Critical Care Bulletin: July 2022

 

Time-varying intensity of oxygen exposure is associated with mortality in critically ill patients with mechanical ventilation

 

by Zhu Zhu, Mingqin Zhou, Yao Wei and Hui Chen 

 

Critical Care volume 26, Article number: 239 (2022) Published: 05 August 2022

 

Background

There is no consensus exists regarding the association between oxygen exposure (arterial oxygen tension or fraction of inspired oxygen) and outcomes for patients with mechanical ventilation. Additionally, whether the association remains persistent over time is unknown. We aimed to explore the association between exposure to different intensities of oxygen exposure over time and 28-day mortality in patients with mechanical ventilation.

Methods

We obtained data from the Medical Information Mart for Intensive Care IV (MIMIC-IV), which included adult (≥ 18 years) patients who received invasive mechanical ventilation for at least 48 h. We excluded patients who received extracorporeal membrane oxygenation (ECMO) or who initiated ventilation more than 24 h after ICU admission. The primary outcome was 28-day mortality. Piece-wise exponential additive mixed models were employed to estimate the strength of associations over time.

Results

A total of 7784 patients were included in the final analysis. Patients had a median duration of invasive mechanical ventilation of 8.1 days (IQR: 3.8–28 days), and the overall 28-day mortality rate was 26.3%. After adjustment for baseline and time-dependent confounders, both daily time-weighted average (TWA) arterial oxygen tension (PaO2) and fraction of inspired oxygen (FiO2) were associated with increased 28-day mortality, and the strength of the association manifested predominantly in the early-middle course of illness. A significant increase in the hazard of death was found to be associated with daily exposure to TWA-PaO2 ≥ 120 mmHg (Hazard ratio 1.166, 95% CI 1.059–1.284) or TWA-FiO2 ≥ 0.5 (Hazard ratio 1.496, 95% CI 1.363–1.641) during the entire course. A cumulative effect of harmful exposure (TWA-PaO2 ≥ 120 mmHg or TWA-FiO2 ≥ 0.5) was also observed.

Conclusion

PaO2 and FiO2 should be carefully monitored in patients with mechanical ventilation, especially during the early-middle course after ICU admission. Cumulative exposure to higher intensities of oxygen exposure was associated with an increased risk of death.

 

Influence of temperature management at 33 °C versus normothermia on survival in patients with vasopressor support after out-of-hospital cardiac arrest: a post hoc analysis of the TTM-2 trial

 

by Joachim Düring, Martin Annborn, Alain Cariou, Michelle S. Chew, Josef Dankiewicz, Hans Friberg, Matthias Haenggi, Zana Haxhija, Janus C. Jakobsen, Halvor Langeland, Fabio Silvio Taccone, Matthew Thomas, Susann Ullén, Matt P. Wise and Niklas Nielsen 

 

Critical Care volume 26, Article number: 231 (2022)  Published: 31 July 2022

 

Background

Targeted temperature management at 33 °C (TTM33) has been employed in effort to mitigate brain injury in unconscious survivors of out-of-hospital cardiac arrest (OHCA). Current guidelines recommend prevention of fever, not excluding TTM33. The main objective of this study was to investigate if TTM33 is associated with mortality in patients with vasopressor support on admission after OHCA.

Methods

We performed a post hoc analysis of patients included in the TTM-2 trial, an international, multicenter trial, investigating outcomes in unconscious adult OHCA patients randomized to TTM33 versus normothermia. Patients were grouped according to level of circulatory support on admission: (1) no-vasopressor support, mean arterial blood pressure (MAP) ≥ 70 mmHg; (2) moderate-vasopressor support MAP < 70 mmHg or any dose of dopamine/dobutamine or noradrenaline/adrenaline dose ≤ 0.25 µg/kg/min; and (3) high-vasopressor support, noradrenaline/adrenaline dose > 0.25 µg/kg/min. Hazard ratios with TTM33 were calculated for all-cause 180-day mortality in these groups.

