Critical Care Pharmacist Attitudes and Perceptions of Neuromuscular Blocker Infusions in ARDS.

BACKGROUND: Current critical care pharmacist (CCP) practices and perceptions related to neuromuscular infusion (NMBI) use for acute respiratory distress syndrome (ARDS) maybe different with the COVID-19 pandemic and the publication of 2020 NMBI practice guidelines. OBJECTIVE: To evaluate CCP practices and perceptions regarding NMBI use for patients with moderate-severe ARDS. METHODS: We developed, tested, and electronically administered a questionnaire (7 parent-, 42 sub-questions) to 409 American College of Clinical Pharmacy (ACCP) Critical Care Practice and Research Network members in 12 geographically diverse states. The questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2<150) whose causes of dyssynchrony were addressed. Two reminders were sent at 10-day intervals. RESULTS: Respondents [131/409 (32%)] primarily worked in a medical intensive care unit (ICU) 102 (78%). Compared to COVID-negative(-) ARDS patients, COVID positive(+) ARDS patients were twice as likely to receive a NMBI (34 ± 18 vs.16 ± 17%; P < 0.01). Respondents somewhat/strongly agreed a NMBI should be reserved until after trials of deep sedation (112, 86%) or proning (92, 81%) and that NMBI reduced barotrauma (88, 67%), dyssynchrony (87, 66%), and plateau pressure (79, 60%). Few respondents somewhat/strongly agreed that a NMBI should be initiated at ARDS onset (23, 18%) or that NMBI reduced 90-day mortality (12, 10%). Only 2/14 potential NMBI risks [paralysis awareness (101, 82%) and prolonged muscle weakness (84, 68%)] were frequently reported to be of high/very high concern. Multiple NMBI titration targets were assessed as very/extremely important including arterial pH (109, 88%), dyssynchrony (107, 86%), and PaO2: FiO2 ratio (82, 66%). Train-of-four (55, 44%) and BIS monitoring (36, 29%) were deemed less important. Preferred NMBI discontinuation criteria included absence of dysschrony (84, 69%) and use ≥48 hour (72, 59%). CONCLUSIONS AND RELEVANCE: Current critical care pharmacists believe NMBI for ARDS patients are best reserved until after trials of deep sedation or proning; unique considerations exist in COVID+ patients. Our results should be considered when ICU NMBI protocols are being developed and bedside decisions regarding NMBI use in ARDS are being formulated.

Physicians' attitudes and perceptions of neuromuscular blocker infusions in ARDS.

PURPOSE: The perceptions and practices of ICU physicians regarding initiating neuromuscular blocker infusions (NMBI) in acute respiratory distress syndrome (ARDS) may not be evidence-based amidst the surge of severe ARDS during the SARS-CoV-2 pandemic and new practice guidelines. We identified ICU physicians' perspectives and practices regarding NMBI use in adults with moderate-severe ARDS. MATERIALS AND METHODS: After extensive development and testing, an electronic survey was distributed to 342 ICU physicians from three geographically-diverse U.S. health systems(n = 12 hospitals). RESULTS: The 173/342 (50.5%) respondents (75% medical) somewhat/strongly agreed a NMBI should be reserved until: after a trial of deep sedation (142, 82%) or proning (59, 34%) and be dose-titrated based on train-of-four monitoring (107, 62%). Of 14 potential NMBI risks, 2 were frequently reported to be of high/very high concern: prolonged muscle weakness with steroid use (135, 79%) and paralysis awareness due to inadequate sedation (114, 67%). Absence of dyssychrony (93, 56%) and use ≥48 h (87, 53%) were preferred NMBI stopping criteria. COVID-19 + ARDS patients were twice as likely to receive a NMBI (56 ± 37 vs. 28 ± 19%, p < 0.01). CONCLUSIONS: Most intensivists agreed NMBI in ARDS should be reserved until after a deep sedation trial. Stopping criteria remain poorly defined. Unique considerations exist regarding the role of paralysis in COVID-19+ ARDS.

