Search

ObjectivesClinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators.DesignA 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process.ParticipantsThirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process.Measurements and main resultsThe final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization.ConclusionsThese recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials.

OBJECTIVE:To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU. DESIGN:Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017. METHODS:Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as "strong," "conditional," or "good" practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified. RESULTS:The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation. CONCLUSIONS:We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Background: Longitudinal analyses of large, detailed adult critical care datasets provide insights into practice trends and generate useful outcome and process benchmarks.Methods: Data representing 991,571 consecutive critical care visits to 160 US adult ICUs from 2009 to 2013 from the eICU Research Institute clinical practice database were used to quantitate patient characteristics, APACHE IV-based acuity predictions, treatments, and outcomes. Analyses for changes over time were performed for patient characteristics, entry and discharge locations, primary admission diagnosis, treatments, adherence to consensus ICU best practices, length of stay (LOS), and inpatient mortality.Results: We detected significant trends for increasing age, BMI, and risk of mortality, higher frequency of admission from an ED and stepdown unit, and more frequent hospital discharge to substance abuse centers and skilled nursing facilities. Significantly more patients were admitted for sepsis, emphysema, coma, congestive heart failure, diabetic ketoacidosis, and fewer were admitted for asthma, unspecified chest pain, coronary artery bypass graft, and stroke care. The frequency of noninvasive mechanical ventilation and adherence to critical care best practices significantly increased, whereas the duration of renal replacement therapies, frequency of transfusions, antimicrobial use, critical care complications, LOS, and inpatient mortality decreased.Conclusions: Analyses of patients, practices, and outcomes from a large geographically dispersed sample of adult ICUs revealed trends of increasing age and acuity, higher rates of adherence to best practice, use of noninvasive mechanical ventilation, and decreased use of antimicrobials, transfusions, and duration of renal replacement therapies. Acuity-adjusted LOS and in hospital mortality decreased. [ABSTRACT FROM AUTHOR]

Study Objective The free fraction of valproate (the pharmacologically active moiety, normally 5-10%) may vary significantly in critically ill patients, but this topic is understudied, with only four prior intensive care unit ( ICU) case reports. The objective of this study was to evaluate the range of valproate plasma protein binding in ICU patients. Design Observational study of consecutive ICU patients. Setting Neurocritical and medical critical care services in a nonuniversity academic medical center. Patients Consecutive ICU patients treated with valproate with serum albumin less than 4 g/dl. Measurements and Main Results Simultaneous total and free trough serum valproate concentrations were measured as were serum creatinine, blood urea nitrogen, albumin, platelets, and transaminase values. The reference concentration range was 50-125 mg/L (total) and 5-17 mg/L (free). Valproate concentrations were categorized as within reference range, low, or high, and as concordant if both concentrations were in the same category. Data are reported as median (interquartile range). Fifteen patients (nine men) were evaluated. The median age was 63 (34-70) years. The valproate dose was 3 g/day (35 mg/kg/day). No patient had a valproate free fraction of 5-10%; the median was 48%, and the range was 15-89%. Total and free concentrations showed poor correlation (0.43) and were concordant in only two patients (both in the reference range). Free valproate concentration was poorly predicted by an equation correcting for albumin (r = 0.45). Suspected adverse drug events occurred in 10 patients: hyperammonemia in 7 of 12 tested (58%), elevated transaminases in 2 of 15 (13%), and thrombocytopenia in 5 of 15 (33%). Conclusions Protein binding of valproate was highly inconsistent in this cohort of ICU patients, and total valproate concentrations did not predict free concentrations, even when correcting for albumin. Additional research to define best practice for dosing and monitoring valproate and the relationship between free valproate concentrations and clinical or adverse effects in ICU patients is needed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Breathing discomfort (dyspnea) during mechanical ventilation in the ICU may contribute to patient distress and complicate care. Assessment of nonverbal cues may allow care-givers to estimate patient breathing discomfort. This study assesses the accuracy of those caregiver estimates. METHODS: Thirty subjects were identified from ventilated, hemodynamically stable patients in the special care unit of Maine Medical Center. Those with impaired neurological function or too unstable to waken were excluded. Subjects provided a subjective score of breathing discomfort (0-10 using a modified Borg scale) during daily wake-up from sedation (sedation-agitation score of 3 or 4). Clinicians (physicians, respiratory therapists, and nurses) then provided a blinded estimate of subject breathing discomfort (0-10) through observation of the subject and inspection of ventilator parameters alone. Subject scores and caregiver estimates were compared. RESULTS: All subjects reported breathing discomfort with median score (interquartile range) of 4 (3-4). Caregiver estimates of breathing discomfort were significantly lower than subject scores (2 [0-3]), and the discrepancy was seen in all professions (physicians 1 point lower [0-2], P = .02; respiratory therapists 1 point lower [0-2], P = .01; nurses 2 points lower [1-3], P < .001). There was a positive correlation between subject breathing discomfort and degree of underestimation (ie, the degree of underestimation increased as the subject scores rose). The 3 most commonly used cues were subjects' facial expression, use of accessory muscles, and nasal flaring. CONCLUSIONS: Significant breathing discomfort is prevalent in mechanically ventilated ICU patients and is underestimated by caregivers, regardless of profession. The increasing disparity in caregiver estimate as breathing discomfort rises may expose patients to levels of dyspnea that promote anxiety and fear. This study demonstrates the need for further development and standardization of methods to assess dyspnea in nonverbal patients. [ABSTRACT FROM AUTHOR]

