Q&A: Understanding how intubation sedatives impact patient outcomes, risk for PTSD

Key takeaways:

• A multicenter, randomized trial is planned to assess ketamine vs. etomidate in patients requiring intubation.
• Researchers hope to determine which sedative improves survival and reduces PTSD symptoms.

There is a lack of evidence on how sedatives used during tracheal intubation impact patient survival and likelihood for PTSD symptoms, and researchers at Vanderbilt University Medical Center plan to find the answer.

With a $7 million award from the Patient-Centered Outcomes Research Institute, Matthew W. Semler, MD, MSc, assistant professor of medicine and biomedical informatics at Vanderbilt University Medical Center, and colleagues will assess ketamine vs. etomidate to determine which sedative medication improves outcomes in ED and ICU patients requiring intubation, according to a Vanderbilt University press release.

Healio spoke with Semler to learn more about tracheal intubation, the mental toll this procedure can have on patients and the proposed benefits this research will provide to both patients and clinicians.

Healio: The press release states that millions of patients undergo tracheal intubation each year. Can you describe what kind of patients are undergoing this procedure and what long-term effects and risks they may face?

Semler: Approximately 1% of the U.S. population (2 million to 3 million adults) experiences critical illness requiring tracheal intubation each year. Patients who require tracheal intubation in the ED or ICU include patients severely ill from cardiac arrest, pneumonia, sepsis or motor vehicle accident.

These patients face significant long-term risks. For example, approximately one in three patients who undergo tracheal intubation in the ED or ICU die in the hospital. The nearly 750,000 adults who die following tracheal intubation in the ED or ICU each year account for approximately 25% of all deaths in the U.S. Among those who survive, between 14% to 34% experience PTSD. For survivors of critical illness, PTSD may last months to years and may negatively impact patients’ marriages, work and quality of life and increase their risk for depression, anxiety, substance use disorder and suicide.

Healio: In this trial, you will be comparing the effectiveness of two sedatives: ketamine and etomidate. Currently, why does a clinician choose one sedative over the other?

Semler: Patients undergoing intubation receive a sedative medication to make them unconscious during the procedure. In the United States, ketamine and etomidate are the two sedative medications most commonly used for intubation in Eds and in medical ICUs. Because rigorous evidence comparing ketamine and etomidate is lacking, use of these medications in clinical practice varies widely based on factors unrelated to the patient, such as the hospital, the unit within the hospital and the specialty of the intubating clinician. In a recent study at one hospital, an individual patient’s chances of receiving ketamine ranged from 0% if intubated by one of the one-third of clinicians who only use etomidate to 100% if intubated by one of the one-third of clinicians who only use ketamine. The location (ED vs. ICU) and specialty of the clinician (emergency medicine vs. pulmonary and critical care medicine) were the only factors associated with whether a patient received ketamine or etomidate. Patient characteristics (age, blood pressure, acute conditions, etc) were not a significant factor. That is to say, because data are insufficient to make an evidence-based choice between ketamine and etomidate as to which treatment is best for an individual patient, the choice in current clinical care is often determined by factors unrelated to the patient, such as the culture of the hospital to which the patient presents or the subspecialty of the physician performing the intubation.

Healio: What is the primary outcome that will be evaluated in this study?

Semler: The primary outcome for our study will be mortality at 1 month. We are seeking to understand whether using one of the two medications can help patients survive the initial hospitalization. If so, then using the better medication could improve survival for a large number of patients each year.

Healio: Why is it also important to assess PTSD symptoms in patients?

Semler: PTSD is a psychiatric disorder triggered by a “shocking, scary or dangerous event,” according to the definition from the National Institute of Mental Health. Critical illness, tracheal intubation and mechanical ventilation can be traumatic and distressing events. Patients may recall the intubation procedure, the feeling of the breathing tube in their throat or being unable to move. While on the breathing machine, patients may experience delirium, frightening hallucinations and delusions. Patients with PTSD after critical illness can be hypervigilant, anxious and troubled by intrusive thoughts, nightmares and flashbacks. Ketamine has been hypothesized to prevent the development of PTSD among critically ill adults undergoing tracheal intubation, but this has never been rigorously studied. If the choice of sedative medication for critically ill adults could prevent the development of PTSD, this could improve mental health and quality of life for hundreds of thousands of patients each year in the U.S.

Healio: How do you expect outcomes of this study to impact patient care and outcomes?

Semler: We hope to find the sedative medication that results in the highest rate of survival and the lowest rate of PTSD after critical illness. Because critical illness requiring tracheal intubation is so common, and because both medicines being compared are inexpensive and already used every day in current clinical care, determining which one results in the best survival and mental health could immediately improve care and patient-centered outcomes for a large number of patients.

Healio: When can clinicians expect to read about the results of this study?

Semler: Multicenter, randomized trials like this one generate the highest level of evidence to inform clinical care, but they also take years to complete. The first year of the award will be mostly focused on getting input from patients, families and community members about the research question and the design of the trial. Then the trial will be performed at six hospitals across the U.S. We anticipate that the results will be available in approximately 4 years.

Reference:

• VUMC receives $7 million award from PCORI to compare breathing tube sedation. https://news.vumc.org/2023/07/18/vumc-receives-7-million-award-from-pcori-to-compare-breathing-tube-sedation. Published July 18, 2023. Accessed July 19, 2023.