Sedation is a common practice in the Intensive Care Unit (ICU), though its overuse (doses higher than those needed by the patient) leads to oversedation with adverse effects such as increase duration of mechanical ventilation (MV), prolonged ICU stay, and delirium.1,2 To minimize these adverse effects, the eCASH (early Comfort using Analgesia, minimal Sedatives and maximal Humane care) approach emphasizes early patient comfort, minimizing sedative use and promoting humane care.3–5 The goal is to keep the patient awake, to minimize sedation and keep it as short as possible, and to avoid the use of benzodiazepines to improve the outcomes in the ICU.6–8 Campaigns have been proposed to prevent oversedation in the ICU, to ensure patient comfort without compromising safety, and to improve the efficiency of bed management.2

Chamorro et al. recommended not to “turn off the brain” unless absolutely necessary, and for the shortest time possible, to avoid oversedation and its adverse effects.9 A decrease in brain activity can alter neurotransmitter balance, increasing neuronal apoptosis and cerebral inflammation, which in turn can induce patient delirium and cognitive impairment. Thus, objective monitoring of the level of sedation is essential in patients requiring deep sedation.

Deep sedation is a risk factor for the development of delirium during hospital admission.10 Delirium, characterized by acute and fluctuating alterations in consciousness and the thinking process, is a common problem in the ICU, affecting up to 80% of all patients undergoing MV.11–13 It is associated with a number of adverse effects including a prolongation of MV, increased mortality, long-term cognitive impairment, and an increased risk of functional disability.14 Furthermore, patients who have received infusions of sedatives and opioids for prolonged periods are at a risk for iatrogenic withdrawal syndrome in the ICU and its associated problems.15

Against this background, the analgosedation and delirium guidelines of the American Society of Critical Care Medicine (SCCM) and the Pan-American and Iberian Federation of Critical Care Medicine and Intensive Care (FEPIMCTI) provide recommendations for the optimal management of analgosedation and delirium in critically ill patients.16,17 The ABCDEF bundle of measures, developed by the SCCM (A: Assess, prevent and manage pain; B: Withdraw sedation and perform spontaneous breathing tests; C: Choice of analgesia and sedation; D: Assess, prevent and manage delirium; E: Early mobility and exercise; F: Family engagement and empowerment), provides an operational framework for implementing such recommendations, with ample evidence of their positive impact upon the outcomes of critical patients.18,19 Despite the familiarity of these measures, their adoption is limited, and the COVID-19 pandemic has even further complicated their implementation, with a negative impact upon analgosedation practices.20–25

Based on the hypothesis that there was a worsening of these practices during the pandemic, with increased oversedation, and that such poor practices persisted after the pandemic, the present study was conducted to assess ICU physician’s perceptions of analgosedation and delirium practices in the Pan-American and Iberian setting before, during and after the COVID-19 pandemic, and to identify the factors associated with persistent oversedation after the pandemic.

The COVID-19 pandemic led to the widespread use of deep sedation strategies in patients with acute respiratory failure requiring MV due to viral pneumonia and acute respiratory distress syndrome (ARDS).28 This practice continued after the pandemic, although 25.9% of respondents considered that the patients were sedated more than necessary during this period. Other studies have reported similar findings. The main risk factor for post-pandemic oversedation, with an OR of 3.1, was found to be the continuation of the deep sedation habits acquired during the pandemic, replacing previous strategies such as the ABCDEF bundle.

The literature highlights the dangers of oversedation, especially when used early, and continuing into the post-pandemic period.29–31 Stephens et al. found early deep sedation in patients undergoing MV for COVID-19 with high benzodiazepine use was associated with increased mortality (aOR 3.44, 95%CI 1.65–7.17, P < .01).26 These authors reported that approximately 70% of the COVID-19 patients undergoing MV received early deep sedation, which was associated with poorer outcomes including fewer ventilator-free days, longer hospital stay and increased mortality.

Additional factors described in other studies, such as the type of hospital (public or private), the number of hospital and ICU beds, or centers with university teaching and critical care training activities, were analyzed but not found to be associated with post-pandemic oversedation in the present study.32–35 In contrast, the nurse-to-patient ratio and the presence of physiotherapists showed a significant association with oversedation, highlighting the importance of ensuring an adequate ratio of health care staff per patient, as reported in previous studies.36

An important and novel observation in our study was the important variability in perceived oversedation among the different geographic regions involved (P < .001). In this regard, 35% of the participants in South America considered that patients were oversedated after the pandemic, compared to 19% in Europe and 15% in North America. These data, which are the first to describe these geographic differences, may reflect a lack of appropriate sedation protocols that prioritize mild sedation, inadequate implementation of the protocols, a lack of adequate monitoring, reduced availability of sedative drugs, and a lack of trained personnel.1

From the pharmacological perspective, global shortages and the need to use the available drugs led to overuse of benzodiazepines and opioids, especially midazolam (19% versus 32%, P = .001), which in turn was associated with post-pandemic oversedation. Oversedation with hypnotic benzodiazepines during the pandemic had a negative impact on patient prognosis, particularly in terms of length of stay and mortality after adjustment for the SOFA score.33–35 The use of benzodiazepines in critically ill patients undergoing MV has been associated with adverse events such as delayed awakening and extubation, prolonged ICU and hospital stay, increased delirium, cognitive impairment and post-ICU syndrome.37–39 Current recommendations emphasize the importance of prioritizing non-benzodiazepine drugs.29,40–44

Another important finding in our study was the association between analgosedation monitoring before the pandemic and the perception of oversedation after the pandemic, which again emphasizes the importance of monitoring in order to ensure adequate management of analgosedation. Analgesia onitoring by the nursing staff (P = .008), the monitoring of the sedation level (P = .02) and its frequency (P = .03), as well as the use of continuous electroencephalography (P = .006) before the pandemic were associated with less oversedation after the pandemic.

