Critical Care Bulletin - March 2024

 

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections

 

Buetti, N., Tabah, A., Setti, N. et al. . 

 

Intensive Care Med (2024). Published: 18 March 2024

 

Purpose

The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI).

Methods

We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators.

Results

Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03–2.14] or within a few hours (OR 1.79, 95% CI 1.34–2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09–1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47–0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44–1.00) or within a few hours (OR 0.51, 95% CI 0.37–0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47–0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00–2.80), and decreasing HDI values were associated with 28-day mortality.

Conclusion

Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.

 

Effects of prone positioning on lung mechanical power components in patients with acute respiratory distress syndrome: a physiologic study

 

by Christoph Boesing, Joerg Krebs, Alice Marguerite Conrad, Matthias Otto, Grietje Beck, Manfred Thiel, Patricia R. M. Rocco, Thomas Luecke and Laura Schaefer 

 

Critical Care volume 28, Article number: 82 (2024) Published: 15 March 2024

 

Background

Prone positioning (PP) homogenizes ventilation distribution and may limit ventilator-induced lung injury (VILI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The static and dynamic components of ventilation that may cause VILI have been aggregated in mechanical power, considered a unifying driver of VILI. PP may affect mechanical power components differently due to changes in respiratory mechanics; however, the effects of PP on lung mechanical power components are unclear. This study aimed to compare the following parameters during supine positioning (SP) and PP: lung total elastic power and its components (elastic static power and elastic dynamic power) and these variables normalized to end-expiratory lung volume (EELV).

Methods

This prospective physiologic study included 55 patients with moderate to severe ARDS. Lung total elastic power and its static and dynamic components were compared during SP and PP using an esophageal pressure-guided ventilation strategy. In SP, the esophageal pressure-guided ventilation strategy was further compared with an oxygenation-guided ventilation strategy defined as baseline SP. The primary endpoint was the effect of PP on lung total elastic power non-normalized and normalized to EELV. Secondary endpoints were the effects of PP and ventilation strategies on lung elastic static and dynamic power components non-normalized and normalized to EELV, respiratory mechanics, gas exchange, and hemodynamic parameters.

Results

Lung total elastic power (median [interquartile range]) was lower during PP compared with SP (6.7 [4.9–10.6] versus 11.0 [6.6–14.8] J/min; P < 0.001) non-normalized and normalized to EELV (3.2 [2.1–5.0] versus 5.3 [3.3–7.5] J/min/L; P < 0.001). Comparing PP with SP, transpulmonary pressures and EELV did not significantly differ despite lower positive end-expiratory pressure and plateau airway pressure, thereby reducing non-normalized and normalized lung elastic static power in PP. PP improved gas exchange, cardiac output, and increased oxygen delivery compared with SP.

Conclusions

In patients with moderate to severe ARDS, PP reduced lung total elastic and elastic static power compared with SP regardless of EELV normalization because comparable transpulmonary pressures and EELV were achieved at lower airway pressures. This resulted in improved gas exchange, hemodynamics, and oxygen delivery.

 

Scrutinizing mechanical circulatory support in cardiogenic shock: Have we jumped the gun?

 

by Enzo Lüsebrink, Hugo Lanz and Holger Thiele 

 

Critical Care volume 28, Article number: 80 (2024) Published: 15 March 2024

 

 

Abstract

Despite increasing therapeutic options and disposable resources, cardiogenic shock (CS) remains a formidable condition with high mortality. Today, veno-arterial extracorporeal membrane oxygenation and microaxial flow devices (Impella, Abiomed, Danvers, USA) are established forms of mechanical circulatory support (MCS) in CS, with increasing application over the years. Despite this trend, incorporation into current ESC (Class IIa, evidence C) and AHA/ACC (Class IIa, evidence B-NR) guidelines is based nearly exclusively on observational results. Despite these recommendations and increasing application, current evidence from randomized controlled trials has not provided clear mortality benefit. Thus, reflection on current evidence is hereby justified.

