Pro/Con debate: Is procalcitonin useful for guiding antibiotic decision making in critically ill patients?

You are concerned about the escalating use of antibiotics in your intensive care unit (ICU). This has put a strain on the ICU budget and is possibly resulting in the emergence of resistant bacteria. You review the situation with your team and one suggestion is to consider using biomarkers such as procalcitonin to better guide appropriate antibiotic decision making

Cognitive and psychosocial outcomes of mechanically ventilated intensive care patients with and without delirium

Abstract Objective Delirium is common in intensive care patients and is associated with short- and long-term adverse outcomes. We investigated the long-term risk of cognitive impairment and post-traumatic stress disorder (PTSD) in intensive care patients with and without delirium. Methods This is a prospective cohort study in ICUs in two Australian university-affiliated hospitals. Patients were eligible if they were older than 18 years, mechanically ventilated for more than 24 h and did not meet exclusion criteria. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. Variables assessing cognitive function and PTSD symptoms were collected at ICU discharge, after 6 and 12 months: Mini-Mental State Examination, Telephone Interview for Cognitive Status, Impact of Events Scale-Revised and Informant Questionnaire for Cognitive Decline (caregiver). Results 103 participants were included of which 36% developed delirium in ICU. Patients with delirium were sicker and had longer duration of mechanical ventilation and ICU length of stay. After 12 months, 41/60 (68.3%) evaluable patients were cognitively impaired, with 11.6% representing the presence of symptoms consistent with dementia. When evaluated by the patient’s caregiver, the patient’s cognitive function was found to be severely impaired in a larger proportion of patients (14/60, 23.3%). Delirium was associated with worse cognitive function at ICU discharge, but not with long-term cognitive function. IES-R scores, measuring PTSD symptoms, were significantly higher in patients who had delirium compared to patients without delirium. In regression analysis, delirium was independently associated with cognitive function at ICU discharge and PTSD symptoms at 12 months. Conclusions Intensive care survivors have significant rates of long-term cognitive decline and PTSD symptoms. Delirium in ICU was independently associated with short-term but not long-term cognitive function, and with long-term PTSD symptoms. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12616001116415, 15/8/2016 retrospectively registered, https://www.anzctr.org.a

Stress response during early sedation with dexmedetomidine compared with usual-care in ventilated critically ill patients

Background: Sedative agents may variably impact the stress response. Dexmedetomidine is a sympatholytic alpha2-adrenergic agonist mainly used as a second-line sedative agent in mechanically ventilated patients. We hypothesised that early sedation with dexmedetomidine as the primary agent would result in a reduced stress response compared to usual sedatives in critically ill ventilated adults. Methods: This was a prospective sub-study nested within a multi-centre randomised controlled trial of early sedation with dexmedetomidine versus usual care. The primary outcome was the mean group differences in plasma levels of stress response biomarkers measured over 5 days following randomisation. Other hormonal, biological and physiological parameters were collected. Subgroup analyses were planned for patients with proven or suspected sepsis. Results: One hundred and three patients were included in the final analysis. Baseline illness severity (APACHE II score), the proportion of patients receiving propofol and the median dose of propofol received were comparable between groups. More of the usual-care patients received midazolam (57.7% vs 33.3%; p = 0.01) and at higher dose (median (95% interquartile range) 0.46 [0.20–0.93] vs 0.14 [0.08–0.38] mg/kg/day; p < 0.01). The geometric mean (95% CI) plasma level of the stress hormones, adrenaline (0.32 [0.26–0.4] vs 0.38 [0.31–0.48]), noradrenaline (4.27 [3.12–5.85] vs 6.2 [4.6–8.5]), adrenocorticotropic hormone (17.1 [15.1–19.5] vs 18.1 [15.9–20.5]) and cortisol (515 [409–648] vs 618 [491–776)] did not differ between dexmedetomidine and usual-care groups, respectively. There were no significant differences in any other assayed biomarkers or physiological parameters Sensitivity analyses showed no effect of age or sepsis. Conclusions: Early sedation with dexmedetomidine as the primary sedative agent in mechanically ventilated critically ill adults resulted in comparable changes in physiological and blood-borne parameters associated with the stress-response as with usual-care sedation