These data are consistent with current scientific evidence, which suggests that frequent monitoring of pain and sedation levels using validated scales on a frequent basis is considered to be essential in order to avoid oversedation and adverse events.16 More recently, an expert consensus has recognized the utility of continuous electroencephalography to guide sedation in adult critically ill patients and recommends its use in all patients undergoing deep sedation (whether or not they are undergoing NMB), when clinical assessment is not possible.45

Another important factor in preventing oversedation and adverse events is adherence to the ABCDEF bundle.46 In our study, adherence to the analgosedation protocol before the pandemic was 60%, rising to 80% for targeted analgosedation and to 90% for mild sedation protocols. These figures indicate a high degree of adherence compared with other studies.47–49 These practices in turn were significantly correlated with lower perceptions of oversedation after the pandemic.50–52

Adherence to the ABCDEF bundle varied across geographical settings. In this regard, the literature describes considerable heterogeneity in different studies, generally reporting poor adherence, with many barriers and facilitating factors.52–54 The pandemic exacerbated the challenges, with work overload and a lack of qualified staff being the main barriers.20 In 2019, Carboni Bisso et al. conducted a study to determine the scope and application of these measures in Argentina. The authors found that despite awareness of the bundle of measures, adherence to them was irregular.55 The same group developed a similar questionnaire during the pandemic and found that the conditions of lockdown and work overload were critical in explaining the limitations in applying the ABCDEF bundle. These observations are consistent with our findings, which point to the important workload of the healthcare staff involved, the lack of experience in caring for critical patients, the fear of the isolation measures to avoid infection among the staff, and safety concerns such as self-extubation or orotracheal tube migration.20 In the SAMDS-ICU study, Luz et al. evaluated the use of the bundle of measures before and during the COVID-19 pandemic, and found that many of the practices were not maintained during the pandemic. The main challenges to adherence to the measures were found to be work overload among the health care staff and a reduced presence critical care trained specialists.21

Lastly, the scarce use of validated scales to monitor delirium during the pandemic, and the decrease in preventive measures were associated with greater oversedation after versus before the pandemic (64.4% versus 46.4%, P < .001). Due to the high percentage of delirium diagnosed in COVID-19, with a 50%–60% incidence of hyperactive delirium in some series, we face an important increase in delirium associated with these inadequate sedation practices.13,56 Recently Owen et al., in over 44,000 patients admitted to the ICU in Canada, reported that the adoption of the ABCDEF bundle reduced the incidence of delirium (two-month decrease of 0.34%, 95%CI 0.18−0.50, P < .01) from 33.48% (95%CI 29.64–37.31) in 2017 to 28.74% (95%CI 25.22–32.26) in 2019.57 In our study, the main barriers facing prevention were a lack of family involvement in the care of the patient in the ICU, difficulties in monitoring analgosedation, and the increased benzodiazepine use, as already described in other studies.58,59

Our study has a number of limitations and strengths. Limitations include the subjectivity of the survey and the heterogeneity of analgosedation management in the different geographical settings. Also, we did not consider the professional hierarchy of the survey participants, which may have influenced the perception of medication use. On the other hand, although a considerable sample size was recruited, some of the participating countries showed a lower response rate, which limits the representativeness of our results.

With regard to the strengths of the study, we were able to secure the participation of many of the FEPIMCTI member countries, with local specialists caring for many patients with analgosedation before, during and after the pandemic. This provided relevant information on the factors influencing the changes in analgosedation practices in our setting.

We believe that knowledge of analgosedation and delirium management practices at the regional level is important for the development of local analgosedation and delirium expert committees or workgroups to discuss or endorse strategies for implementing the ABCDEF toolkit and promoting Zero Sedation.

Before the COVID-19 pandemic, the management of analgosedation was characterized by the predominant use of targeted protocols that favored priority on mild and dynamic sedation in critically ill patients. During the pandemic the percentage of ICU patients receiving deep sedation increased. According to the physicians surveyed, this tendency to use deep sedation continued after the pandemic and was not always justified. The present study found that staff with little to no critical care training or experience, less monitoring of analgosedation, less nursing presence in the ICU, and habits acquired during the pandemic (especially the regular use of benzodiazepines and oversedation) were the main reasons for this perception of the post-pandemic situation. We need to resume socialization and retraining efforts in protocols and bundles of measures for safe patient sedation, and to reduce oversedation in the ICU.

The present study was evaluated and approved by the Red Municipal de Bioética Clínica y Social of the city of Córdoba (Argentina), and abides with the National Law on Personal Data Protection 25.326 (Republic of Argentina) for safeguarding the identity and data of the participants, and guaranteeing full anonymity and confidentiality of the information. Informed consent was obtained from all the participants after receiving an explanation of the aims of the study and the time required to complete it.

RESEARCH CARRIED OUT WITH THE SUPPORT OF: Comité de Analgesia, Sedación y Delirium de la Federación Panamericana e Ibérica de Cuidados Críticos y Terapia Intensiva (FEPIMCTI); URL: https://fepimcti.org/comite-de-expertos/sedacion-y-analgesia/).

The present study has received no partial or total funding, or any type of grant or financial support.