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Past Trials

BOUGIE 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.

Past Trials

CHECK-Up Trial: Up

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.

Keywords: endotracheal intubation; hypoxemia; randomized trial.

Manuscript Title: “A Multicenter, Randomized Trial of Ramped Position vs Sniffing Position During Endotracheal Intubation of Critically Ill Adults.”

Journal: Chest

PMID: 28487139

Past Trials

PreVent Trial

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.).

Manuscript Title: “Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults.”

Journal: New England Journal of Medicine

PMID: 30779528

Past Trials

ICU Survivor Clinic Trial

Objectives: To examine the effect of an interdisciplinary ICU recovery program on process measures and clinical outcomes.

Design: A prospective, single-center, randomized pilot trial.

Setting: Academic, tertiary-care medical center.

Patients: Adult patients admitted to the medical ICU for at least 48 hours with a predicted risk of 30-day same-hospital readmission of at least 15%.

Interventions: Patients randomized to the ICU recovery program group were offered a structured 10-intervention program, including an inpatient visit by a nurse practitioner, an informational pamphlet, a 24 hours a day, 7 days a week phone number for the recovery team, and an outpatient ICU recovery clinic visit with a critical care physician, nurse practitioner, pharmacist, psychologist, and case manager. For patients randomized to the usual care group, all aspects of care were determined by treating clinicians.

Measurements and main results: Among the primary analysis of enrolled patients who survived to hospital discharge, patients randomized to the ICU recovery program (n = 111) and usual care (n = 121) were similar at baseline. Patients in the ICU recovery program group received a median of two interventions compared with one intervention in the usual care group (p < 0.001). A total of 16 patients (14.4%) in the ICU recovery program group and 26 patients (21.5%) in the usual care group were readmitted to the study hospital within 30 days of discharge (p = 0.16). For these patients, the median time to readmission was 21.5 days (interquartile range, 11.5-26.2 d) in the ICU recovery program group and 7 days (interquartile range, 4-21.2 d) in the usual care group (p = 0.03). Four patients (3.6%) in the ICU recovery program and 14 patients (11.6%) in the usual care group were readmitted within 7 days of hospital discharge (p = 0.02). The composite outcome of death or readmission within 30 days of hospital discharge occurred in 20 patients (18%) in the ICU recovery program group and 36 patients (29.8%) in usual care group (p = 0.04).

Conclusions: This randomized pilot trial found that a multidisciplinary ICU recovery program could deliver more interventions for post ICU recovery than usual care. The finding of longer time-to-readmission with an ICU recovery program should be examined in future trials.

Manuscript Title: “Randomized Clinical Trial of an ICU Recovery Pilot Program for Survivors of Critical Illness.”

Journal: Critical Care Medicine

PMID: 31385881

Past Trials

BALANCE Trial

Rationale: The feasibility and clinical outcomes of conservative fluid management after sepsis resuscitation remain unknown.

Objectives: To evaluate the effect of a conservative fluid management protocol on fluid balance and intensive care unit (ICU)-free days among patients with sepsis.

Methods: In a single-center phase II/III randomized trial, we enrolled adults with suspected infection, ≥2 systemic inflammatory response syndrome criteria, and either shock (mean arterial pressure <60 mm Hg or vasopressors) or respiratory insufficiency (mechanical ventilation or oxygen saturation <97% and fraction of inspired oxygen ≥0.3). Patients were randomized 1:1 to usual care or a conservative fluid management protocol. The protocol restricted intravenous fluid administration during shock to treatment of oliguria or increasing vasopressor requirement. In the absence of shock, loop diuretic infusion targeted equal fluid input and output each study day. The primary outcomes were mean daily fluid balance (phase II) and ICU-free days (phase III).