an international survey before and during the COVID-19 pandemic

Funding Information: The Société Française d’Anesthésie et de Réanimation (SFAR), Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC), Sociedad Argentina de Terapia Intensiva (SATI), Sociedad Chilena de Medicina Intensiva (SOCHIMI), Associação de Medicina Intensiva Brasileira (AMIB-Net) and the Brazilian Research in Intensive Care Network (BricNet) supported this survey. We would also like to thank our friend Tiago Rocha for making the amazing logo for this study. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001. Publisher Copyright: © 2022, The Author(s).Background: Since the publication of the 2018 Clinical Guidelines about sedation, analgesia, delirium, mobilization, and sleep deprivation in critically ill patients, no evaluation and adequacy assessment of these recommendations were studied in an international context. This survey aimed to investigate these current practices and if the COVID-19 pandemic has changed them. Methods: This study was an open multinational electronic survey directed to physicians working in adult intensive care units (ICUs), which was performed in two steps: before and during the COVID-19 pandemic. Results: We analyzed 1768 questionnaires and 1539 (87%) were complete. Before the COVID-19 pandemic, we received 1476 questionnaires and 292 were submitted later. The following practices were observed before the pandemic: the Visual Analog Scale (VAS) (61.5%), the Behavioral Pain Scale (BPS) (48.2%), the Richmond Agitation Sedation Scale (RASS) (76.6%), and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) (66.6%) were the most frequently tools used to assess pain, sedation level, and delirium, respectively; midazolam and fentanyl were the most frequently used drugs for inducing sedation and analgesia (84.8% and 78.3%, respectively), whereas haloperidol (68.8%) and atypical antipsychotics (69.4%) were the most prescribed drugs for delirium treatment; some physicians regularly prescribed drugs to induce sleep (19.1%) or ordered mechanical restraints as part of their routine (6.2%) for patients on mechanical ventilation; non-pharmacological strategies were frequently applied for pain, delirium, and sleep deprivation management. During the COVID-19 pandemic, the intensive care specialty was independently associated with best practices. Moreover, the mechanical ventilation rate was higher, patients received sedation more often (94% versus 86.1%, p < 0.001) and sedation goals were discussed more frequently in daily rounds. Morphine was the main drug used for analgesia (77.2%), and some sedative drugs, such as midazolam, propofol, ketamine and quetiapine, were used more frequently. Conclusions: Most sedation, analgesia and delirium practices were comparable before and during the COVID-19 pandemic. During the pandemic, the intensive care specialty was a variable that was independently associated with the best practices. Although many findings are in accordance with evidence-based recommendations, some practices still need improvement.publishersversionpublishe

Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment:A patient-level meta-analysis from randomized controlled trials

Patients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission. We pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73 m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15-89 [CKD 2-4] and GFR0.05). This individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates

Comfort and patient-centred care without excessive sedation:the eCASH concept

We propose an integrated and adaptable approach to improve patient care and clinical outcomes through analgesia and light sedation, initiated early during an episode of critical illness and as a priority of care. This strategy, which may be regarded as an evolution of the Pain, Agitation and Delirium guidelines, is conveyed in the mnemonic eCASH—early Comfort using Analgesia, minimal Sedatives and maximal Humane care. eCASH aims to establish optimal patient comfort with minimal sedation as the default presumption for intensive care unit (ICU) patients in the absence of recognised medical requirements for deeper sedation. Effective pain relief is the first priority for implementation of eCASH: we advocate flexible multimodal analgesia designed to minimise use of opioids. Sedation is secondary to pain relief and where possible should be based on agents that can be titrated to a prespecified target level that is subject to regular review and adjustment; routine use of benzodiazepines should be minimised. From the outset, the objective of sedation strategy is to eliminate the use of sedatives at the earliest medically justifiable opportunity. Effective analgesia and minimal sedation contribute to the larger aims of eCASH by facilitating promotion of sleep, early mobilization strategies and improved communication of patients with staff and relatives, all of which may be expected to assist rehabilitation and avoid isolation, confusion and possible long-term psychological complications of an ICU stay. eCASH represents a new paradigm for patient-centred care in the ICU. Some organizational challenges to the implementation of eCASH are identified.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570