Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study.

BACKGROUND: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND METHODS: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria. RESULTS: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 109/L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare. INTERPRETATION: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

Managing complications of percutaneous tracheostomy and gastrostomy.

Percutaneous tracheostomy and gastrostomy are some of the most commonly performed procedures at bedside in the intensive care unit. While they are generally considered safe, they can be associated with numerous short and long-term complications, many of which can occur long after their placement and cause significant morbidity. Performers of these procedures should possess a comprehensive understanding of procedural indications and contraindications, and know how to recognize and manage complications that may arise. In this review, we highlight complications of percutaneous tracheostomy and describe strategies for their prevention and management, with a special focus on post-tracheostomy tracheal stenosis. Other complications reviewed include bleeding, pneumothorax and subcutaneous emphysema, posterior wall injury, tube displacement, tracheomalacia, tracheoinominate artery fistula, tracheo-esophageal fistula, and stomal cellulitis. Gastrostomy complications and their management are also discussed including bleeding, internal organ injury, necrotizing fasciitis, aspiration pneumonia, buried bumper syndrome, tumor seeding, wound infection, tube displacement, peristomal leakage, and gastric outlet obstruction. In light of the potentially serious outcomes associated with complications of percutaneous tracheostomy and gastrostomy, the emphasis should be placed on risk-reduction strategies to minimize morbidity and mortality. We therefore present detailed pragmatic and comprehensive checklists to serve as a reference for clinicians involved in performing these procedures.

Pulmonary artery enlargement is associated with pulmonary hypertension and decreased survival in severe cystic fibrosis: A cohort study.

BACKGROUND: Pulmonary artery (PA) enlargement, defined as pulmonary artery to ascending aorta diameter ratio (PA:A)>1 on computed tomography (CT), is a marker of pulmonary vascular disease in chronic lung diseases. PA enlargement is prevalent in cystic fibrosis (CF), but its relationship to hemodynamics and prognostic utility in severe CF are unknown. We hypothesized that the PA:A would have utility in identifying pulmonary hypertension (PH) in severe CF and that PA enlargement would be associated with reduced transplant-free survival. METHODS: We conducted a retrospective study of adults with CF undergoing lung transplant evaluation at a single center between 2000 and 2015. CT, right heart catheterization (RHC), and clinical data were collected. The PA:A was measured from a single CT slice. We measured associations between PA:A and invasive hemodynamic parameters including PH defined as a mPAP ≥25mmHg using adjusted linear and logistic regression models. Kaplan-Meier and adjusted Cox regression models were used to measure associations between PA:A>1, RHC-defined PH, and transplant-free survival in severe CF. RESULTS: We analyzed 78 adults with CF that had CT scans available for review, including 44 that also had RHC. RHC-defined PH defined as a mPAP ≥25mmHg was present in 36% of patients with CF undergoing transplant evaluation. The PA:A correlated with mPAP (r = 0.73; 95% CI 3.87-7.80; p<0.001) and PVR (r = 0.42, p = 0.005) and the PA:A>1 was an independent predictor of PH (aOR 4.50; 95% CI 1.05-19.2; p = 0.042). PA:A>1 was independently associated with increased hazards for death or transplant (aHR 2.69; 95% CI 1.41-5.14; P = 0.003). The presence of mPAP ≥25mmHg was independently associated with decreased survival in this cohort. CONCLUSIONS: PA enlargement is associated with pulmonary hemodynamics and PH in severe CF. PA enlargement is an independent prognostic indicator of PH and decreased survival in this population.

Effect of a fluid bolus on cardiovascular collapse among critically ill adults undergoing tracheal intubation (PrePARE): a randomised controlled trial.

BACKGROUND: Tracheal intubation is common in the care of critically ill adults and is frequently complicated by hypotension, cardiac arrest, or death. We aimed to evaluate administration of an intravenous fluid bolus to prevent cardiovascular collapse during intubation of critically ill adults. METHODS: We did a pragmatic, multicentre, unblinded, randomised trial in nine sites (eight ICUs and one emergency department) around the USA. Critically ill adults (≥18 years) undergoing tracheal intubation were randomly assigned (1:1, block sizes of 2, 4, and 6, stratified by study site) to either an intravenous infusion of 500 mL of crystalloid solution or no fluid bolus. The primary outcome, assessed in the intention-to-treat population, was cardiovascular collapse, defined as a new systolic blood pressure <65 mm Hg; new or increased vasopressor receipt between induction and 2 min after tracheal intubation; or cardiac arrest or death within 1 h of tracheal intubation. Adverse events were assessed in the as-treated population. This trial, which is now complete, is registered with ClinicalTrials.gov, number NCT03026777. FINDINGS: Patients were enrolled from Feb 6, 2017, to Jan 9, 2018, when the data and safety monitoring board stopped the trial on the basis of futility. By trial termination, 337 (63%) of 537 screened adults had been randomly assigned. Cardiovascular collapse occurred in 33 (20%) of 168 patients in the fluid bolus group compared with 31 (18%) of 169 patients in the no fluid bolus group (absolute difference 1·3% [95% CI -7·1% to 9·7%]; p=0·76). The individual components of the cardiovascular collapse composite outcome did not differ between groups (new systolic blood pressure <65 mm Hg 11 [7%] in the bolus group vs ten [6%] in the no-bolus group, new or increased vasopressor 32 [19%] vs 31 [18%], cardiac arrest within 1 h seven [4%] vs two [1%], death within 1 h of intubation two [1%] vs one [1%]). In-hospital mortality was not significantly different in the fluid bolus group (48 [29%]) compared with no fluid bolus (59 [35%]). INTERPRETATION: Administration of an intravenous fluid bolus did not decrease the overall incidence of cardiovascular collapse during tracheal intubation of critically ill adults compared with no fluid bolus in this trial. FUNDING: US National Institutes of Health.

