Target Audience and Goal Statement: Critical care providers, hospitalists, neurologists
The goal of this study was to determine whether the sniff test — a non-verbal non-task-dependent test — can predict the likelihood of regaining consciousness and surviving long-term in patients who are unresponsive due to brain injury.
Question Addressed:
- Does the sniff response predict recovery of consciousness and potential long-term outcome in brain-injured patients with disorders of consciousness?
Identifying signs of awareness in brain-injured patients with prolonged disorders of consciousness can be challenging. Use of clinical/behavioral evaluations to differentiate a vegetative state from a minimally conscious state has been associated with a high rate of misdiagnosis, which in turn may result in early withdrawal of life-sustaining treatment.
Action Points
- In a small study conducted in Israel, nasal response to odors predicted likelihood of recovery and long-term survival among brain-injured patients.
- Note that in 25% of the patients who had a positive sniff test, sniffing behavior preceded other behavioral signs of consciousness by up to 2.5 months.
Nasal response to odors — that is, sniffing — predicts likelihood of recovery and long-term survival among brain-injured patients, according to Anat Arzi, PhD, of the University of Cambridge in England, Noam Sobel, PhD, of the Weizmann Institute of Science in Rehovot, Israel, and colleagues.
When 43 patients with severe brain injury were presented with pleasant and unpleasant smells, their sniff responses — modulation of air volume inhaled through their nostrils — reliably predicted whether they would regain consciousness, they reported in Nature.
The sniff test had 100% specificity for predicting whether patients in a vegetative state would recover consciousness but only 62.5% sensitivity, meaning that 37.5% of unresponsive patients who didn’t sniff did eventually regain consciousness.
At the single-patient level, the results were clear, Sobel said. “If you sniff at an odorant, then it’s 100% you will regain consciousness to at least a minimal level, and you will likely live for years,” he told MedPage Today. “If you don’t sniff at an odorant, that is a bad sign, but not all hope is lost.”
And at the group level, sniff responses distinguished patients in vegetative states from those in minimally conscious states.
Sniff response is an implicit measure for odor processing, Arzi explained. “We do not need to ask whether you smelled the odor we presented,” she told MedPage Today. “Instead, we can examine your change in respiration in response to an odor and have a good estimation of your ability to smell.”
In their study, the researchers followed 43 brain-injured patients at the Loewenstein Hospital Rehabilitation Center in Raanana, Israel, for 6 years. Patients were characterized either as having “unresponsive wakefulness syndrome” (also known as a vegetative state), in which they appeared awake but unaware of themselves or their environment, or as being in a minimally conscious state, characterized by irregular periods of awareness. The researchers tested patients during multiple sessions for an average of 3.4 sessions per patient.
During the testing sessions, the researchers measured patients’ nasal airflow with a nasal cannula. They tested two odorant mixtures — a pleasant shampoo scent and unpleasant rotten fish smell — which were absorbed in a cotton pad and placed in a sniff jar.
At the beginning of each session, a researcher explained to the patient that odorants would be presented and nasal respiration would be monitored, even though the researcher had no indication whether the patient heard or understood this. After each session, the patient’s consciousness state was evaluated using the Coma Recovery Scale-Revised and/or the Coma/Near Coma scale. Patients also were assessed periodically with the Loewenstein Communication Scale.
In 25% of the patients who had a positive sniff test, sniffing behavior preceded other behavioral signs of consciousness by up to 2.5 months.
Arzi and team acknowledged limitations to their study. They noted that, in reflection of changes in clinical practice at the hospital where they conducted the study, they had data using two different behavioral assessment protocols. Additionally, the clinical testing schedule dictated the temporal resolution of their estimation regarding the extent to which a sniff-response preceded transition from unresponsive wakefulness syndrome to a minimally conscious state. If the tests had been more frequent, they may have observed different timing for advance detection.
Source Reference: Nature 2020; DOI: 10.1038/s41586-020-2245-5
Study Highlights and Explanation of Findings:
A more precise diagnosis of vegetative and minimally conscious states in patients with a brain injury may improve prognosis, treatment, and recovery, according to 2018 guidelines from the American Academy of Neurology (AAN). A standardized behavioral evaluation should be performed by clinicians with specialized training, immediately after the injury and repeatedly during the first 3 months thereafter to detect shifts in levels of arousal and common medical complications that can lead to less accurate diagnoses.
Likewise, Arzi and colleagues noted that fluctuations of consciousness in disorders of consciousness make it important to analyze the sniff test data per assessment rather than averaging results per patient, to avoid obscuring any differences between a minimally conscious state and unresponsive wakefulness syndrome. They pointed to three sessions with one patient who began in a minimally conscious state, deteriorated to unresponsive wakefulness syndrome, and then recovered to a minimally conscious state, and had returned to functional status at the time of publication.
“This is a cleverly and carefully designed study that adds another much-needed tool to the consciousness-detection toolbox,” noted Joseph Giacino, PhD, of Harvard Medical School, who helped write the 2018 AAN guidance on disorders of consciousness and was not involved in the current research.
Based on available evidence, about four in 10 patients who are deemed unconscious on bedside examination actually retain conscious awareness, he said. “A significant portion of these patients have covert consciousness — preserved cognitive function that cannot be expressed through speech or movement,” he told MedPage Today.
A sniff test offers several clinical advantages, he noted. “It’s accessible and seemingly easy to administer unlike functional neuroimaging, which is recommended to complement behavioral assessment in the 2018 guidelines,” he pointed out.
“It also does not require cognitive effort,” he added. “Conscious patients with severe brain injury often do not have the attentional control to manage the cognitive demands required by functional neuroimaging and EEG-based protocols.”
“Published evidence from Canada in a large cohort of ICU patients with traumatic brain injury [TBI] found that approximately 70% of the deaths were due to withdrawal of treatment and in about 60% of cases, the decision to stop treatment was made within 72 hours,” he said. “It’s possible that a positive sniff test might delay this decision, which is important since we know that about 20% of TBI patients who survive what appears to be catastrophic injury recover to a functionally-independent level by 5 years post-injury.”
While the study has potential in clinical practice, it was a single-center study with a small sample size and important limitations, Giacino observed.
“Between 30% and 60% of patients who sustain severe TBI have diminished or complete loss of smell due to the mechanics of the injury,” he noted. “The authors acknowledge this in suggesting that the relatively low sensitivity of the sniff test may have been attributable to patients with anosmia. The problem is that there is no way to know which patients are anosmic since they are non-communicative.”
Further work is ongoing, Sobel and Arzi noted. “The next step is turning this into an easily applied cell-phone based application that will actually be used,” Sobel said. “In addition, we plan to combine neuroimaging and electrophysiology methods together with the sniff test to uncover the brain activity underlying consciousness recovery,” Arzi added.
Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco
Primary Source
Nature
Secondary Source
MedPage Today
Source Reference: George J “Will a Brain-injured Patient Recover? The Nose May Know” 2020.
https://www.medpagetoday.org/neurology/generalneurology/86754?_ga=2.259579534.503806516.1590619765-265074527.1569866268
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