Size-Dependent Segregation Controls Macrophage Phagocytosis of Antibody-Opsonized Targets.

Macrophages protect the body from damage and disease by targeting antibody-opsonized cells for phagocytosis. Though antibodies can be raised against antigens with diverse structures, shapes, and sizes, it is unclear why some are more effective at triggering immune responses than others. Here, we define an antigen height threshold that regulates phagocytosis of both engineered and cancer-specific antigens by macrophages. Using a reconstituted model of antibody-opsonized target cells, we find that phagocytosis is dramatically impaired for antigens that position antibodies >10 nm from the target surface. Decreasing antigen height drives segregation of antibody-bound Fc receptors from the inhibitory phosphatase CD45 in an integrin-independent manner, triggering Fc receptor phosphorylation and promoting phagocytosis. Our work shows that close contact between macrophage and target is a requirement for efficient phagocytosis, suggesting that therapeutic antibodies should target short antigens in order to trigger Fc receptor activation through size-dependent physical segregation.

Individualized Treatment Effects of Bougie versus Stylet for Tracheal Intubation in Critical Illness.

Rationale: A recent randomized trial found that using a bougie did not increase the incidence of successful intubation on first attempt in critically ill adults. The average effect of treatment in a trial population, however, may differ from effects for individuals. Objective: We hypothesized that application of a machine learning model to data from a clinical trial could estimate the effect of treatment (bougie vs. stylet) for individual patients based on their baseline characteristics ("individualized treatment effects"). Methods: This was a secondary analysis of the BOUGIE (Bougie or Stylet in Patients Undergoing Intubation Emergently) trial. A causal forest algorithm was used to model differences in outcome probabilities by randomized group assignment (bougie vs. stylet) for each patient in the first half of the trial (training cohort). This model was used to predict individualized treatment effects for each patient in the second half (validation cohort). Measurements and Main Results: Of 1,102 patients in the BOUGIE trial, 558 (50.6%) were the training cohort, and 544 (49.4%) were the validation cohort. In the validation cohort, individualized treatment effects predicted by the model significantly modified the effect of trial group assignment on the primary outcome (P value for interaction = 0.02; adjusted qini coefficient, 2.46). The most important model variables were difficult airway characteristics, body mass index, and Acute Physiology and Chronic Health Evaluation II score. Conclusions: In this hypothesis-generating secondary analysis of a randomized trial with no average treatment effect and no treatment effect in any prespecified subgroups, a causal forest machine learning algorithm identified patients who appeared to benefit from the use of a bougie over a stylet and from the use of a stylet over a bougie using complex interactions between baseline patient and operator characteristics.

Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults.

BACKGROUND: Hypoxemia is the most common complication during tracheal intubation of critically ill adults and may increase the risk of cardiac arrest and death. Whether positive-pressure ventilation with a bag-mask device (bag-mask ventilation) during tracheal intubation of critically ill adults prevents hypoxemia without increasing the risk of aspiration remains controversial. METHODS: In a multicenter, randomized trial conducted in seven intensive care units in the United States, we randomly assigned adults undergoing tracheal intubation to receive either ventilation with a bag-mask device or no ventilation between induction and laryngoscopy. The primary outcome was the lowest oxygen saturation observed during the interval between induction and 2 minutes after tracheal intubation. The secondary outcome was the incidence of severe hypoxemia, defined as an oxygen saturation of less than 80%. RESULTS: Among the 401 patients enrolled, the median lowest oxygen saturation was 96% (interquartile range, 87 to 99) in the bag-mask ventilation group and 93% (interquartile range, 81 to 99) in the no-ventilation group (P = 0.01). A total of 21 patients (10.9%) in the bag-mask ventilation group had severe hypoxemia, as compared with 45 patients (22.8%) in the no-ventilation group (relative risk, 0.48; 95% confidence interval [CI], 0.30 to 0.77). Operator-reported aspiration occurred during 2.5% of intubations in the bag-mask ventilation group and during 4.0% in the no-ventilation group (P = 0.41). The incidence of new opacity on chest radiography in the 48 hours after tracheal intubation was 16.4% and 14.8%, respectively (P = 0.73). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, patients receiving bag-mask ventilation had higher oxygen saturations and a lower incidence of severe hypoxemia than those receiving no ventilation. (Funded by Vanderbilt Institute for Clinical and Translational Research and others; PreVent ClinicalTrials.gov number, NCT03026322.).

