Excited Delirium Syndrome (ExDS): Defining Based on a Review of the Literature

Background

Patients present to police, Emergency Medical Services, and the emergency department with aggressive behavior, altered sensorium, and a host of other signs that may include hyperthermia, “superhuman” strength, diaphoresis, and lack of willingness to yield to overwhelming force. A certain percentage of these individuals will go on to expire from a sudden cardiac arrest and death, despite optimal therapy. Traditionally, the forensic community would often classify these as “Excited Delirium” deaths.

Objectives

This article will review selected examples of the literature on this topic to determine if it is definable as a discrete medical entity, has a recognizable history, epidemiology, clinical presentation, pathophysiology, and treatment recommendations.

Discussion

Excited delirium syndrome is characterized by delirium, agitation, acidosis, and hyperadrenergic autonomic dysfunction, typically in the setting of acute-on-chronic drug abuse or serious mental illness or a combination of both.

Conclusions

Based upon available evidence, it is the consensus of an American College of Emergency Physicians Task Force that Excited Delirium Syndrome is a real syndrome with uncertain, likely multiple, etiologies.     

Mutation analysis of cases of sudden unexplained death, 15 years after death: Prompt genetic evaluation after resuscitation can save future lives

Introduction

The aim of this study is to use genetic mutation analysis to determine the cause of sudden unexpected death in young (SUDY) persons with normal autopsy findings, and to provide relatives with an identified cardiac mutation with suitable cardiovascular prevention.

Methods

We performed mutation analysis on blood samples from first-degree relatives of 25 cases with normal autopsy findings identified in the national Swedish study of sudden cardiac death in 15- to 35-year-olds from 1992 to 1999.

Results

We found three families with long QT syndrome through mutation screening, and the mutations were verified in two of the deceased. Eight family members were found to be mutation carriers and have been provided with suitable cardiovascular prevention. Mutation screening also identified a number of common polymorphisms in the individuals screened. Clinical history revealed one family each with short QT syndrome and hypertrophic cardiomyopathy, respectively, but no mutations were found in the family members or in the deceased. Two SCDs each had occurred in two of the affected families.

Conclusion

Cardiac/genetic evaluation of relatives long after SUDY can reveal a diagnosis in 5/25 (20%) of cases. Since DNA extraction of formalin fixed paraffin embedded samples is unreliable, it is important that blood or tissue samples be stored at autopsy of such cases. This can facilitate establishing a diagnosis and thereby save lives in the future.     

Medical conditions and restraint in patients experiencing excited delirium

Background

Law enforcement restraint–related death is frequently associated with excited delirium syndrome (ExDS). Because such deaths are rare, the pathophysiology underlying ExDS deaths remains unknown, making identification of high-risk situations challenging. This study describes the medical conditions and situations surrounding restraint of individuals identified by law enforcement to be experiencing ExDS.

Methods

Individuals with ExDS as determined by law enforcement officers during use of force encounters over a 3-year period were identified. For subjects who were brought to the emergency department after restraint, medical records and police narratives were reviewed to identify circumstances surrounding restraint, abnormalities found during evaluation, and final diagnoses.

Results

Sixty-six cases were identified, of which 43 had emergency department evaluation. On presentation, 36 (84%) were tachycardic and 3 (7%) were hyperthermic; 35 (77%) had toxicology studies positive for stimulants; 2 (5%) had a pH level less than 7.2, and 5 (12%) had an elevated lactate; and 3 (7%) had a creatinine kinase level higher than 1500 U/L. Two (5%) patients were admitted to the hospital for medical reasons: one had had a field pulseless electrical activity arrest prior to restraint and the other was admitted for rhabdomyolysis.

Conclusion

Officer-identified cases of ExDS infrequently involved individuals requiring extensive restraint or with medical conditions that objectively placed them at high risk for sudden death. The low specificity of this syndrome in predicting risk of sudden death may present a challenge to law enforcement and emergency physicians.     

Perioperative plasma melatonin concentration in postoperative critically ill patients: Its association with delirium

Purpose

Delirium is a common complication in postoperative critically ill patients. Although abnormal melatonin metabolism is thought to be one of the mechanisms of delirium, there have been few studies in which the association between alteration of perioperative plasma melatonin concentration and postoperative delirium was assessed.

Materials

We conducted a prospective observational study to assess the association of perioperative alteration of plasma melatonin concentration with delirium in 40 postoperative patients who required intensive care for more than 48 hours. We diagnosed postoperative delirium using Confusion Assessment Method for the intensive care unit and measured melatonin concentration 4 times (before the operation as the preoperative value, 1 hour after the operation, postoperative day 1, and postoperative day 2).

