Journal: New England Journal of Medicine|
PMID: 29485926

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

Journal: Chest
PMID: 29406220

Journal: Chest
PMID: 29223265

Journal: Chest
PMID: 29126526

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

Journal: Chest
PMID: 28487139

Journal: Chest
PMID: 28487139

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 and low blood pressure may occur.  Whether using a checklist prior to placing a breathing tube helps prevent these complications is unknown.  Among 262 patients being placed on a breathing machine at 5 intensive care units across the United States, the CHECK-Up Trial compared use of a checklist to none with regard to the occurrence of low oxygen levels and low blood pressure.  Use of a checklist did not prevent low oxygen levels or low blood pressure.  These findings suggest that using a checklist prior to placing a breathing tube may not be helpful for doctors experienced at placing a breathing tube who work in an intensive care unit.

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.

Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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

Journal: Chest

PMID: 28917549

Journal: Critical Care Medicine
PMID: 28622220

Journal: Journal of Medical Systems
PMID: 28622220

Journal: American Journal of Respiratory and Critical Care Medicine
PMID: 27749094

Patients in the intensive care unit frequently receive IV fluid.  Two basic types of IV fluid exist: 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.  In preparation for a large trial examining this question, the SALT pilot trial aimed to determine whether software tools in the hospital’s electronic health record would produce balanced study groups and divide study participants to either receive balanced crystalloids or saline in a separate and equal way. Results of the study showed that this approach can produce well-balanced study groups and separate the receipt of saline or balanced crystalloids in an effective way.  These findings suggest that electronic health records may be used to efficiently conduct trials comparing treatments commonly used in clinical care.

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

Journal: American Journal of Respiratory and Critical Care Medicine
PMID: 27749094

Journal: Critical Care Medicine
PMID: 28291111

Journal: Critical Care Medicine
PMID: 28291113

Journal: Trials
PMID: 28407811

Journal: Critical Care Medicine
PMID: 28212228

Journal: Trials
PMID: 28302179

Journal: American Journal of Respiratory and Critical Care Medicine
PMID: 27355526

Journal: Critical Care Medicine
PMID: 27355526

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.  Two types of tools exist for helping see a patients’ vocal cords to place a breathing tube: a device with a camera on it (video laryngoscope) and a device without a camera on it (direct laryngoscope).  Whether placing a breathing tube on the first try is easier with a video laryngoscope or a direct laryngoscope is unknown.  Among 150 patients receiving a breathing tube in one intensive care unit, the FELLOW trial found that, while a video laryngoscope made it easier to see the vocal cords, using a video laryngoscope did not make it easier to place a breathing tube on the first try compared with using a direct laryngoscope.  These findings suggest the need for large, multicenter trials examining whether use of a video laryngoscope can make it easier to place a breathing tube on the first try.

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

Journal: Chest
PMID: 27613978