For some patients with severe lung failure, doctors use venovenous ECMO to deliver oxygen while the lungs recover. ECMO can be life-saving, but bleeding is common, and patients receive blood thinners to prevent clots. Whether lower-intensity anticoagulation could reduce bleeding without causing more clots was unknown. The SAFE-ECMO pilot trial compared low- vs moderate-intensity anticoagulation in 26 patients across 3 U.S. centers. The study showed the trial was feasible and that major bleeding occurred less often with low-intensity anticoagulation, with clotting events uncommon in both groups.

SAFE-ECMO Pilot Trial (Low-Intensity vs Moderate-Intensity Anticoagulation)

Venovenous extracorporeal membrane oxygenation (ECMO) can be life-saving for severe respiratory failure, but it is also associated with major complications, especially bleeding. Anticoagulation is routinely used to prevent clotting in the ECMO circuit, but the safest intensity of anticoagulation is uncertain. The SAFE-ECMO pilot trial compared low-intensity versus moderate-intensity anticoagulation strategies to determine whether a large multicenter randomized trial is feasible and to estimate bleeding and clotting risks.

Importance

Bleeding is a common and sometimes fatal complication of venovenous ECMO. Before the SAFE-ECMO Pilot Trial, it was unclear whether lower-intensity anticoagulation could reduce bleeding without causing excess thromboembolic complications, and whether a large randomized trial was feasible.

Objective

To determine the feasibility of a multicenter randomized trial comparing low-intensity versus moderate-intensity anticoagulation during venovenous ECMO, and to estimate effects on major bleeding and thromboembolic events.

Interventions

In a multicenter, parallel-group randomized pilot trial at 3 centers across the United States, critically ill adults receiving venovenous ECMO were randomly assigned to low-intensity or moderate-intensity anticoagulation. Feasibility outcomes included enrollment rate and adherence to the assigned strategy. The primary efficacy outcome was major bleeding, and the primary safety outcome was thromboembolic events, assessed from enrollment through 24 hours after decannulation.

Results

A total of 26 patients were enrolled, and all received their assigned anticoagulation intensity. Major bleeding occurred in 1 of 12 (8.3%) patients in the low-intensity group and 4 of 14 (28.6%) in the moderate-intensity group (absolute risk difference, –20.2 percentage points; 95% CI, –48.6 to 8.1; P = .33). Thromboembolic events were uncommon, occurring in 1 patient (8.3%) assigned to low-intensity anticoagulation and 0 patients assigned to moderate-intensity anticoagulation. No patients died before discharge in the low-intensity group, compared with 2 patients (14.3%) in the moderate-intensity group, both of whom experienced major bleeding events.

Conclusions and Relevance

In this multicenter pilot trial, enrollment and adherence to assigned anticoagulation intensity were feasible for venovenous ECMO patients. Major bleeding events were numerically lower with low-intensity anticoagulation, and thromboembolic events were uncommon. These results support the feasibility of a larger randomized trial to evaluate the safety and effectiveness of lower-intensity anticoagulation strategies during venovenous ECMO.

ClinicalTrials.gov Identifier: NCT04997265
Manuscript Title: Low-Intensity vs Moderate-Intensity Anticoagulation for Venovenous Extracorporeal Membrane Oxygenation: The Strategies for Anticoagulation During Venovenous Extracorporeal Membrane Oxygenation Pilot Trial
Journal: Chest
PMID: 40081660

The SAFE-ECMO pilot trial was a multicenter randomized pilot trial conducted at 3 U.S. centers comparing low-intensity vs moderate-intensity anticoagulation for critically ill adults receiving venovenous ECMO. The primary goal was to test feasibility for a larger trial, measured by enrollment and adherence to the assigned anticoagulation strategy, and all 26 enrolled patients received their assigned intensity of anticoagulation. Major bleeding occurred in 1/12 (8.3%) patients assigned to low-intensity anticoagulation versus 4/14 (28.6%) assigned to moderate-intensity anticoagulation, while thromboembolic events were uncommon (1 vs 0 patients). These results support the feasibility of a larger multicenter trial and suggest that lower-intensity anticoagulation may reduce bleeding risk without a clear increase in thromboembolic complications.