Results

The TTM-2 trial enrolled 1900 patients. Data on primary outcome were available for 1850 patients, with 662, 896, and 292 patients in the, no-, moderate-, or high-vasopressor support groups, respectively. Hazard ratio for 180-day mortality was 1.04 [98.3% CI 0.78–1.39] in the no-, 1.22 [98.3% CI 0.97–1.53] in the moderate-, and 0.97 [98.3% CI 0.68–1.38] in the high-vasopressor support groups with regard to TTM33. Results were consistent in an imputed, adjusted sensitivity analysis.

Conclusions

In this exploratory analysis, temperature control at 33 °C after OHCA, compared to normothermia, was not associated with higher incidence of death in patients stratified according to vasopressor support on admission.

 

Electrical Impedance Tomography in Acute Respiratory Distress Syndrome Management

 

by Jimenez, Jose Victor; Weirauch, Andrew J.; Culter, Christopher A.; Choi, Philip J.; Hyzy, Robert C.

 

Critical Care Medicine: August 2022 - Volume 50 - Issue 8 - p 1210-1223

 

OBJECTIVE: To describe, through a narrative review, the physiologic principles underlying electrical impedance tomography, and its potential applications in managing 

acute respiratory distress syndrome (ARDS). To address the current evidence supporting its use in different clinical scenarios along the ARDS management continuum.

DATA SOURCES: We performed an online search in Pubmed to review articles. We searched MEDLINE, Cochrane Central Register, and clinicaltrials.gov for controlled trials databases.

STUDY SELECTION: Selected publications included case series, pilot-physiologic studies, observational cohorts, and randomized controlled trials. To describe the rationale underlying physiologic principles, we included experimental studies.

DATA EXTRACTION: Data from relevant publications were reviewed, analyzed, and its content summarized.

DATA SYNTHESIS: Electrical impedance tomography is an imaging technique that has aided in understanding the mechanisms underlying multiple interventions used in ARDS management. It has the potential to monitor and predict the response to prone positioning, aid in the dosage of flow rate in high-flow nasal cannula, and guide the titration of positive-end expiratory pressure during invasive mechanical ventilation. The latter has been demonstrated to improve physiologic and mechanical parameters correlating with lung recruitment. Similarly, its use in detecting pneumothorax and harmful patient-ventilator interactions such as pendelluft has been proven effective. Nonetheless, its impact on clinically meaningful outcomes remains to be determined.

CONCLUSIONS: Electrical impedance tomography is a potential tool for the individualized management of ARDS throughout its different stages. Clinical trials should aim to determine whether a specific approach can improve clinical outcomes in ARDS management.

 

 

 

Long-term cognitive functioning is impaired in ICU-treated COVID-19 patients: a comprehensive controlled neuropsychological study

 

by Henriikka Ollila, Riikka Pihlaja, Sanna Koskinen, Annamari Tuulio-Henriksson, Viljami Salmela, Marjaana Tiainen, Laura Hokkanen and Johanna Hästbacka 

 

Critical Care volume 26, Article number: 223 (2022) Published: 20 July 2022

 

Background

Cognitive impairment has emerged as a common post-acute sequela of coronavirus disease 2019 (COVID-19). We hypothesised that cognitive impairment exists in patients after COVID-19 and that it is most severe in patients admitted to the intensive care unit (ICU).

Methods

This prospective controlled cohort study of 213 participants performed at the Helsinki University Hospital and the University of Helsinki, Finland, comprised three groups of patients—ICU-treated (n = 72), ward-treated (n = 49), and home-isolated (n = 44)—with confirmed COVID-19 between March 13 and December 31, 2020, participating in a comprehensive neuropsychological evaluation six months after the acute phase. Our study included a control group with no history of COVID-19 (n = 48). Medical and demographic data were collected from electronic patient records and interviews carried out four months after the acute phase. Questionnaires filled six months after the acute phase provided information about change in cognitive functioning observed by a close informant, as well as the presence of self-reported depressive and post-traumatic symptoms.

Results

The groups differed (effect size η2p = 0.065, p = 0.004) in the total cognitive score, calculated from neuropsychological measures in three domains (attention, executive functions, and memory). Both ICU-treated (p = 0.011) and ward-treated patients (p = 0.005) performed worse than home-isolated patients. Among those with more than 12 years of education, ICU-treated patients performed worse in the attention domain than ward-treated patients (p = 0.021) or non-COVID controls (p = 0.045); ICU-treated male patients, in particular, were impaired in executive functions (p = 0.037).

