Delirium is one of the most common behavioral manifestations of acute brain dysfunction in the intensive care unit (ICU) and is a strong predictor of worse outcome. Routine monitoring for delirium is ...recommended for all ICU patients using validated tools. In delirious patients, a search for all reversible precipitants is the first line of action and pharmacologic treatment should be considered when all causes have been ruled out, and it is not contraindicated. Long-term morbidity has significant consequences for survivors of critical illness and for their caregivers. ICU patients may develop posttraumatic stress disorder related to their critical illness experience.
Acute brain dysfunction (delirium and coma) during critical illness is prevalent and costly, but the pathophysiology remains unclear. The relationship of acute brain dysfunction with endothelial ...function, which is impaired in critical illness and may contribute to alterations in cerebral blood flow and blood-brain barrier permeability, has not been studied. This study sought to determine whether systemic endothelial dysfunction is associated with acute brain dysfunction during critical illness.
In this prospective cohort study, adult medical/surgical intensive care unit patients in shock and/or respiratory failure were enrolled. Endothelial function was assessed at enrollment using peripheral artery tonometry to calculate the reactive hyperemia index, with lower reactive hyperemia index indicative of worse endothelial function. Patients were assessed for coma and delirium with the Richmond Agitation-Sedation Scale and Confusion Assessment Method for the Intensive Care Unit. Multivariable linear regression was used to analyze the association between reactive hyperemia index and (1) delirium/coma-free days among all patients and (2) delirium duration among survivors, both over a 14-day period.
One hundred forty-seven patients with median age of 57 yr and median Acute Physiology and Chronic Health Evaluation II score of 26 were enrolled. After adjusting for age, severity of illness, severe sepsis, preexisting cognitive function, medical versus surgical intensive care unit admission, and prehospital statin use, lower reactive hyperemia index (worse systemic endothelial function) was associated with fewer delirium/coma-free days (P = 0.02) and more delirium days (P = 0.05).
In this study, critically ill patients with lower vascular reactivity indicative of worse systemic endothelial function had increased duration of acute brain dysfunction.
Delirium, a prevalent organ dysfunction in critically ill patients, is independently associated with increased morbidity. This last decade has witnessed an exponential growth in delirium research in ...hospitalized patients, including those critically ill, and this research has highlighted that delirium needs to be better understood mechanistically to help foster research that will ultimately lead to its prevention and treatment. In this invited, evidence-based paper, a multinational and interprofessional group of clinicians and researchers from within the fields of critical care medicine, psychiatry, pediatrics, anesthesiology, geriatrics, surgery, neurology, nursing, pharmacy, and the neurosciences sought to address five questions: (1) What is the current standard of care in managing ICU delirium? (2) What have been the major recent advances in delirium research and care? (3) What are the common delirium beliefs that have been challenged by recent trials? (4) What are the remaining areas of uncertainty in delirium research? (5) What are some of the top study areas/trials to be done in the next 10 years? Herein, we briefly review the epidemiology of delirium, the current best practices for management of critically ill patients at risk for delirium or experiencing delirium, identify recent advances in our understanding of delirium as well as gaps in knowledge, and discuss research opportunities and barriers to implementation, with the goal of promoting an integrated research agenda.
Delirium is a debilitating form of brain dysfunction frequently encountered in the intensive care unit (ICU). It is associated with increased morbidity and mortality, longer lengths of stay, higher ...hospital costs, and cognitive impairment that persists long after hospital discharge. Predisposing factors include smoking, hypertension, cardiac disease, sepsis, and premorbid dementia. Precipitating factors include respiratory failure and shock, metabolic disturbances, prolonged mechanical ventilation, pain, immobility, and sedatives and adverse environmental conditions impairing vision, hearing, and sleep. Historically, antipsychotic medications were the mainstay of delirium treatment in the critically ill. Based on more recent literature, the current Society of Critical Care Medicine (SCCM) guidelines suggest against routine use of antipsychotics for delirium in critically ill adults. Other pharmacologic interventions (e.g., dexmedetomidine) are under investigation and their impact is not yet clear. Nonpharmacologic interventions thus remain the cornerstone of delirium management. This approach is summarized in the ABCDEF bundle (
ssess, prevent, and manage pain;
oth SAT and SBT;
hoice of analgesia and sedation;
elirium: assess, prevent, and manage;
arly mobility and exercise;
amily engagement and empowerment). The implementation of this bundle reduces the odds of developing delirium and the chances of needing mechanical ventilation, yet there are challenges to its implementation. There is an urgent need for ongoing studies to more effectively mitigate risk factors and to better understand the pathobiology underlying ICU delirium so as to identify additional potential treatments. Further refinements of therapeutic options, from drugs to rehabilitation, are current areas ripe for study to improve the short- and long-term outcomes of critically ill patients with delirium.
