Critical Care Pharmacotherapy Research Articles

Major Publications in the Critical Care Pharmacotherapy Literature: 2022.

A number of trials related to critical care pharmacotherapy were published in 2022. We aimed to summarize the most influential publications related to the pharmacotherapeutic care of critically ill patients in 2022. PubMed/Medical Literature Analysis and Retrieval System Online and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2022, and December 31, 2022, were included in this article. Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included and stratified into clinical domains based upon consistent themes. Consensus was obtained on the most influential publication within each clinical domain utilizing an a priori defined three-round modified Delphi process with the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update yielded a total of 704 articles, of which 660 were excluded. The remaining 44 articles were stratified into the following clinical domains: emergency/neurology, cardiovascular, gastroenterology/fluids/nutrition, hematology, infectious diseases/immunomodulation, and endocrine/metabolic. The final article selected from each clinical domain was summarized following a three-round modified Delphi process and included three randomized controlled trials and three systematic review/meta-analyses. Article topics summarized included dexmedetomidine versus other sedatives during mechanical ventilation, beta-blocker treatment in the critically ill, restriction of IV fluids in septic shock, venous thromboembolism prophylaxis in critically ill adults, duration of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia, and low-dose methylprednisolone treatment in severe community-acquired pneumonia. This concise review provides a perspective on articles published in 2022 that are relevant to the pharmacotherapeutic care of critically ill patients and their potential impact on clinical practice.

Major Publications in the Critical Care Pharmacotherapy Literature: 2021.

PubMed/MEDLINE. Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critical care patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2021, and December 31, 2021. Candidate articles were organized by clinical domain based on the emerging themes from all studies. A modified Delphi process was applied to obtain consensus on the most impactful publication within each clinical domain based on overall contribution to scientific knowledge and novelty to the literature. The search revealed 830 articles, of which 766 were excluded leaving 64 candidate articles for the Delphi process. These 64 articles were organized by clinical domain including: emergency/neurology, cardiopulmonary, nephrology/fluids, infectious diseases, metabolic, immunomodulation, and nutrition/gastroenterology. Each domain required the a priori defined three Delphi rounds. The resultant most impactful articles from each domain included five randomized controlled trials and two systematic review/meta-analyses. Topics studied included sedation during mechanical ventilation, anticoagulation in COVID-19, extended infusion beta-lactams, interleukin-6 antagonists in COVID-19, balanced crystalloid resuscitation, vitamin C/thiamine/hydrocortisone in sepsis, and promotility agents during enteral feeding. This synoptic review provides a summary and perspective of the most impactful articles relevant to the pharmacotherapy of critically ill adults published in 2021.

Major Publications in the Critical Care Pharmacotherapy Literature: 2020.

OBJECTIVES:To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2020.DATA SOURCES:The Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update group screened 36 journals monthly for impactful publications.STUDY SELECTION:The group reviewed a total of 119 articles during 2020 according to relevance for practice.DATA EXTRACTION:Articles were selected with consensus and importance to clinical practice from those included in the monthly Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. The group reviewed articles according to Grading of Recommendations, Assessment, Development, and Evaluations criteria. Articles with a 1A grade were selected.DATA SYNTHESIS:Several trials were summarized, including two meta-analyses and five original research trials. Original research trials evaluating vitamin C, hydrocortisone, and thiamine versus hydrocortisone in sepsis, the use of nonsedation strategies, dexmedetomidine in cardiac surgery, remdesivir for severe acute respiratory syndrome coronavirus 2, and thrombectomy in acute ischemic stroke. Two meta-analyses determining the impact of norepinephrine initiation in patients with septic shock and the use of corticosteroids in severe acute respiratory syndrome coronavirus 2 was included.CONCLUSIONS:This clinical review provides summary and perspectives of clinical practice impact on influential critical care pharmacotherapy publications in 2020.

Impact of CytoSorb Hemoadsorption on Sedation Requirements in Patients With Severe COVID-19 on Venovenous Extracorporeal Membrane Oxygenation.