Conclusions

ICU-treated COVID-19 patients, compared to patients with less severe acute COVID-19 or non-COVID controls, showed more severe long-term cognitive impairment. Among those with more than 12 years of education, impairment existed particularly in the domains of attention and for men, of executive functions.

 

Improving the intensive care experience from the perspectives of different stakeholders

 

by Jos M. Latour, Nancy Kentish-Barnes, Theresa Jacques, Marc Wysocki, Elie Azoulay and Victoria Metaxa 

 

Critical Care volume 26, Article number: 218 (2022)  Published: 18 July 2022

 

 

The intensive care unit (ICU) is a complex environment where patients, family members and healthcare professionals have their own personal experiences. Improving ICU experiences necessitates the involvement of all stakeholders. This holistic approach will invariably improve the care of ICU survivors, increase family satisfaction and staff wellbeing, and contribute to dignified end-of-life care. Inclusive and transparent participation of the industry can be a significant addition to develop tools and strategies for delivering this holistic care. We present a report, which follows a round table on ICU experience at the annual congress of the European Society of Intensive Care Medicine. The aim is to discuss the current evidence on patient, family and healthcare professional experience in ICU is provided, together with the panel’s suggestions on potential improvements. Combined with industry, the perspectives of all stakeholders suggest that ongoing improvement of ICU experience is warranted.

 

Oxygenation versus driving pressure for determining the best positive end-expiratory pressure in acute respiratory distress syndrome

 

by Saida Rezaiguia-Delclaux, Léo Ren, Aurélie Gruner, Calypso Roman, Thibaut Genty and François Stéphan 

 

Critical Care volume 26, Article number: 214 (2022)  Published: 13 July 2022

 

Objective

The aim of this prospective longitudinal study was to compare driving pressure and absolute PaO2/FiO2 ratio in determining the best positive end-expiratory pressure (PEEP) level.

Patients and methods

In 122 patients with acute respiratory distress syndrome, PEEP was increased until plateau pressure reached 30 cmH2O at constant tidal volume, then decreased at 15-min intervals, to 15, 10, and 5 cmH2O. The best PEEP by PaO2/FiO2 ratio (PEEPO2) was defined as the highest PaO2/FiO2 ratio obtained, and the best PEEP by driving pressure (PEEPDP) as the lowest driving pressure. The difference between the best PEEP levels was compared to a non-inferiority margin of 1.5 cmH2O.

Main results

The best mean PEEPO2 value was 11.9 ± 4.7 cmH2O compared to 10.6 ± 4.1 cmH2O for the best PEEPDP: mean difference = 1.3 cmH2O (95% confidence interval [95% CI], 0.4–2.3; one-tailed P value, 0.36). Only 46 PEEP levels were the same with the two methods (37.7%; 95% CI 29.6–46.5). PEEP level was ≥ 15 cmH2O in 61 (50%) patients with PEEPO2 and 39 (32%) patients with PEEPDP (P = 0.001).

Conclusion

Depending on the method chosen, the best PEEP level varies. The best PEEPDP level is lower than the best PEEPO2 level. Computing driving pressure is simple, faster and less invasive than measuring PaO2. However, our results do not demonstrate that one method deserves preference over the other in terms of patient outcome.

 

 

Association of vancomycin plus piperacillin–tazobactam with early changes in creatinine versus cystatin C in critically ill adults: a prospective cohort study

Intensive Care Medicine (2022) Published: 14 July 2022

 

Purpose

Although dozens of studies have associated vancomycin + piperacillin–tazobactam with increased acute kidney injury (AKI) risk, it is unclear whether the association represents true injury or a pseudotoxicity characterized by isolated effects on creatinine secretion. We tested this hypothesis by contrasting changes in creatinine concentration after antibiotic initiation with changes in cystatin C concentration, a kidney biomarker unaffected by tubular secretion.