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.).

The use of a standardized order set reduces systemic corticosteroid dose and length of stay for individuals hospitalized with acute exacerbations of COPD: a cohort study.

Background: Systemic corticosteroids (SC) are an integral part of managing acute exacerbations of COPD (AECOPD). However, the optimal dose and duration vary widely in clinical practice. We hypothesized that the use of a "PowerPlan" order set in the electronic health system (EHS) that includes a 5-day SC order would be associated with a reduced steroid dose and length of stay (LOS) for individuals hospitalized with AECOPD. Patients and methods: We conducted a retrospective cohort study of Medicare recipients discharged with an AECOPD diagnosis from our University Hospital from 2014 to 2016. Our EHS-based "COPD PowerPlan" order set included admission, laboratory, pharmacy, and radiology orders for managing AECOPD. The default SC option included intravenous methyl-prednisolone for 24 hours followed by oral prednisone for 4 days. The primary endpoint was the difference in cumulative steroid dose between the PowerPlan and the usual care group. Secondary endpoints included hospital LOS and readmission rates. Results: The 250 patients included for analysis were 62±11 years old, 58% male, with an FEV1 55.1%±23.6% predicted. The PowerPlan was used in 72 (29%) patients. Cumulative steroid use was decreased by 31% in the PowerPlan group (420±224 vs 611±462 mg, P<0.001) when compared with usual care. PowerPlan use was independently associated with decreased LOS (3 days; IQR 2-4 days vs 4 days; IQR 3-6 days, P=0.022) without affecting 30- and 90-day readmission rates. Conclusion: Use of a standardized EHS-based order set to manage AECOPD was associated with a reduction in steroid dose and hospital LOS.

Manual ventilation to prevent hypoxaemia during endotracheal intubation of critically ill adults: protocol and statistical analysis plan for a multicentre randomised trial.

INTRODUCTION: Hypoxaemia is the most common complication during endotracheal intubation of critically ill adults, and it increases the risk of cardiac arrest and death. Manual ventilation between induction and intubation has been hypothesised to decrease the incidence of hypoxaemia, but efficacy and safety data are lacking. METHODS AND ANALYSIS: The Preventing Hypoxemia with Manual Ventilation during Endotracheal Intubation trial is a prospective, multicentre, non-blinded randomised clinical trial being conducted in seven intensive care units in the USA. A total of 400 critically ill adults undergoing endotracheal intubation will be randomised 1:1 to receive prophylactic manual ventilation between induction and endotracheal intubation using a bag-valve-mask device or no prophylactic ventilation. The primary outcome is the lowest arterial oxygen saturation between induction and 2 min after successful endotracheal intubation, which will be analysed as an unadjusted, intention-to-treat comparison of patients randomised to prophylactic ventilation versus patients randomised to no prophylactic ventilation. The secondary outcome is the incidence of severe hypoxaemia, defined as any arterial oxygen saturation of less than 80% between induction and 2 min after endotracheal intubation. Enrolment began on 2 February 2017 and is expected to be complete in May 2018. ETHICS AND DISSEMINATION: The trial was approved by the institutional review boards or designees of all participating centres. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION NUMBER: NCT03026322; Pre-results.

A Multicenter, Randomized Trial of Ramped Position vs Sniffing Position During Endotracheal Intubation of Critically Ill Adults.

BACKGROUND: Hypoxemia is the most common complication during endotracheal intubation of critically ill adults. Intubation in the ramped position has been hypothesized to prevent hypoxemia by increasing functional residual capacity and decreasing the duration of intubation, but has never been studied outside of the operating room. METHODS: Multicenter, randomized trial comparing the ramped position (head of the bed elevated to 25°) with the sniffing position (torso supine, neck flexed, and head extended) among 260 adults undergoing endotracheal intubation by pulmonary and critical care medicine fellows in four ICUs between July 22, 2015, and July 19, 2016. The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after intubation. Secondary outcomes included Cormack-Lehane grade of glottic view, difficulty of intubation, and number of laryngoscopy attempts. RESULTS: The median lowest arterial oxygen saturation was 93% (interquartile range [IQR], 84%-99%) with the ramped position vs 92% (IQR, 79%-98%) with the sniffing position (P = .27). The ramped position appeared to increase the incidence of grade III or IV view (25.4% vs 11.5%, P = .01), increase the incidence of difficult intubation (12.3% vs 4.6%, P = .04), and decrease the rate of intubation on the first attempt (76.2% vs 85.4%, P = .02), respectively. CONCLUSIONS: In this multicenter trial, the ramped position did not improve oxygenation during endotracheal intubation of critically ill adults compared with the sniffing position. The ramped position may worsen glottic view and increase the number of laryngoscopy attempts required for successful intubation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

AMPD1 polymorphism and response to regadenoson.

AIMS:  AMPD1 c.34C > T (rs17602729) polymorphism results in AMPD1 deficiency. We examined the association of AMPD1 deficiency and variability of hemodynamic response to regadenoson. SUBJECTS & METHODS: Genotyping for c.34C>T was performed in 267 patients undergoing regadenoson cardiac stress testing. RESULTS: Carriers of c.34C >T variant exhibited higher relative changes in systolic blood pressure (SBP) compared with wild-type subjects ([%] SBP change to peak: 12 ± 25 vs 5 ± 13%; p = 0.01) ([%] SBP change to nadir: -3 ± 15 vs -7 ± 11%; p = 0.04). Change in heart rate was similar between groups, but side effects were more common in carriers of the variant (+LR = 4.2; p = 0.04). CONCLUSION: AMPD1 deficiency may be involved in the modulation of regadenoson's systemic effects.