Study objectives

To describe preoperative and postoperative sleep disruption and its relationship to postoperative delirium.

Design

Prospective cohort study with 6 time points (3 nights pre-hospitalization and 3 nights post-surgery).

Setting

University medical center.

Patients

The sample consisted of 50 English-speaking patients ≥ 40 years of age scheduled for major non-cardiac surgery, with an anticipated hospital stay ≥ 3 days.

Interventions

None.

Measurements and results

Sleep was measured before and after surgery for a total of 6 days using a wrist actigraph to quantify movement in a continuous fashion. Postoperative delirium was measured by a structured interview using the Confusion Assessment Method. Sleep variables for patients with (n = 7) and without (n = 43) postoperative delirium were compared using the unpaired Student t-tests or χ(2) tests. Repeated measures analysis of variance for the 6 days was used to examine within-subject changes over time and between group differences. The mean age of the patients was 66 ± 11 years (range 43-91 years), and it was not associated with sleep variables or postoperative delirium. The incidence of postoperative delirium observed during any of the 3 postoperative days was 14%. For the 7 patients who subsequently developed postoperative delirium, wake after sleep onset (WASO) as a percentage of total sleep time was significantly higher (44% ± 22%) during the night before surgery compared to the patients who did not subsequently developed delirium (21% ± 20%, p = 0.012). This sleep disruption continued postoperatively, and to a greater extent, for the first 2 nights after surgery. Patients with WASO < 10% did not experience postoperative delirium. Self-reported sleep disturbance did not differ between patients with vs. without postoperative delirium.

Conclusions

In this pilot study of adults over 40 years of age, sleep disruption was more severe before surgery in the patients who experienced postoperative delirium. A future larger study is necessary to confirm our results and determine if poor sleep is associated with delirium in larger samples and what specific sleep problems best predict postoperative delirium in older surgical patients.

Background

Postoperative pain and opioid use are associated with postoperative delirium. We designed a single-center, randomized, placebo-controlled, parallel-arm, double-blinded trial to determine whether perioperative administration of gabapentin reduced postoperative delirium after noncardiac surgery.

Methods

Patients were randomly assigned to receive placebo (N = 347) or gabapentin 900 mg (N = 350) administered preoperatively and for the first 3 postoperative days. The primary outcome was postoperative delirium as measured by the Confusion Assessment Method. Secondary outcomes were postoperative pain, opioid use, and length of hospital stay.

Results

Data for 697 patients were included, with a mean ± SD age of 72 ± 6 yr. The overall incidence of postoperative delirium in any of the first 3 days was 22.4% (24.0% in the gabapentin and 20.8% in the placebo groups; the difference was 3.20%; 95% CI, 3.22% to 9.72%; P = 0.30). The incidence of delirium did not differ between the two groups when stratified by surgery type, anesthesia type, or preoperative risk status. Gabapentin was shown to be opioid sparing, with lower doses for the intervention group versus the control group. For example, the morphine equivalents for the gabapentin-treated group, median 6.7 mg (25th, 75th quartiles: 1.3, 20.0 mg), versus control group, median 6.7 mg (25th, 75th quartiles: 2.7, 24.8 mg), differed on the first postoperative day (P = 0.04).

Conclusions

Although postoperative opioid use was reduced, perioperative administration of gabapentin did not result in a reduction of postoperative delirium or hospital length of stay.

Background

The pathophysiology of delirium is incompletely understood, including what molecular pathways are involved in brain vulnerability to delirium. This study examined whether preoperative plasma neurodegeneration markers were elevated in patients who subsequently developed postoperative delirium through a retrospective case-control study.

Methods

Inclusion criteria were patients of 65 yr of age or older, undergoing elective noncardiac surgery with a hospital stay of 2 days or more. Concentrations of preoperative plasma P-Tau181, neurofilament light chain, amyloid β1-42 (Aβ42), and glial fibrillary acidic protein were measured with a digital immunoassay platform. The primary outcome was postoperative delirium measured by the Confusion Assessment Method. The study included propensity score matching by age and sex with nearest neighbor, such that each patient in the delirium group was matched by age and sex with a patient in the no-delirium group.

Results

The initial cohort consists of 189 patients with no delirium and 102 patients who developed postoperative delirium. Of 291 patients aged 72.5 ± 5.8 yr, 50.5% were women, and 102 (35%) developed postoperative delirium. The final cohort in the analysis consisted of a no-delirium group (n = 102) and a delirium group (n = 102) matched by age and sex using the propensity score method. Of the four biomarkers assayed, the median value for neurofilament light chain was 32.05 pg/ml for the delirium group versus 23.7 pg/ml in the no-delirium group. The distribution of biomarker values significantly differed between the delirium and no-delirium groups (P = 0.02 by the Kolmogorov-Smirnov test) with the largest cumulative probability difference appearing at the biomarker value of 32.05 pg/ml.

Conclusions

These results suggest that patients who subsequently developed delirium are more likely to be experiencing clinically silent neurodegenerative changes before surgery, reflected by changes in plasma neurofilament light chain biomarker concentrations, which may identify individuals with a preoperative vulnerability to subsequent cognitive decline.

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