Hemoadsorption with CytoSorb has been used as an adjunct in the treatment of severe coronavirus disease 2019 (COVID-19)-related respiratory failure. It remains unknown if CytoSorb hemoadsorption will alter sedative and analgesic dosing in critically ill patients on venovenous extracorporeal membrane oxygenation (VV-ECMO). We conducted a retrospective review of patients with severe COVID-19 requiring VV-ECMO for respiratory support. Patients who were enrolled in a clinical study of CytoSorb were compared with patients on VV-ECMO alone. Data were collected for the 72-hour CytoSorb therapy and an additional 72 hours post-CytoSorb, or a corresponding control time period. Sedative and analgesic doses were totaled for each day and converted to midazolam or fentanyl equivalents, respectively. The primary endpoint, change in sedative and analgesic requirements over time, were compared using a two-way mixed analysis of variance. Of the 30 patients cannulated for VV-ECMO for COVID-19, 4 were excluded, leaving 8 patients in the CytoSorb arm and 18 in the Control. There was no effect of CytoSorb therapy on midazolam equivalents over the 72-hour therapy (p = 0.71) or the 72 hours post-CytoSorb (p = 0.11). In contrast, there was a significant effect of CytoSorb therapy on fentanyl equivalents over the first 72 hours (p = 0.01), but this was not consistent over the 72-hours post-CytoSorb (p = 0.23). CytoSorb therapy led to significant increases in analgesic requirements without impacting sedative requirements. Further research is needed to define the relevance of CytoSorb hemoadsorption on critical care pharmacotherapy.

Major publications in the critical care pharmacotherapy literature: 2019.

To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2019. The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 36 journals monthly for impactful articles and reviewed 113 articles during 2019 according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. Articles with a 1A grade, including three clinical practice guidelines, six meta-analyses, and five original research trials are reviewed here from those included in the monthly CCPLU. Clinical practice guidelines on the use of polymyxins and antiarrhythmic drugs in cardiac arrest as well as meta-analyses on antipsychotic use in delirium, stress ulcer prophylaxis (SUP), and vasoactive medications in septic shock and cardiac arrest were summarized. Original research trials evaluated delirium, sedation, neuromuscular blockade, SUP, anticoagulation reversal, and hemostasis. This clinical review and expert opinion provides summary and perspectives of clinical practice impact on influential critical care pharmacotherapy publications in 2019.

Teaching research skills to student pharmacists: A multi-campus, multi-semester applied critical care research elective

Background and purposeResearch electives are commonly offered in doctor of pharmacy programs but are typically limited to one faculty member mentoring individual students at a single site for a semester long self-study experience. The purpose of this paper is to describe pharmacy student experiences and perceptions of the research process after completing a multi-campus, multi-investigator critical care research elective. Educational activity and settingThe Research in Critical Care Pharmacotherapy elective was launched in spring 2019 and implemented a novel approach to the pharmacy research elective that promoted collaborative research across four campuses that may be continued for up to four semesters of credit. FindingsSix second- and third-year doctor of pharmacy students enrolled in the course during the first offering. Three students were located on the main campus with one student on each of the extended campuses. Students completed a median of five unique research activities with at least one student participating in 15 of the 19 activities evaluated. Students were asked to complete a pre- and post-course survey assessing perceived research abilities using the Dreyfus model. There was a significant decrease in the number of novice responses in the post-course survey (pre- 10 vs. post- 2, p = 0.043). SummaryA multi-campus, multi-investigator critical care research elective provided broad research experiences and increased student confidence related to numerous research skills.

Development of the Critical Care Pharmacotherapy Trials Network.

The development of the Critical Care Pharmacotherapy Trials Network (CCPTN) as a model for practice-based pharmacotherapy research is described. The CCPTN was formed in 2010 as a collaborative research network dedicated to scientific investigation in the field of critical care pharmacotherapy. The CCPTN organizational structure is consistent with many professional pharmacy and interdisciplinary organizations and organized into 3 primary domains: executive committee, working committees, and network membership. The network membership consists of critical care investigators dedicated to the mission and vision of the CCPTN and is open to anyone expressing an interest in contributing to high-level research. Network member sites represent the breadth of U.S. critical care practice environments. In addition, network members include individuals with demonstrated expertise in patient safety, administration, research design, grantsmanship, database management, peer review, and scientific writing. In 2015, there were more than 100 site investigators from around the United States and Canada. Projects to date have yielded numerous abstracts, platform presentations, and peer-reviewed publications in high-impact journals. The CCPTN has expanded to form collaborations with researchers in the United Kingdom, Australia, and New Zealand. The CCPTN has identified new potential partnerships and field-based areas for inquiry. Numerous opportunities for continued growth and scientific inquiry in the field of critical care pharmacotherapy research exist for the CCPTN to foster in the coming years. The CCPTN has been a successful model for practice-based pharmacotherapy research and assists its members in expanding critical care pharmacotherapy knowledge.