Gannon WD, Pratt EH, Vogelsong MA, Adkisson WH, Bacchetta M, Bloom SL, Ford DJ, Guenthart BA, Landsperger JS, Qian ET, Rackley CR, Rice TW, Fielding-Singh V, Stokes JW, Stollings JL, Semler MW, Casey JD; Pragmatic Critical Care Research Group. Low-Intensity vs Moderate-Intensity Anticoagulation for Venovenous Extracorporeal Membrane Oxygenation: The Strategies for Anticoagulation During Venovenous Extracorporeal Membrane Oxygenation Pilot Trial. Chest. 2025 Sep;168(3):639-649. doi: 10.1016/j.chest.2025.02.032. Epub 2025 Mar 11. PMID: 40081660

To support seriously ill patients with a breathing machine, doctors must place a breathing tube. Before intubation, doctors give a medicine to make patients unconscious, most commonly ketamine or etomidate. Whether ketamine improves survival compared with etomidate was not known. The RSI trial compared ketamine with etomidate in 2,365 patients across 14 emergency departments and ICUs in the United States. The study showed similar survival with both drugs, but ketamine was associated with more cardiovascular collapse during intubation.

When critically ill patients need a breathing machine, a breathing tube is placed through the mouth and into the windpipe. Before placing the breathing tube, doctors give a medication to induce unconsciousness. In the United States, ketamine and etomidate are the two most commonly used medications for this purpose, but prior studies raised concern that etomidate might worsen outcomes. The RSI trial evaluated whether using ketamine instead of etomidate improves survival or reduces complications during emergency tracheal intubation.

Importance

Among critically ill adults undergoing tracheal intubation, complications during the procedure—including severe low blood pressure and cardiac arrest—can lead to organ injury and death. Before the RSI Trial, it was uncertain whether choosing ketamine rather than etomidate reduces mortality for critically ill adults undergoing emergency intubation.

Objective

To determine the effect of ketamine compared with etomidate for induction of anesthesia on in-hospital death by day 28 among critically ill adults undergoing tracheal intubation in emergency departments and intensive care units.

Interventions

In a randomized trial conducted in 14 emergency departments and ICUs in the United States, critically ill adults undergoing tracheal intubation were randomly assigned to receive ketamine or etomidate for induction of anesthesia. The primary outcome was in-hospital death from any cause by day 28. The secondary outcome was cardiovascular collapse during intubation, defined as systolic blood pressure <65 mm Hg, receipt of a new or increased dose of vasopressors, or cardiac arrest.

Results

Among 2,365 patients included in the trial population, 28-day in-hospital mortality occurred in 330 of 1,173 (28.1%) in the ketamine group and 345 of 1,186 (29.1%) in the etomidate group (adjusted risk difference, –0.8 percentage points; 95% CI, –4.5 to 2.9; P = 0.65). Cardiovascular collapse during intubation occurred in 260 of 1,176 (22.1%) in the ketamine group and 202 of 1,189 (17.0%) in the etomidate group (risk difference, 5.1 percentage points; 95% CI, 1.9 to 8.3). Prespecified safety outcomes were similar in the two groups.

Conclusions and Relevance

Among critically ill adults undergoing tracheal intubation, induction with ketamine did not result in a lower incidence of death by day 28 compared with etomidate, and was associated with a higher incidence of cardiovascular collapse during intubation.

ClinicalTrials.gov Identifier: NCT05277896
Manuscript Title: Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults
Journal: New England Journal of Medicine
PMID: 41369227

To support seriously ill patients with a breathing machine, doctors must choose how the ventilator delivers each breath. Three common modes are volume control, pressure control, and adaptive pressure control, but whether mode choice affects outcomes was uncertain. The MODE trial compared these modes in 566 critically ill patients in a medical ICU. The study showed similar days alive and free from the ventilator across groups, with differences in breathing patterns that may warrant further study.

The MODE trial was a pragmatic, cluster-randomized, crossover pilot trial conducted in a medical ICU evaluating whether the choice of initial ventilator mode affects outcomes for critically ill adults receiving invasive mechanical ventilation. Patients were assigned by month to receive volume control, pressure control, or adaptive pressure control during continuous mandatory ventilation, and the primary outcome was ventilator-free days through 28 days. Among 566 patients, ventilator-free days were similar across groups (median 23, 22, and 24 days, respectively; P = .60). The trial demonstrated feasibility for testing ventilator mode using a pragmatic crossover design and identified differences in intermediate ventilation metrics that support evaluation in a larger trial.

MODE Trial (Ventilator Mode and Ventilator-Free Days)

When critically ill patients need a breathing machine, clinicians must choose a mode of mechanical ventilation. The three most common modes used for mandatory ventilation are volume control, pressure control, and adaptive pressure control, but it is uncertain whether the initial choice of ventilator mode affects outcomes. The MODE trial compared these commonly used ventilator modes in routine ICU care to evaluate whether mode selection influences duration of mechanical ventilation and patient outcomes.

Importance

Mechanical ventilation is a life-sustaining therapy in critical illness, but it can also contribute to lung injury and other complications. Before the MODE Trial, it was unknown whether the choice of ventilator mode during mandatory ventilation affects clinical outcomes for critically ill adults.

