Critical Care Bulletin: October 2024

 

Predicting outcomes in patients with exacerbation of COPD requiring mechanical ventilation

Annals of Intensive Care volume 14, Article number: 159, Published: 20 October 2024

Background

Acute exacerbations of COPD (AECOPD) are common and significantly contribute to mortality in patients with COPD. Prognostic scores can assist clinicians in making tailored decisions to manage AECOPD. In the current study, we therefore aimed to evaluate the performance of the Noninvasive Ventilation Outcomes (NIVO) score, originally designed to assess in-ICU mortality, in predicting 1 year mortality and NIV failure in AECOPD.

Methods

This retrospective study analyzed data from patients hospitalized for AECOPD requiring mechanical ventilation between January 1st, 2018, and December 31st, 2022. Mortality was assessed at the end of ICU stay and 1 year after admission, while NIV failure was defined as intubation or death without intubation.

Results

Among 302 ICU admissions of COPD patients, 190 patients with AECOPD requiring mechanical ventilation were included. Of these, 44 (23%) died in the ICU, 62 out of 184 (34%) failed NIV, and 78 (41%) died within 1 year of admission. Patients who died in ICU or experienced NIV failure had more severe COPD and more impaired blood gas parameters at admission. The NIVO score demonstrated an AUC of 0.68 in predicting 1-year mortality and an AUC of 0.85 in predicting NIV failure. A NIVO score over 7 was associated with higher 1-year mortality and NIV failure (HR of 4.4 [1.8–10.9] and 41.6 [5.6–307.9], respectively).

Conclusion

Beyond predicting in-ICU mortality, the NIVO-score is a reliable tool in predicting 1-year mortality and NIV failure in AECOPD.

 

Oxygen therapy and noninvasive respiratory supports in acute hypoxemic respiratory failure: a narrative review

Annals of Intensive Care volume 14, Article number: 158 (2024)

Background

This narrative review was written by an expert panel to the members of the jury to help in the development of clinical practice guidelines on oxygen therapy.

Results

According to the expert panel, acute hypoxemic respiratory failure was defined as PaO₂ < 60 mm Hg or SpO₂ < 90% on room air, or PaO₂/FiO₂ ≤ 300 mm Hg. Supplemental oxygen should be administered according to the monitoring of SpO₂, with the aim at maintaining SpO₂ above 92% and below 98%. Noninvasive respiratory supports are generally reserved for the most hypoxemic patients with the aim of relieving dyspnea. High-flow nasal cannula oxygen (HFNC) seems superior to conventional oxygen therapy (COT) as a means of avoiding intubation and may therefore be should probably be used as a first-line noninvasive respiratory support in patients requiring more than 6 L/min of oxygen or PaO₂/FiO₂ ≤ 200 mm Hg and a respiratory rate above 25 breaths/minute or clinical signs of respiratory distress, but with no benefits on mortality. Continuous positive airway pressure (CPAP) cannot currently be recommended as a first-line noninvasive respiratory support, since its beneficial effects on intubation remain uncertain. Despite older studies favoring noninvasive ventilation (NIV) over COT, recent clinical trials fail to show beneficial effects with NIV compared to HFNC. Therefore, there is no evidence to support the use of NIV or CPAP as first-line treatment if HFNC is available. Clinical trials do not support the hypothesis that noninvasive respiratory supports may lead to late intubation. The potential benefits of awake prone positioning on the risk of intubation in patients with COVID-19 cannot be extrapolated to patients with another etiology.

Conclusions

Whereas oxygen supplementation should be initiated for patients with acute hypoxemic respiratory failure defined as PaO₂ below 60 mm Hg or SpO₂ < 90% on room air, HFNC should be the first-line noninvasive respiratory support in patients with PaO₂/FiO₂ ≤ 200 mm Hg with increased respiratory rate. Further studies are needed to assess the potential benefits of CPAP, NIV through a helmet and awake prone position in patients with acute hypoxemic respiratory failure not related to COVID-19.

 

Risk Stratification and Management of Acute Respiratory Failure in Patients With Neuromuscular Disease

Critical Care Medicine 52(11):p 1781-1789, November 2024.

OBJECTIVES: 

Guillain-Barré syndrome (GBS) and myasthenia gravis (MG) are the most common causes of acute neuromuscular respiratory failure resulting in ICU admission. This synthetic narrative review summarizes the evidence for the prediction and management of acute neuromuscular respiratory failure due to GBS and MG.

DATA SOURCES: 

We searched PubMed for relevant literature and reviewed bibliographies of included articles for additional relevant studies.

STUDY SELECTION: 

English-language publications were reviewed.

