The Pre-brief
During my ICU rotations in residency, every morning, shortly after signout, an amusing but important ritual commenced. The dutiful nurses would begin to shout from their patient’s rooms. “Mr. Jones! Can you hear me? Mr. Jones, if you can hear me, wiggle your toes!” “Ms. Martha! Open your eyes! Squeeze my hand if you hear my voice!” I couldn’t help but chuckle at the thought of emerging from unconsciousness into an ethereal, dream-like state, and the first thing I hear is “Sir if you can hear me, stick out your tongue!”
Yet the practice of “sedation vacations” is an essential and undoubtedly beneficial part of critical care. In many ICUs, nearly every day, providers perform “spontaneous awakening trials” or “daily interruption of sedatives”. Ceasing sedative infusions allow for patients to demonstrate neurological function, reorient to time and place, and also to prevent drug overaccumulation and oversedation.
The Pros and Cons of Sedation
There are various reasons why we sedate our patients in the ICU, especially those who are mechanically ventilated. Sedation protects our patients from the pain, agitation, anxiety, and discomfort associated with being intubated. Additionally, it decreases excessive oxygen consumption, facilitates nursing care, and expedites safe completion of procedures and imaging.
Sedation also has its drawbacks. The lipophilic nature of commonly used sedatives, like benzodiazepines and propofol, especially when continuously infused over long periods of times, leads to increased accumulation of the drug in the body. This challenges our ability to perform neurological evaluations, and results in more ventilator-associated days, increasing the risk of infection and other complications.
Sedative Agents in the ICU
Critical illness can also alter the pharmacokinetics and pharmacodynamics of drugs due to fluid administration, hemodynamic instability, organ dysfunction, acidosis, and altered molecular interactions. This can lead to unpredictable and prolonged duration of actions of these sedatives.

While drugs are often categorized via their elimination half-lives, these are single compartment models (blood), that may not accurately explain the half-life of a drug that reaches multiple compartments (blood, viscera, fat, muscle) as with sedatives. For the purposes of sedatives, the context-sensitive half-time might be a better measurement for how long it takes a patient to awake from sedation. It is the time required for plasma or blood concentrations of the drug to decrease by 50% after discontinuing the drug.
Spontaneous awakening trials (SATs) arose when clinicians and researchers started to wonder if their patients were staying on the vent longer than necessary and thereby risking complications. Long continuous infusions led to prolonged sedatives and longer time to assess neurologic status for extubation. Instead of depending on clinical gestalt to determine when a patient is ready to be weaned off the ventilator, what if we just woke up the patient and let them guide us?
The Research
A number of studies have been completed since the mid-1990s that explored ventilator weaning via spontaneous awakening trials. While a review is beyond the scope of this post, it is worth taking a look at some of the highlights of the research.
- In one of the original studies assessing the daily interruption of sedatives, Kress et al. conducted a single center, randomized, controlled trial that compared SATs in an intervention group versus the cessation of sedatives based on clinicians judgement in a control group. They found that, compared with the control group, the intervention group spent a median duration of 2.4 days less on mechanical ventilation and 3.5 fewer days in the ICU.
- In the Awakening and Breathing Control (ABC) trial (Girard, Kress, et al.), a multicenter study, researchers paired SATs with spontaneous breathing trials (SBTs). The intervention group underwent SATs daily and then SBTs if tolerated, while the control group relied on an individualized approach determined by the intensivist. 150 patients in the intervention group underwent 895 SATs and passed 837 (94%). In the control group, only 31% of patients (52/168) had their sedatives held before an SBT, suggesting that many of our patients might be ready for SBTs earlier than expected. Overall, those in the intervention group spent more days breathing without assistance, were more alert on the day they passed their SBT screen, required less overall benzodiazepines, and had a four day earlier discharge from the ICU and the hospital.
- In a study by Balas et al, researchers assessed awakening and breathing coordination (daily SATs and SBTs if eligible), delirium management (via CAM-ICU and RASS scores), and early exercise (PT/OT consults) (the ABCDEF bundle) in a single-center study of 5 ICUs. By comparing patients treated in the 8 months prior to the implementation of an ABCDE protocol to the 7 months afterwards, they found that the latter group was more likely to undergo an SAT and an SBT, have more days breathing without the ventilator, was less likely to become delirious, and more likely to be mobilized out of bed.
- One negative study of SATs was a randomized, controlled trial of 16 ICUs over a three year period, performed by Mehta et al. In the control group, researchers implemented a protocolized analgesia and sedation strategy based in opioids and benzodiazepines that used the Richmond Agitation Sedation Scale (RASS) or the Sedation-Agitation Scale (SAS) to determine how to titrate these drugs. In the intervention group, the patients underwent the protocolized strategy plus daily sedation interruptions. Their primary outcome found no difference in time spent on the ventilator in both groups (~7 days). However, this study suffered from some weaknesses including poor adherence to SATs and the absence of often used medications propofol, ketamine, and dexmedetomidine in their sedation strategy.
- The 2018 Clinical Practice Guidelines for Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PADIS) recommends light sedation over deep sedation in intubated, critically ill patients. Their review of the literature found no significant difference between SATs and nursing protocolized care. However, they note that most studies used benzodiazepines for sedation, which are no longer recommended. They also make the caveat that SATs often lead to an increased nursing workload.
Guidelines for Spontaneous Awakening Trials
Let’s say you want to try a spontaneous awakening trial. What are the recommended guidelines?
