Since the inception of modern critical care medicine in the latter half of the 20th century, the focus has been on decreasing short-term mortality during hospitalization. Before the 1990s, little attention was given to the post–intensive care unit (ICU) course, and long-term follow-up studies were rare. More recently, the critical care community has begun to recognize the need for more detailed analyses of the chronic issues that confront patients in the months to years following an ICU stay. In addition to monitoring patients for well-known complications, such as myocardial infarction, pneumonia, and stroke, physicians should be aware of a subset of well-established disease processes specifically associated with the post-ICU course (Table 1). As studies on the long-term characteristics of post-ICU patients emerge, the results will influence the outpatient care of previously critically ill patients, as well as the care they received in the ICU.¹

Clinical Presentation and Treatment

PHYSICAL CONSIDERATIONS

Hospitalization in the ICU usually involves immobilization for several days and, possibly, mechanical ventilation. Alternative forms of nutrition also may be required. Patients often have multiorgan failure or sepsis. Although no specific guidelines are available to distinguish the different populations of ICU patients from one another, certain problems that can develop in these patients should be understood to ensure proper follow-up after discharge.

Anemia. Post-ICU patients often have chronic anemia following discharge. Between 11.0 and 12.7 percent of patients will require transfusion after leaving the ICU.^2,3 While in the ICU, many patients receive myelotoxic drugs, which can inhibit erythrocyte production. Moreover, some cases of anemia result from poor nutritional intake. Other risk factors for developing anemia after leaving the ICU include a history of sepsis, malignancy, female sex, and older age.² Many of these cases will be detected during the ICU stay. However, the threshold for performing a complete blood count, iron panel (iron, ferritin, total iron-binding capacity, transferrin), and reticulocyte count should be very low in the outpatient setting, particularly when patients have dyspnea or generalized fatigue.

Myopathy. Post-ICU patients are often limited by muscular deconditioning that occurs with prolonged immobilization. The net reduction of the myosin:actin ratio after an ICU stay is referred to as critical illness myopathy. After prolonged periods of immobility, patients lose their lean body mass at a rate of 2 percent per day.⁴ In addition to generalized weakness, patients often have decreased mobility because of poor balance control, fear of falling, and joint stiffness. In one study, patients with prolonged ICU stays, poor premorbid health, and longer duration of mechanical ventilation were most likely to have trouble climbing stairs eight weeks after discharge from the ICU.⁵ Prolonged length of stay and hours of mechanical ventilation were also predictive of decreased mobility outdoors. Complications of this deconditioning can persist up to 12 months after discharge.^6,7

During follow-up, it is crucial to identify patients who would benefit from physical rehabilitation beyond basic patient education. Graded exercise programs speed recovery back to prehospitalization abilities. The results of one randomized trial demonstrated that a six-week self-help rehabilitation program was effective in aiding physical recovery and reducing the incidence of depression compared with routine clinic appointments.⁸

Neuropathy. In addition to critical illness myopathy, critical illness polyneuropathy has been reported in ICU patients. It most commonly affects patients with sepsis and multiorgan failure.⁹ Severe neurogenic atrophy and axonal degeneration can lead to acute denervation of sensory and motor nerves, with particular involvement of the lower limbs and respiratory muscles.¹⁰ Although several pathogenetic mechanisms have been proposed, the etiology remains unclear. This type of neuropathy typically resolves within three years after discharge. Long-term treatment consists of extensive rehabilitation. Neuropathic pain medications, such as capsaicin cream (Zostrix), gabapentin (Neurontin) and other anticonvulsants, selective serotonin reuptake inhibitors (SSRIs), and venlafaxine (Effexor), may also be considered. However, no studies have examined their effects on critical illness polyneuropathy.