 

Impact of COVID-19 on posttraumatic stress disorder in ICU survivors: a prospective observational comparative cohort study

 

by Pierre Kalfon, Wissam El-Hage, Marie-Agnès Geantot, Constance Favier, Laetitia Bodet-Contentin, Khaldoun Kuteifan, Pierre-Yves Olivier, Didier Thévenin, Julien Pottecher, Jullien Crozon-Clauzel, Bénédicte Mauchien, Arnaud Galbois, Roland de Varax, Sabine Valera, Philippe Estagnasie, Audrey Berric…

 

Critical Care volume 28, Article number: 77 (2024) Published: 14 March 2024

 

Background

Posttraumatic stress disorder (PTSD) after a stay in the intensive care unit (ICU) can affect one in five ICU survivors. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, admission to the ICU for COVID-19 was stressful due to the severity of this disease. This study assessed whether admission to the ICU for COVID-19 was associated with a higher prevalence of PTSD compared with other causes of ICU admission after adjustment for pre-ICU psychological factors.

Methods

This prospective observational comparative cohort study included 31 ICUs. Eligible patients were adult ICU survivors hospitalized during the first wave of COVID-19 pandemic in France, regardless of the reason for admission. The prevalence of presumptive diagnosis of PTSD at 6 months was assessed using the PTSD Checklist for DSM-5 (PCL-5). Sociodemographics, clinical data, history of childhood trauma (Childhood Trauma Questionnaire [CTQ]), and exposure to potentially traumatic events (Life Events Checklist for DSM-5 [LEC-5]) were assessed.

Results

Of the 778 ICU survivors included during the first wave of COVID-19 pandemic in France, 417 and 361 were assigned to the COVID-19 and non-COVID-19 cohorts, respectively. Fourteen (4.9%) and 11 (4.9%), respectively, presented with presumptive diagnosis of PTSD at 6 months (p = 0.976). After adjusting for age, sex, severity score at admission, use of invasive mechanical ventilation, ICU duration, CTQ and LEC-5, COVID-19 status was not associated with presumptive diagnosis of PTSD using the PCL-5. Only female sex was associated with presumptive diagnosis of PTSD. However, COVID-19 patients reported significantly more intrusion and avoidance symptoms than non-COVID patients (39% vs. 29%, p = 0.015 and 27% vs. 19%, p = 0.030), respectively. The median PCL-5 score was higher in the COVID-19 than non-COVID-19 cohort (9 [3, 20] vs. 4 [2, 16], p = 0.034).

Conclusion

Admission to the ICU for COVID-19 was not associated with a higher prevalence of PTSD compared with admission for another cause during the first wave of the COVID-19 pandemic in France. However, intrusion and avoidance symptoms were more frequent in COVID-19 patients than in non-COVID-19 patients.

 

Flow starvation during square-flow assisted ventilation detected by supervised deep learning techniques

 

by Candelaria de Haro, Verónica Santos-Pulpón, Irene Telías, Alba Xifra-Porxas, Carles Subirà, Montserrat Batlle, Rafael Fernández, Gastón Murias, Guillermo M. Albaiceta, Sol Fernández-Gonzalo, Marta Godoy-González, Gemma Gomà, Sara Nogales, Oriol Roca, Tai Pham, Josefina López-Aguilar…

 

Critical Care volume 28, Article number: 75 (2024) Published: 14 March 2024

 

Background

Flow starvation is a type of patient-ventilator asynchrony that occurs when gas delivery does not fully meet the patients’ ventilatory demand due to an insufficient airflow and/or a high inspiratory effort, and it is usually identified by visual inspection of airway pressure waveform. Clinical diagnosis is cumbersome and prone to underdiagnosis, being an opportunity for artificial intelligence. Our objective is to develop a supervised artificial intelligence algorithm for identifying airway pressure deformation during square-flow assisted ventilation and patient-triggered breaths.

