Delirium in Hospitalized Older Adults Marcantonio, Edward R
New England journal of medicine/The New England journal of medicine,
2017-Oct-12, Volume:
377, Issue:
15
Journal Article
Delirium (acute confusion) complicates 15% to 50% of major operations in older adults and is associated with other major postoperative complications, prolonged length of stay, poor functional ...recovery, institutionalization, dementia, and death. Importantly, delirium may be predictable and preventable through proactive intervention. Yet clinicians fail to recognize and address postoperative delirium in up to 80% of cases. Using the case of Ms R, a 76-year-old woman who developed delirium first after colectomy with complications and again after routine surgery, the diagnosis, prevention, and treatment of delirium in the postoperative setting is reviewed. The risk of postoperative delirium can be quantified by the sum of predisposing and precipitating factors. Successful strategies for prevention and treatment of delirium include proactive multifactorial intervention targeted to reversible risk factors, limiting use of sedating medications (especially benzodiazepines), effective management of postoperative pain, and, perhaps, judicious use of antipsychotics.
Delirium is common after cardiac surgery and may be associated with long-term changes in cognitive function. We examined postoperative delirium and the cognitive trajectory during the first year ...after cardiac surgery.
We enrolled 225 patients 60 years of age or older who were planning to undergo coronary-artery bypass grafting or valve replacement. Patients were assessed preoperatively, daily during hospitalization beginning on postoperative day 2, and at 1, 6, and 12 months after surgery. Cognitive function was assessed with the use of the Mini-Mental State Examination (MMSE; score range, 0 to 30, with lower scores indicating poorer performance). Delirium was diagnosed with the use of the Confusion Assessment Method. We examined performance on the MMSE in the first year after surgery, controlling for demographic characteristics, coexisting conditions, hospital, and surgery type.
The 103 participants (46%) in whom delirium developed postoperatively had lower preoperative mean MMSE scores than those in whom delirium did not develop (25.8 vs. 26.9, P<0.001). In adjusted models, those with delirium had a larger drop in cognitive function (as measured by the MMSE score) 2 days after surgery than did those without delirium (7.7 points vs. 2.1, P<0.001) and had significantly lower postoperative cognitive function than those without delirium, both at 1 month (mean MMSE score, 24.1 vs. 27.4; P<0.001) and at 1 year (25.2 vs. 27.2, P<0.001) after surgery. With adjustment for baseline differences, the between-group difference in mean MMSE scores was significant 30 days after surgery (P<0.001) but not at 6 or 12 months (P=0.056 for both). A higher percentage of patients with delirium than those without delirium had not returned to their preoperative baseline level at 6 months (40% vs. 24%, P=0.01), but the difference was not significant at 12 months (31% vs. 20%, P=0.055).
Delirium is associated with a significant decline in cognitive ability during the first year after cardiac surgery, with a trajectory characterized by an initial decline and prolonged impairment. (Funded by the Harvard Older Americans Independence Center and others.).
Postoperative delirium is common following cardiac surgery and may be affected by choice of analgesic and sedative.
To evaluate the effect of postoperative intravenous (IV) acetaminophen ...(paracetamol) vs placebo combined with IV propofol vs dexmedetomidine on postoperative delirium among older patients undergoing cardiac surgery.
Randomized, placebo-controlled, factorial clinical trial among 120 patients aged 60 years or older undergoing on-pump coronary artery bypass graft (CABG) surgery or combined CABG/valve surgeries at a US center. Enrollment was September 2015 to April 2018, with follow-up ending in April 2019.
Patients were randomized to 1 of 4 groups receiving postoperative analgesia with IV acetaminophen or placebo every 6 hours for 48 hours and postoperative sedation with dexmedetomidine or propofol starting at chest closure and continued for up to 6 hours (acetaminophen and dexmedetomidine: n = 29; placebo and dexmedetomidine: n = 30; acetaminophen and propofol: n = 31; placebo and propofol: n = 30).
The primary outcome was incidence of postoperative in-hospital delirium by the Confusion Assessment Method. Secondary outcomes included delirium duration, cognitive decline, breakthrough analgesia within the first 48 hours, and ICU and hospital length of stay.
