Evidence-based management of analgesia and sedation in COVID-19-associated acute respiratory distress syndrome remains limited. Non-guideline recommended analgesic and sedative medication regimens and deeper sedation targets have been employed for patients with COVID-19 due to exaggerated analgesia and sedation requirements with extended durations of mechanical ventilation. This, coupled with a desire to minimize nurse entry into COVID-19 patient rooms, marked obesity, altered end-organ function, and evolving medication shortages, presents numerous short-and long-term challenges. Alternative analgesic and sedative agents and regimens may pose safety risks and require judicious bedside management for appropriate use. The purpose of this commentary is to provide considerations and solutions for designing safe and effective analgesia and sedation strategies for adult patients with considerable ventilator dyssynchrony and sedation requirements, such as COVID-19.

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A structure-activity relationship study for a series of vitamin D3-based (VD3) analogues that incorporate aromatic A-ring mimics with varying functionality has provided key insight into scaffold features that result in potent, selective Hedgehog (Hh) pathway inhibition. Three analogue subclasses containing (1) a single substitution at the ortho or para position of the aromatic A-ring, (2) a heteroaryl or biaryl moiety, or (3) multiple substituents on the aromatic A-ring were prepared and evaluated. Aromatic A-ring mimics incorporating either single or multiple hydrophilic moieties on a six-membered ring inhibited the Hh pathway in both Hh-dependent mouse embryonic fibroblasts and cultured cancer cells (IC50 values 0.74-10 μM). Preliminary studies were conducted to probe the cellular mechanisms through which VD3 and 5, the most active analogue, inhibit Hh signaling. These studies suggested that the anti-Hh activity of VD3 is primarily attributed to the vitamin D receptor, whereas 5 affects Hh inhibition through a separate mechanism.

Introduction: Atypical antipsychotics are frequently initiated in the intensive care unit (ICU) to treat delirium. Many patients continue on these agents at hospital discharge despite a lack of data to support long-term use. Objectives: The primary aim of this study was to determine underlying risk factors for continuation of antipsychotics at hospital discharge in medical intensive care unit (MICU) and surgical intensive care unit (SICU) patients when evaluated as separate cohorts. Methods: A single-center, retrospective study in patients newly initiated on quetiapine, risperidone, or olanzapine in a 22-bed mixed medical-surgical ICU admitted from January 2017 to July 2018. Results: A total of 78 (62.9%) MICU patients and 46 (37.1%) SICU patients met the inclusion criteria during this time frame. A total of 29 MICU patients (37.2%) were prescribed antipsychotics at hospital discharge compared to 25 SICU patients (54.3%), P = .063. The percentage of MICU patients prescribed antipsychotics at hospital discharge was significantly higher in patients ⩾60 years of age (22 [75.9%] vs 26 [53.1%], P = .045), with a history of dementia (5 [17.2%] vs 1 [2%], P = .015), admitted with hemorrhagic stroke (5 [17.2%] vs 2 [4.1%], P = .049), and initiated on risperidone (3 [10.3%] vs 0%, P = .022). The risk of pre-existing dementia remained significant in a multivariate logistic regression that controlled for confounding variables, odds ratio (OR) = 10 (95% confidence interval [CI]: 1.11-90.5, P = .040). The percentage of SICU patients prescribed antipsychotics at discharge was significantly higher in those with severe traumatic brain injury (TBI; 8 [72.7%] vs 0%, P = .004) and initiated on quetiapine (19 [76%] vs 9 [42.9%], P = .022). Conclusion: Antipsychotics were commonly continued at hospital discharge in both MICU and SICU patients. Several risk factors for continuation of antipsychotics were identified in these two cohorts. Future efforts assessing the appropriateness of antipsychotics at transitions of care are warranted.