Major publications in the critical care pharmacotherapy literature in 2015.

Recently published practice guidelines and research reports on pharmacotherapy in critical care patient populations are summarized. The Critical Care Pharmacotherapy Literature Update (CCPLU) Group is composed of over 50 experienced critical care pharmacists who evaluate 31 peer-reviewed journals monthly to identify literature pertaining to pharmacotherapy in critical care populations. Articles are chosen for summarization in a monthly CCPLU Group publication on the basis of applicability and relevance to clinical practice and strength of study design. From January to December 2015, a total of 121 articles were summarized; of these, 3 articles presenting clinical practice guidelines and 12 articles presenting original research findings were objectively selected for inclusion in this review based on their potential to change or reinforce current evidence-based practice. The reviewed guidelines address the management of intracranial hemorrhage (ICH), adult advanced cardiac life support (ACLS) and post-cardiac arrest care, and the management of supraventricular tachycardia (SVT). The reviewed research reports address topics such as nutrition in critically ill adults, administration of β-lactams for severe sepsis, anticoagulant selection in the context of continuous renal replacement therapy, early goal-directed therapy in septic shock, magnesium use for neuroprotection in acute stroke, and progesterone use in patients with traumatic brain injury. Important recent additions to the critical care pharmacy literature include updated joint clinical practice guidelines on the management of spontaneous ICH, ACLS, and SVT.

Society of critical care medicine discovery: Collaborative critical care research network

Large-scale clinical trials networks are best suited for understanding how care is delivered, generating evidence to minimize unnecessary heterogeneity of patient care, and testing different care patterns and medications to improve clinical outcomes. Discovery, the Critical Care Research Network, was launched in 2017 as a combined effort of the United States Critical Illness and Injury Trials (USCIIT), the Critical Care Pharmacotherapy Trials Network (CCPTN), and the Society of Critical Care Medicine (SCCM). In collaboration with our colleagues we hope to contribute evidence to help improve the care of the critically ill and injured

Major publications in the critical care pharmacotherapy literature: January-December 2014.

Nine recently published articles and one guideline with important implications for critical care pharmacy practice are summarized. The Critical Care Pharmacotherapy Literature Update (CCPLU) group includes more than 40 experienced critical care pharmacists across the United States. Group members monitor 29 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on applicability to practice, relevance, and study design and strength. Hundreds of relevant articles were evaluated by the group in 2014, of which 114 were summarized and disseminated to CCPLU group members. From among those 114 publications, 10 deemed to be of particularly high utility to the critical care practitioner were selected for inclusion in this review for their potential to change practice or reinforce current evidence-based practice. One of the selected articles presents updated recommendations on the management of patients with atrial fibrillation (AF); the other 9 address topics such as albumin replacement in patients with severe sepsis, use of enteral statins for acute respiratory distress syndrome, fibrinolysis for patients with intermediate-risk pulmonary embolism, the use of unfractionated heparin versus bivalirudin for primary percutaneous coronary intervention, and early protocol-based care for septic shock. There were many important additions to the critical care pharmacotherapy literature in 2014, including a joint guideline for the management of AF and reports of clinical trials.

Major publications in the critical care pharmacotherapy literature: January-December 2013.

