The Impact of Opioid Medications on Sleep Architecture and Nocturnal Respiration During Acute Recovery From Moderate to Severe Traumatic Brain Injury: A TBI Model Systems Study
Authors: Martin Aaron M. , Almeida Emily J. , Starosta Amy J. , Hammond Flora M. , Hoffman Jeanne M. , Schwartz Daniel J. , Fann Jesse R. , Bell Kathleen R. , Nakase-Richardson Risa 
Published: September 2021

Objectives:
To describe patient and clinical characteristics associated with receipt of opioid medications and identify differences in sleep quality, architecture, and sleep-related respiration between those receiving and not receiving opioid medications.

Setting:
Acute inpatient rehabilitation care for moderate to severe traumatic brain injury (TBI).

Participants:
A total of 248 consecutive admissions for inpatient rehabilitation care following moderate to severe TBI (average age of 43.6 years), who underwent level 1 polysomnography (PSG) (average time since injury: 120 days) across 6 sites.

Design:
Cross-sectional, secondary analyses.

Main Measures:
The PSG sleep parameters included total sleep time (TST), sleep efficiency (SE), wake after sleep onset, rapid eye movement (REM) latency, sleep staging, and arousal and awakening indices. Respiratory measures included oxygen saturation, central apnea events per hour, obstructive apnea and hypopnea events per hour, and total apnea-hypopnea index.

Results:
After adjustment for number of prescribed medication classes, those receiving opioid medications on the day of PSG experienced increased TST relative to those not receiving opioid medications (estimated mean difference [EMD] = 31.58; 95% confidence interval [CI], 1.9-61.3). Other indices of sleep did not differ significantly between groups. Among respiratory measures those receiving opioids on the day of PSG experienced increased frequency of central sleep apnea events during total (EMD = 2.92; 95% CI, 0.8-5.0) and non-REM sleep (EMD = 3.37; 95% CI, 1.0-5.7) and higher frequency of obstructive sleep apnea events during REM sleep (EMD = 6.97; 95% CI, 0.1-13.8). Compared with those who did not, receiving opioids was associated with lower oxygen saturation nadir during total sleep (EMD = −3.03; 95% CI, −5.6 to −0.4) and a greater number of oxygen desaturations across REM (EMD = 8.15; 95% CI, 0.2-16.1), non-REM (EMD = 7.30; 95% CI, 0.3-14.4), and total sleep (EMD = 8.01; 95% CI, 0.8-15.2) Greater total apnea-hypopnea index was observed during REM (EMD = 8.13; 95% CI, 0.8-15.5) and total sleep (EMD = 7.26; 95% CI, 0.08-14.4) for those receiving opioids.

Conclusion:
Opioid use following moderate to severe TBI is associated with an increase in indicators of sleep-related breathing disorders, a modifiable condition that is prevalent following TBI. As sleep-wake disorders are associated with poorer rehabilitation outcomes and opioid medications may frequently be administered following traumatic injury, additional longitudinal investigations are warranted in determining whether a causal relation between opioids and sleep-disordered breathing in those following moderate to severe TBI exists. Given current study limitations, future studies can improve upon methodology through the inclusion of indication for and dosage of opioid medications in this population when examining these associations.