Bag-Mask Ventilation Versus Apneic Oxygenation During Tracheal Intubation in Critically Ill Adults: A Secondary Analysis of 2 Randomized Trials.

Background: Hypoxemia is common during tracheal intubation in intensive care units. To prevent hypoxemia during intubation, 2 methods of delivering oxygen between induction and laryngoscopy have been proposed: bag-mask ventilation and supplemental oxygen delivered by nasal cannula without ventilation (apneic oxygenation). Whether one of these approaches is more effective for preventing hypoxemia during intubation of critically ill patients is unknown. Methods: We performed a secondary analysis of data from 138 patients enrolled in 2, consecutive randomized trials of airway management in an academic intensive care unit. A total of 61 patients were randomized to receive bag-mask ventilation in a trial comparing bag-mask ventilation to none, and 77 patients were randomized to receive 100% oxygen at 15 L/min by nasal cannula in a trial comparing apneic oxygenation to none. Using multivariable linear regression accounting for age, body mass index, severity of illness, and oxygen saturation at induction, we compared patients assigned to bag-mask ventilation with those assigned to apneic oxygenation regarding lowest oxygen saturations from induction to 2 min after intubation. Results: Patients assigned to bag-mask ventilation and apneic oxygenation were similar at baseline. The median lowest oxygen saturation was 96% (interquartile range [IQR] 89%-100%) in the bag-mask ventilation group and 92% (IQR 84%-99%) in the apneic oxygenation group. After adjustment for prespecified confounders, bag-mask ventilation was associated with a higher lowest oxygen saturation compared to apneic oxygenation (mean difference, 4.2%; 95% confidence interval, 0.7%-7.8%; P = .02). The incidence of severe hypoxemia (oxygen saturation<80%) was 6.6% in the bag-mask ventilation group and 15.6% in the apneic oxygenation group (adjusted odds ratio, 0.33; P = .09). Conclusions: This secondary analysis of patients assigned to bag-mask ventilation and apneic oxygenation during 2 clinical trials suggests that bag-mask ventilation is associated with higher oxygen saturation during intubation compared to apneic oxygenation.

Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial.

Importance: Hypotension is common during tracheal intubation of critically ill adults and increases the risk of cardiac arrest and death. Whether administering an intravenous fluid bolus to critically ill adults undergoing tracheal intubation prevents severe hypotension, cardiac arrest, or death remains uncertain. Objective: To determine the effect of fluid bolus administration on the incidence of severe hypotension, cardiac arrest, and death. Design, Setting, and Participants: This randomized clinical trial enrolled 1067 critically ill adults undergoing tracheal intubation with sedation and positive pressure ventilation at 11 intensive care units in the US between February 1, 2019, and May 24, 2021. The date of final follow-up was June 21, 2021. Interventions: Patients were randomly assigned to receive either a 500-mL intravenous fluid bolus (n = 538) or no fluid bolus (n = 527). Main Outcomes and Measures: The primary outcome was cardiovascular collapse (defined as new or increased receipt of vasopressors or a systolic blood pressure <65 mm Hg between induction of anesthesia and 2 minutes after tracheal intubation, or cardiac arrest or death between induction of anesthesia and 1 hour after tracheal intubation). The secondary outcome was the incidence of death prior to day 28, which was censored at hospital discharge. Results: Among 1067 patients randomized, 1065 (99.8%) completed the trial and were included in the primary analysis (median age, 62 years [IQR, 51-70 years]; 42.1% were women). Cardiovascular collapse occurred in 113 patients (21.0%) in the fluid bolus group and in 96 patients (18.2%) in the no fluid bolus group (absolute difference, 2.8% [95% CI, -2.2% to 7.7%]; P = .25). New or increased receipt of vasopressors occurred in 20.6% of patients in the fluid bolus group compared with 17.6% of patients in the no fluid bolus group, a systolic blood pressure of less than 65 mm Hg occurred in 3.9% vs 4.2%, respectively, cardiac arrest occurred in 1.7% vs 1.5%, and death occurred in 0.7% vs 0.6%. Death prior to day 28 (censored at hospital discharge) occurred in 218 patients (40.5%) in the fluid bolus group compared with 223 patients (42.3%) in the no fluid bolus group (absolute difference, -1.8% [95% CI, -7.9% to 4.3%]; P = .55). Conclusions and Relevance: Among critically ill adults undergoing tracheal intubation, administration of an intravenous fluid bolus compared with no fluid bolus did not significantly decrease the incidence of cardiovascular collapse. Trial Registration: ClinicalTrials.gov Identifier: NCT03787732.