Methods

Multicenter, observational study. Adult critically ill patients under mechanical ventilation > 24 h on square-flow assisted ventilation were included. As the reference, 5 intensive care experts classified airway pressure deformation severity. Convolutional neural network and recurrent neural network models were trained and evaluated using accuracy, precision, recall and F1 score. In a subgroup of patients with esophageal pressure measurement (ΔPes), we analyzed the association between the intensity of the inspiratory effort and the airway pressure deformation.

Results

6428 breaths from 28 patients were analyzed, 42% were classified as having normal-mild, 23% moderate, and 34% severe airway pressure deformation. The accuracy of recurrent neural network algorithm and convolutional neural network were 87.9% [87.6–88.3], and 86.8% [86.6–87.4], respectively. Double triggering appeared in 8.8% of breaths, always in the presence of severe airway pressure deformation. The subgroup analysis demonstrated that 74.4% of breaths classified as severe airway pressure deformation had a ΔPes > 10 cmH2O and 37.2% a ΔPes > 15 cmH2O.

Conclusions

Recurrent neural network model appears excellent to identify airway pressure deformation due to flow starvation. It could be used as a real-time, 24-h bedside monitoring tool to minimize unrecognized periods of inappropriate patient-ventilator interaction.

 

Diaphragm thickness modifications and associated factors during VA-ECMO for a cardiogenic shock: a cohort study

 

by Pierre-Henri Moury, Alexandre Béhouche, Sébastien Bailly, Zoé Durand, Géraldine Dessertaine, Angelina Pollet, Samir Jaber, Samuel Verges and Pierre Albaladejo 

 

Annals of Intensive Care volume 14, Article number: 38 (2024) Published: 08 March 2024

 

Background

The incidence, causes and impact of diaphragm thickness evolution in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock are unknown.

Our study investigates its evolution during the first week of VA-ECMO and its relationship with sweep gas flow settings.

Methods

We conducted a prospective monocentric observational study in a 12-bed ICU in France, enrolling patients on the day of the VA-ECMO implantation. The diaphragm thickness and the diaphragm thickening fraction (as index of contractile activity, dTF; dTF < 20% defined a low contractile activity) were daily measured for one week using ultrasound. Factors associated with diaphragm thickness evolution (categorized as increased, stable, or atrophic based on > 10% modification from baseline to the last measurement), early extubation role (< day4), and patients outcome at 60 days were investigated. Changes in diaphragm thickness, the primary endpoint, was analysed using a mixed-effect linear model (MLM).

Results

Of the 29 included patients, seven (23%) presented diaphragm atrophy, 18 remained stable (60%) and 4 exhibited an increase (17%). None of the 13 early-extubated patients experienced diaphragm atrophy, while 7 (46%) presented a decrease when extubated later (p-value = 0.008). Diaphragm thickness changes were not associated with the dTF (p-value = 0.13) but with sweep gas flow (Beta = − 3; Confidence Interval at 95% (CI) [− 4.8; − 1.2]. p-value = 0.001) and pH (Beta = − 2; CI [− 2.9; − 1]. p-value < 0.001) in MLM. The dTF remained low (< 20%) in 20 patients (69%) at the study’s end and was associated with sweep gas flow evolution in MLM (Beta = − 2.8; 95% CI [− 5.2; − 0.5], p-value = 0.017). Odds ratio of death at 60 days in case of diaphragm atrophy by day 7 was 8.50 ([1.4–74], p = 0.029).

Conclusion

In our study, diaphragm thickness evolution was frequent and not associated with the diaphragm thickening fraction. Diaphragm was preserved from atrophy in case of early extubation with ongoing VA-ECMO assistance. Metabolic disorders resulting from organ failures and sweep gas flow were linked with diaphragm thickness evolution. Preserved diaphragm thickness in VA-ECMO survivors emphasizes the importance of diaphragm-protective strategies, including meticulous sweep gas flow titration.

