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Objective: To demonstrate the usefulness of real-time guidance with CT fluoroscopy to improve the yield of transbronchial needle aspiration (TBNA).Design: Prospective, observational.Setting: A tertiary-care, university-affiliated medical center.Methods: From December 1998 to April 2000, 35 patients underwent CT fluoroscopy-guided TBNA. Patients with subcarinal and precarinal lymph nodes were only included if a previous attempt was nondiagnostic, as the initial yield in this setting with conventional TBNA is high. TBNA was performed using standard technique in a CT-scan suite. Needle location was confirmed with fluoroscopy without IV contrast being used. Specimens were evaluated on-site for adequacy.Results: The procedure had to be aborted in three patients before TBNA could be performed. Samples were obtained in 32 patients. Samples were nondiagnostic in four patients. Adequate tissue was obtained in 28 of 32 patients (87.5%). Twenty-two patients had a specific benign or malignant diagnosis made, and 6 patients had lymphocytes only on the specimen. In follow-up, only one of these six patients proved to have a malignancy. All procedures were performed within a regular interventional CT time slot of 1 h. No TBNA side effects were noted.Conclusion: TBNA under CT fluoroscopic guidance is easy to perform. The yield in all accessible lymph node stations is high. [ABSTRACT FROM AUTHOR]

Background: Failure to wean from prolonged mechanical ventilation (MV) is common in long-term acute care hospitals (LTACHs), but the process of terminal withdrawal of MV in LTACHs is not well described. We compared terminal withdrawal of MV at an LTACH with that in a medical ICU (MICU).Methods: A retrospective medical chart review was done of all patients undergoing terminal withdrawal of MV in an LTACH (n = 30) and in a MICU (n = 74) over a 2-year period.Results: The decision to withdraw MV was more likely initiated by patient or family in the LTACH and by medical staff in the MICU (p < 0.0001). Social workers, pastoral care, and hospital administration were more likely to participate in the withdrawal process at the LTACH compared with the MICU (p < 0.05). Time from initiation of MV to orders for do not resuscitate, comfort measures only, or withdrawal of MV was significantly greater in the LTACH (weeks) compared with the MICU (days) (p < 0.05). The dose of benzodiazepines given during the final 24 h of life was greater in the MICU as compared with the LTACH (p < 0.05). Narcotic and benzodiazepine use in the hour before or after withdrawal of MV did not differ between the two groups. COPD and pneumonia were the most common causes of death among patients undergoing withdrawal of MV at the LTACH, as opposed to septic shock in the MICU (p < 0.05).Conclusions: Terminal withdrawal of MV in the LTACH differs from that in the MICU with regard to decision making, benzodiazepine use, and cause of death. [ABSTRACT FROM AUTHOR]

Context: Zafirlukast is a potent leukotriene antagonist that recently was approved for the treatment of asthma. As use of this drug increases, adverse events that occur at low frequency or in populations not studied in premarketing clinical trials may become evident.Objective: To describe a clinical syndrome associated with zafirlukast therapy.Design: Case series.Patients: Eight adults (7 women and 1 man) with steroid-dependent asthma who received zafirlukast.Main Outcome Measures: Development of a clinical syndrome characterized by pulmonary infiltrates, cardiomyopathy, and eosinophilia following the withdrawal of corticosteroid treatment.Results: The clinical syndrome developed while patients were receiving zafirlukast from 3 days to 4 months and from 3 days to 3 months after corticosteroid withdrawal. All 8 patients developed leukocytosis (range, 14.5-27.6 x 10(9)/L) with eosinophilia (range, 0.19-0.71). Six patients had fever (temperature >38.5 degrees C), 7 had muscle pain, 6 had sinusitis, and 6 had biopsy evidence of eosinophilic tissue infiltration. The clinical syndrome improved with discontinuation of zafirlukast treatment and reinitiation of corticosteroid treatment or addition of cyclophosphamide treatment.Comment: Development of pulmonary infiltrates, cardiomyopathy, and eosinophilia may have occurred independent of zafirlukast use or may have resulted from an allergic response to this medication. We suspect that these patients may have had a primary eosinophilic infiltrative disorder that had been clinically recognized as asthma, was quelled by steroid treatment, and was unmasked following corticosteroid withdrawal facilitated by zafirlukast. [ABSTRACT FROM AUTHOR]

