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Brain Dysfunction

Brain Dysfunction BackgroundChronic critical illness is a devastating syndrome of prolonged respiratory failure and other derangements. To our knowledge, no previous research has addressed brain dysfunction in the chronically critically ill, although this topic is important for medical decision making.MethodsWe studied a prospective cohort of 203 consecutive, chronically critically ill adults transferred to our hospital's respiratory care unit (RCU) after tracheotomy for failure to wean. We measured prevalence and duration of coma and delirium during RCU treatment using the Confusion Assessment Method for the Intensive Care Unit with the Richmond Agitation-Sedation Scale. To assess survivors (at 3 and 6 months after RCU discharge), we used a validated telephone Confusion Assessment Method.ResultsBefore hospitalization, most (153 [75.4%]) of the 203 patients in the study were at home, completely independent (115 [56.7%]), and cognitively intact (116 [82.0%]). In the RCU, 61 (30.0%) were comatose throughout the stay. Approximately half of patients (66 of 142) who were not in coma were delirious. Patients spent an average of 17.9 days (range, 1-153 days) in coma or delirium (average RCU stay, 25.6 days). Half of survivors (79 of 160) had one of these disturbances at RCU discharge. At 6 months, three fourths (151) of the study patients were dead or institutionalized; of 85 survivors, 58 (68.2%) were too profoundly impaired to respond to telephone cognitive assessment, and 53 (62.4%) were dependent in all activities of daily living.ConclusionsSevere, prolonged, and permanent brain dysfunction is a prominent feature of chronic critical illness. These data, together with previous reports of symptom distress and rates of mortality and institutionalization, describe burdens for chronically critically ill patients receiving continued life-prolonging treatment and for their families.Increasing use of intensive care unit (ICU) resources by an aging population has given rise to a new and devastating medical condition: chronic critical illness.Although prolonged dependence on mechanical ventilation is its hallmark, chronic critical illness is not simply an extended period of acute critical illness but a discrete syndrome encompassing distinctive derangements of metabolism, organ physiologic traits, and endocrine and immunologic function.This syndrome has been defined for administrative, research, and clinical purposes by the placement of tracheotomy for failure to wean in the ICU.Chronic critical illness is not a rare condition but rather a serious national health problem affecting a large and rapidly growing populationwho are cared for by general and specialty clinicians across multiple disciplines. The US health system already treats more than 100 000 such patients each year, with annual expenditures of approximately $24 billion.Outcomes reported from a variety of institutions and health care settings (including in-patient respiratory care units, long-term acute care facilities, and nursing homes) remain poor: most chronically critically ill patients are dead within 6 months, and survivors typically require total care in skilled nursing facilities.Before their critical illness, most of these patients lived independently in the community, despite advanced age and comorbid medical conditions.Most had no medical history of cognitive impairment.As critical illness became chronic, however, they developed severe weakness, nutritional deficits, and significant symptom distress, along with persistent dysfunction of multiple organs.They spend weeks to months in hospital, including prolonged ICU stays, receiving numerous medications. For all of these reasons, the risk for brain dysfunction is high.Prognosis for long-term cognitive function is one of the most important factors in medical decision making by patients and surrogates.Many patients consider cognitive impairment to be less acceptable than death as an outcome.It is known that in mechanically ventilated patients with acute critical illness, delirium is common,has a mean duration of 2.4 ICU days,and is associated with higher hospital mortality and morbidity.Yet, to our knowledge, no prior research has addressed cognitive disturbance in the context of chronic critical illness. To expand knowledge and enhance decision making, we undertook this study describing the prevalence and duration of brain dysfunction (coma and delirium) among hospitalized, chronically critically ill patients requiring prolonged mechanical ventilation and other treatments.METHODSRESPIRATORY CARE UNITWe conducted a prospective study in the respiratory care unit (RCU) of our 1100-bed, university-affiliated, urban tertiary referral hospital. The RCU is a 14-bed, in-patient unit for chronically critically ill patients from the hospital's 5 adult ICUs (medical, surgical, cardiothoracic surgical, cardiac, and neurosurgical); it is analogous to the increasing numbers of long-term acute care facilities across the country. Patients are accepted if they no longer need acute ICU care, are mechanically ventilated via tracheotomy, and, in the clinical opinion of the referring ICU physician, are likely to be liberated from the ventilator. Other chronically critically ill patients may not be transferred to the RCU either because of death in the ICU after tracheotomy or because the tracheotomy was placed in preparation for permanent ventilator support, with no expectation that the patient would ever wean. (From 2001 to 2005, when 535 patients were treated in the RCU, 511 patients underwent tracheotomy and were not admitted to the RCU; of the latter group, 230 [45%] died in the hospital.)As supervised by pulmonary and critical care physicians with nurse practitioners, RCU treatment is standardized by a detailed health care map and weaning protocol,but regular care during the study did not include a protocol for sedation or cognitive assessment. Surviving patients are discharged from the RCU on successful liberation from the ventilator or a clinical determination that further efforts to achieve ventilator independence will not succeed.PATIENT ENROLLMENTFrom September 2003 to January 2005, we conducted daily screening to identify eligible patients among all new RCU admissions. We defined eligibility by elective tracheotomy for ICU weaning failure.Tracheotomy under these circumstances reflects the clinical impression that the patient is expected neither to wean nor to die in the immediate future and therefore it serves as a practical point of demarcation between acute and chronic critical illness.It is also the defining criterion of national diagnosis related groups 541 and 542 (formerly diagnosis related group 483),in which a large national dataset of similar patients across many institutions and settings are classified and can be compared. We excluded patients with previous ventilator dependence or RCU admission, patients from other institutions, and those without English proficiency. The institutional review board of Mount Sinai School of Medicine, New York, approved this study, and we obtained informed consent from all subjects or appropriate surrogates.COGNITIVE ASSESSMENTWe conducted cognitive assessments at multiple, longitudinal time points: at study entry (after tracheotomy and transfer from ICU to RCU), biweekly in the RCU, at RCU discharge, and, for surviving patients, at 3 and 6 months after RCU discharge. These intervals included assessments while patients were mechanically ventilated and after ventilator liberation.For RCU cognitive assessments, we used the Confusion Assessment Method for the ICU (CAM-ICU),which includes a preliminary evaluation of consciousness. A trained research nurse (A.F.M.) performed these assessments.To evaluate consciousness, we used the Richmond Agitation-Sedation Scale (RASS),which encompasses 10 levels (0 to +4 indicates increasing agitation and 0 to −5 indicates decreasing consciousness). We deferred delirium assessment for patients initially rated as deeply sedated (RASS level −4) or unarousable (RASS level −5), whom we classified together as comatose; we approached these patients later the same day and performed delirium assessment as possible.Next, we evaluated the patients for 4 basic features of delirium: (1) acute onset or fluctuating course, (2) inattention (evaluated by the Vigilance A Random Letter Test), and (3) disorganized thinking or (4) altered level of consciousness. We defined delirium by the presence of both features 1 and 2 and either feature 3 or feature 4.We conducted postdischarge cognitive assessments by telephone. Because patients able to respond could communicate orally, we used the validated telephone CAMfor this purpose.For patients who could not respond to telephone interviews, we asked responding surrogates about the nature of the patient's inability to participate (cognitive or physical limitation); surrogates reported the patient's level of consciousness and other aspects of cognitive status.OTHER DATA COLLECTIONWe