Mr. A, a 74-year-old man, presented to the emergency department (ED) with a fever and rigor 2 days after an ultrasound-guided transrectal prostate biopsy. He had a history of benign prostate hypertrophy, stage 2 chronic renal failure, hypertension, and hyperlipidemia and was an ex-smoker of 60 pack-years. He was hypotensive and had generalized tonic-clonic seizures at arrival. He was admitted to the intensive care unit (ICU) for septic shock and was treated with intravenous broad-spectrum antibiotics, inotropic support, and anti-epileptic drugs. His ICU admission was complicated by worsening type 1 respiratory failure due to hospital-acquired pneumonia (HAP). Recurrent failed extubation resulted in a tracheostomy 2 weeks later and 1 month after intubation, before he was successfully weaned off ventilatory support. He was transferred out of the ICU after 5 weeks to a medical ward fully dependent on nasogastric feeding. The geriatric medical team engaged allied health professionals for his care, including physiotherapy, occupational therapy, dietitian, and speech-language therapy. Despite fatigue initially limiting his participation in rehabilitation and complications from HAP and upper gastrointestinal bleeding, he gradually showed improvement under the individualized graded exercise program. On discharge after 4 months in hospital, the patient was able to mobilise with a zimmer frame. Within 1 year, tracheostomy decannulation was performed and the patient returned to normal oral feeding, and in 18 months, the patient fully recovered to independence in all activities of daily living (ADLs).

Three years later, the patient presented to the Geriatrics Clinic for auditory and visual hallucinations, insomnia, and nocturnal wandering. He self-reported cognitive decline, particularly short-term memory loss and word-finding difficulty. His family noted increasing agitation and irritability, as well as increasing difficulties using a cellphone and performing prayers. He denied having depression or anxiety. His wife complained of increased stress because of his behavioral changes, in addition to sleep deprivation and disruption of her daily routine. His Montreal Cognitive Assessment (MoCA) score was 7/20, with memory deficits, delayed recall, language, abstraction, naming, visuospatial, and executive function. He was diagnosed as having moderate-to-severe dementia with behavioral and psychological symptoms of dementia and post-intensive care syndrome (PICS).

Ms. T, a 70-year-old woman, presented to the ED with a 4-day history of fever and cough. She had a history of hypertension, hyperlipidemia, and uncomplicated type 2 diabetes mellitus. She was hypoxic and hypotensive despite initial fluid resuscitation and non-invasive ventilatory support. She was admitted to the ICU for severe community-acquired pneumonia, rapid atrial fibrillation, and multi-organ failure. She required short-term hemodialysis for renal support and prolonged intravenous antibiotics for ongoing bacteremia. She underwent a tracheostomy owing to her prolonged need for ventilatory support and nasogastric feeding. After 2 months in the ICU, she was transferred to a geriatric medicine ward and was fully dependent for all ADLs. Her rehabilitation was complicated by fatigue, anxiety, and labile glycemic control. She was discharged after 3 months of hospitalization and was able to transfer to a wheelchair with assistance. Tracheostomy decannulation, normal oral diet, and return to independent mobility were achieved within 1 year. During the clinical follow-up, she reported having anxiety, with occasional flashbacks of her ICU admission. Three years later, she reported having short-term memory loss, which did not affect her ADLs. The patient was diagnosed as having mild cognitive impairment and PICS.

Although survival rates in patients with critical illness and requiring ICU care are increasing, survivors may develop long-term impairments within one or more of the cognitive, psychiatric, and physical domains.¹⁾ This cluster of impairments is known as PICS. This diagnosis excludes patients having traumatic brain injuries or stroke. Similar debilitating effects on family members, particularly psychological symptoms among those caring for the patient in the ICU and after discharge, are termed post-intensive care syndrome-family (PICS-F).