Objective

To determine the effects of volume control, pressure control, and adaptive pressure control ventilation modes on ventilator-free days through 28 days among critically ill adults receiving invasive mechanical ventilation.

Interventions

In a pragmatic, cluster-randomized, crossover pilot trial conducted in a medical ICU between November 1, 2022, and July 31, 2023, patients were assigned by month to receive volume control, pressure control, or adaptive pressure control during continuous mandatory ventilation. The primary outcome was ventilator-free days through 28 days.

Results

Among 566 patients included in the primary analysis, adherence to the assigned mode during the first 72 hours was high (median proportion of assessments in the assigned mode 100% in each group). The median number of ventilator-free days was 23 days in the volume control group, 22 days in the pressure control group, and 24 days in the adaptive pressure control group (P = .60). Intermediate ventilation patterns differed across groups, including the percentage of breaths with tidal volume >8 mL/kg predicted body weight, which was higher with pressure control than with volume control or adaptive pressure control.

Conclusions and Relevance

In this pragmatic pilot trial, ventilator-free days were similar among patients assigned to volume control, pressure control, or adaptive pressure control. The trial demonstrated feasibility of a cluster-randomized crossover design for ventilator mode and identified differences in intermediate ventilation measures that support evaluation in a larger trial.

ClinicalTrials.gov Identifier: NCT05563779
Manuscript Title: Effect of Ventilator Mode on Ventilator-Free Days in Critically Ill Adults: A Randomized Clinical Trial
Journal: Chest
PMID: 40189043

Seitz KP, Lloyd BD, Wang L, Shotwell MS, Qian ET, Muhs AL, Richardson RK, Rooks JC, Hennings-Williams V, Sandoval CE, Richardson WD, Morgan TL, Thompson AN, Hastings PG, Ring TP, Stollings JL, Talbot EM, Krasinski DJ, DeCoursey BR, Marvi TK, DeMasi SC, Gibbs KW, Self WH, Mixon AS, Rice TW, Semler MW, Casey JD; Pragmatic Critical Care Research Group. Effect of Ventilator Mode on Ventilator-Free Days in Critically Ill Adults: A Randomized Clinical Trial. Chest. 2025 Oct;168(4):912-923. doi: 10.1016/j.chest.2025.03.024. Epub 2025 Apr 4. PMID: 40189043

To support critically ill patients, doctors often give intravenous fluids to improve circulation. Two common balanced fluids are Normosol-R and lactated Ringers, but whether one leads to better outcomes was unknown. The BASE trial compared these fluids in 2,084 critically ill patients at an academic medical center in the United States. The study showed similar acid-base measurements and clinical outcomes, including kidney replacement therapy and survival.

The BASE trial was a pragmatic, cluster-randomized, multiple-crossover trial conducted at an academic medical center comparing two commonly used balanced crystalloids—Normosol-R vs lactated Ringers—for IV fluid therapy in critically ill adults. Between June 2018 and January 2019, 2,084 patients were enrolled, and the primary outcome was plasma bicarbonate concentration through 7 days. Plasma bicarbonate values were similar between groups, and there were no meaningful differences in clinical outcomes including new kidney replacement therapy or 30-day mortality. These findings suggest that among balanced crystalloids, choosing Normosol-R rather than lactated Ringers does not improve acid-base status or patient-centered outcomes in critically ill adults.

Qian ET, Brown RM, Jackson KE, Wang L, Stollings JL, Freundlich RE, Wanderer JP, Siew ED, Bernard GR, Self WH, Casey JD, Rice TW, Semler MW; Pragmatic Critical Care Research Group. Normosol-R vs Lactated Ringers in the Critically Ill: A Randomized Trial. Chest. 2025 Aug;168(2):336-345. doi: 10.1016/j.chest.2025.02.008. Epub 2025 Feb 17.  PMID: 39971001

BASE Trial (Normosol-R vs Lactated Ringers in Critical Illness)

Critically ill patients often receive intravenous fluids to support blood pressure, circulation, and organ perfusion. Two commonly used balanced crystalloid solutions are Normosol-R and lactated Ringers, which differ slightly in electrolyte composition and buffering agents. The BASE trial compared these fluids to determine whether the choice between balanced crystalloids affects acid-base status, kidney outcomes, or survival.

Importance

Balanced crystalloid solutions have been associated with improved outcomes compared with saline in some critically ill populations, but it is unclear whether clinically important differences exist between balanced crystalloids. Before the BASE Trial, whether choosing Normosol-R rather than lactated Ringers affects outcomes for critically ill adults was uncertain.