recorded administration of analgesic, sedative, antidepressant, antipsychotic, and psychostimulant medications in the RCU to provide a context for cognitive assessments during RCU treatment. We collected additional information including diagnoses, comorbid conditions, and other data for Acute Physiology and Chronic Health Evaluation IIand Charlson Comorbidity Indexscores; lengths of stay; and site and ventilator status at discharge and follow-up. To measure functional status at multiple time points, we used the motor scale of the Functional Independence Measure (FIM Motor),which includes 13 items (eg, eating, bathing, and walking) that are each scored from 1 (needs total assistance) to 7 (complete independence); total FIM Motor scores range from 13 (completely dependent) to 91 (completely independent). Responses to telephone interviews (used for postdischarge functional assessments) and to in-person interviews (used for in-hospital assessments) are strongly correlated for the FIM Motor,which is well validated. In addition, we calculated the Katz Index of Activities of Daily Living.As a baseline for comparison with our prospective assessments of cognition and function in the hospital and after discharge, we used interviews with families or other appropriate and knowledgeable surrogates at study entry about the patients' status during the 2 weeks before hospitalization. Cognitive status interviews focused on medical history of dementia, decreased level of consciousness, confusion, and memory loss; we also reviewed patients' medical records for evidence of these or other cognitive disturbances. For assessment of baseline functional status, we interviewed families with respect to FIM Motor items, on which surrogate reports are well correlated with information from patients themselves.STATISTICAL ANALYSISWe calculated mean and median daily doses of opioids (in morphine equivalents) and of sedatives (in lorazepam equivalents) as the mean and median, respectively, of the individual mean daily doses given to each patient during the RCU stay. We compared patients with delirium or coma and patients without these forms of brain dysfunction with respect to the percentage of patients receiving medications in these classes and the average daily doses of these medications (&khgr;2test and ttest, respectively). We calculated duration of delirium or coma in the RCU as the number of consecutive days from the first day on which CAM-ICU assessment documented either condition. For each patient, we also calculated the percentage of total RCU days for each cognitive disturbance under study. We used multivariate logistic (discrete outcomes) and multivariate linear (continuous outcomes) regression to examine the association of number of days spent in delirium or coma with RCU length of stay, ventilator liberation, hospital mortality, site of discharge for survivors (home vs post–acute care facility), 3-month and 6-month residence (home vs nursing home), functional status, and mortality, controlling for age, sex, ethnicity, Charlson Comorbidity Index, Acute Physiology and Chronic Health Evaluation II score, and number of acute comorbidities.RESULTSAmong 330 patients who had undergone tracheotomy and were consecutively admitted to the RCU, 230 were eligible (37, 30, 20, and 13 patients were excluded for prior ventilator dependence or RCU treatment, transfer from another hospital, language barrier, or other reasons, respectively), and 203 (88.2%) were enrolled in the study. Consent was refused by 24 patients and was not sought for 3 because death supervened. Eighty-nine surviving patients were discharged from the hospital, and all but 4 (who were lost to follow-up) were followed up for 6 months.PATIENT CHARACTERISTICSTable 1details patient characteristics. Study patients were mainly older adults (median age, 72 years) with multiple medical illnesses and organ failures. Most, however, had been living at home and were functioning independently before their hospitalization. More than 80% (166 of 203) were reported by their families and confirmed by medical records to have no cognitive impairment. The mean (SD) Charlson Comorbidity Index score, Acute Physiology and Chronic Health Evaluation II score, and number of acute comorbid conditions at study entry were 4.5 (2.7), 20.5 (5.1), and 2.3 (2.1), respectively (ie, there was a high severity illness and comorbidity burden). By then, most patients had already been hospitalized for a long period (median duration of illness [interquartile range], 25.0 days [19.0-34.0 days]), including a prolonged ICU stay (16.0 days [11.0-22.0 days]). These patients were treated in the RCU for even longer periods (23.0 days [13.0-35.0 days]). Total duration of exposure to an intensive care environment (ICU plus RCU stay) averaged 45.0 days.Table 1. Characteristics of 203 Chronically Critically Ill Study PatientsCharacteristicValue*Age, median (range), y72 (21-99)Male117 (58)Race/ethnicity White, non-Hispanic106 (52) Black, non-Hispanic53 (26) Hispanic36 (18) Other8 (4)Residence before hospital admission† Private home153 (75) Rehabilitation facility8 (4) Nursing home24 (12) Other16 (8)FIM Motor score at hospital admission,  median (IQR)‡85 (41-91)Independent in all activities of daily living at hospital admission115 (57)Cognitively impaired at hospital admission§37 (18)Cognitively impaired at study entry&par;143 (75)Primary diagnosis at ICU admission Cardiovascular45 (22) Pulmonary75 (37) Neurologic33 (16) Surgical31 (15) Other19 (9)ICU transferring to RCU Medical128 (63) Surgical23 (11) Cardiothoracic2 (1) Neurosurgical40 (20) Cardiac care10 (5)ICU length of stay, median (IQR), d16 (11-22)Causes of prolonged respiratory failure¶ Acute lung disease94 (46) Chronic lung disease35 (17) Cardiac disease34 (16) Neurologic disease57 (28) Surgical or postoperative condition35 (17) Sepsis/multiorgan dysfunction55 (27) Other26 (13)APACHE II Score (at study entry), mean (SD)†20.5 (5.1)Charlson Comorbidity Index Score, mean (SD)4.5 (2.7) Abbreviations: APACHE II, Acute Physiology and Chronic Health Evaluation II; FIM, Functional Independence Measure; ICU, intensive care unit; IQR, interquartile range; OMCT, Orientation-Memory-Concentration Test; RCU, respiratory care unit. *Data are given as number (percentage) except where noted. †Two hundred one patients (data were unavailable for 2 patients). ‡One hundred ninety-nine patients (prehospital functional status was unavailable for 4 patients). As described in the “Methods” section, scores (1 [total assistance] to 7 [completely independent]) on 13 individual motor items in the FIMare summed to form the FIM Motor score, which ranges from 13 (completely dependent) to 91 (completely independent). §Defined as reported by family or evidence in medical records of history of dementia, decreased level of consciousness, confusion, memory loss, or other cognitive impairment.  &par;Defined as a score greater than 10 on the 6-item OMCT(n = 19) or lacking sufficient cognitive capacity to respond to screen (n = 124); 13 others refused administration of the OMCT screen; 47 patients had an OMCT score of 10 or less at study entry. ¶Percentages total more than 100% because prolonged respiratory failure was typically multifactorial.PATIENT OUTCOMESPatient outcomes are presented in Table 2. Of the 203 subjects, 58 (28.6%) died in hospital and less than half (89 [43.8%]) were alive at 6 months. Of 145 hospital survivors, 15 (10.3%) were discharged to home and 107 (73.8%) to a nursing home or another acute care hospital; 48 (33.1%) remained mechanically ventilated. Median (interquartile range) survival of those who died after hospital discharge (n = 56) was 55 days (8-92 days). At 6 months, 32 (15.8%) of the 203 original subjects were living at home (vs 75.4% before hospitalization), 2 of whom were still mechanically ventilated. Approximately two thirds (53 of 85) of 6-month survivors (including 14 [43.8%] of 32 patients at home) were dependent in all activities of daily living.Table 2. Outcomes of 203 Chronically Critically Ill Study PatientsOutcomeValue*Length of stay, median (IQR), d RCU23 (13-35) Hospital54 (13-182)Liberated from mechanical ventilation  at RCU discharge†97 (48)Hospital discharge site Home15 (7) Nursing home or acute care hospital104 (51) Rehabilitation facility25 (12) Died in hospital58 (29)Cumulative mortality RCU39 (19) Hospital58 (29) 3 mo after discharge103 (51) 6 mo after discharge114 (56)FIM Motor score, median (IQR)‡ At RCU discharge§13 (13-24) 3 mo after discharge&par;29 (13-66) 6 mo after discharge¶56 (13-87)Dependent in all activities of daily living at 6 months after discharge53 (62) Abbreviations: FIM, Functional Independence Measure; IQR, interquartile range; RCU, respiratory care unit. *Data are given as number (percentage) except where noted.  †Defined as 168 hours of unassisted breathing, regardless of any subsequent mechanical ventilation.Excludes patients who died in the RCU. ‡FIM Motor scoreranges from 13 (completely dependent) to 91 (completely independent), as explained in the “Methods” section. §One hundred sixty-four patients (39 patients died in the RCU).  &par;Ninety-eight patients (103 patients died, and 1 patient withdrew from study participation before 3 months; 1 could not be contacted). ¶Eighty-five patients (114 patients died, and 2 patients had withdrawn from the study by the 6-month follow-up; time after discharge was less than 6 months for 1 patient as of close of database for these analyses; 1 patient could not be contacted).RESULTS OF COGNITIVE ASSESSMENTSPrevalence of coma and delirium is detailed in Table 3. At RCU admission, 50.2% of patients were comatose, and 14.8% were delirious. Approximately 1 in 3 (61 of 203) study patients were comatose throughout the entire RCU stay. Thirteen (21.3%) of these 61 patients were admitted to the ICU for stroke whereas most of the patients in a persistent coma did not have an underlying, structural injury to the central nervous system. Among patients not in coma, delirium was diagnosed in almost half (66 of 142). Patients spent a mean time of 17.9 days (range, 1-153 days) in coma or delirium (mean RCU length of stay, 26 days), and among RCU survivors, half were comatose or delirious at discharge. Thus, after prolonged, aggressive treatment for chronic critical illness, 58.1% of our original study group either were dead (19.2%) or severely cognitively impaired at RCU discharge (38.9%); 45 (59.2%) of the remaining 76 were functionally dependent in all activities of daily living and required nursing home placement.Table 3. Prevalence of Brain Dysfunction (Coma or Delirium) During Chronic Critical IllnessCognitive Assessment*Patients, No. (%)RCU Treatment PeriodPostdischarge Follow-up, MoRCU AdmissionBiweekly AssessmentRCU Discharge36Comatose or otherwise unresponsive CAM-ICU (RASS −4 or −5)102 (50)77 (38)†58 (36) CAM (telephone)75 (77)‡60 (71)‡Delirious30 (15)56 (28)§21 (13)0 0  Always7 (4) ≥50% and <100% of assessments22 (11) <50% of assessments27 (13)Not delirious or comatose62 (30)63 (31)76 (48)23 (23)25 (29)Refused to respond8 (4)6 (3)5 (3)0 0 Total patients&par;2022021609885 Abbreviations: CAM, Confusion Assessment Method; ICU, intensive care unit; RASS, Richmond Agitation-Sedation Scale; RCU, respiratory care unit. *We assessed brain dysfunction using the CAM-ICU,incorporating the RASS.Patients rated as level −5 (unarousable) or −4 (deeply sedated) on the RASS (classified together as comatose) lacked sufficient consciousness for further evaluation of delirium at that assessment. †We categorized as comatose those patients who were rated as RASS level −4 or −5 at 75% or more of our biweekly approaches. ‡We used the validated telephone CAMfor postdischarge evaluations. §For patients able to respond to CAM-ICU (ie, not comatose on the initial RASS evaluation) at more than 25% of the biweekly approaches, we categorized as delirious those patients found to have at least 1 episode of delirium, and we categorized as not delirious those patients who were never found to be delirious. Some patients categorized as delirious or not delirious for the biweekly assessments may have had 1 or more episodes of coma (but <75% of the CAM-ICU approaches) during this period.  &par;One patient was not approached for cognitive assessment at RCU admission or during biweekly approaches, and 4 among 164 RCU survivors were discharged before completion of the assessment. The numbers of patients for 3-month and 6-month follow-ups were 98 and 85, respectively, as explained in the previous 2 footnotes.The Figureplots prevalence of coma and delirium through week 4 in the RCU. The overall burden of brain dysfunction did not diminish significantly during this period. Delirium tended to be persistent or recurrent for patients who were delirious at RCU admission: 17 (56.7%) of 30 patients who were initially delirious never regained normal consciousness prior to discharge or death. For those whose delirium resolved, the mean (SD) time to resolution was 11.6 (10.4) days. Of 62 patients with normal consciousness on admission, one quarter subsequently developed delirium (11 patients) or coma (5 patients), and of these 16, 7 (43.7%) failed to regain a normal state of consciousness.Figure.We used the Richmond Agitation-Sedation Scaleand the Confusion Assessment Method for the Intensive Care Unitfor biweekly cognitive assessments, as detailed in the “Methods” section. The bar graph shows results of these assessments for 202 study patients through week 4 in the respiratory care unit (RCU) (average length of RCU stay, 3 to 4 weeks).POSTDISCHARGEFollow-up data on brain dysfunction are presented in Table 3. At 6 months, 60 (70.6%) of 85 survivors, including 15 (46.9%) of 32 then living at home, remained profoundly cognitively impaired to the point that they could not participate in telephone mental status testing. Of 25 patients who could communicate by telephone, none was cognitively impaired as measured by the CAM.MEDICATIONSAdministration of medications with the number (percentage) of 203 study patients is given in the following tabulation:   Opioid160 (78.8)Sedative128 (63.1)Antidepressant43 (21.2)Antipsychotic125 (61.6)Psychostimulant19 (9.4)The median daily doses of opioid in parenteral morphine equivalents, and of benzodiazepine (the only sedative used in the RCU) in lorazepam equivalents,were 5.1 mg/d and 1.0 mg/d, respectively. Among 62 patients who presented to the study with intact cognition—that is, neither comatose according to the RASS nor delirious according to the CAM-ICU—35 (92.1%) of 38 who remained intact received a sedative or opioid compared with 16 (100%) of 16 patients who developed brain dysfunction during the RCU stay (P = .34) (8 patients died in the RCU). On average, patients who were comatose or delirious received 2.4 mg/d of morphine equivalents and 1.2 mg/d of lorazepam equivalents in the 2 days prior to brain dysfunction, compared with daily doses of 6.4 mg of morphine equivalents and 1.3 mg of lorazepam equivalents in the cognitively intact group (P = .30 and P = .76, respectively). Of the 16 patients who were initially intact but developed coma or delirium in the RCU, 11 (68.7%) received sedatives, opioids, or antipsychotic drugs during the 24 hours before the first episode of brain dysfunction whereas 9 (56.2%) of 16 received these medications after the episode.MULTIVARIATE ANALYSESThe number of days spent in delirium or coma was significantly associated with an increased likelihood of being discharged to a post–acute care facility as opposed to home (odds ratio, 1.09; 95% confidence interval [CI], 1.00-1.20; P = .047), longer length of hospital stay (parameter estimate, 0.03; 95% CI, 0.02-0.03; P<.001 for association with longer length of stay), and lower FIM Motor scores indicating poorer functional status at 3- and 6-month follow-ups for survivors (for 3-month follow-up: parameter estimate, −0.47; 95% CI, −0.78 to −0.15; P = .004; for 6-month follow-up: parameter estimate, −0.92; 95% CI, –1.4 to −0.43; P<.001). The association of the number of days spent in delirium or coma with 3-month survival for those who survived hospitalization was of borderline significance (odds ratio, 0.98. 95% CI, 0.95-1.00; P = .056). Days spent in delirium or coma was not significantly associated with in-hospital mortality, likelihood of liberation from the ventilator, 6-month mortality, or 3- or 6-month site of residence.COMMENTThere are now estimated to be over 100 000 chronically critically ill patients in the United States each year,and numbers are steadily increasing.These patients, who have survived but not recovered from acute critical illness, have a discrete syndrome: ongoing ventilator dependence, severe debility, and characteristic abnormalities of metabolic and immunologic function, with resulting failure of other organs and recurrent nosocomial infections.The present study suggests that brain dysfunction, manifest as delirium (assessed by CAM-ICU) and coma (levels −4 and −5 on the RASS scale), is another prominent feature of chronic critical illness. In addition, brain dysfunction in these patients is prolonged, and its duration is associated with longer lengths of stay and poorer functional status. Six months after aggressive treatment in a specialized hospital unit, three fourths of our study patients were either dead or institutionalized, and two thirds of survivors remained profoundly cognitively impaired whereas most of these patients had been at home, independent, and without cognitive impairment prior to hospitalization. Less than 10% were living at home without brain dysfunction as measured by CAM at 6 months. Findings of this study have important implications for decision making.Delirium occurs commonly in ICU patients with acute critical illnessand is associated with longer hospital and ICU lengths of stayand higher mortality at 6 months.Our data suggest that patients who survive the ICU but remain ventilator dependent with chronic critical illness have similarly high rates of delirium as well as coma. However, unlike ICU delirium (which has a median duration of 48 hours),these conditions persist