Introduction Enteral clonidine represents a potentially less costly alternative to dexmedetomidine for sedation in intensive care unit ( ICU) patients. This study describes our practice of transitioning selected adult ICU patients from dexmedetomidine to clonidine with a focus on efficacy, safety, and drug acquisition costs. Methods We conducted a single-center prospective observational pilot study from January through March 2014. Consecutive patients 18 years and older treated with dexmedetomidine and transitioned to clonidine were followed. The transition was assessed in five phases: dexmedetomidine maintenance, transition, clonidine maintenance, clonidine taper, and post clonidine. Efficacy data included any occurrence of significant pain, excessive agitation or oversedation, delirium, and need for ancillary psychoactive medications. Safety data included any occurrence of bradycardia, hypotension, new second- or third-degree atrioventricular node blockade, and clonidine withdrawal syndrome. Drug acquisition cost avoidances were estimated using average wholesale price. Results Twenty patients were evaluated. Fifteen (75%) were successfully transitioned from dexmedetomidine within 48 hours of starting clonidine. The initial and maintenance clonidine regimens were 0.3 mg every 6 hours. Clonidine was the sole α2A-receptor agonist administered for 45 hours while in the ICU and for 54 hours outside the ICU. Fentanyl requirements were lower when clonidine was administered as the sole α2A-receptor agonist as compared to dexmedetomidine alone (387 vs. 891 μg/day, p = 0.03). Otherwise, there were no statistically significant differences in efficacy data during the dexmedetomidine and clonidine maintenance phases. No statistically significant differences in safety data were observed. Clonidine withdrawal syndrome criteria were met in one patient. The potential drug acquisition cost avoidance was $819-$2338 per patient during the 3-month study. Conclusions Transitioning from dexmedetomidine to clonidine may be an efficacious, safe, and less costly method of maintaining α2A-receptor agonist therapy in critically ill adults; these results warrant confirmation in expanded studies. [ABSTRACT FROM AUTHOR]

Objective: To revise the "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" published in Critical Care Medicine in 2002. Methods: The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks® database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (-) an intervention. A strong recommendation (either for or against) indicated that the intervention's desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase "We recommend ..." is used throughout. A weak recommendation, either for or against an intervention, indicated that the tradeoff between desirable and undesirable effects was less clear. For all weak recommendations, the phrase "We suggest ..." is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding. Conclusion: These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients. [ABSTRACT FROM AUTHOR]

Objective: To revise the "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" published in Critical Care Medicine in 2002. Methods: The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks® database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (-) an intervention. A strong recommendation (either for or against) indicated that the intervention's desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase "We recommend ..." is used throughout. A weak recommendation, either for or against an intervention, indicated that the tradeoff between desirable and undesirable effects was less clear. For all weak recommendations, the phrase "We suggest ..." is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding. Conclusion: These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients. [ABSTRACT FROM AUTHOR]

Study Objective. To determine a threshold dose for parenteral lorazepam when screening for propylene glycol toxicity with the osmol gap, and to characterize which osmol gap values are more predictive of toxic propylene glycol concentrations and resultant clinical toxicity. Design. Prospective, two-phase observational study. Setting. Thirty-two bed, multidisciplinary intensive care unit. Patients. Thirty-five adult patients receiving any dose of parenteral lorazepam (phase 1), and 14 patients receiving lorazepam in doses of 1 mg/kg/day or higher (phase 2). Measurements and Main Results. Serum osmolality was measured every other day during lorazepam therapy, and the osmol gap (measured osmolality minus calculated osmolarity) was determined. A serum propylene glycol concentration was obtained when the osmol gap first exceeded 10. In phase 1, 35 patients were monitored for 186 patient-days. Ten patients (29%) developed an osmol gap greater than 10; only one (10%) of these patients had propylene glycol concentrations greater than 18 mg/dl. In phase 2, 14 patients received lorazepam at a median dose of 631 mg (interquartile range [IQR] 437-972 mg) over a median of 5.5 days (IQR 4-8.75 days). Nine patients (64%) had propylene glycol concentrations greater than 18 mg/dl; six (67%) of these nine developed transient acute kidney injury, metabolic acidosis, or both. The correlation between osmol gap and propylene glycol concentration was 0.44 (p=0.006). An osmol gap of 10 or greater had a likelihood ratio of 4.4 to predict a propylene glycol concentration greater than 18 mg/dl. An osmol gap of 12 or greater had a likelihood ratio of 2.7 to predict the development of possible propylene glycol clinical toxicity. Conclusion. Screening for propylene glycol toxicity with the osmol gap may be helpful for patients receiving intravenous lorazepam in doses of 1 mg/kg/day or higher. An osmol gap of 10 or greater was predictive of elevated propylene glycol concentrations, and values of 12 or greater were predictive of clinical changes suggestive of propylene glycol toxicity. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the authors refer to the topic diagnosing delirium in ICU patients with primary neurologic diagnosesand the association of delirium with specific outcome, and talks of sepsis, drug toxicity, and environmental influences as potential etiologies of delirium.

