Gérald Chanques

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.

RATIONALE: Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation (MV). Paradoxically, MV itself results in a rapid loss of diaphragmatic strength in animals. However, very little is known about the time course or mechanistic basis for such a phenomenon in humans. OBJECTIVES: To determine in a prospective fashion the time course for development of diaphragmatic weakness during MV; and the relationship between MV duration and diaphragmatic injury or atrophy, and the status of candidate cellular pathways implicated in these phenomena. METHODS: Airway occlusion pressure (TwPtr) generated by the diaphragm during phrenic nerve stimulation was measured in short-term (0.5 h; n = 6) and long-term (>5 d; n = 6) MV groups. Diaphragmatic biopsies obtained during thoracic surgery (MV for 2-3 h; n = 10) and from brain-dead organ donors (MV for 24-249 h; n = 15) were analyzed for ultrastructural injury, atrophy, and expression of proteolysis-related proteins (ubiquitin, nuclear factor-κB, and calpains). MEASUREMENTS AND MAIN RESULTS: TwPtr decreased progressively during MV, with a mean reduction of 32 ± 6% after 6 days. Longer periods of MV were associated with significantly greater ultrastructural fiber injury (26.2 ± 4.8 vs. 4.7 ± 0.6% area), decreased cross-sectional area of muscle fibers (1,904 ± 220 vs. 3,100 ± 329 μm²), an increase of ubiquitinated proteins (+19%), higher expression of p65 nuclear factor-κB (+77%), and greater levels of the calcium-activated proteases calpain-1, -2, and -3 (+104%, +432%, and +266%, respectively) in the diaphragm. CONCLUSIONS: Diaphragmatic weakness, injury, and atrophy occur rapidly in critically ill patients during MV, and are significantly correlated with the duration of ventilator support.

BACKGROUND: The authors conducted a patient-based survey of practices to fully describe the assessment and the management of pain and sedation of a large cohort of mechanically ventilated patients during their first week of intensive care unit (ICU) stay. METHODS: A total of 1,381 adult patients were included in a prospective, observational study in 44 ICUs in France. Pain and sedation assessment, analgesic and sedative use, and analgesic management during procedural pain were collected on days 2, 4, and 6 of the ICU stay. RESULTS: The observed rates of assessment on day 2 for sedation (43%) and analgesia (42%) were significantly smaller than that of use of sedatives (72%) and opioids (90%), also noted on days 4 and 6. The use of protocols/guidelines for sedation/analgesia in the ICU reduced the proportion of patients who were treated, although not evaluated. A large proportion of assessed patients were in a deep state of sedation (40-50%). Minor changes in the dosages of the main prescribed agents for sedation (midazolam, propofol) and analgesia (sufentanil, fentanyl, morphine, remifentanil) were found across 6 days of the patient's ICU stay. Procedural pain was specifically managed for less than 25% of patients; during those procedures, the proportion of patients with pain significantly increased from the baseline pain evaluation. CONCLUSIONS: Excessively deep states of sedation and a lack of analgesia during painful procedures must be prevented. To facilitate systematic pain and sedation assessment and to adjust daily drug dosages accordingly, it seems crucial to promote educational programs and elaboration of protocols/guidelines in the ICU.

OBJECTIVE: To measure the impact of implementation of the systematic evaluation of pain and agitation by nurses using the Behavioral Pain Scale (BPS), the Numerical Rating Scale (NRS) for pain, and the Richmond Agitation Sedation Scale (RASS) associated with medical staff education in analgesia and sedation management in intensive care unit (ICU) patients. DESIGN: Two-phase, prospective, controlled study. SETTING: Twelve-bed medical-surgical ICU in a university hospital. PATIENTS: Consecutive patients staying >24 hrs in ICU. INTERVENTIONS: BPS, NRS, and RASS were measured twice daily, at rest, by independent observers during 21 wks (control group) and after 4 wks of training, by nurses during 29 wks (intervention group). In the intervention group, the treating physician was alerted in case of pain defined by BPS>5 or NRS>3 or in case of agitation defined by RASS>1. MEASUREMENTS AND MAIN RESULTS: A total of 230 patients were included (control group, n=100; intervention group, n=130). Baseline characteristics were not significantly different. The incidence of pain and agitation decreased significantly in the intervention group: 63% vs. 42% (p=.002) and 29% vs. 12% (p=.002), respectively. Rate of severe pain and agitation events defined by NRS>6 and RASS>2, respectively, also decreased significantly. There were significantly more therapeutic changes in the intervention group in the way of an escalation but also in the way of a de-escalation for analgesic and psychoactive drugs. Compared with the control group, there was a marked decrease in the duration of mechanical ventilation (120 [interquartile range 48-312] vs. 65 (24-192) hrs, p=.01) and nosocomial infections rate (17% vs. 8%, p<.05) in the intervention group. There was no significant difference in median length of stay (9 [4, 15] vs. 7 [4, 13] days) and mortality in ICU (12 vs. 15%). CONCLUSIONS: Systematic evaluation of pain and agitation, and analgesics and sedatives need was associated with a decrease in incidence of pain and agitation, duration of mechanical ventilation and nosocomial infections.