in the chronically critically ill for a prolonged period. This occurs despite the fact that doses of sedating drugs are generally lower after tracheotomy and during ventilator weaning.In our study, 65.3% of patients were admitted to the RCU with coma or delirium, more than 25% of those who were initially without coma or delirium developed these conditions in the RCU, and less than half of both groups combined regained normal cognition.Cognitive impairment is often considered to be the heaviest burden of illness and is an outcome that may be even less acceptable than death.Patients, families, and clinicians consider information about expected cognitive outcome to be important specifically for decision making about treatment when critical illness becomes chronic.Our documentation herein of the prevalence and duration of brain dysfunction may help to inform discussions and decisions at that pivotal juncture.There are several limitations to this study. We performed our research in a single hospital's in-patient RCU. Our findings may not apply to patients who have undergone tracheotomy and whose illness is so severe that they cannot survive outside of an ICU (like those in our hospital who underwent tracheotomy but died in the ICU before transfer to the RCU) or those who undergo tracheotomy with the understanding that they are not expected to be liberated but rather to remain mechanically ventilated indefinitely (like those in our hospital who are not referred to the RCU because they are clinically determined to be unweanable). Our eligibility criteria, however, were designed to encompass a broad and generalizable group of patients requiring prolonged mechanical ventilation via tracheotomy after failure to wean in the ICU. Although treated in various care settings (long-term acute care facilities and skilled nursing facilities as well as in-patient hospital units), chronically critically ill patients have comparable characteristics and outcomes, as reported from multiple institutions and reflected in the national diagnosis related group 541-542/483 database.We have described our experience with a large series of patients initially treated in a variety of ICUs, of whom we made over 1700 delirium assessments using instruments (CAM-ICU and RASS) that were rigorously tested in prior work. Because the CAM-ICU was already validated in 2 patient groups,we did not retest it against a reference standard but instead focused on use with a discrete group of patients with prolonged illness and mechanical ventilation. In follow-up after RCU discharge, we used the original CAM (validated telephone version),which is more sensitive than CAM-ICU for diagnosing delirium in nonintubated patients.The number of patients who could respond to cognitive assessment after hospital discharge was limited by the high rates of mortality and institutionalization; patients able to respond to telephone interview were less likely to have delirium and other forms of cognitive impairment than nonresponders, which would have underestimated the true prevalence of postdischarge delirium in the entire study population.CONCLUSIONSAs the general population ages and intensive care treatments are offered to older and sicker patients, clinicians in all fields and disciplines will encounter chronically critically ill patients with increasing frequency. Most of these patients die within 6 months, and most survivors are institutionalized with severe functional impairments. Our previous researchindicates that most patients with chronic critical illness spend weeks to months in the hospital experiencing a multitude of distressing physical and psychological symptoms. The present study suggests that few patients with chronic critical illness avoid delirium or coma and that most of them spend significant time during treatment and thereafter with these severe forms of brain dysfunction. Although regular, comprehensive assessment and treatment of symptoms may reduce suffering, it is less clear that effective treatments exist to address the high prevalence of brain dysfunction observed here. Nor can we be certain that such treatments would improve mortality rates or functional outcomes.The choice to continue life-prolonging treatments when critical illness enters a chronic phase may be made by some patients and families despite poor prognosis for survival and for cognitive and functional recovery. However, accumulating evidence of symptom distress and long-term cognitive and functional impairment calls attention to whether they are truly making informed decisions at the time of tracheotomy and whether ongoing goals of care are routinely discussed during the course of critical illness. Future research should focus on strategies to alleviate symptom burden and to address delirium and other brain dysfunction. In addition, it is essential to examine how information is communicated and how decisions are made about the benefits and burdens of life-prolonging therapies (eg, mechanical ventilation) for the chronically critically ill. In the meantime, options presented to decision makers for these patients should include a time-limited trial of continued respiratory support, with a plan for discontinuation of the ventilator if cognitive and functional recovery do not occur within a reasonable period of time. The levels of disease complexity, physical and psychological suffering, and cognitive impairment also suggest that quality care for these patients should include not only expert pulmonary and critical care but also involvement of a palliative care consultation team.Correspondence:Judith E. Nelson, MD, JD, Box 1232, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029 (judith.nelson@mountsinai.org).Accepted for Publication:June 23, 2006.Author Contributions:Dr Nelson had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Nelson and Morrison. Acquisition of data: Nelson, Mercado, Camhi, and Morrison. Analysis and interpretation of data: Nelson, Tandon, Camhi, Ely, and Morrison. Drafting of the manuscript: Nelson, Camhi, and Morrison. Critical revision of the manuscript for important intellectual content: Nelson, Tandon, Mercado, Ely, and Morrison. Statistical analysis: Tandon and Morrison. Obtained funding: Nelson. Administrative, technical, and material support: Tandon, Mercado, Ely, and Morrison. Study supervision: Nelson and Morrison.Financial Disclosure:Dr Ely has received investigator-initiated, unrestricted grants from Pfizer Inc and from Hospira Inc to evaluate pharmacologic strategies for prevention and treatment of delirium; those projects and their sponsors have no connection to the study reported herein. Dr Ely is also the recipient of similar grants from Eli Lilly and has received honoraria from all 3 companies.Funding/Support:This study was supported by grant R01 AG21172 from the National Institute on Aging (NIA). Dr Nelson is the recipient of an Independent Scientist Award (K02 AG024476) from the NIA. Dr Morrison is the recipient of a Midcareer Investigator Award in Patient-Oriented Research from the NIA (K24 AG022345). Dr Ely is the recipient of a Mentored Patient-Oriented Research Career Development Award from the NIA (K23 AG01023).Role of the Sponsors:The sponsors for this study had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.Acknowledgment:We are grateful to the chronically critically ill patients in our RCU, to their families, and to the dedicated nurse practitioners and RCU staff for their cooperation in this research.REFERENCESDMNiermanedJENelsonedChronic critical illness.Crit Care Clin200218(theme issue)46171512140908SSCarsonPBBachThe epidemiology and costs of chronic critical illness.Crit Care Clin200218461476US Department of Health and Human ServicesCMS programs & information.Centers for Medicare & Medicaid Web site. http://www.cms.hhs.gov. Accessed June 15, 2006DMDewarCJKurekJLambrinosILCohenYZhongPatterns in costs and outcomes for patients with prolonged mechanical ventilation undergoing tracheostomy: an analysis of discharges under diagnosis-related group 483 in New York State from 1992 to 1996.Crit Care Med1999272640264710628603JENelsonDEMeierALitkeDANataleRESiegelRSMorrisonThe symptom burden of chronic critical illness.Crit Care Med2004321527153415241097SSCarsonPBBachLBrzozowskiALeffOutcomes after long-term acute care: an analysis of 133 mechanically ventilated patients.Am J Respir Crit Care Med19991591568157310228128SANasrawayGJButtonWMRandTHudson-JinksMGustafsonSurvivors of catastrophic illness: outcome after direct transfer from intensive care to extended care facilities.Crit Care Med200028192510667494ADasguptaRRiceEMaschaDLitakerJKStollerFour-year experience with a unit for long-term ventilation (respiratory special care unit) at the Cleveland Clinic Foundation.Chest199911644745510453875DJScheinhornDCChaoMStearn-HassenpflugLLaBreeDJHeltsleyPost-ICU mechanical ventilation.Chest1997111165416599187189SKInouyeSTBogardousPCharpentierA multicomponent intervention to prevent delirium in hospitalized older patients.N Engl J Med199934066967610053175ERMarcantonioGJuarezLGoldmanThe relationship of postoperative delirium with psychoactive medications.JAMA1994272151815227966844SKInouyePACharpentierPrecipitating factors for delirium in hospitalized elderly persons: predictive model and interrelationship with baseline vulnerability.JAMA19962758528578596223TRFriedEHBradleyVRTowleHAlloreUnderstanding the treatment preferences of seriously ill patients.N Engl J Med20023461061106611932474JENelsonKKinjoDEMeierKAhmadRSMorrisonWhen critical illness becomes chronic: informational needs of patients and families.J Crit Care200520798916015521EWElySKInouyeGRBernardDelirium in mechanically ventilated patients: validity and reliability of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).JAMA20012862703271011730446EWElyAShintaniBTrumanDelirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit.JAMA20042911753176215082703MCarasaGNespoliNursing the chronically critically ill patient.Crit Care Clin20021849350812140910DMNiermanJIMechanickBone hyperresorption is prevalent in chronically critically ill patients.Chest1998114112211289792587DMNiermanA structure of care for the chronically critically ill.Crit Care Clin20021847749112140909US Department of Health and Human ServicesAcute inpatient prospective payment system overview.Centers for Medicare and Medicaid Services Web site. http://www.cms.hhs.gov/AcuteInpatientPPS. 