For patients in the intensive care unit (ICU), evidence-based treatment such as the ABCDEF bundle (1–4) and ICU diary (5), should be established as part of routine clinical practice because they are strongly linked not only to short-term outcomes of ICU patients (6, 7) but also their long-term function and quality of life (QOL) (8). Recent studies confirmed that the beneficial effects of the ABCDEF bundle are maximized when provided as a combination of elements or as the entire bundle (9, 10).

However, drastic changes in practice related to the COVID-19 pandemic, including unbalanced resources, overwhelmed facility capacity, and strict infectious regulations, occurred world-wide and prevented ICU staff from performing evidence-based approaches to patient care in ICUs (11). Our recent survey demonstrated low implementation rates of each element and the entire ABCDEDF bundle and other supportive ICU care for patients with COVID-19 infections in the ICU (12). We could not assess the total impact of COVID-19 in the ICU because of a lack of data on patients without COVID-19 infections. To overcome low implementation rates which result in poor outcomes of ICU patients (13), a number of studies proposed efficient ways associated with the ICU administrative structure and environment to promote evidence-based ICU care before the pandemic (14–16). Nonetheless, clinical data on promoting factors and barriers during the pandemic are lacking and these factors could vary when treating patients without or with COVID-19 infections because the policy of less physical contact in a short time while wearing protective personal equipment was generally enforced only for patients with COVID-19 infections. Moreover, low- and middle-income countries are more vulnerable to these resource-dependent changes (17).

Therefore, we conducted a 1-day point prevalence study, to investigate the implementation rate of evidence-based ICU care for both patients without and with COVID-19 infections and the impact of COVID-19 infections on implementation on a world-wide scale to capture the current clinical practice situation. We sought to identify ICU-related factors associated with implementation in the ICU.

This world-wide 1-day prevalence study demonstrates that implementation of the entire ABCDEF bundle, or its individual elements and an ICU diary for patients without and with COVID-19 infections is extremely low even though the implementation rate of specific individual elements of the ABCDEF bundle was different for the two groups. The presence of COVID-19 infection was not a factor preventing implementation. A variety of ICU-related factors were identified as independently associated facilitators or barriers for the implementation of the ABCDEF bundle, and these were different for each element, comparing patients without and with COVID-19 infections.

Implementation of the ABCDEF bundle is much lower in this study compared with that reported by a survey before the pandemic (13, 21), but similar to a survey conducted in the early stages of the COVID-19 pandemic on 3 June and 1 July 2020 (12) (Table 5). These results suggest that COVID-19 affects the care of not only patients with COVID-19 infections but also patients without COVID-19 infections and this effect may have been present since the beginning of the pandemic. Numerous studies strongly show that each element of the ABCDEF bundle or an ICU diary itself has a beneficial effect on patient outcomes (7, 22–26), while low and incomplete implementation can result in adverse outcomes including increased time of ventilatory support, longer ICU and hospital lengths of stay, increased incidence of delirium, functional disability, and increased medical costs and mortality (13, 27). Efficient ways to incorporate evidence-based ICU care into clinical practice during the pandemic are urgently needed. To note, the studies included in Table 5 had various methods to collect data, hence the simple comparison might lead to the misleading. Further and continuous international surveys with same methodology are necessary to follow the implementation rate of the ABCDEF bundle in future. In addition, studies to investigate the effects of the ABCDEF bundle and other evidence-based ICU care are expected.

Differences in the implementation of elements of the ABCDEF bundle might be caused by differences in underlying diseases and ICU length of stay between the two groups. Patients with COVID-19 infections, admitted to the ICU because of severe respiratory failure (28), need longer mechanical ventilation treatment with more sedation and require more intense sedation monitoring compared to patients without COVID-19 infections who have a variety of reasons for admission to the ICU but result in a shorter ICU length of stay. This might lead to more frequent implementation of element C for patients with COVID-19 infections. However, the deeply sedated state could result in non-implementation of element A as seen in patients with COVID-19 infections because few pain assessment tools can be used in heavily sedated patients. The strong respiratory drive and effort associated with COVID-19 infections could be a factor contributing to progression of lung injury (29–31) and could prevent conduct of SAT and SBT for patients with COVID-19 infection, to avoid further exacerbation of the lung injury. However, element F of the ABCDEF bundle was more frequently performed for patients with COVID-19 infections, especially using electronic devices (using a monitor such as phone/video). COVID-19 brought technological expansion in the fields of remote and tele-practice which have been applied to the COVID-19 situation (32). However, it might result in overlooking patients without COVID-19 infections who received less online benefits as shown in this survey, and also need involvement of their families. In the context of an increasing trend for implementation of element E (33, 34), COVID-19 brought it to a previous level, but into more resource-unbalanced and time-restricted settings. As the guideline suggests, it is important to note that evidence-based ICU care, such as the ABCDEF bundle and ICU diary, should be incorporated into clinical practice for all ICU patients regardless of their underlying diseases or the ICU length of stay (1–4, 16, 35).

After adjusting for the backgrounds of hospitals and ICUs and the baseline condition of patients, the presence of COVID-19 infection was not a barrier to the implementation of each element of the ABCDEF bundle. For elements D, E, and F, the presence of COVID-19 was significantly associated with their implementation. The warnings of high risk for and high incidence of delirium in the early stage of the pandemic may be a factor (36) or the use of online systems in patients with COVID-19 infections (32) might contribute to these results. In addition, this could be a strong message that the impact of the COVID-19 pandemic broadly affected patients without and with COVID-19 infections and special considerations are necessary to improve the quality of ICU care for both types of patients.