Results: At the completion of phase II (n = 30), the difference in mean daily fluid balance between groups (-398 mL) was less than the prespecified threshold (-500 mL) and the trial was stopped. Patients in the conservative fluid management (n = 15) and usual care (n = 15) groups experienced similar cumulative fluid input (8450 mL vs 7049 mL; P = .90) of which only 14% was intravenous crystalloid or colloid. Loop diuretic infusion occurred more frequently in the conservative fluid management group (40% vs 0%; P = .02), and cumulative fluid output was 10 645 mL in the conservative fluid management group compared to 6286 mL in the usual care group (P = .39). Hemodynamic, respiratory, and renal function did not differ between the groups.

Conclusions: In this phase II trial, a conservative fluid management protocol did not decrease mean daily fluid balance by more than 500 mL among patients with sepsis.

Registration: Clinicaltrials.gov; NCT02159079.

Keywords: acute kidney injury; intravenous fluid; sepsis.

Conflict of interest statement

CONFLICTS OF INTEREST

All authors completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors declared no potential conflicts of interest with the current work. W.H.S. reported serving on advisory boards for Venaxis, Inc., Ferring Pharmaceuticals, and Cempra Pharmaceuticals, and as a consultant for Abbott Point-of-Care. T.W.R. reported serving on an advisory board for Avisa Pharma, LLC and as the Director of Medical Affairs for Cumberland Pharmaceuticals, Inc.

Manuscript Title: “Conservative Fluid Management After Sepsis Resuscitation: A Pilot Randomized Trial.”

Journal: Journal of Intensive Care Medicine

PMID: 30630380

Past Trials

PREPAREII 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.

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

Past Trials

SMART Trial

Background: Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes.

Methods: In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. The primary outcome was a major adverse kidney event within 30 days – a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) – all censored at hospital discharge or 30 days, whichever occurred first.

Results: Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P=0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P=0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P=0.60).

Conclusions: Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779 .).

Manuscript Title: “Balanced Crystalloids versus Saline in Critically Ill Adults.”

Journal: New England Journal of Medicine

PMID: 29485925

Past Trials

SALT-ED Trial

Background: Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU).

Methods: We conducted a single-center, pragmatic, multiple-crossover trial comparing balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) with saline among adults who were treated with intravenous crystalloids in the emergency department and were subsequently hospitalized outside an ICU. The type of crystalloid that was administered in the emergency department was assigned to each patient on the basis of calendar month, with the entire emergency department crossing over between balanced crystalloids and saline monthly during the 16-month trial. The primary outcome was hospital-free days (days alive after discharge before day 28). Secondary outcomes included major adverse kidney events within 30 days – a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) – all censored at hospital discharge or 30 days, whichever occurred first.

Results: A total of 13,347 patients were enrolled, with a median crystalloid volume administered in the emergency department of 1079 ml and 88.3% of the patients exclusively receiving the assigned crystalloid. The number of hospital-free days did not differ between the balanced-crystalloids and saline groups (median, 25 days in each group; adjusted odds ratio with balanced crystalloids, 0.98; 95% confidence interval [CI], 0.92 to 1.04; P=0.41). Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P=0.01).

Conclusions: Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital-free days between treatment with balanced crystalloids and treatment with saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SALT-ED ClinicalTrials.gov number, NCT02614040 .).

Conflict of interest statement

Dr. Self reports receiving advisory board fees from Venaxis, Cempra Pharmaceuticals, Ferring Pharmaceuticals, and Biotest, consulting fees from Abbott Point of Care, and travel support from Gilead Sciences; and Dr. Rice, receiving consulting fees from Cumberland Pharmaceuticals and Avisa Pharma. No other potential conflict of interest relevant to this article was reported.

Manuscript Title: “Balanced Crystalloids versus Saline in Noncritically Ill Adults.”

Journal: New England Journal of Medicine

PMID: 29485926

Past Trials

CHECK-Up Trial: Checklist

Background: Hypoxemia and hypotension are common complications during endotracheal intubation of critically ill adults. Verbal performance of a written, preintubation checklist may prevent these complications. We compared a written, verbally performed, preintubation checklist with usual care regarding lowest arterial oxygen saturation or lowest systolic BP experienced by critically ill adults undergoing endotracheal intubation.