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Brain Dysfunction

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American Medical Association
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Copyright 2006 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
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2168-6106
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2168-6114
DOI
10.1001/archinte.166.18.1993
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17030833
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Abstract

BackgroundChronic critical illness is a devastating syndrome of prolonged respiratory failure and other derangements. To our knowledge, no previous research has addressed brain dysfunction in the chronically critically ill, although this topic is important for medical decision making.MethodsWe studied a prospective cohort of 203 consecutive, chronically critically ill adults transferred to our hospital's respiratory care unit (RCU) after tracheotomy for failure to wean. We measured prevalence and duration of coma and delirium during RCU treatment using the Confusion Assessment Method for the Intensive Care Unit with the Richmond Agitation-Sedation Scale. To assess survivors (at 3 and 6 months after RCU discharge), we used a validated telephone Confusion Assessment Method.ResultsBefore hospitalization, most (153 [75.4%]) of the 203 patients in the study were at home, completely independent (115 [56.7%]), and cognitively intact (116 [82.0%]). In the RCU, 61 (30.0%) were comatose throughout the stay. Approximately half of patients (66 of 142) who were not in coma were delirious. Patients spent an average of 17.9 days (range, 1-153 days) in coma or delirium (average RCU stay, 25.6 days). Half of survivors (79 of 160) had one of these disturbances at RCU discharge. At 6 months, three fourths (151) of the study patients were dead or institutionalized; of 85 survivors, 58 (68.2%) were too profoundly impaired to respond to telephone cognitive assessment, and 53 (62.4%) were dependent in all activities of daily living.ConclusionsSevere, prolonged, and permanent brain dysfunction is a prominent feature of chronic critical illness. These data, together with previous reports of symptom distress and rates of mortality and institutionalization, describe burdens for chronically critically ill patients receiving continued life-prolonging treatment and for their families.Increasing use of intensive care unit (ICU) resources by an aging population has given rise to a new and devastating medical condition: chronic critical illness.Although prolonged dependence on mechanical ventilation is its hallmark, chronic critical illness is not simply an extended period of acute critical illness but a discrete syndrome encompassing distinctive derangements of metabolism, organ physiologic traits, and endocrine and immunologic function.This syndrome has been defined for administrative, research, and clinical purposes by the placement of tracheotomy for failure to wean in the ICU.Chronic critical illness is not a rare condition but rather a serious national health problem affecting a large and rapidly growing populationwho are cared for by general and specialty clinicians across multiple disciplines. The US health system already treats more than 100 000 such patients each year, with annual expenditures of approximately $24 billion.Outcomes reported from a variety of institutions and health care settings (including in-patient respiratory care units, long-term acute care facilities, and nursing homes) remain poor: most chronically critically ill patients are dead within 6 months, and survivors typically require total care in skilled nursing facilities.Before their critical illness, most of these patients lived independently in the community, despite advanced age and comorbid medical conditions.Most had no medical history of cognitive impairment.As critical illness became chronic, however, they developed severe weakness, nutritional deficits, and significant symptom distress, along with persistent dysfunction of multiple organs.They spend weeks to months in hospital, including prolonged ICU stays, receiving numerous medications. For all of these reasons, the risk for brain dysfunction is high.Prognosis for long-term cognitive function is one of the most important factors in medical decision making by patients and surrogates.Many patients consider cognitive impairment to be less acceptable than death as an outcome.It is known that in mechanically ventilated patients with acute critical illness, delirium is common,has a mean duration of 2.4 ICU days,and is associated with higher hospital mortality and morbidity.Yet, to our knowledge, no prior research has addressed cognitive disturbance in the context of chronic critical illness. To expand knowledge and enhance decision making, we undertook this study describing the prevalence and duration of brain dysfunction (coma and delirium) among hospitalized, chronically critically ill patients requiring prolonged mechanical ventilation and other treatments.METHODSRESPIRATORY CARE UNITWe conducted a prospective study in the respiratory care unit (RCU) of our 1100-bed, university-affiliated, urban tertiary referral hospital. The RCU is a 14-bed, in-patient unit for chronically critically ill patients from the hospital's 5 adult ICUs (medical, surgical, cardiothoracic surgical, cardiac, and neurosurgical); it is analogous to the increasing numbers of long-term acute care facilities across the country. Patients are accepted if they no longer need acute ICU care, are mechanically ventilated via tracheotomy, and, in the clinical opinion of the referring ICU physician, are likely to be liberated from the ventilator. Other chronically critically ill patients may not be transferred to the RCU either because of death in the ICU after tracheotomy or because the tracheotomy was placed in preparation for permanent ventilator support, with no expectation that the patient would ever wean. (From 2001 to 2005, when 535 patients were treated in the RCU, 511 patients underwent tracheotomy and were not admitted to the RCU; of the latter group, 230 [45%] died in the hospital.)As supervised by pulmonary and critical care physicians with nurse practitioners, RCU treatment is standardized by a detailed health care map and weaning protocol,but regular care during the study did not include a protocol for sedation or cognitive assessment. Surviving patients are discharged from the RCU on successful liberation from the ventilator or a clinical determination that further efforts to achieve ventilator independence will not succeed.PATIENT ENROLLMENTFrom September 2003 to January 2005, we conducted daily screening to identify eligible patients among all new RCU admissions. We defined eligibility by elective tracheotomy for ICU weaning failure.Tracheotomy under these circumstances reflects the clinical impression that the patient is expected neither to wean nor to die in the immediate future and therefore it serves as a practical point of demarcation between acute and chronic critical illness.It is also the defining criterion of national diagnosis related groups 541 and 542 (formerly diagnosis related group 483),in which a large national dataset of similar patients across many institutions and settings are classified and can be compared. We excluded patients with previous ventilator dependence or RCU admission, patients from other institutions, and those without English proficiency. The institutional review board of Mount Sinai School of Medicine, New York, approved this study, and we obtained informed consent from all subjects or appropriate surrogates.COGNITIVE ASSESSMENTWe conducted cognitive