This study demonstrates the diversity of independent factors associated with the implementation of each element of the ABCDEF bundle in addition to variations comparing non-COVID-19 and COVID-19 settings. These results particularly show that a promising strategy to introduce or implement a specific element of the bundle in an ICU could vary and should be designed depending on the context and local situation in which it will be implemented. For many elements in the ABCDEF bundle, regardless of COVID-19 status, a specific protocol and presence of a target/goal for ICU care were consistently identified as facilitating independent factors. However, this study also showed the low frequency to equip the specific protocol in each ICU, or 50% or less, which could be considered as one of the major barriers to be managed regardless of the presence of COVID-19. As many studies successfully showed a pivotal role for implementation or introduction of ICU care, this simple, but not time- or resource-consuming approach could be a key stimulus and should be routine in the ICU to facilitate efficient implementation of evidence-based approaches to ICU care (12, 16, 37, 38). Tele-medicine, which is getting public interest and recommended in several elements such as elements E (39) and F (37, 40), could be also an alternative to promote implementation instead of strict regulations regarding infection control or family visits. This is a relatively novel field of intensive care. Therefore, the impact of tele-medicine on implementation of evidence-based ICU care and its effect on outcomes should be investigated in a large prospective cohort study or randomized controlled study. The professionals dedicated to the ICU and the individual with primary responsibility could be decided by a policy maker in the hospital or ICU director based on what is to be achieved (41–44). The income level, used as a resource barometer, might show that less resources prevent implementation of evidence-based approaches (17, 37, 45). Relatively resource-intense care, such as a 1:1 nurse-patient ratio and daily multidisciplinary rounds, were not independently associated with implementation of the ABCDEF bundle, consistent with a previous report (12). ICUs in lower income countries performed more element F in this survey. These countries might apply relatively flexible visiting hours, which was also detected as a facilitating factor for element F, for a family rather than being in a high-income country.

This study has several acknowledged limitations. First, the limited number of patients and participating countries (Japan accounts for 40%) could lead to selection bias and limit generalizability to other ICUs and countries. These numbers might not be enough for the multivariable analysis with a number of covariates. Although the survey date captured a peak in the wave in Japan (46), the status of the pandemic in each area could affect the results. In addition, some COVID-19 hotspots, such as the USA, Brazil, and Russia, were under-represented. Second, the nature of a point prevalence study does not define a causal relationship and reflects the overwhelming situation at participating sites. This point prevalence study took place entirely on 1 day. Third, potential confounding factors associated with implementation, such as disease-related factors, were not investigated. Finally, an odds ratio with a relatively broad confidence interval may indicate an unstable model created by multivariate analysis. For example, Tele-ICU availability and Visiting hours might not be suitable to be incorporated into the multivariable analysis. Interpreting the results into the clinical world needs cautions regarding these statistical aspects. Further investigation and observations are necessary to validate these results.

Though having a COVID-19 infection was not associated with a failure to implement evidence-based ICU care, the implementation rates for the entire ABCDEF bundle, each of its elements and the ICU diary for patients without and with COVID-19 infections, were various, but extremely low on the whole regardless of the presence of COVID-19 infection. Since the impact of the COVID-19 pandemic on evidence-based ICU care varies depending on the conditions in each ICU, strategies to facilitate the implementation of each element of the ABCDEF bundle must be tailored to each institution.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Ethics Committee of the Saiseikai Utsunomiya Hospital. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.

KL, KN, HK, PN, EE, SK, KT, SI, and ON: study conception and design. KL, KN, HK, PN, EE, SK, and KT: statistical analysis or interpretation of data and drafting the manuscript. KN, HK, ME, PN, EE, SK, KT, MG, BL, CC, JB, SI, AL, and ON: critical review and revision of the manuscript for important intellectual insight. PN, EE, SK, KT, SI, AL, and ON: study supervision. KL, KN, HK, ME, PN, EE, SK, MG, BL, CC, JB, SI, and ON: recruitment the participating ICUs in overseas countries. KN confirmed that all authors meet authorship criteria according to ICMJE. All authors drafted the manuscript for important intellectual content, contributed to revision of the final version of the manuscript, approved the final version submitted, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

KL reports personal fees from MERA and receives a salary from TXP Medical completely outside the submitted work. KN reports personal fees from Abbott Laboratory, Nestle, TERUMO, GETINGE, Asahi Kasei Pharma, Ono Pharmaceutical, Japan Blood Products Organization, Nihon Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Toray, and Baxter, and grants from Asahi Kasei Pharma outside the submitted work. HK receives a salary from the Japanese Society for Early Mobilization (non-profit society) as a chair (full time) outside the submitted work. EE reports grants from the VA/NIH; personal fees from Pfizer, Orion, and Lilly; personal fees from Masimo; and grants from Kohler outside the submitted work. SI reports personal fees from MERA, Abbott Laboratory, Teijin Pharma, Nestle, and Nihon Pharmaceutical. ON reports grants from Asahi Kasei Pharma, Ono Pharmaceutical, Baxter, Maruishi Pharmaceutical, Torii Pharmaceutical, Teijin Pharma, Shionogi Pharmaceutical, and Fuso Pharmaceutical outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.