Results

Postoperative delirium occurred in 13 (33%) of the patients. Although there was no significant difference in preoperative melatonin concentration, Δ melatonin concentration at 1 hour after the operation was significantly lower in patients with delirium than in those without delirium (− 1.1 vs 0 pg/mL, P = .036). After adjustment of relevant confounders, Δ melatonin concentration was independently associated with risk of delirium (odds ratio, 0.50; P = .047).

Conclusions

Delta melatonin concentration at 1 hour after the operation has a significant independent association with risk of postoperative delirium.     

Factors associated with persistent delirium after intensive care unit admission in an older medical patient population

Purpose

This study was designed to identify factors associated with persistent delirium in an older medical intensive care unit (ICU) population.

Materials and Methods

This is a prospective cohort study of 309 consecutive medical ICU patients 60 years or older. Persistent delirium was defined as delirium occurring in the ICU and continuing upon discharge to the ward. The Confusion Assessment Method was used to assess for delirium. Patient demographics, severity of illness, and medication data were collected. Univariate and multivariate analysis were used to assess factors associated with persistent delirium.

Results

Of 309 consecutive admissions to the ICU, 173 patients had ICU delirium, survived the ICU stay, and provided ward data. One-hundred patients (58%) had persistent delirium. In a multivariable logistic regression model, factors significantly associated with persistent delirium included age more than 75 years (odds ratio [OR], 2.52; 95% confidence interval [CI], 1.23-5.16), opioid (morphine equivalent) dose greater than 54 mg/d (OR, 2.90; 95% CI, 1.15-7.28), and haloperidol (OR, 2.88; 95% CI, 1.38-6.02); change in code status to “do not resuscitate” (OR, 2.62; 95% CI 0.95-7.35) and dementia (OR, 1.93; 95% CI 0.95-3.93) had less precise associations.

Conclusions

Age, use of opioids, and haloperidol were associated with persistent delirium. Further research is needed regarding the use of haloperidol and opioids on persistent delirium.     

Serotonin syndrome after therapeutic hypothermia for cardiac arrest: A case series

Aim

To describe causes, manifestations, and diagnosis of serotonin syndrome following therapeutic hypothermia (TH) after cardiac arrest.

Methods

Retrospective case series from a tertiary academic medical center.

Results

Three male patients suffered witnessed out-of-hospital cardiac arrests and were treated with induced TH. Initial cardiac rhythms included asystole in two and ventricular fibrillation in one. Following completion of rewarming, all three developed neurological signs unexpected for their clinical condition. These included rigidity, hyperreflexia, diffuse tremors, ankle clonus, and marked agitated delirium. Patients also were febrile, hypertensive, and tachycardic. A diagnosis of serotonin syndrome was made in all cases and serotonergic medications were discontinued. All three patients recovered consciousness and two made a full neurological recovery. One patient remained dependent on others for activities of daily living at the time of hospital discharge because of short-term memory impairment.

Conclusions

Unexpected neurologic findings and prolonged high fever following recovery from TH can be manifestations of serotonin syndrome rather than post-cardiac arrest anoxic brain injury.     

Effect of telmisartan on QT interval variability and autonomic control in hypertensive patients with left ventricular hypertrophy

Objectives

The aim of the study was to examine the effect of the antihypertensive AT1 receptors antagonist telmisartan on cardiovascular autonomic function and QT dispersion in hypertensive patients with LVH.

Methods

Twenty-five patients (18 males and seven women, mean age 49.8 ± 5.2 years) with mild essential arterial hypertension and LVH were compared with 25 age-matched healthy controls. All the participants underwent a complete clinical examination, including electrocardiogram for QT interval measurements and 24 h ambulatory ECG monitoring for measurement of heart rate variability. The ECG, 24 h ambulatory ECG, and echocardiogram were repeated after eight weeks of treatment.

Results

At baseline, hypertensive patients showed QT dispersion (p < 0.001) and QTc dispersion (p < 0.001) significantly higher than control subjects. An eight-week telmisartan treatment significantly reduced blood pressure (p < 0.0001), without significant change in left ventricular mass. Telmisartan-based treatment induced an increased vagal activity without significant change of sympathetic activity and a reduction of QT dispersion (p < 0.001) and QTc dispersion (p < 0.001).

Conclusions

These data suggest that therapy with telmisartan significantly improves the sympathovagal balance increasing parasympathetic activity, and cardiac electrical stability reducing the heterogeneity of ventricular repolarization in hypertensive subjects. These effects could contribute to reduce arrhythmias as well as sudden cardiac death in at-risk hypertensive patients.     

