Background

Postoperative delirium and cognitive dysfunction are frequent phenomena in older patients; however, few studies have examined the temporal relationship between these two conditions in the early postoperative period. Therefore, this study aimed to determine if postoperative delirium and postoperative cognitive dysfunction (POCD) coexist after major noncardiac surgery.

Methods

This was a prospective cohort study of patients who were ≥ 65 yr of age undergoing noncardiac surgery. Patients were evaluated preoperatively and for two days postoperatively for delirium and POCD. Delirium was determined using the Confusion Assessment Method, and POCD was measured by three cognitive tests addressing changes in executive function, memory, attention, and concentration. For each postoperative day, patients' neurologic status was categorized into three mutually exclusive categories: delirium, POCD, or neither condition.

Results

Four hundred sixty-one patients aged ≥ 65 yr of age were studied, and 421 patients with complete postoperative cognitive testing were reported. Eighty percent of patients experienced either delirium or POCD on the first day after surgery. Seventy percent of patients who had delirium on the first postoperative day also had delirium on the second postoperative day. Sixty-three percent of patients who had POCD on postoperative day one continued to have POCD on the next day. Sixteen percent of patients with delirium on day one were non-delirious on day two but met criteria for POCD on day two. Conversely, 15% of patients with POCD on day one became delirious on day two. Only 13% of patients did not experience delirium or POCD on either day after surgery.

Conclusions

Eighty percent of surgical patients experienced some form of cognitive dysfunction the day after surgery, and few recovered by the second day after surgery.

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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