Quality of critical care clinical practice guidelines involving pharmacotherapy recommendations.

PURPOSE: To assess the quality of critical care clinical practice guidelines (CPGs) involving pharmacotherapy recommendations. METHODS: A systematic electronic search was performed using PubMed, MEDLINE, and Embase for critical care CPGs published between 2012 and 2022 and involving pharmacotherapy recommendations. The Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument was employed to appraise CPG quality through independent assessment by 2 appraisers. RESULTS: Twenty-one CPGs were evaluated. The number of recommendations in each guideline ranged from 2 to 250, with a total of 1,604 recommendations. The number of strong (vs weak) recommendations in each guideline ranged from 0 to 31, with a total of 116 strong recommendations, or 7.23% of the total number of recommendations. There was at least 1 pharmacist author for 9 (43%) of the guidelines. The AGREE II domains for which mean quality scores of evaluated guidelines were highest were scope and purpose (0.88; 95% CI, 0.85-0.92), rigor of development (0.80; 95% CI, 0.77-0.83), clarity of presentation (0.84; 95% CI, 0.81-0.87), and editorial independence (0.86; 95% CI, 0.79-0.94), while those for which mean scores were lowest were stakeholder involvement (0.69; 95% CI, 0.63-0.75) and applicability (0.49; 95% CI, 0.43-0.55). Involvement of a pharmacist in CPG development was associated with significantly higher scoring for stakeholder involvement (P = 0.0356). CONCLUSION: Strong recommendations accounted for less than 10% of the recommendations in the evaluated CPGs. Moreover, there are concerns related to guideline applicability (ie, advice or tools for putting recommendations into practice) and stakeholder involvement (ie, inclusion of individuals from all relevant groups). It is important to involve pharmacists in CPGs with pharmacotherapy recommendations.

Drug dosing in hospitalized obese patients with COVID-19.

Obesity is highly prevalent in hospitalized patients admitted with COVID-19. Evidence based guidelines are available for COVID-19-related therapies but dosing information specific to patients with obesity is lacking. Failure to account for the pharmacokinetic alterations that exist in this population can lead to underdosing, and treatment failure, or overdosing, resulting in an adverse effect. The objective of this manuscript is to provide clinicians with guidance for making dosing decisions for medications used in the treatment of patients with COVID-19. A detailed literature search was conducted for medications listed in evidence-based guidelines from the National Institutes of Health with an emphasis on pharmacokinetics, dosing and obesity. Retrieved manuscripts were evaluated and the following prioritization strategy was used to form the decision framework for recommendations: clinical outcome data > pharmacokinetic studies > adverse effects > physicochemical properties. Most randomized controlled studies included a substantial number of patients who were obese but few had large numbers of patients more extreme forms of obesity. Pharmacokinetic data have described alterations with volume of distribution and clearance but this variability does not appear to warrant dosing modifications. Future studies should provide more information on size descriptors and stratification of data according to obesity and body habitus.

Implications of obesity for drug administration and absorption from subcutaneous and intramuscular injections: A primer.

PURPOSE: To discuss the potential implications of obesity for drug administration and absorption from subcutaneous (SC) and intramuscular (IM) injection sites. SUMMARY: The SC and IM routes are useful for the parenteral administration of medications to optimize pharmacokinetic properties such as time to onset and duration of effect, for cost considerations, or for ease of administration, such as when intravenous access is unavailable. The choice of SC or IM injection depends on the specific medication, with SC administration preferred for products such as insulin where a slower and more sustained response is desirable, while IM administration is usually preferred for products such as vaccines where more rapid absorption leads to a more rapid antibody response. Obesity has the potential to influence the rate and extent of absorption, as well as adverse effects, of medications administered by the SC or IM route through changes in SC tissue composition and depth or by inadvertent administration of IM medications into SC tissue because of improper needle length. Potential adverse effects associated with IM or SC injections in addition to pain, bruising, and hematoma formation include sciatic nerve injury, particularly with IM injection in the upper outer quadrant of the buttock; bone contusion or rarely osteonecrosis if the IM injection is excessively deep; and granulomas, fat necrosis, and calcification with SC injection. CONCLUSION: Issues related to medication absorption in obese patients are likely to become more prominent in the future with increasing approvals of a wide range of biotherapeutic agents administered by SC injection. Studies should be directed toward these and other agents to assist with dosing decisions in this challenging population.