Ten recently published articles with important implications for critical care pharmacotherapy are summarized. The Critical Care Pharmacotherapy Literature Update (CCPLU) group is a national assembly of experienced intensive care unit (ICU) pharmacists across the United States. Group members monitor 25 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on (1) applicability to critical care practice, (2) relevance to pharmacy practitioners, and (3) quality of evidence or research methodology. Hundreds of relevant articles were evaluated by the group during the period January-December 2013, of which 98 were summarized and disseminated nationally to CCPLU group members. Among those 98 publications, 10 deemed to be of particularly high utility to critical care practitioners were included in this review. The 10 articles address topics such as rapid lowering of blood pressure in patients with intracranial hemorrhage, adjunctive therapy to prevent renal injury due to acute heart failure, triple-drug therapy to improve neurologic outcomes after cardiac arrest, and continuous versus intermittent infusion of β-lactam antibiotics in severe sepsis. There were many important additions to the critical care pharmacotherapy literature in 2013, including an updated guideline on the management of myocardial infarction and reports on advances in research focused on improving outcomes in patients with stroke or cardiac arrest and preventing the spread of drug-resistant pathogens in the ICU.

Major publications in the critical care pharmacotherapy literature: February 2012 through February 2013

Recent impactful additions to the professional literature on the role of pharmacotherapy in treating the critically ill are summarized. An unusually large number of updated practice guidelines and other publications with broad critical care pharmacotherapy ramifications appeared in the primary biomedical literature during the designated review period (February 2012-February 2013). Hundreds of relevant articles were evaluated by the Critical Care Pharmacotherapy Literature Update group (CCPLU), a national group of pharmacists who routinely monitor 25 peer-reviewed journals for emerging evidence that pertains to rational medication use in the intensive care unit (ICU) setting. From among those articles, 64 were summarized for dissemination to CCPLU members; the 8 publications deemed to have the greatest utility for critical care practitioners, as determined by CCPLU through a voting process, were selected for inclusion in this review, with preference given to evidence meeting high standards of methodological quality. The summaries presented here include (1) important new recommendations on management of pain, agitation, and delirium in critically ill patients, (2) a comprehensive update of a practice guideline issued in 2008 by the Surviving Sepsis Campaign, (3) novel strategies for the prevention and/or treatment of hyperglycemia in critical care, and (4) reports on clinical trials of promising alternative methods of sedation for use in weaning patients from mechanical ventilation. This review provides synopses of practice guidelines and other recent additions to the professional literature pertaining to rational medication use in the ICU practice setting.

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Introduction: Over the last decade several critical care clinical trial groups (CCCTG, ANZICS, USCIITG) have been created to foster critical care research. Complex critical care pharmacotherapy issues are often a secondary consideration of these groups. The Critical Care Pharmacotherapy Trials Netwo

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Introduction: A competent workforce is essential for an effective health care system. In order to maintain clinical competence in an area of practice, individuals must possess and maintain a therapeutic knowledge base sufficient to provide appropriate care to patients. Hypothesis: Implementation of a pharmacy department critical care resource increases pharmacists’ competence and/or clinical confidence when evaluating medication therapy in critically ill patients. Methods: This is a single center, survey based study conducted at a large, academic teaching hospital. As part of a formative survey, all inpatient pharmacists (N=106) were queried to establish need for a critical care resource and to assess topics of interest. Identified topics and requested material were compiled and developed into an electronically available resource on the department’s intranet. Pharmacists staffing critical care areas (N=50) were then requested to complete a pre- and post- survey that included both clinically based objective questions as well as subjective questions relating to their level of confidence before and after the resource’s implementation. Results: Twenty pharmacists (40%) voluntarily participated in the assessment survey process, however only 50% appropriately completed both the pre- and post-implementation surveys. After implementation of the critical care resource, 84% of responses to the objective questions were correct compared to 76% pre-implementation. 80% of responders utilized the critical care resource to aid in answering the clinical questions on the post-implementation survey. Sedation, analgesia, antibiotic selection, and endocrine were critical care concepts with the most improvement in the number of correct responses between the pre- and post-implementation surveys. 90% of responders rated their comfort level in answering critical care pharmacotherapy questions as slightly or extremely comfortable after the resource became available. Conclusions: The resource was positively received and there was an observed overall increase in pharmacists’ competence and clinical confidence after the implementation. Future plans are to use this resource to help develop a formal written critical care competency assessment tool.