DATA EXTRACTION: 

Data regarding study methodology, patient population, evaluation metrics, respiratory interventions, and clinical outcomes were qualitatively assessed.

DATA SYNTHESIS: 

No single tool has sufficient sensitivity and specificity for the prediction of acute neuromuscular respiratory failure requiring mechanical ventilation. Multimodal assessment, integrating history, examination maneuvers (single breath count, neck flexion strength, bulbar weakness, and paradoxical breathing) and pulmonary function testing are ideal for risk stratification. The Erasmus GBS Respiratory Insufficiency Score is a validated tool useful for GBS. Noninvasive ventilation can be effective in MG but may not be safe in early GBS. Airway management considerations are similar across both conditions, but dysautonomia in GBS requires specific attention. Extubation failure is common in MG, and early tracheostomy may be beneficial for MG. Prolonged ventilatory support is common, and good functional outcomes may occur even when prolonged ventilation is required.

CONCLUSIONS: 

Multimodal assessments integrating several bedside indicators of bulbar and respiratory muscle function can aid in evidence-based risk stratification for respiratory failure among those with neuromuscular disease. Serial evaluations may help establish a patient’s trajectory and to determine timing of respiratory intervention.

 

Direct Laryngoscopy Versus Video Laryngoscopy for Intubation in Critically Ill Patients: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomized Trials*

Critical Care Medicine 52(11):p 1674-1685, November 2024.

OBJECTIVES: 

Given the uncertainty regarding the optimal approach to laryngoscopy for the intubation of critically ill adult patients, we conducted a systematic review and meta-analysis to compare video laryngoscopy (VL) vs. direct laryngoscopy (DL) for intubation in emergency department and ICU patients.

DATA SOURCES: 

We searched MEDLINE, PubMed, Embase, Cochrane Library, and unpublished sources, from inception to February 27, 2024.

STUDY SELECTION: 

We included randomized controlled trials (RCTs) of critically ill adult patients randomized to VL compared with DL for endotracheal intubation.

DATA EXTRACTION: 

Reviewers screened abstracts, full texts, and extracted data independently and in duplicate. We pooled data using a random-effects model, assessed risk of bias using the modified Cochrane tool and certainty of evidence using the Grading Recommendations Assessment, Development, and Evaluation approach. We pre-registered the protocol on PROSPERO (CRD42023469945).

DATA SYNTHESIS: 

We included 20 RCTs (n = 4569 patients). Compared with DL, VL probably increases first pass success (FPS) (relative risk [RR], 1.13; 95% CI, 1.06–1.21; moderate certainty) and probably decreases esophageal intubations (RR, 0.47; 95% CI, 0.27–0.82; moderate certainty). VL may result in fewer aspiration events (RR, 0.74; 95% CI, 0.51–1.09; low certainty) and dental injuries (RR, 0.46; 95% CI, 0.19–1.11; low certainty) and may have no effect on mortality (RR, 0.97; 95% CI, 0.88–1.07; low certainty) compared with DL.

CONCLUSIONS: 

In critically ill adult patients undergoing intubation, the use of VL, compared with DL, probably leads to higher rates of FPS and probably decreases esophageal intubations. VL may result in fewer dental injuries as well as aspiration events compared with DL with no effect on mortality.

Hypothermia versus normothermia in patients with cardiac arrest and shockable rhythm: a secondary analysis of the TTM-2 study

Critical Care volume 28, Article number: 335, Published: 15 October 2024

Background

The aim of this study was to assess whether hypothermia increased survival and improved functional outcome when compared with normothermia in out-of-hospital cardiac arrest (OHCA) patients with similar characteristics than in previous randomized studies showing benefits for hypothermia.

Methods

Post hoc analysis of a pragmatic, multicenter, randomized clinical trial (TTM-2, NCT02908308). In this analysis, the subset of patients included in the trial who had similar characteristics to patients included in one previous randomized trial and randomized to hypothermia at 33 °C or normothermia (i.e. target < 37.8 °C) were considered. The primary outcome was survival at 6 months; secondary outcomes included favorable functional outcome at 6 months, defined as a modified Rankin scale of 0–3. Time-to-death and the occurrence of adverse events were also reported.

Results

From a total of 1891 included in the TTM-2 study, 600 (31.7%) were included in the analysis, 294 in the hypothermia and 306 in the normothermia group. At 6 months, 207 of the 294 patients (70.4%) in the hypothermia group and 220 of the 306 patients (71.8%) in the normothermia group had survived (relative risk with hypothermia, 0.96; 95% confidence interval [CI], 0.81 to 1.15; P = 0.71). Also, 198 of the 294 (67.3%) in the hypothermia group and 202 of the 306 (66.0%) in the normothermia group had a favorable functional outcome (relative risk with hypothermia, 1.03; 95% CI, 0.87 to 1.23; P = 0.79). There was a significant increase in the occurrence of arrythmias in the hypothermia group (62/294, 21.2%) when compared to the normothermia group (43/306, 14.1%—OR 1.49, 95% CI 1.05–2.14; p = 0.026).