 

Immediate vs. culture-initiated antibiotic therapy in suspected non-severe ventilator-associated pneumonia: a before–after study (DELAVAP)

 

by Maëlle Martin, Solène Forveille, Jean-Baptiste Lascarrou, Amélie Seguin, Emmanuel Canet, Jérémie Lemarié, Maïté Agbakou, Luc Desmedt, Gauthier Blonz, Olivier Zambon, Stéphane Corvec, Aurélie Le Thuaut and Jean Reignier

 

Annals of Intensive Care volume 14, Article number: 33 (2024) Published: 27 February 2024

 

Background

Ventilator-associated pneumonia (VAP) is the leading nosocomial infection in critical care and is associated with adverse outcomes. When VAP is suspected, starting antibiotic therapy (AT) immediately after pulmonary sampling may expose uninfected patients to unnecessary treatment, whereas waiting for bacteriological confirmation may delay AT in infected patients. As no robust data exist to choose between these strategies, the decision must balance the pre-test diagnostic probability, clinical severity, and risk of antimicrobial resistance. The objective of this study in patients with suspected non-severe VAP was to compare immediate AT started after sampling to conservative AT upon receipt of positive microbiological results. The outcomes were antibiotic sparing, AT suitability, and patient outcomes.

Methods

This single-center, before–after study included consecutive patients who underwent distal respiratory sampling for a first suspected non-severe VAP episode (no shock requiring vasopressor therapy or severe acute respiratory distress syndrome). AT was started immediately after sampling in 2019 and upon culture positivity in 2022 (conservative strategy). The primary outcome was the number of days alive without AT by day 28. The secondary outcomes were mechanical ventilation duration, day-28 mortality, and AT suitability (active necessary AT or spared AT).

Results

The immediate and conservative strategies were applied in 44 and 43 patients, respectively. Conservative and immediate AT were associated with similar days alive without AT (median [interquartile range], 18.0 [0–21.0] vs. 16.0 [0–20.0], p = 0.50) and without broad-spectrum AT (p = 0.53) by day 28. AT was more often suitable in the conservative group (88.4% vs. 63.6%, p = 0.01), in which 27.9% of patients received no AT at all. No significant differences were found for mechanical ventilation duration (median [95%CI], 9.0 [6–19] vs. 9.0 [6–24] days, p = 0.65) or day-28 mortality (hazard ratio [95%CI], 0.85 [0.4–2.0], p = 0.71).

Conclusion

In patients with suspected non-severe VAP, waiting for microbiological confirmation was not associated with antibiotic sparing, compared to immediate AT. This result may be ascribable to low statistical power. AT suitability was better with the conservative strategy. None of the safety outcomes differed between groups. These findings would seem to allow a large, randomized trial comparing immediate and conservative AT strategies.

 

Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia

 

by Chel Hee Lee, Mohammad M. Banoei, Mariam Ansari, Matthew P. Cheng, Francois Lamontagne, Donald Griesdale, David E. Lasry, Koray Demir, Vinay Dhingra, Karen C. Tran, Terry Lee, Kevin Burns, David Sweet, John Marshall, Arthur Slutsky, Srinivas Murthy…

 

Critical Care volume 28, Article number: 63 (2024) Published: 27 February 2024

 

Rationale

Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair.

Objective

To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis.

Methods

We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC–MS/MS and DI-MS/MS analytical platforms.

Results

Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms.

Conclusion

Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.

 

Long-stay ICU patients with frailty: mortality and recovery outcomes at 6 months

 

by Hannah Wozniak, Tal Sarah Beckmann, Andre Dos Santos Rocha, Jérôme Pugin, Claudia-Paula Heidegger and Sara Cereghetti 

 

Annals of Intensive Care volume 14, Article number: 31 (2024) Published: 24 February 2024

 

Background

Prolonged intensive care unit (ICU) stay is associated with physical, cognitive, and psychological disabilities. The impact of baseline frailty on long-stay ICU patients remains uncertain. This study aims to investigate how baseline frailty influences mortality and post-ICU disability 6 months after critical illness in long-stay ICU patients.