Objective

To determine whether use of Normosol-R compared with lactated Ringers affects plasma bicarbonate concentration through 7 days and clinical outcomes among critically ill adults.

Interventions

In a pragmatic, cluster-randomized, multiple-crossover trial at an academic medical center in the United States, critically ill adults were assigned to receive Normosol-R or lactated Ringers for IV fluid therapy. The primary outcome was the plasma bicarbonate concentration between enrollment and 7 days. Secondary outcomes included new receipt of kidney replacement therapy and death by day 30.

Results

Between June 2018 and January 2019, 2,084 patients were enrolled. Plasma bicarbonate concentration through 7 days did not differ between groups (mean difference, –0.12 mmol/dL; 95% CI, –0.61 to 0.36; P = .61). New kidney replacement therapy occurred in 6.0% of patients in the Normosol-R group and 5.0% in the lactated Ringers group (absolute risk difference, 1.0%; 95% CI, –1.2% to 3.1%). Death by day 30 occurred in 16.3% of patients in the Normosol-R group and 16.0% in the lactated Ringers group (absolute risk difference, 0.3%; 95% CI, –2.9% to 3.6%).

Conclusions and Relevance

Among critically ill adults, use of Normosol-R did not improve plasma bicarbonate concentration or clinical outcomes compared with lactated Ringers. These findings suggest that among balanced crystalloids, the choice between these two solutions does not meaningfully change patient-centered outcomes.

ClinicalTrials.gov Identifier: NCT03537898
Manuscript Title: Normosol-R vs Lactated Ringers in the Critically Ill: A Randomized Trial
Journal: Chest
PMID: 39971001

When patients need a breathing machine, a breathing tube is placed through the mouth and into the windpipe. During placement of the breathing tube, patients may experience serious problems with low oxygen levels. Doctors give oxygen through a mask before the procedure to prevent low oxygen levels. Two types of oxygen mask are commonly used, non-invasive ventilation and facemask oxygen. Both provide oxygen. Non-invasive ventilation also provides positive pressure to open the lungs and provide breaths when a patient’s breathing slows or stops. Both types of masks are FDA approved and both are frequently used in emergency department (ED) and intensive care unit (ICU). The PREOXI study focused on determining if one type of mask is better than the other.

Importance

Among critically ill adults undergoing tracheal intubation, hypoxemia increases the risk of cardiac arrest and death. Before the PREOXI Trial, the effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation was uncertain.

Objective

To determine the effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation among critically ill adults. Design, setting, and participants: the PRagmatic trial Examining OXygenation prior to Intubation (PREOXI) was a multi-center, parallel-group, non-blinded, randomized clinical trial among 1,301 patients undergoing tracheal intubation in 24 emergency departments and intensive care units across the United States.

Interventions

Patients were randomly assigned to receive preoxygenation with either noninvasive ventilation (n=645) or an oxygen mask (n=656). Main outcomes and measures: the primary outcome was hypoxemia during intubation, defined by an oxygen saturation of less than 85% during the interval between induction of anesthesia and 2 minutes after tracheal intubation. The secondary outcome was the lowest oxygen saturation during the interval between induction of anesthesia and 2 minutes after tracheal intubation.

Results

Among the 1,301 patients enrolled, hypoxemia occurred in 57 patients (9.1%) in the noninvasive ventilation group and in 118 (18.5%) in the oxygen- mask group (difference, -9.4 percentage points; 95% confidence interval [CI], – 13.2 to -5.6; P<0.001). Cardiac arrest occurred in 1 patient (0.2%) in the noninvasive-ventilation group and in 7 patients (1.1%) in the oxygen-mask group (difference, -0.9 percentage points; 95% CI, -1.8 to -0.1_> Aspiration occurred in 6 patients (0.9%) in the noninvasive-ventilation group and in 9 patients (1.4%) in the oxygen-mask group (difference, -0.4 percentage points; 95% CI, -1.6 to 0.7).

Materials

Ventilator Model	Manufacturer	NIV Capability	Required Software Version
Puritan Bennett 980	Medtronic	Yes	IE SyncTM Software Version 2.8 and Above	Manual
Servo-I	Getinge Maquet	Yes	Base Software (v3.0 or higher)	Manual
Servo-U	Getinge Maquet	Yes	Base Software (v2.0 or higher)	Manual
Hamilton G5	Hamilton Medical	Yes	Base Software (v2.0 or higher)	Manual
Carescape R860	General Electric (GE)	Yes	Base Software (v10 or higher)	Manual
Infinity	C500 Dräger	Yes	SW 2.n	Manual
Evita	XL Dräger	Yes	Software Version 4.n or higher, latest Version 6.0	Manual
Puritan Bennett 840 (PB840)	Medtronic	Yes	Software Version 7.3 or higher	Manual

Conclusions and Relevance

Among critically ill adults undergoing tracheal intubation, preoxygenation with noninvasive ventilation resulted in a lower incidence of hypoxemia during intubation than preoxygenation with an oxygen mask.