Conclusions

In this study, hypothermia at 33˚C did not improve survival or functional outcome in a subset of patients with similar cardiac arrest characteristics to patients in whom benefit from hypothermia was shown in prior studies.

 Biomarkers in cardiogenic shock: old pals, new friends

Annals of Intensive Care volume 14, Article number: 157, Published: 16 October 2024

Abstract

In cardiogenic shock, biomarkers should ideally help make the diagnosis, choose the right therapeutic options and monitor the patient in addition to clinical and echocardiographic indices. Among “old” biomarkers that have been used for decades, lactate detects, quantifies, and follows anaerobic metabolism, despite its lack of specificity. Renal and liver biomarkers are indispensable for detecting the effect of shock on organ function and are highly predictive of poor outcomes. Direct biomarkers of cardiac damage such as cardiac troponins, B-type natriuretic and N-terminal pro-B-type natriuretic peptides have a good prognostic value, but they lack specificity to detect a cardiogenic cause of shock, as many factors influence their plasma concentrations in critically ill patients. Among the biomarkers that have been more recently described, dipeptidyl peptidase-3 is one of the most interesting. In addition to its prognostic value, it could represent a therapeutic target in cardiogenic shock in the future as a specific antibody inhibits its activity. Adrenomedullin is a small peptide hormone secreted by various tissues, including vascular smooth muscle cells and endothelium, particularly under pathological conditions. It has a vasodilator effect and has prognostic value during cardiogenic shock. An antibody inhibits its activity and so adrenomedullin could represent a therapeutic target in cardiogenic shock. An increasing number of inflammatory biomarkers are also of proven prognostic value in cardiogenic shock, reflecting the inflammatory reaction associated with the syndrome. Some of them are combined to form prognostic proteomic scores. Alongside clinical variables, biomarkers can be used to establish biological “signatures” characteristic of the pathophysiological pathways involved in cardiogenic shock. This helps describe patient subphenotypes, which could in the future be used in clinical trials to define patient populations responding specifically to a treatment.

 

 

Impact of sleep disturbances on outcomes in intensive care units

Critical Care volume 28, Article number: 331, Published: 09 October 2024

Background

Sleep deprivation is common in intensive care units (ICUs) and may alter respiratory performance. Few studies have assessed the role of sleep disturbances on outcomes in critically ill patients.

Objectives

We hypothesized that sleep disturbances may be associated with poor outcomes in ICUs.

Methods

Post-hoc analysis pooling three observational studies assessing sleep by complete polysomnography in 131 conscious and non-sedated patients included at different times of their ICU stay. Sleep was assessed early in a group of patients admitted for acute respiratory failure while breathing spontaneously (n = 34), or under mechanical ventilation in patients with weaning difficulties (n = 45), or immediately after extubation (n = 52). Patients admitted for acute respiratory failure who required intubation, those under mechanical ventilation who had prolonged weaning, and those who required reintubation after extubation were considered as having poor clinical outcomes. Durations of deep sleep, rapid eye movement (REM) sleep, and atypical sleep were compared according to the timing of polysomnography and the clinical outcomes.

Results

Whereas deep sleep remained preserved in patients admitted for acute respiratory failure, it was markedly reduced under mechanical ventilation and after extubation (p < 0.01). Atypical sleep was significantly more frequent in patients under mechanical ventilation than in those breathing spontaneously (p < 0.01). REM sleep was uncommon at any time of their ICU stay. Patients with complete disappearance of REM sleep (50% of patients) were more likely to have poor clinical outcomes than those with persistent REM sleep (24% vs. 9%, p = 0.03).

Conclusion

Complete disappearance of REM sleep was significantly associated with poor clinical outcomes in critically ill patients.

 

Blood trauma in veno-venous extracorporeal membrane oxygenation: low pump pressures and low circuit resistance matter

Critical Care volume 28, Article number: 330, Published: 08 October 2024

Background

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become standard of care in patients with the most severe forms of acute respiratory distress syndrome. However, hemolysis and bleeding are one of the most frequent side effects, affecting mortality. Despite the widespread use of VV ECMO, current protocols lack detailed, in-vivo data-based recommendations for safe ECMO pump operating conditions. This study aims to comprehensively analyze the impact of VV ECMO pump operating conditions on hemolysis by combining in-silico modeling and clinical data analysis.