Introduction: We hypothesized that delirium symptoms may respond differently to antipsychotic therapy. The purpose of this paper was to retrospectively compare duration and time to first resolution of individual delirium symptoms from the database of a randomized, double-blind, placebo-controlled study comparing quetiapine (Q) or placebo (P), both with haloperidol rescue, for critically ill patients with delirium.Methods: Data for 10 delirium symptoms from the eight-domain, intensive care delirium screening checklist (ICDSC) previously collected every 12 hours were extracted for 29 study patients. Data between the Q and P groups were compared using a cut-off P-value of ≤ 0.10 for this exploratory study.Results: Baseline ICDSC scores (5 (4 to 7) (Q) vs 5 (4 to 6)) (median, interquartile range (IQR)) and % of patients with each ICDSC symptom were similar in the two groups (all P > 0.10). Among patients with the delirium symptom at baseline, use of Q may lead to a shorter time (days) to first resolution of symptom fluctuation (4 (Q) vs. 14, P = 0.004), inattention (3 vs. 8, P = .10) and disorientation (2 vs. 10, P = 0.10) but a longer time to first resolution of agitation (3 vs. 1, P = 0.04) and hyperactivity (5 vs. 1, P = 0.07). Among all patients, Q-treated patients tended to spend a smaller percent of time with inattention (47 (0 to 67) vs. 78 (43 to 100), P = 0.025), hallucinations (0 (0 to 17) vs. 28 (0 to 43), P = 0.10) and symptom fluctuation (47 (19 to 67) vs. 89 (33 to 00), P = 0.04] and there was a trend for Q-treated patients to spend a greater percent of time at an appropriate level of consciousness (26% (13 to 63%) vs. 14% (0 to 33%), P = 0.17].Conclusions: Our exploratory analysis suggests that quetiapine may resolve several intensive care unit (ICU) delirium symptoms faster than the placebo. Individual symptom resolution appears to differ in association with the pharmacologic intervention (that is, P vs Q, both with as needed haloperidol). Future studies evaluating antipsychotics in ICU patients with delirium should measure duration and resolution of individual delirium symptoms and their relation to long-term outcomes. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare no conflicts of interest.

Background: Constipation is frequent in critically ill adults receiving opioids. Naloxegol (N), a peripherally acting mu-receptor antagonist (PAMORA), may reduce constipation. The objective of this trial was to evaluate the efficacy and safety of N to prevent constipation in ICU adults receiving opioids. Methods and Patients . In this single-center, double-blind, randomized trial, adults admitted to a medical ICU receiving IV opioids (≥100 mcg fentanyl/day), and not having any of 17 exclusion criteria, were randomized to N (25 mg) or placebo (P) daily randomized to receive N (25mg) or placebo (P) and docusate 100 mg twice daily until ICU discharge, 10 days, or diarrhea (≥3 spontaneous bowel movement (SBM)/24 hours) or a serious adverse event related to study medication. A 4-step laxative protocol was initiated when there was no SBM ≥3 days., Results: Only 318 (20.6%) of the 1542 screened adults during the 1/17-10/19 enrolment period met all inclusion criteria. Of these, only 19/381 (4.9%) met all eligibility criteria. After 7 consent refusals, 12 patients were randomized. The study was stopped early due to enrolment futility. The N ( n  = 6) and P ( n  = 6) groups were similar. The time to first SBM (N 41.4 ± 31.7 vs. P 32.5 ± 25.4 hours, P  = 0.56) was similar. The maximal daily abdominal pressure was significantly lower in the N group (N 10 ± 4 vs. P 13 ± 5, P  = 0.002). The median (IQR) daily SOFA scores were higher in N (N 7 (4, 8) vs. P 4 (3, 5), P  < 0.001). Laxative protocol use was similar (N 83.3% vs. P 66.6%; P  = 0.51). Diarrhea prevalence was high but similar (N 66.6% vs. P 66.6%; P  = 1.0). No patient experienced opioid withdrawal., Conclusions: Important recruitment challenges exist for ICU trials evaluating the use of PAMORAs for constipation prevention. Despite being underpowered, our results suggest time to first SBM with naloxegol, if different than P, may be small. The effect of naloxegol on abdominal pressure, SOFA, and the interaction between the two requires further research., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2022 Matthew S. Duprey et al.)