Methods: A multicenter trial in which 262 adults undergoing endotracheal intubation were randomized to a written, verbally performed, preintubation checklist (checklist) or no preintubation checklist (usual care). The coprimary outcomes were lowest arterial oxygen saturation and lowest systolic BP between the time of procedural medication administration and 2 min after endotracheal intubation.

Results: The median lowest arterial oxygen saturation was 92% (interquartile range [IQR], 79-98) in the checklist group vs 93% (IQR, 84-100) with usual care (P = .34). The median lowest systolic BP was 112 mm Hg (IQR, 94-133) in the checklist group vs 108 mm Hg (IQR, 90-132) in the usual care group (P = .61). There was no difference between the checklist and usual care in procedure duration (120 vs 118 s; P = .49), number of laryngoscopy attempts (one vs one attempt; P = .42), or severe life-threatening procedural complications (40.8% vs 32.6%; P = .20).

Conclusions: The verbal performance of a written, preprocedure checklist does not increase the lowest arterial oxygen saturation or lowest systolic BP during endotracheal intubation of critically ill adults compared with usual care.

Trial registry: ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

Keywords: adult; airway management; checklist; critical care; endotracheal; intubation; ventilation.

Manuscript Title: “A Multicenter Randomized Trial of a Checklist for Endotracheal Intubation of Critically Ill Adults.”

Journal: Chest

PMID: 28917549

Past Trials

SALT Trial

Rationale: Saline is the intravenous fluid most commonly administered to critically ill adults, but it may be associated with acute kidney injury and death. Whether use of balanced crystalloids rather than saline affects patient outcomes remains unknown.

Objectives: To pilot a cluster-randomized, multiple-crossover trial using software tools within the electronic health record to compare saline to balanced crystalloids.

Methods: This was a cluster-randomized, multiple-crossover trial among 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 to May 31, 2015. The intravenous crystalloid used in the unit alternated monthly between saline (0.9% sodium chloride) and balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A). Enrollment, fluid delivery, and data collection were performed using software tools within the electronic health record. The primary outcome was the difference between study groups in the proportion of isotonic crystalloid administered that was saline. The secondary outcome was major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or persistent renal dysfunction.

Measurements and main results: Patients assigned to saline (n = 454) and balanced crystalloids (n = 520) were similar at baseline and received similar volumes of crystalloid by 30 days (median [interquartile range]: 1,424 ml [500-3,377] vs. 1,617 ml [500-3,628]; P = 0.40). Saline made up a larger proportion of the isotonic crystalloid given in the saline group than in the balanced crystalloid group (91% vs. 21%; P < 0.001). MAKE30 did not differ between groups (24.7% vs. 24.6%; P = 0.98).

Conclusions: An electronic health record-embedded, cluster-randomized, multiple-crossover trial comparing saline with balanced crystalloids can produce well-balanced study groups and separation in crystalloid receipt. Clinical trial registered with www.clinicaltrials.gov (NCT 02345486).

Trial registration: ClinicalTrials.gov NCT02345486.

Keywords: acute kidney injury; critical illness; crystalloid; intravenous fluid; saline.

Manuscript Title: “Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial.”

Journal: American Journal of Respiratory and Critical Care Medicine

PMID: 27749094

Past Trials

FELLOW Trial: VL/DL

Objective: To evaluate the effect of video laryngoscopy on the rate of endotracheal intubation on first laryngoscopy attempt among critically ill adults.

Design: A randomized, parallel-group, pragmatic trial of video compared with direct laryngoscopy for 150 adults undergoing endotracheal intubation by Pulmonary and Critical Care Medicine fellows.

Setting: Medical ICU in a tertiary, academic medical center.

Patients: Critically ill patients 18 years old or older.

Interventions: Patients were randomized 1:1 to video or direct laryngoscopy for the first attempt at endotracheal intubation.