Electroconvulsive therapy as a treatment for protracted refractory delirium in the intensive care unit—Five cases and a review

Purpose

Delirium in the intensive care unit (ICU) is conventionally treated pharmacologically but can progress into a protracted state refractory to medical treatment—a potentially life-threatening condition in itself.

Methods

We treated 5 cases of severe protracted delirium in our ICU with electroconvulsive therapy (ECT) after failure of conventional medical therapy.

Results

The delirious state of long standing agitation, anxiety, and discomfort was controlled in all patients. Electroconvulsive therapy was effective in controlling delirium in 4 patients. The last patient became calm, relieved of stress, and able to cooperate with the ventilator but remained in a state of posttraumatic amnesia after a head trauma.

Conclusion

Although controversial, ECT is nevertheless recognized as an efficient and safe treatment for various psychiatric illnesses including delirium. Considering the significantly increased mortality and severe cognitive decline associated with delirium in the ICU, we find ECT to be a valuable treatment option for this vulnerable patient population. It can be considered when agitation cannot be controlled with medical treatment, when agitation and delirium make weaning impossible, or prolonged deep sedation the only alternative.     

Brain autopsy findings in intensive care unit patients previously suffering from delirium: A pilot study

Purpose

Delirium affects 50% to 80% of intensive care unit (ICU) patients and is associated with increased risk of mortality. Given the paucity of data reporting the neuropathologic findings in ICU patients experiencing delirium, the purpose of this pilot, hypothesis-generating study was to evaluate brain autopsies in ICU patients who suffered from delirium to explore possible neuroanatomical correlates.

Materials and Methods

Using delirium databases at Vanderbilt University, we identified patients who had delirium in the ICU and subsequently died and received a brain autopsy during the same hospitalization. Brain autopsy reports were collected retrospectively on all 7 patients who met these criteria.

Results

Patients' mean age was 55 (SD ± 8.4) years, and median number of days spent with delirium was 7 (±5 interquartile range). In 6 (86%) of 7 patients, pathologic lesions normally attributed to hypoxia or ischemia were noted in the hippocampus, pons, and striatum. Hippocampal lesions represented the most common neuropathologic site of injury, present in 5 (71%) of 7 patients.

Conclusions

Hypoxic ischemic injury in multiple locations of the brain was a common finding. The biological plausibility of hippocampal lesions as a contributor to long-term cognitive impairment warrants postmortem investigation on a larger scale with comparison to patients not experiencing ICU delirium.     

Prevalence and Outcome of High-Risk QT Prolongation Recorded in the Emergency Department from an Institution-Wide QT Alert System

Background

QT prolongation is an independent risk factor for sudden death, stroke, and all-cause mortality. However, additional studies have shown that in certain settings, QT prolongation may be transient and a result of external factors.

Pitfalls in the Care of the Psychiatric Patient in the Emergency Department

Background

Care of the psychiatric patient in the Emergency Department (ED) is evolving. As with other disease states, there are a number of pitfalls that complicate the care of the psychiatric patient.

Objective

The purpose of this article is to update Emergency Physicians concerning the pitfalls in caring for the psychiatric patient, and possible solutions to deal with these pitfalls.

Discussion

The article will address the burden of the psychiatric patient, staff attitudes, medical clearance process, treatment of the agitated patient, suicidal patients, and admission decisions.

Conclusions

Alternative care resources, collaboration with Psychiatry, staff education, improvement in the medical clearance process, proper use of restraint and seclusion, and appropriate choice of medication for agitated patients can help avoid some of the top pitfalls in the care of the psychiatric patient in the ED.     

Emotional consequences of intensive care unit delirium and delusional memories after intensive care unit admission: a systematic review

Purpose

The aim of this study was to review literature exploring the emotional consequences of delirium and delusional memories in intensive care unit patients.

Methods

A systematic review was performed using PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and PsychINFO.

Results

Fourteen articles were eligible for this review. Five of them assessed delirium during intensive care unit admission, and the remainder assessed delusional memories during or after admission. No association was found for delirium and adverse emotional outcome. Data regarding delusional memories and emotional outcome were heterogenic. Some studies presented worse scores on posttraumatic stress disorder screening tools in patients with delusional memories, whereas other studies found better scores in patients with delirium or delusional memories.

Conclusions

Based on current literature, no relationship could be shown for delirium and emotional outcome. Regarding delusional memories and adverse emotional outcome, results were in contradiction.     

