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.