Non-intensive care unit (ICU) cohorts have shown an association between inflammatory disturbances and delirium, though these relationships have not been studied in critically ill patients. This study ...sought to investigate the relationship between two inflammatory biomarkers, procalcitonin and C-reactive protein (CRP), and duration of acute brain dysfunction in ventilated patients.
Patients enrolled in the Maximizing Efficacy of Targeted Sedation and Reducing Neurological Dysfunction (MENDS) trial were assessed daily for delirium using the Confusion Assessment Method-ICU. Plasma levels of procalcitonin and CRP were obtained within 24 hours of enrollment. Proportional odds logistic regression was used to examine the association between procalcitonin and CRP separately with delirium/coma-free days, adjusting for age, acute physiology score (APS) of the Acute Physiology And Chronic Health Evaluation (APACHE) II, sedation group (dexmedetomidine vs. lorazepam), and sepsis. Secondary analyses examined the association of these markers with other organ dysfunctions and 28-day survival.
Eighty-seven patients were included in this analysis. The median age of the patients was 60 years with APACHE II scores of 28; 68% had sepsis within 48 hours of admission. Higher levels of procalcitonin were associated with fewer delirium/coma-free days odds ratio (OR), 0.5; 95% confidence interval (CI), 0.3 to 1.0; P = 0.04, whereas higher CRP levels showed trends towards fewer delirium/coma-free days (OR, 0.6; 95% CI, 0.3 to 1.1; P = 0.08). Similar relationships were found regardless of the presence of sepsis. No associations were found between procalcitonin or CRP with 28-day survival (P = 0.40 and 0.16, respectively).
In our pilot study, high baseline inflammatory biomarkers predicted prolonged periods of acute brain dysfunction, implicating inflammation as an important mechanism in the pathophysiology of delirium and coma during critical illness, irrespective of whether patients had sepsis or not.
To validate a diagnostic instrument for pediatric delirium in critically ill children, both ventilated and nonventilated, that uses standardized, developmentally appropriate measurements.
A ...prospective observational cohort study investigating the Pediatric Confusion Assessment Method for Intensive Care Unit (pCAM-ICU) patients in the pediatric medical, surgical, and cardiac intensive care unit of a university-based medical center.
A total of 68 pediatric critically ill patients, at least 5 years of age, were enrolled from July 1, 2008, to March 30, 2009.
None.
Criterion validity including sensitivity and specificity and interrater reliability were determined using daily delirium assessments with the pCAM-ICU by two critical care clinicians compared with delirium diagnosis by pediatric psychiatrists using Diagnostic and Statistical Manual, 4th Edition, Text Revision criteria.
A total of 146 paired assessments were completed among 68 enrolled patients with a mean age of 12.2 yrs. Compared with the reference standard for diagnosing delirium, the pCAM-ICU demonstrated a sensitivity of 83% (95% confidence interval, 66-93%), a specificity of 99% (95% confidence interval, 95-100%), and a high interrater reliability (κ = 0.96; 95% confidence interval, 0.74-1.0).
The pCAM-ICU is a highly valid reliable instrument for the diagnosis of pediatric delirium in critically ill children chronologically and developmentally at least 5 yrs of age. Use of the pCAM-ICU may expedite diagnosis and consultation with neuropsychiatry specialists for treatment of pediatric delirium. In addition, the pCAM-ICU may provide a means for delirium monitoring in future epidemiologic and interventional studies in critically ill children.
To demonstrate the feasibility of a placebo-controlled trial of antipsychotics for delirium in the intensive care unit and to test the hypothesis that antipsychotics would improve days alive without ...delirium or coma.
Randomized, double-blind, placebo-controlled trial.
Six tertiary care medical centers in the US.
One hundred one mechanically ventilated medical and surgical intensive care unit patients.
Patients were randomly assigned to receive haloperidol or ziprasidone or placebo every 6 hrs for up to 14 days. Twice each day, frequency of study drug administration was adjusted according to delirium status, level of sedation, and side effects.
The primary end point was the number of days patients were alive without delirium or coma. During the 21-day study period, patients in the haloperidol group spent a similar number days alive without delirium or coma (median interquartile range, 14.0 6.0-18.0 days) as did patients in the ziprasidone (15.0 9.1-18.0 days) and placebo groups (12.5 1.2-17.2 days; p = 0.66). No differences were found in secondary clinical outcomes, including ventilator-free days (p = .25), hospital length of stay (p = .68), and mortality (p = .81). Ten (29%) patients in the haloperidol group reported symptoms consistent with akathisia, compared with six (20%) patients in the ziprasidone group and seven (19%) patients in the placebo group (p = .60), and a global measure of extrapyramidal symptoms was similar between treatment groups (p = .46).
A randomized, placebo-controlled trial of antipsychotics for delirium in mechanically ventilated intensive care unit patients is feasible. Treatment with antipsychotics in this limited pilot trial did not improve the number of days alive without delirium or coma, nor did it increase adverse outcomes. Thus, a large trial is needed to determine whether use of antipsychotics for intensive care unit delirium is appropriate.
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