A multifaceted educational intervention to prevent delirium in older inpatients: A before and after study

Background

Systematically targeting modifiable risk factors for delirium may reduce its incidence. However, research interventions have not become part of routine clinical practice. Particular approaches to the education of clinical staff may improve their practice and patient outcomes.

Objectives

To evaluate the effectiveness of a multifaceted educational program in preventing delirium in hospitalised older patients and improving staff practice, knowledge and confidence.

Design

A before and after study.

Setting

A 22-bed general medical ward of a district hospital in Sydney, Australia.

Participants

Patients were aged 65 years and over and not delirious upon admission. Of 568 eligible patients, 129 were recruited pre-intervention (3 withdrew initial consent) and 129 patients post-intervention.

Methods

Prior to the intervention, in order to establish a baseline, patients were assessed early after admission and again at discharge. The intervention was a one-hour lecture on delirium focusing on prevention for medical and nursing staff followed by weekly interactive tutorials with delirium resource staff and ward modifications. Following the initial education session, data were gathered in a second group of medical ward patients at the same time-points to ascertain the effectiveness of the intervention. Pre and post-intervention data were analysed to determine change in staff objective knowledge and self-ratings of confidence and clinical practice in relation to delirium. The main outcome measures were incident delirium and change in staff practice, confidence and knowledge.

Results

The mean age of patients was 81. The pre and post-intervention groups were comparable, aside from greater co morbidity in the pre-intervention group (F(1, 253) = 9.20, p = 0.003). Post-intervention there was a significant reduction in incident delirium (19% vs. 10.1%, X² = 4.14, p = 0.042), and improved function on discharge (mean improvement 5.3 points, p < 0.001, SD 13.31, 95% CI −7.61 to −2.97). Staff objective knowledge of delirium improved post-intervention and their confidence assessing and managing delirious patients. Staff addressed more risk factors for delirium post-intervention (8.1 vs. 9.8, F(1, 253) = 73.44, p < 0.001).

Conclusions

A low-cost educational intervention reduced the incidence of delirium and improved function in older medical patients and staff knowledge and practice addressing risk factors for delirium. The program is readily transferable to other settings, but requires replication due to limitations of the before and after design.     

Functional electrical stimulation with cycling in the critically ill: A pilot case-matched control study

Purpose

The purpose was to determine (a) safety and feasibility of functional electrical stimulation (FES)-cycling and (b) compare FES-cycling to case-matched controls in terms of functional recovery and delirium outcomes.

Materials and methods

Sixteen adult intensive care unit patients with sepsis ventilated for more than 48 hours and in the intensive care unit for at least 4 days were included. Eight subjects underwent FES-cycling in addition to usual care and were compared to 8 case-matched control individuals. Primary outcomes were safety and feasibility of FES-cycling. Secondary outcomes were Physical Function in Intensive Care Test scored on awakening, time to reach functional milestones, and incidence and duration of delirium.

Results

One minor adverse event was recorded. Sixty-nine out of total possible 95 FES sessions (73%) were completed. A visible or palpable contraction was present 80% of the time. There was an improvement in Physical Function in Intensive Care Test score of 3.9/10 points in the intervention cohort with faster recovery of functional milestones. There was also a shorter duration of delirium in the intervention cohort.

Conclusions

The delivery of FES-cycling is both safe and feasible. The preliminary findings suggest that FES-cycling may improve function and reduce delirium. Further research is required to confirm the findings of this study and evaluate the efficacy of FES-cycling.     

Effect of preadmission sunlight exposure on intensive care unit–acquired delirium: A multicenter study

Purpose

It is assumed that there is a relation between light exposure and delirium incidence. The aim of our study was to determine the effect of prehospital light exposure on the incidence of intensive care unit (ICU)–acquired delirium.

Materials and Methods

Data from 3 ICUs in the Netherlands were analyzed retrospectively. Delirium was assessed with the Confusion Assessment Method for the ICU. Daily light intensity data were obtained from meteorological stations in the vicinity of the 3 hospitals. The association between light intensity and delirium incidence was analyzed using logistic regression analysis adjusting for known covariates for delirium.

Results

Data of 3198 patients, aged (mean ± SD) 61.9 ± 15.3 years with Acute Physiology and Chronic Health Evaluation II score 16.4 ± 6.6 were analyzed. Delirium incidence was 31.2% and did not vary significantly throughout the year. Twenty-eight-day preadmission photoperiod was highest in spring and lowest in winter; however, no association between light exposure and delirium incidence was found (odds ratio, 1.00; 95% confidence interval, 0.99-1.00; P = 0.72). Furthermore, delirium was significantly associated with age, infection, use of sedatives, Acute Physiology and Chronic Health Evaluation II score, and diagnosis of neurological disease or trauma.