ClinicalTrials.gov Identifier: NCT05267652
Manuscript Title: Noninvasive Ventilation for Preoxygenation during Emergency
Intubation

Journal: New England Journal of Medicine
PMID: 38869091

Patients in the emergency department and intensive care unit who are suspected of having infections are treated with antibiotics. Most patients received either cefepime or piperacillin-tazobactam, antibiotics targeting resistant gram-negative bacteria. The two antibiotics are believed to have different risks. Cefepime may cause “neurotoxicity” (symptoms like agitation or coma). Piperacillin-tazobactam may cause kidney injury. To learn whether cefepime or piperacillin-tazobactam affects the chances of experiencing neurotoxicity or kidney injury, we conducted a research study called the ACORN study. A total of 1,172 patients receiving antibiotics for resistant gram-negative bacteria in the Vanderbilt Emergency Department or Intensive Care Unit participated in the study. The results of the study suggested that cefepime does cause neurotoxicity but piperacillin- tazobactam does not cause kidney injury and may be a safer alternative for patients being treated in the emergency department or intensive care unit.

Importance

Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial.

Objective

To determine whether the choice between cefepime and piperacillin- tazobactam affects the risks of acute kidney injury or neurological dysfunction. Design, setting, and participants: The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022.

Interventions

Patients were randomized in a 1:1 ratio to cefepime or piperacillin- tazobactam.

Main outcomes and measures

The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and
coma within 14 days.

Results

There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin- tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]).

Conclusions and relevance

Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction.

ClinicalTrials.gov Identifier: NCT05094154.
Manuscript Title: Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With
Acute Infection: The ACORN Randomized Clinical Trial.
Journal: JAMA
PMID: 37837651

Location: NIH Collaboratory Grand Rounds
Presenter(s): Jon Casey and Matthew Prekker

Location: Critical Care Reviews Meeting 2023
Presenter(s): Matthew Prekker and Matt Semler

What we need to learn

When a patient needs a breathing machine, a breathing tube is placed through the mouth and into the windpipe. Difficulty placing the breathing tube may cause serious problems with low oxygen levels, low blood pressure, or injury to the windpipe or lungs. To place the breathing tube, doctors use a tool called a “scope” to see past the tongue for placement of the breathing tube in the windpipe. Two types of “scope” are commonly used. One is called a “video laryngoscope” and another is called a “direct laryngoscope”. The DEVICE trial compared use of a video laryngoscope with use of a direct laryngoscope in 1,417 patients in 7 emergency departments and 10 intensive care units across the United States. The study showed that use of a video laryngoscope increased the probability of successful breathing tube placement on the first attempt.

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. Before the DEVICE trial it remained unknown whether use of a video laryngoscope or use of a direct laryngoscopes was better for patients.’

Objective

To compare the effect of use of a video laryngoscope versus a direct laryngoscope on successful intubation on the first attempt among critically ill adults undergoing tracheal intubation in the acute care setting. Design, setting, and participants: The DirEct Versus Video LaryngosCopE (DEVICE) trial was a multi-center, parallel-group, non-blinded, randomized clinical trial among 1,417 critically ill adults undergoing orotracheal intubation in 7 emergency departments and 10 ICUs in 11 medical centers across the United States.

Interventions

Patients were randomly assigned to the video laryngoscope group (n =705) or the direct laryngoscope group (n = 712).

Main outcomes and measures

The primary outcome was successful intubation on the first attempt. The secondary outcome was the incidence of severe complications.

Results

Among 1417 patients who were included in the final analysis, successful intubation on the first attempt occurred in 600 patients (85.1%) in the video-laryngoscope group and in 504 patients (70.8%) in the direct-laryngoscope group (absolute risk difference, 14.3 percentage points; 95% CI, 9.9 to 18.7; P<0.001). A total of 151 patients (21.4%) in the video-laryngoscope group and 149 patients (20.9%) in the direct- laryngoscope group had a severe complication during intubation (absolute risk difference,

0.5 percentage points; 95% CI, −3.9 to 4.9). Safety outcomes, including esophageal intubation, injury to the teeth, and aspiration, were similar in the two groups.

Conclusions and relevance: Among critically ill adults undergoing tracheal intubation in an emergency department or ICU, the use of a video laryngoscope resulted in a higher incidence of successful intubation on the first attempt than the use of a direct laryngoscope.