Methods

We combined data from 580 patients treated with VV ECMO in conjunction with numerical predictions of hemolysis using computational fluid dynamics and reduced order modeling of the Rotaflow (Getinge) and DP3 (Xenios) pumps. Blood trauma parameters across 94,779 pump operating points were associated with numerical predictions of shear induced hemolysis.

Results

Minimal hemolysis was observed at low pump pressures and low circuit resistance across all flow rates, whereas high pump pressures and circuit resistance consistently precipitated substantial hemolysis, irrespective of flow rate. However, the lower the flow rate, the more pronounced the influence of circuit resistance on hemolysis became. Numerical models validated against clinical data demonstrated a strong association (Spearman’s r = 0.8) between simulated and observed hemolysis, irrespective of the pump type.

Conclusions

Integrating in-silico predictions with clinical data provided a novel approach in understanding and potentially reducing blood trauma in VV ECMO. This study further demonstrated that a key factor in lowering side effects of ECMO support is the maintenance of low circuit resistance, including oxygenators with the lowest possible resistance, the shortest feasible circuit tubing, and cannulae with an optimal diameter.

 

A narrative review on antimicrobial dosing in adult critically ill patients on extracorporeal membrane oxygenation

Critical Care volume 28, Article number: 326, Published: 04 October 2024

Abstract

The optimal dosing strategy of antimicrobial agents in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) is unknown. We conducted comprehensive review of existing literature on effect of ECMO on pharmacokinetics and pharmacodynamics of antimicrobials, including antibacterials, antifungals, and antivirals that are commonly used in critically ill patients. We aim to provide practical guidance to clinicians on empiric dosing strategy for these patients. Finally, we discuss importance of therapeutic drug monitoring, limitations of current literature, and future research directions.

 

European Society of Intensive Care Medicine guidelines on end of life and palliative care in the intensive care unit

Intensive Care Med (2024). Published 03 October 2024

Abstract

The European Society of Intensive Care Medicine (ESICM) has developed evidence-based recommendations and expert opinions about end-of-life (EoL) and palliative care for critically ill adults to optimize patient-centered care, improving outcomes of relatives, and supporting intensive care unit (ICU) staff in delivering compassionate and effective EoL and palliative care. An international multi-disciplinary panel of clinical experts, a methodologist, and representatives of patients and families examined key domains, including variability across countries, decision-making, palliative-care integration, communication, family-centered care, and conflict management. Eight evidence-based recommendations (6 of low level of evidence and 2 of high level of evidence) and 19 expert opinions were presented. EoL legislation and the importance of respecting the autonomy and preferences of patients were given close attention. Differences in EoL care depending on country income and healthcare provision were considered. Structured EoL decision-making strategies are recommended to improve outcomes of patients and relatives, as well as staff satisfaction and mental health. Early integration of palliative care and the use of standardized tools for symptom assessment are suggested for patients at high risk of dying. Communication training for ICU staff and printed communication aids for families are advocated to improve outcomes and satisfaction. Methods for enhancing family-centeredness of care include structured family conferences and culturally sensitive interventions. Conflict-management protocols and strategies to prevent burnout among healthcare professionals are also considered. The work done to develop these guidelines highlights many areas requiring further research.

 

The Impact of Point-of-Care Ultrasound-Guided Resuscitation on Clinical Outcomes in Patients With Shock: A Systematic Review and Meta-Analysis

Critical Care Medicine 52(11):p 1661-1673, November 2024.

OBJECTIVE: 

To determine the impact of point-of-care ultrasound (POCUS)-guided resuscitation on clinical outcomes in adult patients with shock.

DATA SOURCE: 

We searched MEDLINE, Embase, and unpublished sources from inception to December 2023.

STUDY SELECTION: 

We included randomized controlled trials (RCTs) that examined the use of POCUS to guide resuscitation in patients with shock.

DATA EXTRACTION: 

We collected data regarding study and patient characteristics, POCUS protocol, control group interventions, and outcomes.

DATA SYNTHESIS: 

We identified 18 eligible RCTs. POCUS slightly influences physicians’ plans for IV fluid (IVF) and vasoactive medication prescription (moderate certainty), but results in little to no changes in the administration of IVF (low to high certainty) or inotropes (high certainty). POCUS may result in no change in the number of CT scans performed (low certainty) but probably reduces the number of diagnostic echocardiograms performed (moderate certainty). POCUS-guided resuscitation probably reduces 28-day mortality (relative risk [RR] 0.88; 95% CI, 0.78–0.99), the duration of vasoactive medication (mean difference –0.73 d; 95% CI, –1.16 to –0.30), and the need for renal replacement therapy (RRT) (RR 0.80; 95% CI, 0.63–1.02) (low to moderate certainty evidence), and lactate clearance (high certainty evidence). POCUS-guided resuscitation may results in little to no difference in ICU or hospital admissions, ICU and hospital length of stay, and the need for mechanical ventilation (MV) (low to moderate certainty evidence). There is an uncertain effect on the risk of acute kidney injury and the duration of MV or RRT (very low certainty evidence).