Validation of the Critical-Care Pain Observation Tool-Neuro in brain-injured adults in the intensive care unit: a prospective cohort study.

BACKGROUND: Pain assessment in brain-injured patients in the intensive care unit (ICU) is challenging and existing scales may not be representative of behavioral reactions expressed by this specific group. This study aimed to validate the French-Canadian and English revised versions of the Critical-Care Pain Observation Tool (CPOT-Neuro) for brain-injured ICU patients. METHODS: A prospective cohort study was conducted in three Canadian and one American sites. Patients with a traumatic or a non-traumatic brain injury were assessed with the CPOT-Neuro by trained raters (i.e., research staff and ICU nurses) before, during, and after nociceptive procedures (i.e., turning and other) and non-nociceptive procedures (i.e., non-invasive blood pressure, soft touch). Patients who were conscious and delirium-free were asked to provide their self-report of pain intensity (0-10). A first data set was completed for all participants (n = 226), and a second data set (n = 87) was obtained when a change in the level of consciousness (LOC) was observed after study enrollment. Three LOC groups were included: (a) unconscious (Glasgow Coma Scale or GCS 4-8); (b) altered LOC (GCS 9-12); and (c) conscious (GCS 13-15). RESULTS: Higher CPOT-Neuro scores were found during nociceptive procedures compared to rest and non-nociceptive procedures in both data sets (p < 0.001). CPOT-Neuro scores were not different across LOC groups. Moderate correlations between CPOT-Neuro and self-reported pain intensity scores were found at rest and during nociceptive procedures (Spearman rho > 0.40 and > 0.60, respectively). CPOT-Neuro cut-off scores ≥ 2 and ≥ 3 were found to adequately classify mild to severe self-reported pain ≥ 1 and moderate to severe self-reported pain ≥ 5, respectively. Interrater reliability of raters' CPOT-Neuro scores was supported with intraclass correlation coefficients > 0.69. CONCLUSIONS: The CPOT-Neuro was found to be valid in this multi-site sample of brain-injured ICU patients at various LOC. Implementation studies are necessary to evaluate the tool's performance in clinical practice.

Effect of Use of a Bougie vs Endotracheal Tube With Stylet on Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial.