The article evaluates the impact of individual manifestations of delirium on patient outcome in the U.S. In addition, it also describe the critically ill adults, and validate nurses' bedside item assessments from the Intensive Care Delirium Screening Checklist (ICDSC). It concludes that agitation was associated with a higher risk of mortality in nondelirious patients. Moreover, each of the eight ICDSC items is highly discriminating for the diagnosis of delirium.

The authors reflect on the "Sedation Lightening and Evaluation of A Protocol (SLEAP)" study by S. Mehta and colleagues which was published in the periodical "Critical Care Medicine." Topics discussed include the study centers on intensive care unit (ICU) delirium frequency, risk factors and related outcomes, assessment methods for ICU delirium, and manifestation of delirium.

An introduction is presented in which the editors discuss a report within the issue by Y. Skrobik and colleagues, which focuses on the characterization of benzodiazepine as a risk factor for delirium.

Introduction Prophylactic antibiotics (PRO) reduce the incidence of early-onset pneumonia in comatose patients with structural brain injury, but have not been examined in cardiac arrest survivors undergoing targeted temperature management (TTM). We investigated the effect of PRO on the development of pneumonia in that population. Methods We conducted a retrospective cohort study comparing patients treated with PRO to those not receiving PRO (no-PRO) using Northern Hypothermia Network registry data. Cardiac arrest survivors ≥18 years of age with a GCS < 8 at hospital admission and treated with TTM at 32–34 °C were enrolled in the registry. Differences were analyzed in univariate analyses and with logistic regression models to evaluate independent associations of clinical factors with incidence of pneumonia and good functional outcome. Results 416 of 1240 patients (33.5%) received PRO. Groups were similar in age, gender, arrest location, initial rhythm, and time from collapse to return of spontaneous circulation. PRO patients had less pneumonia (12.6% vs. 54.9%, p < 0.001) and less sepsis (1.2 vs. 5.7%, p < 0.001) compared to no-PRO patients. ICU length of stay (98 vs. 100 h, p = 0.2) and incidence of a good functional outcome (41.1 vs. 36.6%, p = 0.19) were similar between groups. Backwards stepwise logistic regression demonstrated PRO were independently associated with a lower incidence of pneumonia (OR 0.09, 95% 0.06–0.14, p < 0.001) and a similar incidence of good functional outcome. Conclusions Prophylactic antibiotics were associated with a reduced incidence of pneumonia but a similar rate of good functional outcome. [ABSTRACT FROM AUTHOR]

Objective: To describe and analyze the development and psychometric properties of subjective sedation scales developed for critically ill adult patients. Data Sources: PubMed, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, ISI Web of Science, and the International Pharmaceutical Abstracts. Study Selection: English-only publications through December 2012 with at least 30 patients older than 18 years, which included the key words of adult, critically ill, subjective sedation scale, sedation scale, validity, and reliability. Data Extraction: Two independent reviewers evaluated the psychometric properties using a standardized sedation scale psychometric scoring system. Data Synthesis: Among the 19,000+ citations extracted for the 2013 Society of Critical Care Medicine's Clinical Practice Guidelines for the Management of Pain, Agitation and Delirium and from December 2010 to 2012, 36 articles were identified compassing 11 sedation scales. The scale development process, psychometric properties, feasibility, and implementation of sedation scales were analyzed using a 0-20 scoring system. Two scales demonstrated scores indicating "very good" published psychometric properties: Richmond Agitation-Sedation Scale (19.5) and the Sedation-Agitation Scale (19). Scores with "moderate" properties include the Vancouver Interaction and Calmness Scale (1 4.3), Adaptation to the Intensive Care Environment (1 3.7), Ramsay Sedation Scale (1 3.2), Minnesota Sedation Assessment Tool (13), and the Nursing Instrument for the Communication of Sedation (1 2.8). Scales with "low" properties included the Motor Activity Assessment Scale (11 .5) and the Sedation Intensive Care Score (10.5). The New Sheffield Sedation Scale (8.5) and the Observer's Assessment of Alertness/Seda- tion Scale (3.7) demonstrated "very low" published properties. Conclusions: Based on the current literature, and using a prede- termined psychometric scoring system, the Richmond Agitation-Sedation Scale and the Sedation-Agitation Scale are the most valid and reliable subjective sedation scales for use in critically ill adult patients. [ABSTRACT FROM AUTHOR]

The article discusses a prospective, observational study on the link between adverse reaction and mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. Some of the adverse events include arrhythmias, pneumonia and seizures. The study found that bleeding and infection were not related to high mortality in the study.