assessments at multiple, longitudinal time points: at study entry (after tracheotomy and transfer from ICU to RCU), biweekly in the RCU, at RCU discharge, and, for surviving patients, at 3 and 6 months after RCU discharge. These intervals included assessments while patients were mechanically ventilated and after ventilator liberation.For RCU cognitive assessments, we used the Confusion Assessment Method for the ICU (CAM-ICU),which includes a preliminary evaluation of consciousness. A trained research nurse (A.F.M.) performed these assessments.To evaluate consciousness, we used the Richmond Agitation-Sedation Scale (RASS),which encompasses 10 levels (0 to +4 indicates increasing agitation and 0 to −5 indicates decreasing consciousness). We deferred delirium assessment for patients initially rated as deeply sedated (RASS level −4) or unarousable (RASS level −5), whom we classified together as comatose; we approached these patients later the same day and performed delirium assessment as possible.Next, we evaluated the patients for 4 basic features of delirium: (1) acute onset or fluctuating course, (2) inattention (evaluated by the Vigilance A Random Letter Test), and (3) disorganized thinking or (4) altered level of consciousness. We defined delirium by the presence of both features 1 and 2 and either feature 3 or feature 4.We conducted postdischarge cognitive assessments by telephone. Because patients able to respond could communicate orally, we used the validated telephone CAMfor this purpose.For patients who could not respond to telephone interviews, we asked responding surrogates about the nature of the patient's inability to participate (cognitive or physical limitation); surrogates reported the patient's level of consciousness and other aspects of cognitive status.OTHER DATA COLLECTIONWe recorded administration of analgesic, sedative, antidepressant, antipsychotic, and psychostimulant medications in the RCU to provide a context for cognitive assessments during RCU treatment. We collected additional information including diagnoses, comorbid conditions, and other data for Acute Physiology and Chronic Health Evaluation IIand Charlson Comorbidity Indexscores; lengths of stay; and site and ventilator status at discharge and follow-up. To measure functional status at multiple time points, we used the motor scale of the Functional Independence Measure (FIM Motor),which includes 13 items (eg, eating, bathing, and walking) that are each scored from 1 (needs total assistance) to 7 (complete independence); total FIM Motor scores range from 13 (completely dependent) to 91 (completely independent). Responses to telephone interviews (used for postdischarge functional assessments) and to in-person interviews (used for in-hospital assessments) are strongly correlated for the FIM Motor,which is well validated. In addition, we calculated the Katz Index of Activities of Daily Living.As a baseline for comparison with our prospective assessments of cognition and function in the hospital and after discharge, we used interviews with families or other appropriate and knowledgeable surrogates at study entry about the patients' status during the 2 weeks before hospitalization. Cognitive status interviews focused on medical history of dementia, decreased level of consciousness, confusion, and memory loss; we also reviewed patients' medical records for evidence of these or other cognitive disturbances. For assessment of baseline functional status, we interviewed families with respect to FIM Motor items, on which surrogate reports are well correlated with information from patients themselves.STATISTICAL ANALYSISWe calculated mean and median daily doses of opioids (in morphine equivalents) and of sedatives (in lorazepam equivalents) as the mean and median, respectively, of the individual mean daily doses given to each patient during the RCU stay. We compared patients with delirium or coma and patients without these forms of brain dysfunction with respect to the percentage of patients receiving medications in these classes and the average daily doses of these medications (&khgr;2test and ttest, respectively). We calculated duration of delirium or coma in the RCU as the number of consecutive days from the first day on which CAM-ICU assessment documented either condition. For each patient, we also calculated the percentage of total RCU days for each cognitive disturbance under study. We used multivariate logistic (discrete outcomes) and multivariate linear (continuous outcomes) regression to examine the association of number of days spent in delirium or coma with RCU length of stay, ventilator liberation, hospital mortality, site of discharge for survivors (home vs post–acute care facility), 3-month and 6-month residence (home vs nursing home), functional status, and mortality, controlling for age, sex, ethnicity, Charlson Comorbidity Index, Acute Physiology and Chronic Health Evaluation II score, and number of acute comorbidities.RESULTSAmong 330 patients who had undergone tracheotomy and were consecutively admitted to the RCU, 230 were eligible (37, 30, 20, and 13 patients were excluded for prior ventilator dependence or RCU treatment, transfer from another hospital, language barrier, or other reasons, respectively), and 203 (88.2%) were enrolled in the study. Consent was refused by 24 patients and was not sought for 3 because death supervened. Eighty-nine surviving patients were discharged from the hospital, and all but 4 (who were lost to follow-up) were followed up for 6 months.PATIENT CHARACTERISTICSTable 1details patient characteristics. Study patients were mainly older adults (median age, 72 years) with multiple medical illnesses and organ failures. Most, however, had been living at home and were functioning independently before their hospitalization. More than 80% (166 of 203) were reported by their families and confirmed by medical records to have no cognitive impairment. The mean (SD) Charlson Comorbidity Index score, Acute Physiology and Chronic Health Evaluation II score, and number of acute comorbid conditions at study entry were 4.5 (2.7), 20.5 (5.1), and 2.3 (2.1), respectively (ie, there was a high severity illness and comorbidity burden). By then, most patients had already been hospitalized for a long period (median duration of illness [interquartile range], 25.0 days [19.0-34.0 days]), including a prolonged ICU stay (16.0 days [11.0-22.0 days]). These patients were treated in the RCU for even longer periods (23.0 days [13.0-35.0 days]). Total duration of exposure to an intensive care environment (ICU plus RCU stay) averaged 45.0 days.Table 1. Characteristics of 203 Chronically Critically Ill Study PatientsCharacteristicValue*Age, median (range), y72 (21-99)Male117 (58)Race/ethnicity White, non-Hispanic106 (52) Black, non-Hispanic53 (26) Hispanic36 (18) Other8 (4)Residence before hospital admission† Private home153 (75) Rehabilitation facility8 (4) Nursing home24 (12) Other16 (8)FIM Motor score at hospital admission,  median (IQR)‡85 (41-91)Independent in all activities of daily living at hospital admission115 (57)Cognitively impaired at hospital admission§37 (18)Cognitively impaired at study entry&par;143 (75)Primary diagnosis at ICU admission Cardiovascular45 (22) Pulmonary75 (37) Neurologic33 (16) Surgical31 (15) Other19 (9)ICU transferring to RCU Medical128 (63) Surgical23 (11) Cardiothoracic2 (1) Neurosurgical40 (20) Cardiac care10 (5)ICU length of stay, median (IQR), d16 (11-22)Causes of prolonged respiratory failure¶ Acute lung disease94 (46) Chronic lung disease35 (17) Cardiac disease34 (16) Neurologic disease57 (28) Surgical or postoperative condition35 (17) Sepsis/multiorgan dysfunction55 (27) Other26 (13)APACHE II Score (at study entry), mean (SD)†20.5 (5.1)Charlson Comorbidity Index Score, mean (SD)4.5 (2.7) Abbreviations: APACHE II, Acute Physiology and Chronic Health Evaluation II; FIM, Functional Independence Measure; ICU, intensive care unit; IQR, interquartile range; OMCT, Orientation-Memory-Concentration Test; RCU, respiratory care unit. *Data are given as number (percentage) except where noted. †Two hundred one patients (data were unavailable for 2 patients). ‡One hundred ninety-nine patients (prehospital functional status was unavailable for 4 patients). As described in the “Methods” section, scores (1 [total assistance] to 7 [completely independent]) on 13 individual motor items in the FIMare summed to form the FIM Motor score, which ranges from 13 (completely dependent) to 91 (completely independent). §Defined as reported by family or evidence in medical records of history of dementia, decreased level of consciousness, confusion, memory loss, or other cognitive impairment.  &par;Defined as a score greater than 10 on the 6-item OMCT(n = 19) or lacking sufficient cognitive capacity to respond to screen (n = 124); 13 others refused administration of the OMCT screen; 47 patients had an OMCT score of 10 or less at study entry. ¶Percentages total more than 100% because prolonged respiratory failure was typically multifactorial.PATIENT OUTCOMESPatient outcomes are presented in Table 2. Of the 203 subjects, 58 (28.6%) died in hospital and less than half (89 [43.8%]) were alive at 6 months. Of 145 hospital survivors, 15 (10.3%) were discharged to home and 107 (73.8%) to a nursing home or another acute care hospital; 48 (33.1%) remained mechanically ventilated. Median (interquartile range) survival of those who died after hospital discharge (n = 56) was 55 days (8-92 days). At 6 months, 32 (15.8%) of the 203 original subjects were living at home (vs 75.4% before hospitalization), 2 of whom were still mechanically ventilated. Approximately two thirds (53 of 85) of 6-month survivors (including 14 [43.8%] of 32 patients at home) were dependent in all activities of daily living.Table 2. Outcomes of 203 Chronically Critically Ill Study PatientsOutcomeValue*Length of stay, median (IQR), d RCU23 (13-35) Hospital54 (13-182)Liberated from mechanical ventilation  at RCU discharge†97 (48)Hospital discharge site Home15 (7) Nursing home or acute care hospital104 (51) Rehabilitation facility25 (12) Died in hospital58 (29)Cumulative mortality RCU39 (19) Hospital58 (29) 3 mo after discharge103 (51) 6 mo after discharge114 (56)FIM Motor score, median (IQR)‡ At RCU discharge§13 (13-24) 3 mo after discharge&par;29 (13-66) 6 mo after discharge¶56 (13-87)Dependent in all activities of daily living at 6 months after discharge53 (62) Abbreviations: FIM, Functional Independence Measure; IQR, interquartile range; RCU, respiratory care unit. *Data are given as number (percentage) except where noted.  †Defined as 168 hours of unassisted breathing, regardless of any subsequent mechanical ventilation.Excludes patients who died in the RCU. ‡FIM Motor scoreranges from 13 (completely dependent) to 91 (completely independent), as explained in the “Methods” section. §One hundred sixty-four patients (39 patients died in the RCU).  &par;Ninety-eight patients (103 patients died, and 1 patient withdrew from study participation before 3 months; 1 could not be contacted). ¶Eighty-five patients (114 patients died, and 2 patients had withdrawn from the study by the 6-month follow-up; time after discharge was less than 6 months for 1 patient as of close of database for these analyses; 1 patient could not be contacted).RESULTS OF COGNITIVE ASSESSMENTSPrevalence of coma and delirium is detailed in Table 3. At RCU admission, 50.2% of patients were comatose, and 14.8% were delirious. Approximately 1 in 3 (61 of 203) study patients were comatose throughout the entire RCU stay. Thirteen (21.3%) of these 61 patients were admitted to the ICU for stroke whereas most of the patients in a persistent coma did not have an underlying, structural injury to the central nervous system. Among patients not in coma, delirium was diagnosed in almost half (66 of 142). Patients spent a mean time of 17.9 days (range, 1-153 days) in coma or delirium (mean RCU length of stay, 26 days), and among RCU survivors, half were comatose or delirious at discharge. Thus, after prolonged, aggressive treatment for chronic critical illness, 58.1% of our original study group either were dead (19.2%) or severely cognitively impaired at RCU discharge (38.9%); 45 (59.2%) of the remaining 76 were functionally dependent in all activities of daily living and required nursing home placement.Table 3. Prevalence of Brain Dysfunction (Coma or Delirium) During Chronic Critical IllnessCognitive Assessment*Patients, No. (%)RCU Treatment PeriodPostdischarge Follow-up, MoRCU AdmissionBiweekly AssessmentRCU Discharge36Comatose or otherwise unresponsive CAM-ICU (RASS −4 or −5)102 (50)77 (38)†58 (36) CAM (telephone)75 (77)‡60 (71)‡Delirious30 (15)56 (28)§21 (13)0 0  Always7 (4) ≥50% and <100% of assessments22 (11) <50% of assessments27 (13)Not delirious or comatose62 (30)63 (31)76 (48)23 (23)25 (29)Refused to respond8 (4)6 (3)5 (3)0 0 Total patients&par;2022021609885 Abbreviations: CAM, Confusion Assessment Method; ICU, intensive care unit; RASS, Richmond Agitation-Sedation Scale; RCU, respiratory care unit. *We assessed brain dysfunction using the CAM-ICU,incorporating the RASS.Patients rated as level −5 (unarousable) or −4 (deeply sedated) on the RASS (classified together as comatose) lacked sufficient consciousness for further evaluation of delirium at that assessment. †We categorized as comatose those patients who were rated as RASS level −4 or −5 at 75% or more of our biweekly approaches. ‡We used the validated telephone CAMfor postdischarge evaluations. §For patients able to respond to CAM-ICU (ie, not comatose on the initial RASS evaluation) at more than 25% of the biweekly approaches, we categorized as delirious those patients found to have at least 1 episode of delirium, and we categorized as not delirious those patients who were never found to be delirious. Some patients categorized as delirious or not delirious for the biweekly assessments may have had 1 or more episodes of coma (but <75% of the CAM-ICU approaches) during this period.  &par;One patient was not approached for cognitive assessment at RCU admission or during biweekly approaches, and 4 among 164 RCU survivors were discharged before completion of the assessment. The numbers of patients for 3-month and 6-month follow-ups were 98 and 85, respectively, as explained in the previous 2 footnotes.The Figureplots prevalence of coma and delirium through week 4 in the RCU. The overall burden of brain dysfunction did not diminish significantly during this period. Delirium tended to be persistent or recurrent for patients who were delirious at RCU admission: 17 (56.7%) of 30 patients who were initially delirious never regained normal consciousness prior to discharge or death. For those whose delirium resolved, the mean (SD) time to resolution was 11.6 (10.4) days. Of 62 patients with normal consciousness on admission, one quarter subsequently developed delirium (11 patients) or coma (5 patients), and of these 16, 7 (43.7%) failed to regain a normal state of consciousness.Figure.We used the Richmond Agitation-Sedation Scaleand the Confusion Assessment Method for the Intensive Care Unitfor biweekly cognitive assessments, as detailed in the “Methods” section. The bar graph shows results of these assessments for 202 study patients through week 4 in the respiratory care unit (RCU) (average length of RCU stay, 3 to 4 weeks).POSTDISCHARGEFollow-up data on brain dysfunction are presented in Table 3. At 6 months, 60 (70.6%) of 85 survivors, including 15 (46.9%) of 32 then living at home, remained profoundly cognitively impaired to the point that they could not participate in telephone mental status testing. Of 25 patients who could communicate by telephone, none was cognitively impaired as measured by the CAM.MEDICATIONSAdministration of medications with the number (percentage) of 203 study patients is given in the following tabulation:   Opioid160 (78.8)Sedative128 (63.1)Antidepressant43 (21.2)Antipsychotic125 (61.6)Psychostimulant19 (9.4)The median daily doses of opioid in parenteral morphine equivalents, and of benzodiazepine (the only sedative used in the RCU) in lorazepam equivalents,were 5.1 mg/d and 1.0 mg/d, respectively. Among 62 patients who presented to the study with intact cognition—that is, neither comatose according to the RASS nor delirious according to the CAM-ICU—35 (92.1%) of 38 who remained intact received a sedative or opioid compared with 16 (100%) of 16 patients who developed brain dysfunction during the RCU stay (P = .34) (8 patients died in the RCU). On average, patients who were comatose or delirious received 2.4 mg/d of morphine equivalents and 1.2 mg/d of lorazepam equivalents in the 2 days prior to brain dysfunction, compared with daily doses of 6.4 mg of morphine equivalents and 1.3 mg of lorazepam equivalents in the cognitively intact group (P = .30 and P = .76, respectively). Of the 16 patients who were initially intact but developed coma or delirium in the RCU, 11 (68.7%) received sedatives, opioids, or antipsychotic drugs during the 24 hours before the first episode of brain dysfunction whereas 9 (56.2%) of 16 received these medications after the episode.MULTIVARIATE ANALYSESThe number of days spent in delirium or coma was significantly associated with an increased likelihood of being discharged to a post–acute care facility as opposed to home (odds ratio, 1.09; 95% confidence interval [CI], 1.00-1.20; P = .047), longer length of hospital stay (parameter estimate, 0.03; 95% CI, 0.02-0.03; P<.001 for association with longer length of stay), and lower FIM Motor scores indicating poorer functional status at 3- and 6-month follow-ups for survivors (for 3-month follow-up: parameter estimate, −0.47; 95% CI, −0.78 to −0.15; P = .004; for 6-month follow-up: parameter estimate, −0.92; 95% CI, –1.4 to −0.43; P<.001). The association of the number of days spent in delirium or coma with 3-month survival for those who survived hospitalization was of borderline significance (odds ratio, 0.98. 