Importance: For critically ill adults undergoing emergency tracheal intubation, failure to intubate the trachea on the first attempt occurs in up to 20% of cases and is associated with severe hypoxemia and cardiac arrest. Whether using a tracheal tube introducer ("bougie") increases the likelihood of successful intubation compared with using an endotracheal tube with stylet remains uncertain. Objective: To determine the effect of use of a bougie vs an endotracheal tube with stylet on successful intubation on the first attempt. Design, Setting, and Participants: The Bougie or Stylet in Patients Undergoing Intubation Emergently (BOUGIE) trial was a multicenter, randomized clinical trial among 1102 critically ill adults undergoing tracheal intubation in 7 emergency departments and 8 intensive care units in the US between April 29, 2019, and February 14, 2021; the date of final follow-up was March 14, 2021. Interventions: Patients were randomly assigned to use of a bougie (n = 556) or use of an endotracheal tube with stylet (n = 546). Main Outcomes and Measures: The primary outcome was successful intubation on the first attempt. The secondary outcome was the incidence of severe hypoxemia, defined as a peripheral oxygen saturation less than 80%. Results: Among 1106 patients randomized, 1102 (99.6%) completed the trial and were included in the primary analysis (median age, 58 years; 41.0% women). Successful intubation on the first attempt occurred in 447 patients (80.4%) in the bougie group and 453 patients (83.0%) in the stylet group (absolute risk difference, -2.6 percentage points [95% CI, -7.3 to 2.2]; P = .27). A total of 58 patients (11.0%) in the bougie group experienced severe hypoxemia, compared with 46 patients (8.8%) in the stylet group (absolute risk difference, 2.2 percentage points [95% CI, -1.6 to 6.0]). Esophageal intubation occurred in 4 patients (0.7%) in the bougie group and 5 patients (0.9%) in the stylet group, pneumothorax was present after intubation in 14 patients (2.5%) in the bougie group and 15 patients (2.7%) in the stylet group, and injury to oral, glottic, or thoracic structures occurred in 0 patients in the bougie group and 3 patients (0.5%) in the stylet group. Conclusions and Relevance: Among critically ill adults undergoing tracheal intubation, use of a bougie did not significantly increase the incidence of successful intubation on the first attempt compared with use of an endotracheal tube with stylet. Trial Registration: ClinicalTrials.gov Identifier: NCT03928925

A call for collaboration and consensus on training for endotracheal intubation in the medical intensive care unit.

Endotracheal intubation (EI) is a potentially lifesaving but high-risk procedure in critically ill patients. While the ACGME mandates that trainees in pulmonary and critical care medicine (PCCM) achieve competence in this procedure, there is wide variation in EI training across the USA. One study suggests that 40% of the US PCCM trainees feel they would not be proficient in EI upon graduation. This article presents a review of the EI training literature; the recommendations of a national group of PCCM, anesthesiology, emergency medicine, and pediatric experts; and a call for further research, collaboration, and consensus guidelines.

Management of Difficult Tracheal Intubation: A Closed Claims Analysis.

BACKGROUND: Difficult or failed intubation is a major contributor to morbidity for patients and liability for anesthesiologists. Updated difficult airway management guidelines and incorporation of new airway devices into practice may have affected patient outcomes. The authors therefore compared recent malpractice claims related to difficult tracheal intubation to older claims using the Anesthesia Closed Claims Project database. METHODS: Claims with difficult tracheal intubation as the primary damaging event occurring in the years 2000 to 2012 (n = 102) were compared to difficult tracheal intubation claims from 1993 to 1999 (n = 93). Difficult intubation claims from 2000 to 2012 were evaluated for preoperative predictors and appropriateness of airway management. RESULTS: Patients in 2000 to 2012 difficult intubation claims were sicker (78% American Society of Anesthesiologists [ASA] Physical Status III to V; n = 78 of 102) and had more emergency procedures (37%; n = 37 of 102) compared to patients in 1993 to 1999 claims (47% ASA Physical Status III to V; n = 36 of 93; P < 0.001 and 22% emergency; n = 19 of 93; P = 0.025). More difficult tracheal intubation events occurred in nonperioperative locations in 2000 to 2012 than 1993 to 1999 (23%; n = 23 of 102 vs. 10%; n = 10 of 93; P = 0.035). Outcomes differed between time periods (P < 0.001), with a higher proportion of death in 2000 to 2012 claims (73%; n = 74 of 102 vs. 42%; n = 39 of 93 in 1993 to 1999 claims; P < 0.001 adjusted for multiple testing). In 2000 to 2012 claims, preoperative predictors of difficult tracheal intubation were present in 76% (78 of 102). In the 97 claims with sufficient information for assessment, inappropriate airway management occurred in 73% (71 of 97; κ = 0.44 to 0.66). A "can't intubate, can't oxygenate" emergency occurred in 80 claims with delayed surgical airway in more than one third (39%; n = 31 of 80). CONCLUSIONS: Outcomes remained poor in recent malpractice claims related to difficult tracheal intubation. Inadequate airway planning and judgment errors were contributors to patient harm. Our results emphasize the need to improve both practitioner skills and systems response when difficult or failed tracheal intubation is encountered.