CONCLUSIONS: 

POCUS-guided resuscitation in shock may yield important patient and health system benefits. Due to lack of sufficient evidence, we were unable to explore how the thresholds of operator competency, frequency, and timing of POCUS scans impact patient outcomes.

 

Relationship between SARS-CoV-2 infection and ICU-acquired candidemia in critically ill medical patients: a multicenter prospective cohort study

Critical Care volume 28, Article number: 320, Published: 27 September 2024

Background

While SARS-CoV2 infection has been shown to be a significant risk-factor for several secondary bacterial, viral and Aspergillus infections, its impact on intensive care unit (ICU)-acquired candidemia (ICAC) remains poorly explored.

Method

Using the REA-REZO network (French surveillance network of ICU-acquired infections), we included all adult patients hospitalized for a medical reason of admission in participating ICUs for at least 48 h from January 2020 to January 2023. To account for confounders, a non-parsimonious propensity score matching was performed. Rates of ICAC according to SARS-CoV2 status were compared in matched patients. Factors associated with ICAC in COVID-19 patients were also assessed using a Fine-Gray model.

Results

A total of 55,268 patients hospitalized at least 48 h for a medical reason in 101 ICUs were included along the study period. Of those, 13,472 were tested positive for a SARS-CoV2 infection while 284 patients developed an ICAC. ICAC rate was higher in COVID-19 patients in both the overall population and the matched patients’ cohort (0.8% (107/13,472) versus 0.4% (173/41,796); p < 0.001 and 0.8% (93/12,241) versus 0.5% (57/12,241); p = 0.004, respectively). ICAC incidence rate was also higher in those patients (incidence rate 0.51 per 1000 patients-days in COVID-19 patients versus 0.32 per 1000 patients-days; incidence rate ratio: 1.58 [95% CI:1.08–2.35]; p = 0.018). Finally, patients with ICAC had a higher ICU mortality rate (49.6% versus 20.2%; p < 0.001).

Conclusion

In this large multicenter cohort of ICU patients, although remaining low, the rate of ICAC was higher among COVID-19 patients.

 

Impact of airway closure and lung collapse on inhaled nitric oxide effect in acute lung injury: an experimental study

Annals of Intensive Care  volume 14, Article number: 149, Published: 23 September 2024

Background

Efficacy of inhaled therapy such as Nitric Oxide (iNO) during mechanical ventilation may depend on airway patency. We hypothesized that airway closure and lung collapse, countered by positive end-expiratory pressure (PEEP), influence iNO efficacy. This could support the role of an adequate PEEP titration for inhalation therapy. The main aim of this study was to assess the effect of iNO with PEEP set above or below the airway opening pressure (AOP) generated by airway closure, on hemodynamics and gas exchange in swine models of acute respiratory distress syndrome. Fourteen pigs randomly underwent either bilateral or asymmetrical two-hit model of lung injury. Airway closure and lung collapse were measured with electrical impedance tomography as well as ventilation/perfusion ratio (V/Q). After AOP detection, the effect of iNO (10ppm) was studied with PEEP set randomly above or below regional AOP. Respiratory mechanics, hemodynamics, and gas-exchange were recorded.

Results

All pigs presented airway closure (AOP > 0.5cmH₂O) after injury. In bilateral injury, iNO was associated with an improved mean pulmonary pressure from 49 ± 8 to 42 ± 7mmHg; (p = 0.003), and ventilation/perfusion matching, caused by a reduction in pixels with low V/Q and shunt from 16%[IQR:13–19] to 9%[IQR:4–12] (p = 0.03) only at PEEP set above AOP. iNO had no effect on hemodynamics or gas exchange for PEEP below AOP (low V/Q 25%[IQR:16–30] to 23%[IQR:14–27]; p = 0.68). In asymmetrical injury, iNO improved pulmonary hemodynamics and ventilation/perfusion matching independently from the PEEP set. iNO was associated with improved oxygenation in all cases.

Conclusions

In an animal model of bilateral lung injury, PEEP level relative to AOP markedly influences iNO efficacy on pulmonary hemodynamics and ventilation/perfusion match, independently of oxygenation.