A critical appraisal of the quality of critical care pharmacotherapy clinical practice guidelines and their strength of recommendations

Clinical practice guideline (CPG) quality assessment is important before applying their recommendations. Determining whether recommendation strength is consistent with supporting quality of evidence is also essential. We aimed to determine quality of critical care pharmacotherapy CPGs and to assess whether high quality evidence supports strong pharmacotherapy recommendations. MEDLINE (1966-February 2008), EMBASE (1980-February 2008), National Guideline Clearinghouse (February 2008) and personal files were searched to identify CPGs. Four appraisers evaluated each guideline using the appraisal of guidelines, research and evaluation (AGREE) instrument. AGREE assesses 23 items in six domains that include scope/purpose, stakeholder involvement, rigor of development, clarity, applicability and editorial independence. Standardized domain scores (0-100%) were determined to decide whether to recommend a guideline for use. One appraiser extracted strong pharmacotherapy recommendations and supporting evidence quality. Twenty-four CPGs were included. Standardized domain scores were clarity [69% (95% confidence interval (CI) 62-76%)], scope/purpose [62% (95% CI 55-68%)], rigor of development [51% (95% CI 42-60%)], editorial independence [39% (95% CI 26-52%)], stakeholder involvement [32% (95% CI 26-37%)] and applicability [19% (95% CI 12-26%)]. The proportion of guidelines that could be strongly recommended, recommended with alterations and not recommended was 25, 37.5 and 37.5%, respectively. High quality evidence supported 36% of strong pharmacotherapy recommendations. Variation in AGREE domain scores explain why one-third of critical care pharmacotherapy CPGs cannot be recommended. Only one-third of strong pharmacotherapy recommendations were supported by high quality evidence. We recommend appraisal of guideline quality and the caliber of supporting evidence prior to applying recommendations.

Critical care pharmacotherapy: issues and approaches.

Critically ill patients are a unique group with potentially altered pharmacokinetic and pharmacodynamic characteristics. The provision of optimal care to these patients is best accomplished via an intensivist-led multidisciplinary team. Included on this team should be a pharmacist specifically trained in critical care. The presence of a critical care pharmacist has been documented to not only decrease the cost of drug use in this setting but to improve the quality of care as well. Further investigations should focus on the impact of these interventions on outcomes. These will include pharmacoeconomic outcomes as well as their impact on other parts of the healthcare system in order to avoid cost shifting and improve morbidity and mortality.

New advances in the pharmacologic approach to circulatory shock

Anesthesiologists continue to play important roles in all aspects of critical care medicine. Although a unique pharmacology has evolved for use in the intensive care unit (ICU),’ much of the pharmacologic approach to the critically ill patient remains similar to the pharmacologic approach used for other perioperative conditions. Perhaps no area of critical care pharmacotherapy has evolved with more rapidity or more frustration than the pharmacologic approach to the treatment of circulatory shock. The purpose of this review is to detail our present approach to the treatment of this life-threatening condition, and to provide insight into the new avenues for therapy. Circulatory shock is an important cause of morbidity and mortality in acutely ill, hospitalized patients. Although commonly divided into four major types of circulatory shock (cardiogenic, hypovolemic, obstructive, and distributive), all forms of circulatory shock involve inadequate tissue perfusion and inadequate cellular oxygen (0,) delivery.* Cardiogenic shock is most often a consequence of acute myocardial infarction (MI), but it can also be a secondary consequence of valvular heart disease, worsening of congestive heart failure, myocardial trauma, and. so forth. Hypovolemic shock is usually due to hemorrhage, but it may also be a consequence of adrenal insufftciency or diabetes insipidus. Obstructive shock is usually due to pulmonary embolism or pericardial tamponade. Finally, distributive shock includes circulatory shock due to anaphylaxis, spinal cord shock, or, most commonly, septic shock. It is in the area of the treatment of septic shock that most new information has been realized. F!ecent evidence supports the concept that we may be missing the potential for cardiogenic or obstructive shock by failing to recognize myocardial injury in critically ill patients,3 and failing to recognize the extremely high prevalence of deep venous thrombosis in medical ICU patients despite the administration of prophylactic therapy.4 Thus, it may be that patients are predisposed to myocardial injury, which may develop into cardiogenic shock, and that patients may be at risk for the development of obstructive shock due to pulmonary emboli. Theise two recent realizations prompt me to suggest that screening critically injured patients for the possibility of myocardial injury if they have been traumatically injured is reasonable, and that patients should probably be screened with Doppler ultrasound for deep venous thrombosis. Before getting into some of the new treatment strategies used in septic shock