Noninvasive ventilation is well established as the ventilatory modality of first choice to treat acute or acute-on-chronic hypercapnic respiratory failure in patients with COPD by improving dyspnea and gas exchange, avoiding the need for intubation, and reducing morbidity and mortality rates. Noninvasive ventilation also offers benefit for patients with COPD and with accompanying pneumonia or with hypercapnic respiratory failure in postextubation, postoperative, and do not intubate settings. Noninvasive ventilation, in addition, offers benefit in other forms of acute hypercapnic respiratory failure, including those caused by asthma, cystic fibrosis, and obesity hypoventilation. A newer form of noninvasive ventilatory assistance, high-flow nasal cannula, has emerged in recent years as a technique to not only oxygenate effectively but also to improve ventilatory efficiency and reduce the work of breathing in patients with severe COPD. Results of recent studies indicate that high-flow nasal cannula therapy can benefit some patients with acute hypercapnic respiratory failure, either instead of or in combination with noninvasive ventilation, but more study is needed., Competing Interests: The remaining authors have disclosed no conflicts of interest., (Copyright © 2019 by Daedalus Enterprises.)

Background: Delays in antibiotic administration after severe sepsis recognition increases mortality. While physician and pharmacy-related barriers to early antibiotic initiation have been well evaluated, those factors that affect the speed by which critical care nurses working in either the emergency department or the intensive care unit setting initiate antibiotic therapy remains poorly characterized., Aim: To evaluate the knowledge, practices and perceptions of critical care nurses regarding antibiotic initiation in patients with newly recognised septic shock., Methods: A validated survey was distributed to 122 critical care nurses at one 320-bed academic institution with a sepsis protocol advocating intravenous(IV) antibiotic initiation within 1hour of shock recognition., Results: Among 100 (82%) critical care nurses responding, nearly all (98%) knew of the existence of the sepsis protocol. However, many critical care nurses stated they would optimise blood pressure [with either fluid (38%) or both fluid and a vasopressor (23%)] before antibiotic initiation. Communicated barriers to rapid antibiotic initiation included: excessive patient workload (74%), lack of awareness IV antibiotic(s) ordered (57%) or delivered (69%), need for administration of multiple non-antibiotic IV medications (54%) and no IV access (51%)., Conclusions: Multiple nurse-related factors influence IV antibiotic(s) initiation speed and should be incorporated into sepsis quality improvement efforts., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Among older adults, polypharmacy is a sequelae of admission to the intensive care unit and is associated with increased medication-associated adverse events, drug interactions, and health care costs. Delirium is prevalent in critically ill geriatric patients and medications remain an underappreciated modifiable risk for delirium in this setting. This article reviews the literature on polypharmacy and delirium, with a focus on highlighting the relationships between polypharmacy and delirium in critically ill, older adults. Discussed are clinician strategies on how to recognize and reduce medication-associated delirium and recommendations that help prevent polypharmacy when interventions to reduce the burden of delirium in this vulnerable population are being formulated., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Successful application of noninvasive ventilation (NIV) for acute respiratory failure (ARF) requires patient cooperation and comfort. The efficacy and safety of early IV dexmedetomidine when added to protocolized, as-needed IV midazolam and fentanyl remain unclear., Methods: Adults with ARF and within 8 h of starting NIV were randomized to receive IV dexmedetomidine (0.2 μg/kg/h titrated every 30 min to 0.7 μg/kg/h to maintain a Sedation-Agitation Scale [SAS] score of 3 to 4) or placebo in a double-blind fashion up to 72 h, until NIV was stopped for ≥ 2 h, or until intubation. Patients with agitation (SAS ≥ 5) or pain (visual analog scale ≥ 5 of 10 cm) 15 min after each dexmedetomidine and placebo increase could receive IV midazolam 0.5 to 1.0 mg or IV fentanyl 25 to 50 μg, respectively, at a minimum interval of every 3 h., Results: The dexmedetomidine (n = 16) and placebo (n = 17) groups were similar at baseline. Use of early dexmedetomidine did not improve NIV tolerance (score, 1 of 4; OR, 1.44; 95% CI, 0.44-4.70; P = .54) nor, vs. placebo, led to a greater median (interquartile range) percent time either tolerating NIV (99% [61%-100%] vs. 67% [40%-100%], P = .56) or remaining at the desired sedation level (SAS score = 3 or 4, 100% [86%-100%] vs. 100% [100%-100%], P = .28], or fewer intubations (P = .79). Although use of dexmedetomidine was associated with a greater duration of NIV vs placebo (37 [16-72] vs. 12 [4-22] h, P = .03), the total ventilation duration (NIV + invasive) was similar (3.3 [2-4] days vs. 3.8 [2-5] days, P = .52). More patients receiving dexmedetomidine had one or more episodes of deep sedation vs placebo (SAS ≤ 2, 25% vs. 0%, P = .04). Use of midazolam (P = .40) and episodes of either severe bradycardia (heart rate ≤ 50 beats/min, P = .18) or hypotension (systolic BP ≤ 90 mm Hg, P = .64) were similar., Conclusions: Initiating dexmedetomidine soon after NIV initiation in patients with ARF neither improves NIV tolerance nor helps to maintain sedation at a desired goal. Randomized, multicenter trials targeting patients with initial intolerance are needed to further elucidate the role for dexmedetomidine in this population.