ClinicalTrials.gov Identifier: NCT05239195
Manuscript Title: Video versus Direct Laryngoscopy for Tracheal Intubation of
Critically Ill Adults.
Journal: New England Journal of Medicine
PMID: 37326325

More information

This study is called “Direct Versus Video Laryngoscope (DEVICE)” and is funded by the U.S. Department of Defense. Our goal is to learn whether a “scope” with a video screen or a “scope” without a video screen is better for placing a breathing tube and preventing problems with oxygen levels and blood pressure. Participating in this study will not impact the quality of care patients receive. For each patient:

• When the doctors feel a “scope” with a video screen would be best for a patient, the team will use a “scope” with a video screen.
• When the doctors feel that a “scope” without a video screen would be best for a patient, the team will use a “scope” without a video screen.
• When the doctors do not have a preference, the patient will be assessed against the inclusion / exclusion criteria and when appropriate, enrolled in DEVICE. Once the patient is enrolled in DEVICE, the type of “scope” is assigned randomly, meaning that every patient will have a fair and equal chance of getting either type of “scope.”

Questions

If you have any questions or concerns about this study, you may contact the Principal Investigator, Dr. Jonathan Casey. He will be glad to answer any study-related questions. Dr. Casey’s phone number is (615) 208-6139. If you have questions about your rights as a research participant, or concerns or complaints about the research, you may also contact the Vanderbilt Human Research Protections Program at (615)- 322-2918.

Participating Sites

Vanderbilt; Denver Health; Ochsner; University of Washington; Duke University; University of Alabama, Birmingham; Baylor, Scott &White; University of Colorado, Denver; Hennepin County Medical Center; Wake Forest; Brooke Army Medical Center, Beth Israel Deaconess,

Trial Update

On November 17^th 2022, the investigators were notified by the Data and Safety Monitoring Board that the DEVICE trial had met the prespecified stopping criteria at the time of the single interim analysis.  Enrollment in the trial was stopped and investigators and clinicians at participating sites were notified.

People who survive critical illness frequently suffer from problems with their strength, thinking, and mental health for months after returning home from the hospital.  To test whether a structured program with specific follow-up visits and resources could prevent the need to be readmitted to the hospital for patients who had previously been treated for critical illness in the ICU, we conducted this pilot study. The study found that patients enrolled in the recovery program received more interventions than those not in the program and went a slightly longer time without hospital readmission. Patients in the ICU recovery program also appeared to experience a lower frequency of death or hospital readmission within 30 days.  Although uncertain because this was only a pilot study, these findings suggest that future research is needed to determine whether programs to help patients recovering from critical illness can prevent death and readmission and improve patients physical, mental, and social function.

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

Many patients in the intensive care unit (ICU) receive oxygen through a breathing machine. Doctors, nurses, and respiratory therapist adjust the amount of oxygen given through the breathing machine to target oxygen levels, but the ideal oxygen level to target is unknown. To understand which oxygen level is best for patients, we conducted a research study called the PILOT study. A total of 2,541 patients on breathing machines in the Vanderbilt intensive care unit participated in the study and had their clinicians target an oxygen level of 90%, 94%, or 98%. The results of the study suggested that patients did equally well when their clinicians targeted an oxygen level of 90%, 94%, or 98%.

Background: Invasive mechanical ventilation in critically ill adults involves adjusting the fraction of inspired oxygen to maintain arterial oxygen saturation. The oxygen- saturation target that will optimize clinical outcomes in this patient population remains unknown.

Methods

In a pragmatic, cluster-randomized, cluster-crossover trial conducted in the emergency department and medical intensive care unit at an academic center, we assigned adults who were receiving mechanical ventilation to a lower target for oxygen saturation as measured by pulse oximetry (Spo2) (90%; goal range, 88 to 92%), an intermediate target (94%; goal range, 92 to 96%), or a higher target (98%; goal range, 96 to 100%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilator-free days) through day 28. The secondary outcome was death by day 28, with data censored at hospital discharge.

Results

A total of 2541 patients were included in the primary analysis. The median number of ventilator-free days was 20 (interquartile range, 0 to 25) in the lower-target group, 21 (interquartile range, 0 to 25) in the intermediate-target group, and 21 (interquartile range, 0 to 26) in the higher-target group (P = 0.81). In-hospital death by day 28 occurred in 281 of the 808 patients (34.8%) in the lower-target group, 292 of the 859 patients (34.0%) in the intermediate-target group, and 290 of the 874 patients (33.2%) in the higher-target group. The incidences of cardiac arrest, arrhythmia, myocardial infarction, stroke, and pneumothorax were similar in the three groups.