Nighttime Extubation Does Not Increase Risk of Reintubation, Length of Stay, or Mortality: Experience of a Large, Urban, Teaching Hospital.

BACKGROUND: In the intensive care unit (ICU), extubation failure has been associated with greater resource utilization and worsened clinical outcomes. Most recently, nighttime extubation (NTE) has been reported as a risk factor for increased ICU and hospital mortality. We hypothesized that, in a large, urban, university-affiliated hospital with multidisciplinary assessment for extubation, rigorously protocolized extubation algorithms, and expert airway managers available at all times of day for assessment of high-risk extubations, NTE would not confer additional risk of adverse clinical outcomes. METHODS: This was a retrospective cohort study of mechanically ventilated adults at a single university-affiliated hospital. NTE was defined as occurring between 7:00 PM and 6:59 AM the following day. All data were extracted from the institution's electronic medical record. Multivariable regression analyses were used to assess associations between NTE and reintubation, ICU and hospital length of stay (LOS), and mortality with adjustments for demographic and clinical covariates defined a priori. Palliative, unplanned, and routine postoperative extubations were excluded in sensitivity analyses. RESULTS: Of 2241 patients, 204 of 2241 (9.1%) underwent NTE. The rates of reintubation (NTE 6.9% versus daytime extubation [DTE] 12.4%; adjusted odds ratio [95% confidence interval {CI}], 0.78 [0.43-1.41]; P = .41) and in-hospital mortality (NTE 3.4% versus DTE 5.9%; adjusted odds ratio [95% CI], 0.72 [0.28-1.84]; P = .49) were not found to differ. NTE, compared to DTE, was associated with shorter duration of mechanical ventilation (median [interquartile range], 1 [0-1] days vs 2 [1-4] days; adjusted ratio of geometric means [RGMs] [95% CI], 0.64 [0.54-0.70]; P < .001), ICU (2 [1-5] days vs 4 [2-10] days; adjusted RGMs [95% CI], 0.65 [0.57-0.75]; P < .001), and hospital LOS (6 [3-18] days vs 13 [6-25] days; adjusted RGMs [95% CI], 0.64 [0.56-0.74]; P < .001). These results were unchanged in sensitivity analyses. CONCLUSIONS: Patients who underwent NTE were not at increased risk of reintubation or in-hospital mortality. In addition, NTE was associated with a shortened duration of mechanical ventilation and hospital LOS. In health care systems with similar critical care delivery models, NTE may coincide with reduced resource utilization in appropriately selected patients.

CLINICAL PRACTICE GUIDELINES FOR THE PERIOPERATIVE NUTRITION, METABOLIC, AND NONSURGICAL SUPPORT OF PATIENTS UNDERGOING BARIATRIC PROCEDURES - 2019 UPDATE: COSPONSORED BY AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY, THE OBESITY SOCIETY, AMERICAN SOCIETY FOR METABOLIC & BARIATRIC SURGERY, OBESITY MEDICINE ASSOCIATION, AND AMERICAN SOCIETY OF ANESTHESIOLOGISTS - EXECUTIVE SUMMARY.