It is important to be aware of this condition in older patients. The number of older people with critical illnesses is increasing with an increase in the aging population. Compared with other patient populations, older patients account for more ICU admissions and have a high risk of delirium, which is a risk factor for developing cognitive dysfunction in PICS.^2,3)

Approximately 50%–70% of all ICU survivors have at least one PICS-related impairment, which can persist for up to 15 years after discharge.⁴⁾ A study of Medicare beneficiaries (mean age of 76.9 years) found that 60% of 1,520 ICU hospitalizations with severe sepsis were associated with worsening cognitive or physical functioning 1 year after hospitalization, with 16.7% of survivors showing moderate-to-severe cognitive impairment.^5,6) A retrospective cohort study of 21,520 Medicare patients revealed that ICU stays of 3 days or longer, sepsis severity, older age, frailty, depression, and dementia increased the odds of physical disability in older adults receiving home care.⁷⁾ Another study reported that 15% of older ICU survivors had a new diagnosis of dementia 3 years post-ICU stay, with almost 40% of new dementia cases diagnosed during the first year post-ICU stay.⁸⁾

The major risk factors for cognitive PICS include delirium, poor cognitive reserve, sepsis, and acute respiratory distress syndrome. The duration of delirium is reportedly an independent risk factor for cognitive impairment at 6 and 12 months.⁹⁾ However, there is no strong evidence suggesting that older adults are at a higher risk for cognitive PICS than are younger adults. A prospective study of 821 ICU patients showed similar cognitive and executive function scores between patients aged 65 years and older and younger patients at 3 and 12 months after discharge.²⁾ Patients with a higher level of education, an indicator of cognitive reserve, had a lower risk of this complication at 3 and 12 months.¹⁰⁾ Severe sepsis survivors were three times more likely to develop moderate-to-severe cognitive dysfunction. It is unclear whether cognitive dysfunction is due to acute respiratory distress syndrome itself, complications from sepsis, or the use of mechanical ventilation.

The main cognitive functions affected include attention or concentration, mental processing speed, memory, and executive function. The latter two are necessary for engaging in purposeful, goal-directed behaviors. Loss of these functions tends to impair rehabilitation participation, resulting in poor functional outcomes. Survivors have self-reported severe cognitive impairment after ICU discharge that has persisted for up to 2 years.¹¹⁾

Approximately 50% of older ICU survivors show functional recovery after critical illness, with a median recovery time of 3 months.⁶⁾ Older survivors of severe sepsis developed 1.5 new limitations in ADLs, compared with 0.5 in their non-ICU counterparts.¹²⁾ Older survivors who were mechanically ventilated were 30% more likely to have an ADL disability.¹³⁾ The physical impairments result in a need for increased support after hospital discharge.

Pre-existing functional disability, cognitive impairment, and frailty are strongly associated with physical PICS or ICU-acquired weakness (ICU-AW). Prolonged mechanical ventilation (>7 days), immobility, ongoing inflammatory response syndrome from sepsis, and multi-organ dysfunction are also associated with the development of ICU-AW. The pathophysiology of this condition is as follows: microvascular ischemia, catabolism, and prolonged immobility cause skeletal muscle wasting, whereas microvascular injury results in nerve ischemia, nerve-related sodium channel dysfunction, and mitochondrial injury. This leads to critical illness-related neuropathy, myopathy, or both.¹⁴⁾

The BRAIN-ICU study found that physical disability significantly contributed to poor mental health and quality of life at 3 and 12 months post discharge.¹⁵⁾ However, the nature of this interaction among physical impairment, mental health, and quality of life in ICU survivors requires further evaluation.

Patients who develop critical illnesses have higher incidences of premorbid psychiatric illness than do patients who do not require ICU hospitalization and the general population.¹⁶⁾ Whereas ICU survivors have a 4- to 6-fold higher rate of psychiatric comorbidities than in the general population, those with psychiatric PICS tend to have underlying pre-existing psychiatric disorders. Depression, anxiety, and post-traumatic stress disorder (PTSD) are the three common manifestations of psychiatric PICS, occurring in 19%–37%, 32%–40%, and 19%–22% of patients, respectively.⁶⁾