Among 121 patients randomized (median age, 69 years; 19 women 15.8%), 120 completed the trial. Patients treated with IV acetaminophen had a significant reduction in delirium (10% vs 28% placebo; difference, -18% 95% CI, -32% to -5%; P = .01; HR, 2.8 95% CI, 1.1-7.8). Patients receiving dexmedetomidine vs propofol had no significant difference in delirium (17% vs 21%; difference, -4% 95% CI, -18% to 10%; P = .54; HR, 0.8 95% CI, 0.4-1.9). There were significant differences favoring acetaminophen vs placebo for 3 prespecified secondary outcomes: delirium duration (median, 1 vs 2 days; difference, -1 95% CI, -2 to 0), ICU length of stay (median, 29.5 vs 46.7 hours; difference, -16.7 95% CI, -20.3 to -0.8), and breakthrough analgesia (median, 322.5 vs 405.3 µg morphine equivalents; difference, -83 95% CI, -154 to -14). For dexmedetomidine vs propofol, only breakthrough analgesia was significantly different (median, 328.8 vs 397.5 µg; difference, -69 95% CI, -155 to -4; P = .04). Fourteen patients in both the placebo-dexmedetomidine and acetaminophen-propofol groups (46% and 45%) and 7 in the acetaminophen-dexmedetomidine and placebo-propofol groups (24% and 23%) had hypotension.
Among older patients undergoing cardiac surgery, postoperative scheduled IV acetaminophen, combined with IV propofol or dexmedetomidine, reduced in-hospital delirium vs placebo. Additional research, including comparison of IV vs oral acetaminophen and other potentially opioid-sparing analgesics, on the incidence of postoperative delirium is warranted.
ClinicalTrials.gov Identifier: NCT02546765.
Major postoperative complications and delirium contribute independently to adverse outcomes and high resource use in patients who undergo major surgery; however, their interrelationship is not well ...examined.
To evaluate the association of major postoperative complications and delirium, alone and combined, with adverse outcomes after surgery.
Prospective cohort study in 2 large academic medical centers of 566 patients who were 70 years or older without recognized dementia or a history of delirium and underwent elective major orthopedic, vascular, or abdominal surgical procedures with a minimum 3-day hospitalization between June 18, 2010, and August 8, 2013. Data analysis took place from December 13, 2013, through May 1, 2015.
Major postoperative complications, defined as life-altering or life-threatening events (Accordion Severity grade 2 or higher), were identified by expert-panel adjudication. Delirium was measured daily with the Confusion Assessment Method and a validated medical record review method. The following 4 subgroups were analyzed: (1) no complications or delirium; (2) complications only; (3) delirium only; and (4) complications and delirium. Adverse outcomes included a length of stay (LOS) of more than 5 days, institutional discharge, and rehospitalization within 30 days of discharge.
In the 566 participants, the mean (SD) age was 76.7 (5.2) years, 236 (41.7%) were male, and 523 (92.4%) were white. Forty-seven patients (8.3%) developed major complications and 135 (23.9%) developed delirium. Compared with no complications or delirium as the reference group, major complications only contributed to prolonged LOS only (relative risk RR, 2.8; 95% CI, 1.9-4.0); by contrast, delirium only significantly increased all adverse outcomes, including prolonged LOS (RR, 1.9; 95% CI, 1.4-2.7), institutional discharge (RR, 1.5; 95% CI, 1.3-1.7), and 30-day readmission (RR, 2.3; 95% CI, 1.4-3.7). The subgroup with complications and delirium had the highest rates of all adverse outcomes, including prolonged LOS (RR, 3.4; 95% CI, 2.3-4.8), institutional discharge (RR, 1.8; 95% CI, 1.4-2.5), and 30-day readmission (RR, 3.0; 95% CI, 1.3-6.8). Delirium exerted the highest attributable risk at the population level (5.8%; 95% CI, 4.7-6.8) compared with all other adverse events (prolonged LOS, institutional discharge, or readmission).
Major postoperative complications and delirium are separately associated with adverse events and demonstrate a combined effect. Delirium occurs more frequently and has a greater effect at the population level than other major complications.