Objective: The development of these updated clinical practice guidelines (CPGs) was commissioned by the American Association of Clinical Endocrinologists (AACE), The Obesity Society, American Society of Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists Boards of Directors in adherence with the AACE 2017 protocol for standardized production of CPGs, algorithms, and checklists. Methods: Each recommendation was evaluated and updated based on new evidence from 2013 to the present and subjective factors provided by experts. Results: New or updated topics in this CPG include: contextualization in an adiposity-based chronic disease complications-centric model, nuance-based and algorithm/checklist-assisted clinical decision-making about procedure selection, novel bariatric procedures, enhanced recovery after bariatric surgery protocols, and logistical concerns (including cost factors) in the current health-care arena. There are 85 numbered recommendations that have updated supporting evidence, of which 61 are revised and 12 are new. Noting that there can be multiple recommendation statements within a single numbered recommendation, there are 31 (13%) Grade A, 42 (17%) Grade B, 72 (29%) Grade C, and 101 (41%) Grade D recommendations. There are 858 citations, of which 81 (9.4%) are evidence level (EL) 1 (highest), 562 (65.5%) are EL 2, 72 (8.4%) are EL 3, and 143 (16.7%) are EL 4 (lowest). Conclusion: Bariatric procedures remain a safe and effective intervention for higher-risk patients with obesity. Clinical decision-making should be evidence based within the context of a chronic disease. A team approach to perioperative care is mandatory, with special attention to nutritional and metabolic issues. A1C = hemoglobin A1c; AACE = American Association of Clinical Endocrinologists; ABCD = adiposity-based chronic disease; ACE = American College of Endocrinology; ADA = American Diabetes Association; AHI = Apnea-Hypopnea Index; ASA = American Society of Anesthesiologists; ASMBS = American Society of Metabolic and Bariatric Surgery; BMI = body mass index; BPD = biliopancreatic diversion; BPD/DS = biliopancreatic diversion with duodenal switch; CI = confidence interval; CPAP = continuous positive airway pressure; CPG = clinical practice guideline; CRP = C-reactive protein; CT = computed tomography; CVD = cardiovascular disease; DBCD = dysglycemia-based chronic disease; DS = duodenal switch; DVT = deep venous thrombosis; DXA = dual-energy X-ray absorptiometry; EFA = essential fatty acid; EL = evidence level; EN = enteral nutrition; ERABS = enhanced recovery after bariatric surgery; FDA = U.S. Food and Drug Administration; G4G = Guidelines for Guidelines; GERD = gastroesophageal reflux disease; GI = gastrointestinal; HCP = health-care professional(s); HTN = hypertension; ICU = intensive care unit; IGB = intragastric balloon(s); IV = intravenous; LAGB = laparoscopic adjustable gastric band; LAGBP = laparoscopic adjustable gastric banded plication; LGP = laparoscopic greater curvature (gastric) plication; LRYGB = laparoscopic Roux-en-Y gastric bypass; LSG = laparoscopic sleeve gastrectomy; MetS = metabolic syndrome; NAFLD = nonalcoholic fatty liver disease; NASH = nonalcoholic steatohepatitis; NSAID = nonsteroidal anti-inflammatory drug; OA = osteoarthritis; OAGB = one-anastomosis gastric bypass; OMA = Obesity Medicine Association; OR = odds ratio; ORC = obesity-related complication(s); OSA = obstructive sleep apnea; PE = pulmonary embolism; PN = parenteral nutrition; PRM = pulmonary recruitment maneuver; RCT = randomized controlled trial; RD = registered dietician; RDA = recommended daily allowance; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; SIBO = small intestinal bacterial overgrowth; TOS = The Obesity Society; TSH = thyroid-stimulating hormone; T1D = type 1 diabetes; T2D = type 2 diabetes; VTE = venous thromboembolism; WE = Wernicke encephalopathy; WHO = World Health Organization.

Inclined position is associated with improved first pass success and laryngoscopic view in prehospital endotracheal intubations.