Methods

In this retrospective cohort study, we assessed patients hospitalized for ≥ 7 days in the ICU between May 2018 and May 2021, following them for up to 6 months or until death. Based on the Clinical Frailty Scale (CFS) at ICU admissions, patients were categorized as frail (CFS ≥ 5), pre-frail (CFS 3–4) and non-frail (CFS 1–2). Kaplan–Meier curves and a multivariate Cox model were used to examine the association between frailty and mortality. At the 6 month follow-up, we assessed psychological, physical, cognitive outcomes, and health-related quality of life (QoL) using descriptive statistics and linear regressions.

Results

We enrolled 531 patients, of which 178 (33.6%) were frail, 200 (37.6%) pre-frail and 153 (28.8%) non-frail. Frail patients were older, had more comorbidities, and greater disease severity at ICU admission. At 6 months, frail patients presented higher mortality rates than pre-frail and non-frail patients (34.3% (61/178) vs. 21% (42/200) vs. 13.1% (20/153) respectively, p < 0.01). The rate of withdrawing or withholding of care did not differ significantly between the groups. Compared with CFS 1–2, the adjusted hazard ratios of death at 6 months were 1.7 (95% CI 0.9–2.9) for CFS 3–4 and 2.9 (95% CI 1.7–4.9) for CFS ≥ 5. At 6 months, 192 patients were seen at a follow-up consultation. In multivariate linear regressions, CFS ≥ 5 was associated with poorer physical health-related QoL, but not with poorer mental health-related QoL, compared with CFS 1–2.

Conclusion

Frailty is associated with increased mortality and poorer physical health-related QoL in long-stay ICU patients at 6 months. The admission CFS can help inform patients and families about the complexities of survivorship during a prolonged ICU stay.

 

Improving management of ARDS: uniting acute management and long-term recovery

 

by Nicola Latronico, M. Eikermann, E. W. Ely and D. M. Needham 

 

Critical Care volume 28, Article number: 58 (2024) Published: 23 February 2024

 

Acute Respiratory Distress Syndrome (ARDS) is an important global health issue with high in-hospital mortality. Importantly, the impact of ARDS extends beyond the acute phase, with increased mortality and disability for months to years after hospitalization. These findings underscore the importance of extended follow-up to assess and address the Post-Intensive Care Syndrome (PICS), characterized by persistent impairments in physical, cognitive, and/or mental health status that impair quality of life over the long-term. Persistent muscle weakness is a common physical problem for ARDS survivors, affecting mobility and activities of daily living. Critical illness and related interventions, including prolonged bed rest and overuse of sedatives and neuromuscular blocking agents during mechanical ventilation, are important risk factors for ICU-acquired weakness. Deep sedation also increases the risk of delirium in the ICU, and long-term cognitive impairment. Corticosteroids also may be used during management of ARDS, particularly in the setting of COVID-19. Corticosteroids can be associated with myopathy and muscle weakness, as well as prolonged delirium that increases the risk of long-term cognitive impairment. The optimal duration and dosage of corticosteroids remain uncertain, and there's limited long-term data on their effects on muscle weakness and cognition in ARDS survivors. In addition to physical and cognitive issues, mental health challenges, such as depression, anxiety, and post-traumatic stress disorder, are common in ARDS survivors. Strategies to address these complications emphasize the need for consistent implementation of the evidence-based ABCDEF bundle, which includes daily management of analgesia in concert with early cessation of sedatives, avoidance of benzodiazepines, daily delirium monitoring and management, early mobilization, and incorporation of family at the bedside. In conclusion, ARDS is a complex global health challenge with consequences extending beyond the acute phase. Understanding the links between critical care management and long-term consequences is vital for developing effective therapeutic strategies and improving the quality of life for ARDS survivors.

 

Extracorporeal cardiopulmonary resuscitation versus conventional CPR in cardiac arrest: an updated meta-analysis and trial sequential analysis

 

by Christopher Jer Wei Low, Ryan Ruiyang Ling, Kollengode Ramanathan, Ying Chen, Bram Rochwerg, Tetsuhisa Kitamura, Taku Iwami, Marcus Eng Hock Ong and Yohei Okada 

 

Critical Care volume 28, Article number: 57 (2024)  Published: 21 February 2024

 

Background

Extracorporeal cardiopulmonary resuscitation (ECPR) may reduce mortality and improve neurological outcomes in patients with cardiac arrest. We updated our existing meta-analysis and trial sequential analysis to further evaluate ECPR compared to conventional CPR (CCPR).