Introduction: While one controlled trial found that a daily awakening and spontaneous breathing trial (DA-SBT) decreases time on mechanical ventilation (MV), there is a paucity of real-world data surrounding the development, implementation, and impact of DA-SBT protocols. We describe a multidisciplinary process improvement effort in 2, 10-bed medical intensive care units (MICUs) at a 330-bed academic medical center that focused on the development, implementation, and evaluation of a new DA-SBT protocol., Methods: A DA-SBT protocol, developed using results from a nursing survey literature and available institutional resources, was implemented after extensive clinician education and institution of quality reminders to boost use. Postprotocol compliance was evaluated. Use of sedation, DA and SBT practices, and clinical outcomes were retrospectively compared between the before and after DA-SBT protocol groups (ie, consecutive MICU patients requiring a continuously infused sedative [CIS] ≥24 hours)., Results: In the after group (n = 32), the DA and SBT compliances were 44% and 84%, respectively. Compared with the before group (n = 33), after group patients received CIS on fewer days of MV (100% vs 67%, P = .003) and had their CIS down-titrated by ≥25% on more days of CIS (40% vs 71%, P = .006). Neither total CIS dose (P = .49), total MV days (P = .75), days of MV where a SBT occurred (P = .38), nor episodes of self-extubation (15% vs 6%, P = .43) differed between the 2 groups., Conclusion: Despite the implementation of a DA-SBT protocol that was individualized to clinician preferences and institutional resources and accompanied by substantial education and reminders for use, compliance to the DA component of this protocol was low and duration of MV remained unchanged. Additional quality improvement strategies are needed to overcome barriers to DA-SBT protocol use that may not exist in controlled clinical trials.