PURPOSE: In hospital-based studies, patients intubated by physicians while in an inclined position compared to supine position had a higher rate of first pass success and lower rate of peri-intubation complications. We evaluated the impact of patient positioning on prehospital endotracheal intubation in an EMS system with rapid sequence induction capability. We hypothesized that patients in the inclined position would have a higher first-pass success rate. METHODS: Prehospital endotracheal intubation cases performed by paramedics between 2012 and 2017 were prospectively collected in airway registries maintained by a metropolitan EMS system. We included all adult (age ≥ 18 years) non-traumatic, non-arrest patients who received any attempt at intubation. Patients were categorized according to initial positioning: supine or inclined. The primary outcome measure was first pass success with secondary outcomes of laryngoscopic view and challenges to intubation. RESULTS: Of the 13,353 patients with endotracheal intubation attempted by paramedics during the study period, 4879 were included for analysis. Of these, 1924 (39.4%) were intubated in the inclined position. First pass success was 86.3% among the inclined group versus 82.5% for the supine group (difference 3.8%, 95% CI: 1.5%-6.1%). First attempt laryngeal grade I view was 62.9% in the inclined group versus 57.1% for the supine group (difference 5.8%, 2.0-9.6). Challenges to intubation were more frequent in the supine group (42.3% versus 38.8%, difference 3.5%, 0.6-6.3). CONCLUSION: Inclined positioning was associated with a better grade view and higher rate of first pass success. The technique should be considered as a viable approach for prehospital airway management.

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU.

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.

Airway Management Practice in Adults With an Unstable Cervical Spine: The Harborview Medical Center Experience.

BACKGROUND: Airway management in the presence of acute cervical spine injury (CSI) is challenging. Because it limits cervical spine motion during tracheal intubation and allows for neurological examination after the procedure, awake fiberoptic bronchoscopy (FOB) has traditionally been recommended. However, with the widespread availability of video laryngoscopy (VL), its use has declined dramatically. Our aim was to describe the frequency of airway management techniques used in patients with CSI at our level I trauma center and report the incidence of neurological injury attributable to airway management. METHODS: Adults presenting to the operating room with CSI without a tracheal tube in situ between September 2010 and June 2017 were included. All patients were intubated in the presence of manual-in-line stabilization, a hard cervical collar, or surgical traction. Worsening neurological status was defined as new motor or sensory deficits on postoperative examination. RESULTS: Two hundred fifty-two patients were included, of which 76 (30.2%) had preexisting neurological deficits. VL was the most frequent initial airway management technique used (49.6%). Asleep FOB was commonly performed alone (30.6%) or in conjunction with VL (13.5%). Awake FOB was rarely performed (2.3%), as was direct laryngoscopy (2.8%). All techniques were associated with high first-attempt success rates, and no cases of neurological injury attributable to airway management technique were identified. CONCLUSIONS: Among patients with acute CSI at a high-volume academic trauma center, VL was the most commonly used initial intubation technique. Awake FOB and direct laryngoscopy were performed infrequently. No cases of neurological deterioration secondary to airway management occurred with any method. Assuming care is taken to limit neck movement, providers should use the intubation technique with which they have the most comfort and skill.

Content validation of behaviours and autonomic responses for the assessment of pain in critically ill adults with a brain injury.

BACKGROUND: The evidence shows that brain-injured patients express behaviours that are related to their level of consciousness (LOC), and different from other patients in the intensive care unit (ICU). Therefore, existing behavioural scales should be revised to enhance their content and validity for use in these patients. OBJECTIVES: The aim was to evaluate the content relevance of behaviours and autonomic responses for pain assessment of brain-injured ICU patients from the perspective of critical care clinicians. METHODS: A total of 77 clinicians from four adult neuroscience ICUs (three from Canada and one from the United States) participated in this descriptive study. A physician/nurse ratio of 21% (13/61) was reached in this quota sample, and three physiotherapists also participated. They completed a content validation questionnaire of 19 items rated on clarity and relevance based on the patient's LOC. Item Content Validity Index (I-CVI), and modified kappa (κ*) were calculated. Values higher than 0.78 and 0.75 respectively were considered excellent. RESULTS: Regardless of the patient's LOC, brow lowering, grimacing, and trying to reach the pain site were rated as the most relevant behaviours by clinicians, with excellent values of I-CVI>0.78 and κ*>0.75. Eyes tightly closed, moaning and verbal complaints of pain also obtained excellent values in altered LOC and conscious patients. Eye weeping obtained excellent values only in conscious patients. Other items showed fair (0.40-0.59) to good (0.60-0.74) values, while blinking and coughing showed poor values (<0.40) at various LOC. CONCLUSIONS: Facial expressions, movements towards the pain site, and vocalisation of pain were the most relevant pain-related behaviours rated by critical care clinicians. The relevance of some behaviours (e.g., moaning and verbal complaints of pain) varied across LOCs, thereby calling forth adaptations of behavioural pain scales to allow for interpretation in the context of a patient's LOC and ability to express specific behaviours.