95% CI, 0.95-1.00; P = .056). Days spent in delirium or coma was not significantly associated with in-hospital mortality, likelihood of liberation from the ventilator, 6-month mortality, or 3- or 6-month site of residence.COMMENTThere are now estimated to be over 100 000 chronically critically ill patients in the United States each year,and numbers are steadily increasing.These patients, who have survived but not recovered from acute critical illness, have a discrete syndrome: ongoing ventilator dependence, severe debility, and characteristic abnormalities of metabolic and immunologic function, with resulting failure of other organs and recurrent nosocomial infections.The present study suggests that brain dysfunction, manifest as delirium (assessed by CAM-ICU) and coma (levels −4 and −5 on the RASS scale), is another prominent feature of chronic critical illness. In addition, brain dysfunction in these patients is prolonged, and its duration is associated with longer lengths of stay and poorer functional status. Six months after aggressive treatment in a specialized hospital unit, three fourths of our study patients were either dead or institutionalized, and two thirds of survivors remained profoundly cognitively impaired whereas most of these patients had been at home, independent, and without cognitive impairment prior to hospitalization. Less than 10% were living at home without brain dysfunction as measured by CAM at 6 months. Findings of this study have important implications for decision making.Delirium occurs commonly in ICU patients with acute critical illnessand is associated with longer hospital and ICU lengths of stayand higher mortality at 6 months.Our data suggest that patients who survive the ICU but remain ventilator dependent with chronic critical illness have similarly high rates of delirium as well as coma. However, unlike ICU delirium (which has a median duration of 48 hours),these conditions persist in the chronically critically ill for a prolonged period. This occurs despite the fact that doses of sedating drugs are generally lower after tracheotomy and during ventilator weaning.In our study, 65.3% of patients were admitted to the RCU with coma or delirium, more than 25% of those who were initially without coma or delirium developed these conditions in the RCU, and less than half of both groups combined regained normal cognition.Cognitive impairment is often considered to be the heaviest burden of illness and is an outcome that may be even less acceptable than death.Patients, families, and clinicians consider information about expected cognitive outcome to be important specifically for decision making about treatment when critical illness becomes chronic.Our documentation herein of the prevalence and duration of brain dysfunction may help to inform discussions and decisions at that pivotal juncture.There are several limitations to this study. We performed our research in a single hospital's in-patient RCU. Our findings may not apply to patients who have undergone tracheotomy and whose illness is so severe that they cannot survive outside of an ICU (like those in our hospital who underwent tracheotomy but died in the ICU before transfer to the RCU) or those who undergo tracheotomy with the understanding that they are not expected to be liberated but rather to remain mechanically ventilated indefinitely (like those in our hospital who are not referred to the RCU because they are clinically determined to be unweanable). Our eligibility criteria, however, were designed to encompass a broad and generalizable group of patients requiring prolonged mechanical ventilation via tracheotomy after failure to wean in the ICU. Although treated in various care settings (long-term acute care facilities and skilled nursing facilities as well as in-patient hospital units), chronically critically ill patients have comparable characteristics and outcomes, as reported from multiple institutions and reflected in the national diagnosis related group 541-542/483 database.We have described our experience with a large series of patients initially treated in a variety of ICUs, of whom we made over 1700 delirium assessments using instruments (CAM-ICU and RASS) that were rigorously tested in prior work. Because the CAM-ICU was already validated in 2 patient groups,we did not retest it against a reference standard but instead focused on use with a discrete group of patients with prolonged illness and mechanical ventilation. In follow-up after RCU discharge, we used the original CAM (validated telephone version),which is more sensitive than CAM-ICU for diagnosing delirium in nonintubated patients.The number of patients who could respond to cognitive assessment after hospital discharge was limited by the high rates of mortality and institutionalization; patients able to respond to telephone interview were less likely to have delirium and other forms of cognitive impairment than nonresponders, which would have underestimated the true prevalence of postdischarge delirium in the entire study population.CONCLUSIONSAs the general population ages and intensive care treatments are offered to older and sicker patients, clinicians in all fields and disciplines will encounter chronically critically ill patients with increasing frequency. Most of these patients die within 6 months, and most survivors are institutionalized with severe functional impairments. Our previous researchindicates that most patients with chronic critical illness spend weeks to months in the hospital experiencing a multitude of distressing physical and psychological symptoms. The present study suggests that few patients with chronic critical illness avoid delirium or coma and that most of them spend significant time during treatment and thereafter with these severe forms of brain dysfunction. Although regular, comprehensive assessment and treatment of symptoms may reduce suffering, it is less clear that effective treatments exist to address the high prevalence of brain dysfunction observed here. Nor can we be certain that such treatments would improve mortality rates or functional outcomes.The choice to continue life-prolonging treatments when critical illness enters a chronic phase may be made by some patients and families despite poor prognosis for survival and for cognitive and functional recovery. However, accumulating evidence of symptom distress and long-term cognitive and functional impairment calls attention to whether they are truly making informed decisions at the time of tracheotomy and whether ongoing goals of care are routinely discussed during the course of critical illness. Future research should focus on strategies to alleviate symptom burden and to address delirium and other brain dysfunction. In addition, it is essential to examine how information is communicated and how decisions are made about the benefits and burdens of life-prolonging therapies (eg, mechanical ventilation) for the chronically critically ill. In the meantime, options presented to decision makers for these patients should include a time-limited trial of continued respiratory support, with a plan for discontinuation of the ventilator if cognitive and functional recovery do not occur within a reasonable period of time. The levels of disease complexity, physical and psychological suffering, and cognitive impairment also suggest that quality care for these patients should include not only expert pulmonary and critical care but also involvement of a palliative care consultation team.Correspondence:Judith E. Nelson, MD, JD, Box 1232, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029 (judith.nelson@mountsinai.org).Accepted for Publication:June 23, 2006.Author Contributions:Dr Nelson had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Nelson and Morrison. Acquisition of data: Nelson, Mercado, Camhi, and Morrison. Analysis and interpretation of data: Nelson, Tandon, Camhi, Ely, and Morrison. Drafting of the manuscript: Nelson, Camhi, and Morrison. Critical revision of the manuscript for important intellectual content: Nelson, Tandon, Mercado, Ely, and Morrison. Statistical analysis: Tandon and Morrison. Obtained funding: Nelson. Administrative, technical, and material support: Tandon, Mercado, Ely, and Morrison. Study supervision: Nelson and Morrison.Financial Disclosure:Dr Ely has received investigator-initiated, unrestricted grants from Pfizer Inc and from Hospira Inc to evaluate pharmacologic strategies for prevention and treatment of delirium; those projects and their sponsors have no connection to the study reported herein. Dr Ely is also the recipient of similar grants from Eli Lilly and has received honoraria from all 3 companies.Funding/Support:This study was supported by grant R01 AG21172 from the National Institute on Aging (NIA). Dr Nelson is the recipient of an Independent Scientist Award (K02 AG024476) from the NIA. Dr Morrison is the recipient of a Midcareer Investigator Award in Patient-Oriented Research from the NIA (K24 AG022345). 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Journal

JAMA Internal Medicine – American Medical Association

Published: Oct 9, 2006

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