Conclusions

Among critically ill adults receiving invasive mechanical ventilation, the number of ventilator-free days did not differ among groups in which a lower, intermediate, or higher Spo2 target was used.

ClinicalTrials.gov Identifier:
NCT03537937.
Manuscript Title: Oxygen-Saturation Targets for Critically Ill Adults Receiving
Mechanical Ventilation
Journal: New England Journal of Medicine

PMID: 36278971

Patients in the intensive care unit who require treatment with a breathing machine may develop serious problems with blood pressure or heart rhythm while the breathing tube is being placed.  To learn whether problems with blood pressure or heart rhythms could be prevented by giving patients fluid through an IV, we led a research study called PREPARE.  The PREPARE trial included 337 patients from 8 intensive care units and one emergency department. The trial found that giving fluid through an IV did not prevent seriously low blood pressure, but that the fluid might have been helpful for some patients receiving oxygen through a mask before the procedure (called “non-invasive ventilation”).  These results suggested that IV fluid might prevent low blood pressure among patients on non-invasive ventilation prior to placement of a breathing tube And were the basis for the PREPAREII trial (described above).

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.

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

Journal: Lancet Respiratory Medicine

PMID: 31585796

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”

To support seriously ill patients with a breathing machine, doctors must place a breathing tube.  One-in-five times doctors cannot place the breathing tube on the first try.  When the breathing tube cannot be placed on the first try, the risks to the patient for low oxygen levels or blood pressure are higher.  Doctors use two different rod-like devices to help guide a breathing tube it the right place.  One is called a “bougie” and another is called a “stylet”.  Both have been used for many years, but whether one was better than the other for placing a breathing tube on the first attempt was not known.  The BOUGIE trial compared use of a bougie with use of a stylet for 1100 patients in 7 emergency departments and 8 intensive care units across the United States.  The study showed that using a bougie and using a stylet were equally safe and effective.

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.

When a patient requiring a breathing machine is ready to be disconnected from that machine, providing additional oxygen support using a mask over the patient’s mouth (called “non-invasive ventilation”) or a large tube under their nose (called “high flow nasal cannula”) had been reported to decrease the likelihood of the patient needing to be put back on the breathing machine. The PROPER Trial assessed over 750 intensive care unit patients to determine whether additional oxygen support with non-invasive ventilation or high flow nasal cannula reduced the need to go back on a breathing machine within 96 hours after initially being taken off. The results showed that receiving the additional support did not prevent the need to go back on a breathing machine. These findings suggest doctors can provide support with the devices for some patients who they think will benefit, but do not need to provide support with these devices for every patient.

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

Patients being treated for sepsis, a serious infection that can lower blood pressure, are often treated with fluids through an IV. Previous studies have shown that a positive fluid balance, or more fluids taken in than out, may be connected to problems with kidney and lung function. The BALANCE pilot trial enrolled 30 patients; 15 patients received fluid in a conservative and restrictive manner, and 15 patients were given the typical fluid care. Results showed that the conservative fluid approach did not decrease fluid balance for patients with sepsis.  These findings suggest that future research on fluid treatment for sepsis will need to find ways to achieve bigger differences in the amount of fluid being received between the approaches being examined.

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

For patients on a breathing machine, doctors may secure the breathing tube in place using either adhesive tape or an endotracheal tube fastener.  The ETTS Trial compared the securement technique of adhesive tape versus an endotracheal tube fastener for patients in the medical intensive care unit expected to require a breathing machine for more than 24 hours. Safety and efficacy of the two techniques were compared by evaluating the presence of lip ulcers, the tube becoming dislodged from the patient, ventilator-associated pneumonia, or facial skin tears. Results of the study showed that the use of the endotracheal tube fastener reduced the rate of lip ulcers, tube dislodgement, and skin tears compared to the use of adhesive tape. The findings suggest that using an endotracheal tube fastener will reduce the rate of these events, may improve patient safety, and may decrease the cost of care.

Background: The optimal securement method of endotracheal tubes is unknown but should prevent dislodgement while minimizing complications. The use of an endotracheal tube fastener might reduce complications among critically ill adults undergoing endotracheal intubation.

Methods: In this pragmatic, single-center, randomized trial, critically ill adults admitted to the medical intensive care unit (MICU) and expected to require invasive mechanical ventilation for greater than 24 h were randomized to adhesive tape or endotracheal tube fastener at the time of intubation. The primary endpoint was a composite of any of the following: presence of lip ulcer, endotracheal tube dislodgement (defined as moving at least 2 cm), ventilator-associated pneumonia, or facial skin tears anytime between randomization and the earlier of death or 48 h after extubation. Secondary endpoints included duration of mechanical ventilation and ICU and in-hospital mortality.

