BACKGROUND Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes. METHODS In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. The primary outcome was a major adverse kidney event within 30 days — a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) — all censored at hospital discharge or 30 days, whichever occurred first. RESULTS Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P = 0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P = 0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P = 0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P = 0.60). CONCLUSIONS Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779.)

BACKGROUND Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU). METHODS We conducted a single-center, pragmatic, multiple-crossover trial comparing balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) with saline among adults who were treated with intravenous crystalloids in the emergency department and were subsequently hospitalized outside an ICU. The type of crystalloid that was administered in the emergency department was assigned to each patient on the basis of calendar month, with the entire emergency department crossing over between balanced crystalloids and saline monthly during the 16-month trial. The primary outcome was hospital-free days (days alive after discharge before day 28). Secondary outcomes included major adverse kidney events within 30 days — a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) — all censored at hospital discharge or 30 days, whichever occurred first. RESULTS A total of 13,347 patients were enrolled, with a median crystalloid volume administered in the emergency department of 1079 ml and 88.3% of the patients exclusively receiving the assigned crystalloid. The number of hospital-free days did not differ between the balanced-crystalloids and saline groups (median, 25 days in each group; adjusted odds ratio with balanced crystalloids, 0.98; 95% confidence interval [CI], 0.92 to 1.04; P = 0.41). Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P = 0.01). CONCLUSIONS Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital-free days between treatment with balanced crystalloids and treatment with saline.

Background Critical illness is associated with cognitive impairment, but mental health and functional disabilities in general intensive care unit (ICU) survivors are inadequately characterized and there are a paucity of data regarding the relationship between age and delirium and these outcomes. Methods In this prospective, multisite cohort study, we enrolled medical/surgical ICU patients with respiratory failure or shock, collected detailed demographics and in-hospital variables, and assessed survivors at 3 and 12 months with measures of depression, posttraumatic stress disorder (PTSD) and functional disability. We used linear and proportional odds logistic regression to examine the independent associations between age and delirium duration versus mental health and functional disabilities. Findings We enrolled 821 patients with a median (interquartile range) age of 61 (51, 71), assessing 448 patients and 382 patients 3 and 12 months after discharge. At 3- and 12-month follow-up, 37% (149/407) and 33% (116/347) of subjects reported at least mild depression, driven primarily by somatic rather than cognitive symptoms. Depressive symptoms were common even among those with no proxy reported history of depression, reported at 3- and 12-month follow-up by 30% (76/255) and 29% (62/217) of these individuals. At either follow-up assessment, only 7% (27/415, 24/361) of subjects had symptoms consistent with PTSD. Disabilities in basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs) were present in 32% (139/428) and 26% (108/422) of individuals at 3 months and in 27% (102/374) and 23%(87/372) at 12 months. Mental health and functional difficulties were prevalent in young and old patients. Although older age was frequently associated with mental health and functional disabilities, no consistent association was observed between delirium and these outcomes. Interpretation In contrast with early single-center reports, data from this large, multicenter investigation reveal depression is much more common than PTSD after critical illness and is driven by somatic symptoms indicative of physical disabilities rather than by cognitive symptoms. Poor mental health and functional disability were common, and persistent in up to a quarter of patients.

In this multicenter cohort study, one or more post-intensive care syndrome problems were present in the majority of survivors, but co-occurring problems were present in only one out of four. Education was protective from post-intensive care syndrome problems and frailty predictive of the development of post-intensive care syndrome problems. Future studies are needed to understand better the heterogeneous subtypes of post-intensive care syndrome and to identify modifiable risk factors.

BACKGROUND There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522.)

National Institutes of Health and the Department of Veterans Affairs.

Regular exercise has multiple benefits for physical and mental health, including the body’s ability to combat infections. The current COVID-19 pandemic and the social distancing measures employed to curtail the impact of the infection are likely to reduce the amount of usual physical activity being performed by most individuals, including habitual exercisers. The uncertainties relating to the impact of the SARS-CoV-2 virus on the heart may cause increased anxiety, particularly in athletes who need to sustain a vigorous exercise regime in order to maintain their skills and fitness in preparation for return to competition after a short re-training period. The aim of this document is to provide practical answers to pertinent questions being posed by the sporting community, in an attempt to offer reassurance, promote safe participation in exercise during as well as after the COVID-19 pandemic and provide a framework of management for physicians caring for athletes.

As critical illness survivorship increases, patients and health care providers are faced with management of long-term sequelae including cognitive and functional impairment. Longitudinal studies have demonstrated impairments persisting at least 1–5 years after hospitalization for critical illness. Cognitive domains impacted include memory, attention, and processing speed. Functional impairments include physical weakness, reduced endurance, and dependence on others for basic tasks of daily living such as bathing or feeding. In characterizing the trajectory of long-term recovery, multiple risk factors have been identified for subsequent impairment, including increased severity of illness and severe sepsis, prolonged mechanical ventilation, and delirium. Preadmission status including frailty, high level of preexisting comorbidities, and baseline cognitive dysfunction are also associated with impairment after critical illness. Development of cognitive and functional impairment is likely multifactorial, and multiple mechanistic theories have been proposed. Neuroinflammation, disruption of the blood–brain barrier, and structural alterations in the brain have all been observed in patients with long-term cognitive dysfunction. Systemic inflammation has also been associated with alterations in muscle integrity and function, which is associated with intensive care unit–acquired weakness and prolonged functional impairment. Efforts to ease the burden of long-term impairments include prevention strategies and rehabilitation interventions after discharge. Delirium is a well-established risk factor for long-term cognitive dysfunction, and using delirium-prevention strategies may be important for cognitive protection. Current evidence favors minimizing overall sedation exposure, careful selection of sedation agents including avoidance of benzodiazepines, and targeted sedation goals to avoid oversedation. Daily awakening and spontaneous breathing trials and early mobilization have shown benefit in both cognitive and functional outcomes. Multifactorial prevention bundles are useful tools in improving care provided to patients in the intensive care unit. Data regarding cognitive rehabilitation are limited, while studies on functional rehabilitation have conflicting results. Continued investigation and implementation of prevention strategies and rehabilitation interventions will hopefully improve the quality of life for the ever-increasing population of critical illness survivors.