To further continue the alphabet one-upmanship, the Society of Critical Care Medicine established the ICU Liberation Bundle (ABCDEF, now including Family Engagement and Empowerment). Here they advise using the ABC trial’s “Wake Up and Breathe Protocol.” This recommendation is echoed by the Agency for Healthcare Research and Quality.
The SAT consists of two parts: a safety screen and the actual assessment.
- First the ICU team must identify patients who are on full ventilator support and responding to verbal stimuli. These patients are eligible for an SAT.
- However, patients are ineligible if they meet any of the following criteria:
- Receiving sedative infusions for alcohol withdrawal or seizures
- Requiring increasing doses of sedative for agitation
- Increased intracranial pressure
- Active myocardial ischemia in the past 24 hours
- Receiving paralytics (neuromuscular blockers)
- If the patient passes the safety screen all sedatives and analgesics for sedation are ceased. However, medications for pain are continued as required.
- Patients must be able to do one of the following:
- Perform three out of four of tasks: open their eyes, squeeze a hand, look at their caregiver, or stick out their tongue
- Go at least four hours without:
- Sustained or increasing anxiety, agitation, or pain
- Tachypnea (> 35 breaths per minute) for at least 5 minutes
- Demonstrating SpO2 < 88% for at least 5 minutes
- Have acute cardiac dysrhythmias
- Demonstrate signs of respiratory distress (tachycardia, bradycardia, accessory muscle use, dyspnea, diaphoresis)
- If the patient fails the SAT, the sedation is restarted at half the original dosage and then titrated for pain and sedation.
- But if the patient passes the SAT, then the patient moves on to a spontaneous breathing trial!
But wait a minute… What is a spontaneous breathing trial? Stay tuned to a future post of The Vitals!
The Debrief
- Sedation protects our patients from the pain, agitation, anxiety, and discomfort associated with being intubated. Additionally, it decreases excessive oxygen consumption, facilitates nursing care, and expedites safe completion of procedures and imaging.
- The lipophilic nature of commonly used sedatives, especially when continuously infused over long periods of times, leads to increased accumulation of the drug in the body. This challenges our ability to perform neurological evaluations, and results in more ventilator-associated days, increasing the risk of infection and other complications.
- Spontaneous awakening trials (SATs) arose when clinicians and researchers started to wonder if their patients were staying on the vent longer than necessary and thereby risking complications. Long continuous infusions led to prolonged sedation and longer time to assess neurologic status for extubation.
- A number of studies have found that daily awakening trials have a number of benefits, including decreased time on the ventilator, less delirium, a lower complication rate, and an earlier discharge from the ICU and the hospital.
- The ABC trial’s “Wake Up and Breathe” protocol is a standardized checklist that guides clinicians in assessing if their patients are eligible and if they can pass a spontaneous awakening and a spontaneous breathing trial.
References
- Devlin, John W. PharmD, FCCM (Chair); Skrobik, Yoanna MD, FRCP(c), MSc, FCCM (Vice-Chair); GĂ©linas, CĂ©line RN, PhD; Needham, Dale M. MD, PhD; et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU, Critical Care Medicine: September 2018 – Volume 46 – Issue 9 – p e825-e873 doi:10.1097/CCM.0000000000003299.
- Kress JP, Pohlman AS, O’Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000 May 18;342(20):1471-7. doi: 10.1056/NEJM200005183422002. PMID: 10816184.
- Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a ran- domised controlled trial. Lancet. 2008;371:126-134.Â
- Hughes CG, Girard TD, Pandharipande PP. Daily sedation interruption versus targeted light sedation strategies in ICU patients. Crit Care Med. 2013 Sep;41(9 Suppl 1):S39-45. doi: 10.1097/CCM.0b013e3182a168c5. Erratum in: Crit Care Med. 2013 Nov;41(11):e400. PMID: 23989094.
- Balas MC,Vasilevskis EE, Olsen KM, et al. Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/ mobility bundle. Crit Care Med. 2014;42:1024-1036.Â
- Mehta S, Burry L, Cook D, et al. Daily sedation inter- ruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA. 2012;308:1985-1992.
- Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton DL, Haponik EF. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med. 1996 Dec 19;335(25):1864-9. doi: 10.1056/NEJM199612193352502. PMID: 8948561.
- Reade MC, Finfer S. Sedation and delirium in the intensive care unit. N Engl J Med. 2014 Jan 30;370(5):444-54. doi: 10.1056/NEJMra1208705. PMID: 24476433.
- Comprehensive Critical Care: Adult 2nd Edition Chapter 42 – Sedatives, Analgesics, and Neuromuscular Blockade in the ICU
- ICU Liberation 2nd Edition Chapter 3 – Spontaneous Awakening and Breathing Trials – https://www.sccm.org/getattachment/86464100-4b13-4da5-b3d1-39a9a4cceb64/Spontaneous-Awakening-and-Breathing-Trials
- Sedation in COVID-19 – https://advances.massgeneral.org/research-and-innovation/article.aspx?id=1355
- Spontaneous Awakening Trials and Spontaneous Breathing Trials Literature Review. Content last reviewed January 2017. Agency for Healthcare Research and Quality, Rockville, MD. https://www.ahrq.gov/hai/tools/mvp/modules/technical/sat-sbt-lit-review.html
- Coordinated Spontaneous Awakening and Breathing Trials Protocol. Content last reviewed January 2017. Agency for Healthcare Research and Quality, Rockville, MD.    https://www.ahrq.gov/hai/tools/mvp/modules/technical/sat-sbt-protocol.html