Results: Of 500 patients randomized over a 12-month period, 162 had a duration of mechanical ventilation less than 24 h and 40 had missing outcome data, leaving 153 evaluable patients randomized to tube fastener and 145 evaluable patients randomized to adhesive tape. Baseline characteristics were similar between the groups. The primary endpoint occurred 13 times in 12 (7.8%) patients in the tube fastener group and 30 times in 25 (17.2%) patients in the adhesive tape group (p = 0.014) for an overall incidence of 22.0 versus 52.6 per 1000 ventilator days, respectively (p = 0.020). Lip ulcers occurred in 4 (2.6%) versus 11 (7.3%) patients, or an incidence rate of 6.5 versus 19.5 per 1000 patient ventilator days (p = 0.053) in the fastener and tape groups, respectively. The endotracheal tube was dislodged 7 times in 6 (3.9%) patients in the tube fastener group and 16 times in 15 (10.3%) patients in the tape group (p = 0.03), reflecting incidences of 11.9 and 28.1 per 1000 ventilator days, respectively. Facial skin tears were similar between the groups. Mechanical ventilation duration and ICU and hospital mortality did not differ.

Conclusion: The use of the endotracheal tube fastener to secure the endotracheal tubes reduces the rate of a composite outcome that included lip ulcers, facial skin tears, or endotracheal tube dislodgement compared to adhesive tape.

Trial registration: ClinicalTrials.gov NCT03760510. Retrospectively registered on November 30, 2018.

Keywords: Critical care; Endotracheal tube; Endotracheal tube dislodgement; Facial skin tear; Intensive care units; Lip ulcer; Mechanical ventilation; Tube fastener.

Manuscript Title: “The effect of adhesive tape versus endotracheal tube fastener in critically ill adults: the endotracheal tube securement (ETTS) randomized controlled trial.”

Journal: Critical Care

PMID: 31064406

Low oxygen level is the most common complication that arises when a critically ill patient is being placed on a breathing machine. Whether providing oxygen and ventilation with a bag-mask device prior to placement of a breathing tube prevents low oxygen levels had been unknown.  Among 401 patients in 7 intensive care units, the PreVent trial found that providing oxygen and ventilation with a bag-mask device was safe, maintained higher oxygen level and prevented dangerously low oxygen levels.  These findings may improve the safety of breathing tube placement for many seriously 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.).

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

Journal: New England Journal of Medicine

PMID: 30779528

Patients in the intensive care unit frequently receive IV fluid.  For more than 100 years, two basic types of IV fluid have been available: saline (which contains more chloride than human blood) and balanced crystalloids (which contains about the same amount of chloride as human blood).  No large trials had previously evaluated which fluid resulted in the best outcomes for patients.  Among almost 16,000 patients in 5 intensive care units, the SMART trial found that using balanced crystalloids instead of saline decreased the risk of death, dialysis, or lasting kidney problems.  These findings suggest that most hospitalized patients without a specific reason for receiving saline should be treated with balanced crystalloids when an IV fluid is needed.

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

Patients in the emergency department are frequently given fluids through an IV as a treatment for a wide variety of injuries and medical complications. Historically, the most common fluid given to patients had been saline.  Saline contains a higher concentration of chloride than that of human blood, which could have negative effects on patients’ kidneys and blood vessels. Another type of fluid, called “balanced crystalloids”, has a chloride concentration more similar to that of human blood.  Whether using balanced crystalloids would result in better outcomes than using saline had been unknown.  Among approximately 13,000 patients receiving fluid in an emergency department prior to admission to the hospital, the  SALT-ED trial found using balanced crystalloids rather than saline did not increase the number of days alive outside the hospital but did decrease patients chances of dying, receiving dialysis, or having lasting kidney problems.  These findings suggest that balanced crystalloids should be used rather than saline for most patients receiving IV fluid in an emergency department.

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

For patients being placed on a breathing machine, a breathing tube must be placed in the mouth.  During placement of a breathing tube, low oxygen levels may occur.  Whether placing a breathing tube while the patient’s head and shoulders were elevated (“ramped position”) could prevent low oxygen levels compared to placement of a breathing tube with the patient laying flat (“sniffing position”) was not known.  Among 260 patients in 4 intensive care units, the CHECK-UP trial found that placing a breathing tube in the ramped position did not prevent low oxygen levels.  Placing a breathing tube in the ramped position appeared to be more difficult than placing a breathing tube with the patient in the sniffing position.  These findings suggest that, for many patients in the intensive care unit, placing a breathing tube in the sniffing position may be simpler and easier than in the ramped position.

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