Objective: To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as-needed haloperidol., Design: Prospective, randomized, double-blind, placebo-controlled study., Setting: Three academic medical centers., Patients: Thirty-six adult intensive care unit patients with delirium (Intensive Care Delirium Screening Checklist score > or = 4), tolerating enteral nutrition, and without a complicating neurologic condition., Interventions: Patients were randomized to receive quetiapine 50 mg every 12 hrs or placebo. Quetiapine was increased every 24 hrs (50 to 100 to 150 to 200 mg every 12 hrs) if more than one dose of haloperidol was given in the previous 24 hrs. Study drug was continued until the intensive care unit team discontinued it because of delirium resolution, therapy > or = 10 days, or intensive care unit discharge., Measurements and Main Results: Baseline characteristics were similar between the quetiapine (n = 18) and placebo (n = 18) groups. Quetiapine was associated with a shorter time to first resolution of delirium [1.0 (interquartile range [IQR], 0.5-3.0) vs. 4.5 days (IQR, 2.0-7.0; p =.001)], a reduced duration of delirium [36 (IQR, 12-87) vs. 120 hrs (IQR, 60-195; p =.006)], and less agitation (Sedation-Agitation Scale score > or = 5) [6 (IQR, 0-38) vs. 36 hrs (IQR, 11-66; p =.02)]. Whereas mortality (11% quetiapine vs. 17%) and intensive care unit length of stay (16 quetiapine vs. 16 days) were similar, subjects treated with quetiapine were more likely to be discharged home or to rehabilitation (89% quetiapine vs. 56%; p =.06). Subjects treated with quetiapine required fewer days of as-needed haloperidol [3 [(IQR, 2-4)] vs. 4 days (IQR, 3-8; p = .05)]. Whereas the incidence of QTc prolongation and extrapyramidal symptoms was similar between groups, more somnolence was observed with quetiapine (22% vs. 11%; p = .66)., Conclusions: Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation. Future studies should evaluate the effect of quetiapine on mortality, resource utilization, post-intensive care unit cognition, and dependency after discharge in a broader group of patients.

Critically ill patients have severe sleep disruption and typically encounter loss of circadian sleep pattern, steep fragmentation, increasing proportions of transitional stages of sleep, and loss of slow wave and rapid eye movement sleep. Mechanical ventilation is associated with these same sleep abnormalities, but what is attributable to the intensive care unit environment versus mechanical ventilation itself may be difficult to discern. Recent studies have shown that the ventilator mode and inappropriate settings can contribute to sleep fragmentation, and it is important to avoid overventilation that can induce central apneas when using spontaneous breathing modes. Noninvasive ventilation in the acute setting seems to be associated with the same sleep abnormalities as invasive ventilation. Long-term noninvasive positive pressure ventilation assists ventilation nocturnally and improves for patients with chronic respiratory failure caused by restrictive thoracic disorders.

Study Objective: To evaluate the impact of a hospital-acquired pneumonia (HAP) protocol on appropriateness of empiric antibiotic therapy, antibiotic deescalation, antibiotic duration, patient mortality, and length of stay., Design: Before- and after-study of protocol implementation., Setting: A 450-bed, academic medical center., Patients: One hundred consecutive patients with proven or suspected HAP., Intervention: Implementation of an HAP protocol that was based on the 2005 American Thoracic Society-Infectious Diseases Society of America guidelines and included extensive education of clinicians and monitoring by pharmacists., Measurements and Main Results: Before protocol implementation, 50 patients with HAP were evaluated against protocol criteria. After protocol implementation, a second cohort of 50 patients with HAP was evaluated. Compared with the preprotocol group, implementation of the protocol led to an increase in both the proportion of patients who received appropriate empiric antibiotic coverage (17 [34%] vs 31 [62%] patients, p=0.005) and appropriate antibiotic deescalation (21 [42%] vs 36 [72%] patients, p=0.002) according to protocol recommendations but did not affect the appropriateness of empiric antibiotic therapy based on final lung culture data (34 [68%] vs 41 [82%] patients, p=0.11). Compared with the preprotocol group, use of the protocol decreased the duration of intravenous antibiotic therapy (median [range] 9 [2-21] vs 7 [1-16] days, p=0.024), was associated with a trend for a shorter duration of stay in the intensive care unit (median [range] 19 [2-57] vs 11 [3-76] days, p=0.065), and did not significantly affect mortality (5 [10%] vs 8 [16%] patients, p=0.37). Pharmacists performed 59 interventions to support the protocol in 29 patients in the postprotocol group, of which 48% were accepted., Conclusions: Implementation of an HAP protocol improved appropriate empiric antibiotic use and decreased the duration of antibiotic therapy without adversely affecting patient outcomes.