Methods

We searched three international databases from 1 January 2000 through 1 November 2023, for randomised controlled trials or propensity score matched studies (PSMs) comparing ECPR to CCPR in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). We conducted an updated random-effects meta-analysis, with the primary outcome being in-hospital mortality. Secondary outcomes included short- and long-term favourable neurological outcome and survival (30 days–1 year). We also conducted a trial sequential analysis to evaluate the required information size in the meta-analysis to detect a clinically relevant reduction in mortality.

Results

We included 13 studies with 14 pairwise comparisons (6336 ECPR and 7712 CCPR) in our updated meta-analysis. ECPR was associated with greater precision in reducing overall in-hospital mortality (OR 0.63, 95% CI 0.50–0.79, high certainty), to which the trial sequential analysis was concordant. The addition of recent studies revealed a newly significant decrease in mortality in OHCA (OR 0.62, 95% CI 0.45–0.84). Re-analysis of relevant secondary outcomes reaffirmed our initial findings of favourable short-term neurological outcomes and survival up to 30 days. Estimates for long-term neurological outcome and 90-day–1-year survival remained unchanged.

Conclusions

We found that ECPR reduces in-hospital mortality, improves neurological outcome, and 30-day survival. We additionally found a newly significant benefit in OHCA, suggesting that ECPR may be considered in both IHCA and OHCA.

 

 

Ketamine versus etomidate as an induction agent for tracheal intubation in critically ill adults: a Bayesian meta-analysis

 

by Takatoshi Koroki, Yuki Kotani, Takahiko Yaguchi, Taisuke Shibata, Motoki Fujii, Stefano Fresilli, Mayuko Tonai, Toshiyuki Karumai, Todd C. Lee, Giovanni Landoni and Yoshiro Hayashi 

 

Critical Care volume 28, Article number: 48 (2024)  Published: 17 February 2024

 

Background

Tracheal intubation is a high-risk intervention commonly performed in critically ill patients. Due to its favorable cardiovascular profile, ketamine is considered less likely to compromise clinical outcomes. This meta-analysis aimed to assess whether ketamine, compared with other agents, reduces mortality in critically ill patients undergoing intubation.

Methods

We searched MEDLINE, Embase, and the Cochrane Library from inception until April 27, 2023, for randomized controlled trials and matched observational studies comparing ketamine with any control in critically ill patients as an induction agent. The primary outcome was mortality at the longest follow-up available, and the secondary outcomes included Sequential Organ Failure Assessment score, ventilator-free days at day 28, vasopressor-free days at day 28, post-induction mean arterial pressure, and successful intubation on the first attempt. For the primary outcome, we used a Bayesian random-effects meta-analysis on the risk ratio (RR) scale with a weakly informative neutral prior corresponding to a mean estimate of no difference with 95% probability; the estimated effect size will fall between a relative risk of 0.25 and 4. The RR and 95% credible interval (CrI) were used to estimate the probability of mortality reduction (RR < 1). The secondary outcomes were assessed with a frequentist random-effects model. We registered this study in Open Science Framework (https://osf.io/2vf79/).

Results

We included seven randomized trials and one propensity-matched study totaling 2978 patients. Etomidate was the comparator in all the identified studies. The probability that ketamine reduced mortality was 83.2% (376/1475 [25%] vs. 411/1503 [27%]; RR, 0.93; 95% CrI, 0.79–1.08), which was confirmed by a subgroup analysis excluding studies with a high risk of bias. No significant difference was observed in any secondary outcomes.

Conclusions

All of the included studies evaluated ketamine versus etomidate among critically ill adults requiring tracheal intubation. This meta-analysis showed a moderate probability that induction with ketamine is associated with a reduced risk of mortality.