Post-operative cognitive dysfunction is associated with morbidity and mortality. However, its neuropathogenesis remains largely to be determined. Neuroinflammation and accumulation of β-amyloid (Aβ) ...have been reported to contribute to cognitive dysfunction in humans and cognitive impairment in animals. Our recent studies have established a pre-clinical model in mice, and have found that the peripheral surgical wounding without the influence of general anesthesia induces an age-dependent Aβ accumulation and cognitive impairment in mice. We therefore set out to assess the effects of peripheral surgical wounding, in the absence of general anesthesia, on neuroinflammation in mice with different ages. Abdominal surgery under local anesthesia was established in 9 and 18 month-old mice. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Iba1 positive cells (the marker of microglia activation), CD33, and cognitive function in mice were determined. The peripheral surgical wounding increased the levels of TNF-α, IL-6, and Iba1 positive cells in the hippocampus of both 9 and 18 month-old mice, and age potentiated these effects. The peripheral surgical wounding increased the levels of CD33 in the hippocampus of 18, but not 9, month-old mice. Finally, anti-inflammatory drug ibuprofen ameliorated the peripheral surgical wounding-induced cognitive impairment in 18 month-old mice. These data suggested that the peripheral surgical wounding could induce an age-dependent neuroinflammation and elevation of CD33 levels in the hippocampus of mice, which could lead to cognitive impairment in aged mice. Pending further studies, anti-inflammatory therapies may reduce the risk of postoperative cognitive dysfunction in elderly patients.
Frailty assessment may inform surgical risk and prognosis not captured by conventional surgical risk scores.
To evaluate the evidence for various frailty instruments used to predict mortality, ...functional status, or major adverse cardiovascular and cerebrovascular events (MACCEs) in older adults undergoing cardiac surgical procedures.
MEDLINE and EMBASE (without language restrictions), from their inception to 2 May 2016.
Cohort studies evaluating the association between frailty and mortality or functional status at 6 months or later in patients aged 60 years or older undergoing major or minimally invasive cardiac surgical procedures.
2 reviewers independently extracted study data and assessed study quality.
Mobility, disability, and nutrition were frequently assessed domains of frailty in both types of procedures. In patients undergoing major procedures (n = 18 388; 8 studies), 9 frailty instruments were evaluated. There was moderate-quality evidence to assess mobility or disability and very-low- to low-quality evidence for using a multicomponent instrument to predict mortality or MACCEs. No studies examined functional status. In patients undergoing minimally invasive procedures (n = 5177; 17 studies), 13 frailty instruments were evaluated. There was moderate- to high-quality evidence for assessing mobility to predict mortality or functional status. Several multicomponent instruments predicted mortality, functional status, or MACCEs, but the quality of evidence was low to moderate. Multicomponent instruments that measure different frailty domains seemed to outperform single-component ones.
Heterogeneity of frailty assessment, limited generalizability of multicomponent frailty instruments, few validated frailty instruments, and potential publication bias.
Frailty status, assessed by mobility, disability, and nutritional status, may predict mortality at 6 months or later after major cardiac surgical procedures and functional decline after minimally invasive cardiac surgery.
National Institute on Aging and National Heart, Lung, and Blood Institute.
Abstract Introduction As the relationship between delirium and long-term cognitive decline has not been well-explored, we evaluated this association in a prospective study. Methods SAGES is an ...ongoing study involving 560 adults age 70 years or more without dementia scheduled for major surgery. Delirium was assessed daily in the postoperative period using the Confusion Assessment Method. General Cognitive Performance (GCP) and the Informant Questionnaire for Cognitive Decline in the Elderly were assessed preoperatively then repeatedly out to 36 months. Results On average, patients with postoperative delirium had significantly lower preoperative cognitive performance, greater immediate (1 month) impairment, equivalent recovery at 2 months, and significantly greater long-term cognitive decline relative to the nondelirium group. Proxy reports corroborated the clinical significance of the long-term cognitive decline in delirious patients. Discussion Cognitive decline after surgery is biphasic and accelerated among persons with delirium. The pace of long-term decline is similar to that seen with mild cognitive impairment.
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