Methods

We included patients enrolled in the Molecular Epidemiology of SepsiS in the ICU (MESSI) prospective cohort who were treated for ≥ 48 h with vancomycin + piperacillin–tazobactam or vancomycin + cefepime. Kidney function biomarkers [creatinine, cystatin C, and blood urea nitrogen (BUN)] were measured before antibiotic treatment and at day two after initiation. Creatinine-defined AKI and dialysis were examined through day-14, and mortality through day-30. Inverse probability of treatment weighting was used to adjust for confounding. Multiple imputation was used to impute missing baseline covariates.

Results

The study included 739 patients (vancomycin + piperacillin–tazobactam n = 297, vancomycin + cefepime n = 442), of whom 192 had cystatin C measurements. Vancomycin + piperacillin–tazobactam was associated with a higher percentage increase of creatinine at day-two 8.04% (95% CI 1.21, 15.34) and higher incidence of creatinine-defined AKI: rate ratio (RR) 1.34 (95% CI 1.01, 1.78). In contrast, vancomycin + piperacillin–tazobactam was not associated with change in alternative biomarkers: cystatin C: − 5.63% (95% CI − 18.19, 8.86); BUN: − 4.51% (95% CI − 12.83, 4.59); or clinical outcomes: dialysis: RR 0.63 (95% CI 0.31, 1.29); mortality: RR 1.05 (95%CI 0.79, 1.41).

Conclusions

Vancomycin + piperacillin–tazobactam was associated with creatinine-defined AKI, but not changes in alternative kidney biomarkers, dialysis, or mortality, supporting the hypothesis that vancomycin + piperacillin–tazobactam effects on creatinine represent pseudotoxicity.

 

Patient Harm and Institutional Avoidability of Out-of-Hours Discharge From Intensive Care: An Analysis Using Mixed Methods*

 

by Vollam, Sarah; Gustafson, Owen; Morgan, Lauren; Pattison, Natalie; Thomas, Hilary; Watkinson, Peter 

 

Critical Care Medicine: July 2022 - Volume 50 - Issue 7 - p 1083-1092

 

OBJECTIVES: Out-of-hours discharge from ICU to the ward is associated with increased in-hospital mortality and ICU readmission. Little is known about why this occurs. We map the discharge process and describe the consequences of out-of-hours discharge to inform practice changes to reduce the impact of discharge at night.

 DESIGN: This study was part of the REcovery FoLlowing intensive CarE Treatment mixed methods study. We defined out-of-hours discharge as 16:00 to 07:59 hours. We undertook 20 in-depth case record reviews where in-hospital death after ICU discharge had been judged “probably avoidable” in previous retrospective structured judgment reviews, and 20 where patients survived. We conducted semistructured interviews with 55 patients, family members, and staff with experience of ICU discharge processes. These, along with a stakeholder focus group, informed ICU discharge process mapping using the human factors–based functional analysis resonance method.

SETTING: Three U.K. National Health Service hospitals, chosen to represent different hospital settings.

SUBJECTS: Patients discharged from ICU, their families, and staff involved in their care. INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Out-of-hours discharge was common. Patients and staff described out-of-hours discharge as unsafe due to a reduction in staffing and skill mix at night. Patients discharged out-of-hours were commonly discharged prematurely, had inadequate handover, were physiologically unstable, and did not have deterioration recognized or escalated appropriately. We identified five interdependent function keys to facilitating timely ICU discharge: multidisciplinary team decision for discharge, patient prepared for discharge, bed meeting, bed manager allocation of beds, and ward bed made available.

CONCLUSIONS: We identified significant limitations in out-of-hours care provision following overnight discharge from ICU. Transfer to the ward before 16:00 should be facilitated where possible. Our work highlights changes to help make day time discharge more likely. Where discharge after 16:00 is unavoidable, support systems should be implemented to ensure the safety of patients discharged from ICU at night.