Metabolic Bone Disease. In addition to muscular deconditioning leading to weakness, it is important to consider metabolic bone disease in post-ICU patients. Many of these patients are exposed to bone-demineralizing drugs, such as steroids (Table 2); experience limited weight-bearing for prolonged periods, leading to bone hyperresorption; or develop vitamin D deficiency because of poor nutrition, lack of sunlight, and renal and hepatic dysfunction. In one review, 92 percent of the chronically critically ill patients studied had bone hyperresorption and 42 percent had vitamin D deficiency.¹¹ This bone loss can lead to osteoporosis with vertebral and hip fractures. Although there is no evidence suggesting that post-ICU patients should be screened differently than other populations, physicians should review U.S. Preventive Services Task Force recommendations on osteoporosis screening and should consider prolonged immobility to be a pertinent risk factor in women older than 60 years. For patients meeting T-score and clinical criteria, the preventive use of bisphosphonates may be beneficial.

Tracheoarterial Fistula and Tracheal Stenosis. Many ICU patients require tracheostomy for airway management. Complications, such as tracheoarterial fistulas or tracheal stenosis, are exceedingly rare.^12,13 Although younger age and repeated intubations are risk factors for complications, there is no established association between complications and duration of tracheostomy.¹⁴ These complications should be considered in patients of any age with dyspnea or stridor and a compatible history. If complications are suspected, bronchoscopy or computed tomography should be performed.

Nutrition. Nutritional issues related to the ICU hospital course, including appetite, oral intake, and dietary supplements, should also be addressed during outpatient visits. The patient’s weight should be monitored closely and compared with preadmission values. Patients may experience changes in taste that affect their appetite. Previous intubation/tracheostomy may lead to swallowing difficulties, as well as weakness and lack of coordination of pharyngeal muscles.⁶ In cases of prolonged absence of oral intake, the bowel mucosa atrophies. Furthermore, absence of lipids in proximal small bowel prevents cholecystokinin-mediated contraction of the gallbladder, leading to bile stasis and potentially acalculous cholecystitis. During one study that included severely septic ICU patients, a loss of approximately 2 lb, 11 oz (1.21 kg; 13 percent) of total body protein occurred over 21 days.⁴ In the first 10 days, 67 percent of the lost protein came from skeletal muscle, but after that it was predominantly from the viscera. The threshold for referral to a nutritionist should be low to ensure proper caloric and vitamin intake.

Sexual Dysfunction. Sexual dysfunction is common among post-ICU patients. Rates of sexual dysfunction range from 16 to 42.6 percent one year after discharge.^15,16 Although these rates may not be higher than in the general population, sexual problems are more likely to be discounted or overlooked in the presence of other comorbidities. Sexual dysfunction can include lack of desire, impotence, and shortness of breath with exertion. Causes that should be considered include surgical disfigurement or psychological concerns about the relapse of illness with sexual activity. During the evaluation, it is important to eliminate other potential etiologies, including chronic medical conditions, medications, and surgery. Furthermore, there is a strong correlation between sexual dysfunction and symptoms of posttraumatic stress disorder (PTSD; P = .019).¹⁶ No known studies have examined the effectiveness of commonly used phosphodiesterase-5 selective inhibitors in this subset population.

PSYCHOLOGICAL CONSIDERATIONS

The term ICU syndrome is sometimes used to include anxiety, depression, and PTSD, all of which have a higher prevalence in the post-ICU patient. Unfortunately, neither a uniform method for evaluating the different diagnoses nor established follow-up times for evaluation exist.

PTSD. PTSD is the psychiatric condition most extensively studied in the post-ICU patient. Symptoms of PTSD, regardless of inciting trauma, include intrusive phenomena (nightmares, flashbacks), persistent reexperiencing, avoidance of reminders of the event, thoughts or feelings related to trauma, and hyper-arousal (insomnia, hypervigilance). These symptoms often lead to sleep alterations, outbursts, and increased startle reaction. The perception of illness and threat to life, rather than the actual severity of the illness, is an accurate predictor of PTSD development.^17–19