Measurements and main results: Patients assigned to video (n = 74) and direct (n = 76) laryngoscopy were similar at baseline. Despite better glottic visualization with video laryngoscopy, there was no difference in the primary outcome of intubation on the first laryngoscopy attempt (video 68.9% vs direct 65.8%; p = 0.68) in unadjusted analyses or after adjustment for the operator’s previous experience with the assigned device (odds ratio for video laryngoscopy on intubation on first attempt 2.02; 95% CI, 0.82-5.02, p = 0.12). Secondary outcomes of time to intubation, lowest arterial oxygen saturation, complications, and in-hospital mortality were not different between video and direct laryngoscopy.

Conclusions: In critically ill adults undergoing endotracheal intubation, video laryngoscopy improves glottic visualization but does not appear to increase procedural success or decrease complications.

Manuscript Title: “Randomized Trial of Video Laryngoscopy for Endotracheal Intubation of Critically Ill Adults.”

Journal: Critical Care Medicine

PMID: 27355526

Past Trials

FELLOW Trial: AO

Rationale: Hypoxemia is common during endotracheal intubation of critically ill patients and may predispose to cardiac arrest and death. Administration of supplemental oxygen during laryngoscopy (apneic oxygenation) may prevent hypoxemia.

Objectives: To determine if apneic oxygenation increases the lowest arterial oxygen saturation experienced by patients undergoing endotracheal intubation in the intensive care unit.

Methods: This was a randomized, open-label, pragmatic trial in which 150 adults undergoing endotracheal intubation in a medical intensive care unit were randomized to receive 15 L/min of 100% oxygen via high-flow nasal cannula during laryngoscopy (apneic oxygenation) or no supplemental oxygen during laryngoscopy (usual care). The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after completion of endotracheal intubation.

Measurements and main results: Median lowest arterial oxygen saturation was 92% with apneic oxygenation versus 90% with usual care (95% confidence interval for the difference, -1.6 to 7.4%; P = 0.16). There was no difference between apneic oxygenation and usual care in incidence of oxygen saturation less than 90% (44.7 vs. 47.2%; P = 0.87), oxygen saturation less than 80% (15.8 vs. 25.0%; P = 0.22), or decrease in oxygen saturation greater than 3% (53.9 vs. 55.6%; P = 0.87). Duration of mechanical ventilation, intensive care unit length of stay, and in-hospital mortality were similar between study groups.

Conclusions: Apneic oxygenation does not seem to increase lowest arterial oxygen saturation during endotracheal intubation of critically ill patients compared with usual care. These findings do not support routine use of apneic oxygenation during endotracheal intubation of critically ill adults. Clinical trial registered with www.clinicaltrials.gov (NCT 02051816).

Manuscript Title: “Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the Critically Ill.”

Journal: American Journal of Respiratory and Critical Care Medicine

PMID: 27355526

Past Trials

Proper Trial

Rationale: Respiratory support (noninvasive ventilation or high-flow nasal cannula) applied at the time of extubation has been reported to reduce reintubation rates, but concerns regarding effectiveness have limited uptake into practice.

Objectives: To determine if providing postextubation respiratory support to all patients undergoing extubation in a medical ICU would decrease the incidence of reintubation.

Methods: We conducted a pragmatic, two-armed, cluster-crossover trial of adults undergoing extubation from invasive mechanical ventilation between October 1, 2017, and March 31, 2019, in the medical ICU of an academic medical center. Patients were assigned to either protocolized postextubation respiratory support (a respiratory therapist-driven protocol in which patients with suspected hypercapnia received noninvasive ventilation and patients without suspected hypercapnia received high-flow nasal cannula) or usual care (postextubation management at the discretion of treating clinicians). The primary outcome was reintubation within 96 hours of extubation.

Measurements and Main Results: A total of 751 patients were enrolled. Of the 359 patients assigned to protocolized support, 331 (92.2%) received postextubation respiratory support compared with 66 of 392 patients (16.8%) assigned to usual care, a difference driven by differential use of high-flow nasal cannula (74.7% vs. 2.8%). A total of 57 patients (15.9%) in the protocolized support group experienced reintubation compared with 52 patients (13.3%) in the usual care group (odds ratio, 1.23; 95% confidence interval, 0.82 to 1.84; P = 0.32).