Conclusions

The incidence of delirium does not differ per season and prior sunlight exposure does not play a role of importance in the development of ICU-acquired delirium.     

Evaluation of a sound environment intervention in an ICU: A feasibility study

Background

Currently, it is well known that the sound environment in intensive care units (ICU) is substandard. Therefore, there is a need of interventions investigating possible improvements. Unfortunately, there are many challenges to consider in the design and performance of clinical intervention studies including sound measurements and clinical outcomes.

Safety and efficacy of intravenous combination sedatives in the ED

Objective

The objective of the study is to determine the safety of intravenously administered combination sedatives in the emergency department (ED).

Methods

This was a retrospective study of alcohol-intoxicated patients in the ED. We examined the incidence of adverse events in agitated patients who received combination sedatives intravenously and compared the efficacy of combination sedatives and single-agent sedatives.

Results

Of 1300 patient visits, there was a single adverse event, a dystonic reaction, in the combination sedative group, for an adverse event rate of less than 1%. Patients who received combination sedatives were less likely to require a second dose of sedative medication than patients who received a single-agent sedative (21% vs 44%).

Conclusions

Combination sedatives appear to be safe when administered intravenously in the ED. Combination sedatives may be more effective than single-agent sedatives in agitated alcohol-intoxicated patients.     

Risk factors for the development of early-onset delirium and the subsequent clinical outcome in mechanically ventilated patients

Objectives

The aim of the study was to investigate the risk factors of developing early-onset delirium in mechanically ventilated patients and determine the subsequent clinical outcomes.

Methods

Confusion assessment method for the intensive care unit (ICU) was used to assess the enrolled mechanically ventilated patients for delirium. The risk factors of developing delirium and clinical outcomes were determined in these subjects.

Results

Delirium was present in 31 (21.7%) of 143 patients in the first 5 days. In multivariable analysis, hypoalbuminemia (odds ratio, 5.94; 95% confidence interval, 1.23-28.77) and sepsis (odds ratio, 3.65; 95% confidence interval, 1.03-12.9) increased the risk of developing delirium in mechanically ventilated patients. The patients with delirium had a higher in-hospital mortality (67.7% vs 33.9%, respectively; P = .001) and longer duration of mechanical ventilation (19.5 ± 15.8 vs 9.3 ± 8.8 days, respectively; P = .003) than patients without delirium. The incidence of nosocomial pneumonia was increased in delirious patients (64.5% vs 38.4%, P = .01) compared with nondelirious patients, whereas the lengths of ICU or hospital stay were similar between both groups.

Conclusions

Mechanically ventilated patients with sepsis or hypoalbuminemia were more vulnerable to develop delirium in their early stay in the ICU. Early-onset delirium is associated with prolonged duration of mechanical ventilation and higher incidence of nosocomial pneumonia, leading to a higher mortality.     

Validity and Reliability of the CAM-ICU Flowsheet to diagnose delirium in surgical ICU patients

Purpose

Delirium occurs frequently in critical care but often remains undiagnosed because delirium monitoring is often dismissed as being too time-consuming. This study determined the validity and reliability of the “CAM-ICU Flowsheet,” a practical, time-sparing algorithm to assess the 4 delirium criteria in intubated patients.

Materials and Methods

With permission from our institution's ethics committee, patients of a 31-bed surgical intensive care unit department were screened for delirium (1) by a psychiatrist as the reference rater using the 4 delirium criteria of the Diagnostic and Statistical Manual of Mental Diseases, Fourth Edition (DSM-IV), and (2) by 2 physician investigators using a German translation of the CAM-ICU Flowsheet.

Results

Fifty-four surgical ICU patients underwent the complete protocol assessment with paired observations; 46% were diagnosed with delirium by the reference rater (n = 25), 9% had hyperactive delirium (n = 5), and 37% were hypoactive (n = 20). The CAM-ICU Flowsheet investigators had sensitivities of 88% (95% confidence interval, 69%-98%) and 92% (74%-99%), specificities of 100% (85%-100%), very high interrater reliability (κ, 0.96; 0.87-1.00), and needed 50 seconds (interquartile range, 40-120 seconds) in patients with delirium vs 45 seconds (interquartile range, 40–75 seconds) in those without delirium to complete assessments.

Conclusions

The CAM-ICU Flowsheet has high sensitivity, high specificity, and very high interrater reliability. False-negative ratings can occur infrequently and mostly reflect the fluctuating course of delirium. The CAM-ICU Flowsheet is a valid, reliable, and quickly performed bedside delirium instrument.