Three to six months after patients are discharged from the ICU, rates of PTSD symptoms range from 22 to 50 percent; however, fewer patients (1.9 to 25.5 percent) meet diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th ed.^20,21 Younger patients, particularly those who have experienced a traumatic event such as traumatic brain injury, and those on prolonged mechanical ventilation have an increased incidence of PTSD. History of acute respiratory distress syndrome (ARDS) is also a risk factor for PTSD. In one study, investigators found increased prevalence up to eight years after discharge.²²

In addition to the psychological trauma of having a near-death experience, other factors might also play a role in the development of PTSD. The use of sedatives and neuromuscular blocking agents in the ICU for acute lung injury is associated with subsequent depression and PTSD symptoms six to 41 months after discharge.^23,24 SSRIs should be considered in patients who meet criteria for or show significant symptoms of PTSD.

Depression. Post-ICU patients need to be monitored for signs of major depressive disorder. Rates of depression two to three months following discharge range from 9.8 to 30 percent, although rates tend to be higher in patients with ARDS or acute lung injury.^7,23,25,26 In younger post-ICU patients, inability to return to work and prolonged periods of sedation are significant risk factors for depression. Patients should be monitored closely for signs and symptoms of depression in this setting, and pharmacologic and behavior therapy should be initiated when appropriate.

Anxiety Disorders. Anxiety disorders can slow the recovery of post-ICU patients. Rates of anxiety disorders in these patients have been as high as 25 percent two years after discharge.²⁶ Patients who had delirium during their ICU stay have shown decreased ability to remember facts about their stay at 18 to 24 months.²⁷ Studies confirm the association between delirium during hospitalization and amnesia.^28,29 The absence of factual memories about the hospitalization is associated with higher rates of anxiety and PTSD.³⁰ More progressive treatment for anxiety disorders in these patients includes tours of the ICU several months following discharge and psychotherapy focused on recalling factual memories.

Cognitive Impairment. Patients in the ICU are exposed to many different medications that can impair their memory recall, including opiates, benzodiazepines, propofol (Diprivan), adrenaline, and steroids. Furthermore, depending on the severity of their illness, patients can experience transient hypoxemic episodes that may lead to memory impairment. Multiple studies have linked ICU hospitalization with impairments in memory, attention, and concentration up to nine to 12 months following discharge.^24,26,31 Thirty percent of post-ICU patients who had ARDS were still globally impaired at one year, and 78 percent were impaired in one or more domains.²⁶ These cognitive difficulties can have a major impact on quality of life after ICU hospitalization and may explain the relatively slow return to work in patients who were previously employed.

Sleep Disturbance. As a result of any of the previously mentioned psychological conditions, or independently, the ICU stay may lead to sleep disturbances, which can also contribute to ongoing fatigue.⁷ Sleep disturbances are common in this patient group, and special attention should be made to patients following ARDS and use of mechanical ventilation, because these are likely independent risk factors.³²

SOCIAL CONSIDERATIONS

Social considerations must be examined in post-ICU patients. Some patients respond to severe illness with avoidant behavior. Compared with men, women have a greater tendency toward social isolation after mechanical ventilation.³² Forty-five percent of patients at six months reported going out less often.⁶ Physicians should inquire about the patient’s immediate family, specifically how they are coping with the patient’s illness. PTSD symptoms have been found to be present in approximately 33 percent of family members of ICU survivors.³³ Risk factors for the development of PTSD among family members include the feeling that medical information was incomplete and that they did not sufficiently contribute to the medical decision making.³³ In response to a critical illness, the family may experience anxiety and depression that manifests as overprotective behavior. These feelings, coupled with unrealistic expectations that the patient may have of his or her capabilities, can lead to frustration and conflict.³⁰

End-of-Life Issues

For years after discharge, post-ICU patients have higher mortality rates. Therefore, it is important for the primary care physician to address end-of-life issues with the patient, if not previously addressed. This should include ensuring that the patient has a documented health care proxy, in case the patient is unable to make decisions competently, and a living will.