Conclusions: Among a broad population of critically ill adults undergoing extubation from invasive mechanical ventilation at an academic medical center, protocolized postextubation respiratory support, primarily characterized by an increase in the use of high-flow nasal cannula, did not prevent reintubation compared with usual care.Clinical trial registered with www.clinicaltrials.gov (NCT0328831).

Trial registration: ClinicalTrials.gov NCT03288311.

Keywords: invasive mechanical ventilation; noninvasive respiratory support; reintubation.

Manuscript Title: “Protocolized Postextubation Respiratory Support to Prevent Reintubation: A Randomized Clinical Trial.”

Journal: American Journal of Respiratory and Critical Care Medicine

PMID: 33794131

Leadership Team

Christopher J. Lindsell PhD

Vanderbilt University Medical Center

Christopher Lindsell is a collaborative biostatistician who is a leader in the application of rigorous of biostatistical methods in the acute care environment, and to the intersection between emergency care and public health. He has led data coordinating centers for numerous multi-center clinical trials, including FDA-regulated trials, and for epidemiological studies. He holds patents on risk stratification in septic shock, and he has contributed significantly to a number of NIH-funded networks, including the CTSA. His current focus is on learning health systems, leveraging clinical processes and data systems to enhance learning from pragmatic trials and observational studies, and for designing and implementing dissemination and implementation research.

Leadership Team

Wesley H. Self, MD, MPH

Vanderbilt University Medical Center

Dr. Self is a physician-scientist focusing on improving the treatment of patients with infectious diseases and critical illness in the emergency department. His research involves disease entities such as pneumonia, sepsis, influenza, and soft tissue infections. He leads emergency department-based clinical trials, epidemiologic studies, and patient safety initiatives.

Leadership Team

David R Janz, MD, MSc

David R Janz, MD, MSc
Louisiana State University School of Medicine 
Director of Medical Critical Care Services at University Medical Center. I earned my medical degree at the LSU School of Medicine New Orleans followed by completion of an Internal Medicine residency, Pulmonary/Critical Care fellowship and Masters of Science in Clinical Investigation at Vanderbilt University, Nashville, TN. I am board certified in Internal Medicine, Pulmonary Medicine, and Critical Care Medicine.

Leadership Team

Derek W. Russell, MD

University of Alabama at Birmingham Medical Center
Dr. Russell received his initial medical training (MD) at the University of Texas Medical Branch with his internal medicine internship and residency completed at Vanderbilt University. Dr. Russell began a clinical and research fellowship in pulmonary and critical care medicine at UAB in 2014. Following his fellowship, he joined the UAB faculty in July 2017. His research and clinical interests relate to the role of neutrophils and extracellular vesicles in pulmonary diseases characterized by neutrophilic inflammation and parenchymal damage such as COPD and ARDS, as well as pragmatic clinical trials on the management of critically ill patients. Dr. Russell has published and presented work on endotracheal intubation, management of respiratory failure, pragmatic clinical trials in the MICU, neutrophils in COPD, matrikines in COPD, exhaled breath biomarkers in ARDS and extracellular vesicles in neutrophilic inflammation. His ongoing work explores the role of neutrophil-derived exosomes in matrix destruction and lung disease.

Leadership Team

Matthew E Prekker, MD MPH

Matthew E Prekker, MD MPH
Hennepin County Medical Center, Minneapolis, MN 

Through specialization in both Emergency Medicine and Pulmonary & Critical Care Medicine, Dr. Prekker provides acute care for patients in the Emergency Department and Medical ICU as well as maintaining a practice as a pulmonary consultant and clinic physician. He has special expertise in resuscitation from critical illness, including airway management, mechanical ventilation, and extracorporeal membrane oxygenation.