement in the first 24 hours was noted in the pediatric bivaluridin group with an odds ratio of 0.28 (p = 0.02). Groups did not differ in regard to laboratories per day, anticoagulant dose adjustments, or ischemic complications.

CONCLUSIONS: 

When compared with heparin-based systemic anticoagulation, bivalirudin demonstrated feasibility and safety as established by the absence of increases in identifiable adverse outcomes while manifesting substantial improvements in hospital mortality in adult patients. Further studies are necessary to corroborate these findings and further elucidate the role of bivalirudin during extracorporeal membrane oxygenation support.

 

High-flow nasal oxygen cannula vs. noninvasive mechanical ventilation to prevent reintubation in sepsis: a randomized controlled trial

 

by Surat Tongyoo, Porntipa Tantibundit, Kiattichai Daorattanachai, Tanuwong Viarasilpa, Chairat Permpikul and Suthipol Udompanturak 

 

Annals of Intensive Care volume 11, Article number: 135 (2021)

 

Background

High-flow nasal oxygen cannula (HFNC) and noninvasive mechanical ventilation (NIV) can prevent reintubation in critically ill patients. However, their efficacy in post-extubated sepsis patients remains unclear. The objective of this study was to compare the efficacy of HFNC vs. NIV to prevent reintubation in post-extubated sepsis patients.

Methods

We conducted a single-centre, prospective, open-labelled, randomised controlled trial at the medical intensive care unit of Siriraj Hospital, Mahidol University, Bangkok, Thailand. Sepsis patients who had been intubated, recovered, and passed the spontaneous breathing trial were enrolled and randomly assigned in a 1:1 ratio to receive either HFNC or NIV support immediately after extubation. The primary outcome was rate of reintubation at 72 h after extubation.

Results

Between 1st October 2017 and 31st October 2019, 222 patients were enrolled and 112 were assigned to the HFNC group and 110 to the NIV group. Both groups were well matched in baseline characteristics. The median [IQR] age of the HFNC group was 66 [50–77] vs. 65.5 [54–77] years in the NIV group. The most common causes of intubation at admission were shock-related respiratory failure (57.1% vs. 55.5%) and acute hypoxic respiratory failure (34.8% vs. 40.9%) in the HFNC and NIV groups, respectively. The duration of mechanical ventilation before extubation was 5 [3–8] days in the HFNC group vs. 5 [3–9] days in the NIV group. There was no statistically significant difference in the primary outcome: 20/112 (17.9%) in the HFNC group required reintubation at 72 h compared to 20/110 (18.2%) in the NIV group [relative risk (RR) 0.99: 95% confidence interval (CI) (0.70–1.39); P = 0.95]. The 28-day mortality was not different: 8/112 (7.1%) with HFNC vs. 10/110 (9.1%) with NIV (RR 0.88: 95% CI (0.57–1.37); P = 0.59).

Conclusions

Among sepsis patients, there was no difference between HFNC and NIV in the prevention of reintubation at 72 h after extubation.

 

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

 by Antoni Torres, Anna Motos, Jordi Riera, Laia Fernández-Barat, Adrián Ceccato, Raquel Pérez-Arnal, Dario García-Gasulla, Oscar Peñuelas, José Angel Lorente, Alejandro Rodriguez, David de Gonzalo-Calvo, Raquel Almansa, Albert Gabarrús, Rosario Menéndez, Jesús F. Bermejo-Martin, Ricard Ferrer… 

 Critical Care volume 25, Article number: 331 Published: 13 September 2021

Background

Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission.

Methods

Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes.

Results

Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0–171.2] to 180.0 [135.4–227.9] mmHg and the ventilatory ratio from 1.73 [1.33–2.25] to 1.96 [1.61–2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01–1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01–1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93–1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47).

Conclusions

Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.

 

Critical Care Bulletin: September 2021

 

To prone or not to prone ARDS patients on ECMO

by Oriol Roca, Andrés Pacheco and Marina García-de-Acilu 

Critical Care volume 25, Article number: 315 (2021) Published: 31 August 2021

The prone position is recommended as a supportive therapy in patients with moderate- to-severe acute respiratory distress syndrome (ARDS). It is usually associated with improved oxygenation and pulmonary mechanics as the result of a more homogeneous distribution of mechanical forces and better ventilation/perfusion (V/Q) matching. These effects lead to a lower risk of aggravating preexisting lung injury and, ultimately, a decrease in mortality. Despite widespread use of the prone position in patients with ARDS, even in awake non-intubated spontaneously breathing patients, its use dramatically decreases once the patient has been placed on extracorporeal membrane oxygenation (ECMO). In this chapter, we discuss the available evidence regarding use of the prone position in ARDS patients treated with ECMO.

 

Monitoring and modifying brain oxygenation in patients at risk of hypoxic ischaemic brain injury after cardiac arrest

 

by Markus Benedikt Skrifvars, Mypinder Sekhon and Erik Anders Åneman 

Critical Care volume 25, Article number: 312 (2021) Published: 31 August 2021

The majority of adverse clinical outcomes following successful resuscitation from cardiac arrest, are attributable to hypoxic ischemic brain injury [1]. The cornerstone of hypoxic ischemic brain injury management has traditionally focused on preventing secondary ischemic injury, following the return of spontaneous circulation (ROSC) [2]. Among the various mechanisms implicated in the pathophysiology of secondary injury, post-resuscitation cerebral ischemia is linked to central physiologic variables that may be modifiable [3]. Observational data demonstrate associations between perturbations in physiologic variables known to reduce cerebral blood flow (CBF)—such as arterial hypotension [4] and hypocapnia [5]—and adverse clinical outcome. This adds credence to the importance of optimizing cerebral oxygen delivery, to mitigate secondary ischemic injury. Recently, sentinel randomized controlled trials (RCTs) aimed at augmenting mean arterial pressure (MAP)—a key physiologic determinant of cerebral oxygen delivery—have yielded important insights into the importance of mitigating secondary cerebral ischemia [6, 7]. Although it did not establish a definitive link to improved neurological outcome, the COMACARE study demonstrated reduced levels of neurofilament light, a biomarker of brain injury, in patients undergoing an augmented MAP strategy following ROSC [8]. Patients may continue to experience episodes of brain hypoxia following cardiac arrest, despite goal-directed therapy and augmented MAP, with considerable heterogeneity in the underlying cerebrovascular hemodynamics in individual patients [9]. Thus, a targeted approach to the individualized management of hypoxic ischemic brain injury in the post-resuscitation phase requires the longitudinal monitoring of brain oxygenation—providing clinicians with real time physiologic data points to optimize cerebral oxygen delivery, similar to that applied in patients with traumatic brain injury (TBI) [10]. Near infrared spectroscopy (NIRS) provides an easily implemented and virtually complication-free way to monitor regional cerebral oxygen saturation (rSO2) in critically ill patients. The insertion of oxygen sensing catheters provides a real time assessment of the partial pressure of oxygen in brain tissue (PbtO2). This approach has gained widespread use following neurotrauma.

In this narrative review, we discuss the available means for monitoring the occurrence of brain ischemia in patients at risk of hypoxic ischemic brain injury. Specifically, we decided to review the evidence for non-invasive monitoring, using NIRS and invasive monitoring via the insertion of tissue oxygen monitors and jugular bulb catheters. These two approaches to monitoring brain oxygenation have different advantages and limitations (Fig. 1). We also discuss ways to modify cerebral oxygenation, with a special focus on MAP and blood carbon dioxide and oxygen levels.