Giuseppe Citerio

Was not provided for this article.

Background: Delirium is clinically classified into hypoactive or hyperactive motoric subtypes, which may have different responses to treatment. We assessed heterogeneity in treatment effects according to baseline motoric subtype in the AID‐ICU trial, which randomised adult ICU patients with delirium to haloperidol versus placebo. Methods: In this post hoc study of the AID‐ICU trial, we used adjusted Bayesian linear and logistic regression models to assess potential differential effects of haloperidol on 90‐day outcomes according to motor subtypes. Effect estimates are reported as absolute differences within and between subtypes (mean differences (MD)/risk differences (RD) and differences in MDs/RDs), with probabilities of any benefit, any harm and differential effects between subtypes. Results: Of 987 participants, 540 (54.7%) had hypoactive and 447 (45.3%) had hyperactive delirium at randomisation. Haloperidol was associated with more days alive out of hospital in both subgroups, with a 76.5% probability of a larger intervention effect in those with hyperactive delirium (difference in MDs 2.9 days; 95% CrI −4.8 to 10.6). Similar results were obtained for days alive without delirium/coma and days alive without mechanical ventilation. Haloperidol was associated with lower mortality in both subgroups, with a 73% probability of larger benefit in hyperactive delirium (difference in RDs −3.7%‐points; 95% CrI −15.3 to 7.8). We found no relevant differences in serious adverse reactions or use of rescue medications. Conclusion: Compared with placebo, haloperidol was associated with moderate to high probabilities of benefit in both hypoactive and hyperactive delirium, with moderate probabilities of greater effects in hyperactive delirium. Further research is warranted to confirm these results. Editorial Comment: In this post hoc analysis of the AID‐ICU trial, haloperidol was associated with moderate to high probabilities of benefit in both hypoactive and hyperactive delirium, with a tendency towards greater treatment effects in hyperactive delirium. Trial Registration: ClinicalTrials.gov number: NCT03392376; EudraCT number, 2017‐003829‐15

OBJECTIVE: To describe site-level ICU organizational policies and implementation of pain, agitation, and delirium (PAD) best practices before the COVID-19 pandemic, and perceived changes during the pandemic. DESIGN: International site-level questionnaire study. SETTING: Participating sites completed a standardized electronic Case Report Form between January 5, 2022 and March 31, 2023. PATIENTS/CENTERS: Ninety-three ICUs caring for adult patients from 79 hospitals across 27 countries in North America, South America, and Europe. INTERVENTIONS: Each ICU submitted data on site characteristics, staffing, implementation of PAD protocols and assessment tools prepandemic, and perceived changes during the COVID-19 pandemic. Descriptive statistics and multivariable logistic regressions were performed using R. MEASUREMENTS AND MAIN RESULTS: Of 93 ICUs, 63% were university-affiliated, and 59% reported a closed physician staffing model. Most managed mixed patient populations (78%), with a nurse-to-patient ratio for ventilated patients of 1:2 (45%) or 1:1 (39%). Physiotherapists and pharmacists were available in 83% and 68% of ICUs, respectively. Over 75% reported routine use of validated PAD scales, most commonly Richmond Agitation Sedation Scale (86%), Confusion Assessment Method for ICU (59%), and Numeric Rating Scale (44%). Protocols were most available for spontaneous breathing trials (60%) and sedation (58%), followed by delirium (53%), mobilization (47%), and pain (46%). University affiliation and 1:1 nurse staffing was associated with reported use of delirium or mobilization protocols. The presence of a weaning protocol was associated with higher odds of daily sedation interruption (adjusted odds ratio [aOR] 3.80; 95% CI, 1.43–10.89; p = 0.009), and use of sedation protocols (aOR 5.95; 95% CI, 2.29–16.86; p < 0.001). Nearly one-half of ICUs reported drug shortages during the pandemic, and 62% prohibited any visitation. CONCLUSIONS: ICU organizational structures and reported PAD practices vary widely worldwide. Despite international guidelines, many ICUs lack consistent implementation of evidence-based sedation, analgesia, and delirium management strategies.