 

 

The gut–liver axis in sepsis: interaction mechanisms and therapeutic potential

 

by Xue Zhang, Hong Liu, Kenji Hashimoto, Shiying Yuan and Jiancheng Zhang 

 

Critical Care volume 26, Article number: 213 (2022) Published: 13 July 2022

 

Sepsis is a potentially fatal condition caused by dysregulation of the body's immune response to an infection. Sepsis-induced liver injury is considered a strong independent prognosticator of death in the critical care unit, and there is anatomic and accumulating epidemiologic evidence that demonstrates intimate cross talk between the gut and the liver. Intestinal barrier disruption and gut microbiota dysbiosis during sepsis result in translocation of intestinal pathogen-associated molecular patterns and damage-associated molecular patterns into the liver and systemic circulation. The liver is essential for regulating immune defense during systemic infections via mechanisms such as bacterial clearance, lipopolysaccharide detoxification, cytokine and acute-phase protein release, and inflammation metabolic regulation. When an inappropriate immune response or overwhelming inflammation occurs in the liver, the impaired capacity for pathogen clearance and hepatic metabolic disturbance can result in further impairment of the intestinal barrier and increased disruption of the composition and diversity of the gut microbiota. Therefore, interaction between the gut and liver is a potential therapeutic target. This review outlines the intimate gut–liver cross talk (gut–liver axis) in sepsis.

 

Imaging the acute respiratory distress syndrome: past, present and future

 

Intensive Care Medicine volume 48, pages 995–1008 (2022) Published: 14 July 2022

 

In patients with the acute respiratory distress syndrome (ARDS), lung imaging is a fundamental tool in the study of the morphological and mechanistic features of the lungs. Chest computed tomography studies led to major advances in the understanding of ARDS physiology. They allowed the in vivo study of the syndrome’s lung features in relation with its impact on respiratory physiology and physiology, but also explored the lungs’ response to mechanical ventilation, be it alveolar recruitment or ventilator-induced lung injuries. Coupled with positron emission tomography, morphological findings were put in relation with ventilation, perfusion or acute lung inflammation. Lung imaging has always been central in the care of patients with ARDS, with modern point-of-care tools such as electrical impedance tomography or lung ultrasounds guiding clinical reasoning beyond macro-respiratory mechanics. Finally, artificial intelligence and machine learning now assist imaging post-processing software, which allows real-time analysis of quantitative parameters that describe the syndrome’s complexity. This narrative review aims to draw a didactic and comprehensive picture of how modern imaging techniques improved our understanding of the syndrome, and have the potential to help the clinician guide ventilatory treatment and refine patient prognostication.

 

Bleeding and thrombotic events in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study

 

Intensive Care Medicine volume 48, pages 1039–1052 (2022) Published: 13 July 2022

 

Purpose

To describe bleeding and thrombotic events and their risk factors in patients receiving extracorporeal membrane oxygenation (ECMO) for severe 

coronavirus disease 2019

 (COVID-19) and to evaluate their impact on in-hospital mortality.

Methods

The ECMOSARS registry included COVID-19 patients supported by ECMO in France. We analyzed all patients included up to March 31, 2022 without missing data regarding bleeding and thrombotic events. The association of bleeding and thrombotic events with in-hospital mortality and pre-ECMO variables was assessed using multivariable logistic regression models.

Results

Among 620 patients supported by ECMO, 29% had only bleeding events, 16% only thrombotic events and 20% both bleeding and thrombosis. Cannulation site (18% of patients), ear nose and throat (12%), pulmonary bleeding (9%) and intracranial hemorrhage (8%) were the most frequent bleeding types. Device-related thrombosis and pulmonary embolism/thrombosis accounted for most of thrombotic events. In-hospital mortality was 55.7%. Bleeding events were associated with in-hospital mortality (adjusted odds ratio (adjOR) = 2.91[1.94–4.4]) but not thrombotic events (adjOR = 1.02[0.68–1.53]). Intracranial hemorrhage was strongly associated with in-hospital mortality (adjOR = 13.5[4.4–41.5]). Ventilation duration before ECMO ≥ 7 days and length of ECMO support were associated with bleeding. Thrombosis-associated factors were fibrinogen ≥ 6 g/L and length of ECMO support.

Conclusions

In a nationwide cohort of COVID-19 patients supported by ECMO, bleeding incidence was high and associated with mortality. Intracranial hemorrhage incidence was higher than reported for non-COVID patients and carried the highest risk of death. Thrombotic events were less frequent and not associated with mortality. Length of ECMO support was associated with a higher risk of both bleeding and thrombosis, supporting the development of strategies to minimize ECMO duration.