This paper briefly summarizes the ERMS project and presents the developed model by showing results from environmental fates and risk calculations of a discharge from offshore drilling operations. The developed model calculates environmental risks for the water column and sediments resulting from exposure to toxic stressors (e.g., chemicals) and nontoxic stressors (e.g., suspended particles, sediment burial). The approach is based on existing risk assessment techniques described in the European Union technical guidance document on risk assessment and species sensitivity distributions. The model calculates an environmental impact factor, which characterizes the overall potential impact on the marine environment in terms of potentially impacted water volume and sediment area. The ERMS project started in 2003 and was finalized in 2007. In total, 28 scientific reports and 9 scientific papers have been delivered from the ERMS project (http://www.sintef.no/erms).

Background: While nurses play a key role in identifying delirium, several authors have noted variability in their ability to recognize delirium. We sought to measure the impact of a simple educational intervention on the ability of intensive care unit (ICU) nurses to clinically identify delirium and to use a standardized delirium scale correctly., Methods: Fifty ICU nurses from two different hospitals (university medical and community teaching) evaluated an ICU patient for pain, level of sedation and presence of delirium before and after an educational intervention. The same patient was concomitantly, but independently, evaluated by a validated judge (rho = 0.98) who acted as the reference standard in all cases. The education consisted of two script concordance case scenarios, a slide presentation regarding scale-based delirium assessment, and two further cases., Results: Nurses' clinical recognition of delirium was poor in the before-education period as only 24% of nurses reported the presence or absence of delirium and only 16% were correct compared with the judge. After education, the number of nurses able to evaluate delirium using any scale (12% vs 82%, P < 0.0005) and use it correctly (8% vs 62%, P < 0.0005) increased significantly. While judge-nurse agreement (Spearman rho) for the presence of delirium was relatively high for both the before-education period (r = 0.74, P = 0.262) and after-education period (r = 0.71, P < 0.0005), the low number of nurses evaluating delirium before education lead to statistical significance only after education. Education did not alter nurses' self-reported evaluation of delirium (before 76% vs after 100%, P = 0.125)., Conclusion: A simple composite educational intervention incorporating script concordance theory improves the capacity for ICU nurses to screen for delirium nearly as well as experts. Self-reporting by nurses of completion of delirium screening may not constitute an adequate quality assurance process.

Noninvasive ventilation (NIV), the provision of ventilatory assistance without an artificial airway, has emerged as an important ventilatory modality in critical care. This has been fueled by evidence demonstrating improved outcomes in patients with respiratory failure due to COPD exacerbations, acute cardiogenic pulmonary edema, or immunocompromised states, and when NIV is used to facilitate extubation in COPD patients with failed spontaneous breathing trials. Numerous other applications are supported by weaker evidence. A trial of NIV is justified in patients with acute respiratory failure due to asthma exacerbations and postoperative states, extubation failure, hypoxemic respiratory failure, or a do-not-intubate status. Patients must be carefully selected according to available guidelines and clinical judgment, taking into account risk factors for NIV failure. Patients begun on NIV should be monitored closely in an ICU or other suitable setting until adequately stabilized, paying attention not only to vital signs and gas exchange, but also to comfort and tolerance. Patients not having a favorable initial response to NIV should be considered for intubation without delay. NIV is currently used in only a select minority of patients with acute respiratory failure, but with technical advances and new evidence on its proper application, this role is likely to further expand.

The selection of patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) to receive noninvasive ventilation (NIV) is challenging, partly because there are few reliable selection criteria. The study by Rana and colleagues in the previous issue of Critical Care identifies metabolic acidosis and a lower oxygenation index as predictors of NIV failure, although it is unable to identify threshold values. It also demonstrates that treating patients with NIV for ALI/ARDS and shock is an exercise in futility. Future studies need to focus on criteria that will enable selection of patients for whom NIV will have a high likelihood of success.