Background: Neurological ICU survivors may experience a distinct long-term burden dominated by functional disability. We compared six- and twelve-month functional outcomes and recovery trajectories between neurological and non-neurological ICU survivors.Methods: Adult ICU hospital survivors from two harmonized prospective follow-up registries were eligible. Hospital survivors with complete propensity-score variables were matched 1:1 using propensity scores based on age, sex, and SAPS II. Individual outcomes were analyzed in outcome-specific available-case samples, while longitudinal analyses included patients contributing repeated measurements at 6 and/or 12 months. The primary outcome was poor functional outcome at six months, defined as Glasgow Outcome Scale–Extended (GOSE) ≤4. Secondary functional and physical outcomes included Barthel Index <80, handgrip strength, six-minute walk test, and EQ-5D functional domains. Other domains were considered exploratory.Findings: Overall, 4,058 ICU patients were included, comprising 1,007 neurological and 3,051 non-neurological patients. Among 2,235 hospital survivors, the matched cohort included 1,252 patients, with 626 per group. At six months, neurological survivors had more frequent poor GOSE (164/291, 56% vs 65/291, 22%) and Barthel Index <80 (144/289, 50% vs 56/310, 18%). In overlap-weighted analyses, neurological status was associated with poor GOSE (OR 5.13, 95% CI 3.67–7.15), Barthel Index <80 (OR 4.87, 95% CI 3.47–6.84), lower handgrip strength (MD −11.63%, 95% CI −17.84 to −5.41), and directionally lower six-minute walk performance.Interpretation: Neurological ICU survivors had substantially higher long-term functional disability than matched non-neurological ICU survivors. These findings support post-ICU pathways focused on functional rehabilitation.

Background: Patients with traumatic brain injury (TBI) frequently undergo extracranial surgery (ES). These procedures may be lifesaving (LS), such as haemorrhage or damage-control interventions, or non-lifesaving (NLS), including definitive fracture fixation or wound closure. Whether ES independently affects neurological recovery remains unclear. Methods: We analysed adult ICU patients with polytrauma and structural TBI (ISS ≥ 16, AIS Brain ≥ 3, and at least one extracranial injury as AIS ≥ 3) enrolled in the prospective multicentre CENTER-TBI cohort across 65 European sites. Predictors of extracranial surgery (ES) were evaluated using a cause-specific Cox proportional hazards model with competing risks, considering death before surgery as a competing event. LS and NLS categories were assigned by local investigators based on urgency. Associations between ES category (LS, NLS, or no-ES) and six-month unfavourable neurological outcome (GOSE ≤ 4) were assessed using multivariable logistic regression adjusted for IMPACT extended prognostic variables. Sensitivity analyses excluding patients who died within 48 h and secondary analysis in ICU survivors evaluated six-month outcome while minimizing immortal time bias from later NLS procedures. Results: Of 870 patients, 369 (42.4%) underwent ES: 168 (19.3%) LS and 201 (23.1%) NLS. LS patients were younger, had higher ISS, greater haemodynamic instability, more severe shock, and higher transfusion requirements compared with NLS and no-ES groups. Unadjusted six-month unfavourable outcome rates did not differ significantly (48.9% no-ES, 51.8% LS, 42.3% NLS; p = 0.2). LS remained associated with worse neurological outcome after adjustment (OR 1.86, 95% CI 1.15–3.01; p = 0.011), whereas NLS was not. Results remained consistent across sensitivity analyses, the multiple imputation model, and the secondary analysis. Conclusions: Emergency/damage-control extracranial surgery operationally classified as LS identified a phenotype of patients with greater extracranial injury burden and physiological instability, associated with worse long-term neurological outcome. This association should be interpreted as reflecting injury severity and treatment indication rather than a direct detrimental effect of surgery itself. NLS procedures were not independently associated with unfavourable recovery. Trial registration: ClinicalTrials.gov Identifiers: NCT02210221.