Effects of 14 Versus 21 Days of Nimodipine Therapy on Neurological Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients.

BACKGROUND: Oral nimodipine is standard therapy for patients suffering an aneurysmal subarachnoid hemorrhage (aSAH). During a national drug shortage, nimodipine therapy was shortened from a 21-day course to a 14-day course at our institution. OBJECTIVE: The objective of this study was to compare neurological outcomes among patients who had previously received the standard duration of therapy compared with those who received a shortened duration as a result of the national drug shortage. METHODS: This retrospective cohort study evaluated adult patients receiving nimodipine for aSAH from January 2012 to August 2013. Neurological outcome, graded by Modified Rankin Scale (mRS) at hospital discharge, was compared between patients receiving a shortened course and those receiving the standard duration of nimodipine. RESULTS: A total of 199 aSAH patients were included in the analysis. There were 164 patients in the standard-duration and 35 patients in the shortened-duration group. Baseline patient severity of illness, assessed by SAPS II (Simplified Acute Physiology Score), and severity of aSAH, assessed by Fisher grade, and Hunt and Hess grade scores, did not differ between the treatment groups. A shortened duration of nimodipine was not associated with a higher risk of a poor neurological outcome defined by mRS (odds ratio = 1.85; 95% CI = 0.54-6.32; P = 0.32). Mortality rates were similar between the groups. CONCLUSIONS: A 14-day course of nimodipine therapy was not associated with worse neurological outcomes in aSAH patients at one institution. More studies are needed prior to recommending a shortened duration of nimodipine therapy in all aSAH patients.

Head-Elevated Patient Positioning Decreases Complications of Emergent Tracheal Intubation in the Ward and Intensive Care Unit.

BACKGROUND: Based on the data from elective surgical patients, positioning patients in a back-up head-elevated position for preoxygenation and tracheal intubation can improve patient safety. However, data specific to the emergent setting are lacking. We hypothesized that back-up head-elevated positioning would be associated with a decrease in complications related to tracheal intubation in the emergency room environment. METHODS: This retrospective study was approved by the University of Washington Human Subjects Division (Seattle, WA). Eligible patients included all adults undergoing emergent tracheal intubation outside of the operating room by the anesthesiology-based airway service at 2 university-affiliated teaching hospitals. All intubations were through direct laryngoscopy for an indication other than full cardiopulmonary arrest. Patient characteristics and details of the intubation procedure were derived from the medical record. The primary study endpoint was the occurrence of a composite of any intubation-related complication: difficult intubation, hypoxemia, esophageal intubation, or pulmonary aspiration. Multivariable logistic regression was used to estimate the odds of the primary endpoint in the supine versus back-up head-elevated positions with adjustment for a priori-defined potential confounders (body mass index and a difficult intubation prediction score [Mallampati, obstructive sleep Apnea, Cervical mobility, mouth Opening, Coma, severe Hypoxemia, and intubation by a non-Anesthesiologist score]). RESULTS: Five hundred twenty-eight patients were analyzed. Overall, at least 1 intubation-related complication occurred in 76 of 336 (22.6%) patients managed in the supine position compared with 18 of 192 (9.3%) patients managed in the back-up head-elevated position. After adjusting for body mass index and the Mallampati, obstructive sleep Apnea, Cervical mobility, mouth Opening, Coma, severe Hypoxemia, and intubation by a non-Anesthesiologist score, the odds of encountering the primary endpoint during an emergency tracheal intubation in a back-up head-elevated position was 0.47 (95% confidence interval, 0.26-0.83; P = 0.01). CONCLUSIONS: Placing patients in a back-up head-elevated position, compared with supine position, during emergency tracheal intubation was associated with a reduced odds of airway-related complications.