Clinical outcomes of concomitant use of enteral and intravenous sedatives and analgesics in mechanically ventilated patients with COVID-19.

PURPOSE: To evaluate potential differences in days on mechanical ventilation for patients with coronavirus disease 2019 (COVID-19) based on route of administration of analgesic and sedative medications: intravenous (IV) alone vs IV + enteral (EN). SUMMARY: This institutional review board-approved study evaluated ventilation time and fentanyl or midazolam requirements with or without concurrent EN hydromorphone and lorazepam. Patients were included in the study if they were 18 to 89 years old and were admitted to the intensive care unit with a positive severe acute respiratory syndrome coronavirus 2 reverse transcription and polymerase chain reaction or antigen test and respiratory failure requiring invasive mechanical ventilation for more than 72 hours. In total, 100 patients were evaluated, 60 in the IV-only group and 40 in the IV + EN group. There was not a significant difference in ventilation time between the groups (mean [SD], 19.6 [12.8] days for IV + EN vs 15.6 [11.2] days for IV only; P = 0.104). However, fentanyl (2,064 [847] µg vs 2,443 [779] µg; P < 0.001) and midazolam (137 [72] mg vs 158 [70] mg; P = 0.004) requirements on day 3 were significantly higher in the IV-only group, and the increase in fentanyl requirements from day 1 to day 3 was greater in the IV-only group than in the IV + EN group (378 [625] µg vs 34 [971] µg; P = 0.033). CONCLUSION: Addition of EN analgesic and sedative medications to those administered by the IV route did not change the duration of mechanical ventilation in patients with COVID-19, but the combination may reduce IV opioid requirements, decreasing the impact of IV medication shortages.

Proposed guidance on cost-avoidance studies in pharmacy practice.

PURPOSE: Cost-avoidance studies of pharmacist interventions are common and often the first type of study conducted by investigators to quantify the economic impact of clinical pharmacy services. The purpose of this primer is to provide guidance for conducting cost-avoidance studies pertaining to clinical pharmacy practice. SUMMARY: Cost-avoidance studies represent a paradigm conceptually different from traditional pharmacoeconomic analysis. A cost-avoidance study reports on cost savings from a given intervention, where the savings is estimated based on a counterfactual scenario. Investigators need to determine what specifically would have happened to the patient if the intervention did not occur. This assessment can be fundamentally flawed, depending on underlying assumptions regarding the pharmacists' action and the patient trajectory. It requires careful identification of the potential consequence of nonaction, as well as probability and cost assessment. Given the uncertainty of assumptions, sensitivity analyses should be performed. A step-by-step methodology, formula for calculations, and best practice guidance is provided. CONCLUSIONS: Cost-avoidance studies focused on pharmacist interventions should be considered low-level evidence. These studies are acceptable to provide pilot data for the planning of future clinical trials. The guidance provided in this article should be followed to improve the quality and validity of such investigations.

Caring for the COVID Patient: A Clinical Pharmacist's Perspective.

Physicians and nurses have received many accolades in commercial and scientific media for their heroic efforts in caring for patients with COVID-19. These accolades are appropriate and deserved. However, there are a number of clinical pharmacists involved in the daily care of patients who are caring and competent practitioners, and also deserve our thanks and praise. The purpose of this article is to provide the impactful comments of a front-line, critical care pharmacist dedicated to providing the best possible care for patients with COVID-19 in a medical intensive care unit.