Delirium, insomnia in hospitalization and ramelteon

Ramelteon acts on a highly selective melatonin (MT1/MT2) receptor agonist. During delirium in postoperative and critically ill patients, a disruption of the sleep-wake cycle is frequently observed. Melatonin has a key role in the regulation of the sleep-wake cycle, so this raised the hypothesis that alterations in the metabolism of melatonin might play an important role in the development of delirium. Ramelteon and exogenous melatonin may have a prophylactic treatment for frail older persons at high risk for delirium that is safe, effective, and easily implementable in daily practice. However, there is currently insufficient evidence that ramelteon and exogenous melatonin is effective in preventing or treating postoperative delirium and sleep disorders in the critically ill patient.     

Melatonin therapy to improve nocturnal sleep in critically ill patients: encouraging results from a small randomised controlled trial

Introduction  

Sleep disturbances are common in critically ill patients and when sleep does occur it traverses the day-night periods. The reduction in plasma melatonin levels and loss of circadian rhythm observed in critically ill patients receiving mechanical ventilation may contribute to this irregular sleep-wake pattern. We sought to evaluate the effect of exogenous melatonin on nocturnal sleep quantity in these patients and, furthermore, to describe the kinetics of melatonin after oral administration in this patient population, thereby guiding future dosing schedules.     

Does improving sleep for the critically ill reduce the incidence and duration of delirium? An evidence-based review

Delirium is associated with poor patient outcome. Critical-care nurses maintain that patients with disrupted sleep appear to develop delirium. We sought to explore whether improving sleep in the critically ill patients reduced the incidence and duration of delirium. Our review of five relevant studies suggests that there is low-quality evidence that improving sleep may reduce the incidence of delirium. The bidirectional association between delirium and sleep stymies research in this area, and thus, establishing cause and effect, is difficult. Research exploring other patient-centred outcomes, such as pain intensity, suggests that enhancing sleep may improve these outcomes.     

Sleep and circadian rhythm disturbances in intensive care unit (ICU)-acquired delirium: a case–control study

ObjectiveThe relationships among sleep, circadian rhythm, and intensive care unit (ICU)-acquired delirium are complex and remain unclear. This study aimed to examine the pathophysiological mechanisms of sleep and circadian rhythm disturbances in patients with ICU-acquired delirium.MethodsThis study included critical adult patients aged 18 to 75 years who were treated in the ICU. Twenty-four-hour polysomnography was performed and serum melatonin and cortisol levels were measured six times during polysomnography. Receiver operating characteristic curves and binomial logistic regression were used to evaluate the potential of sleep, melatonin, and cortisol as indicators of delirium in the ICU.ResultsPatients with delirium (n = 24) showed less rapid eye movement (REM) sleep compared with patients without delirium (n = 24, controls). Melatonin levels were lower and cortisol levels were higher in the delirium group than in the control group. REM sleep, melatonin, and cortisol were significantly associated with delirium. The optimal cutoff values of REM sleep and mean melatonin and cortisol levels that predicted delirium were ≤1.05%, ≤422.09 pg/mL, and ≥212.14 ng/mL, respectively.ConclusionsREM sleep, and melatonin and cortisol levels are significantly associated with the risk of ICU-acquired delirium. Improved sleep and readjustment of circadian rhythmicity may be therapeutic targets of ICU-acquired delirium.     

Do earplugs stop noise from driving critical care patients into delirium?

ABSTRACT: Quality sleep is a problem for the critically ill who are cared for in an environment where interventions night and day are common, staff members are constantly present in relatively high numbers, and treatment is accompanied by a range of changing warning tones and alarms and lights. These critical care units are generally designed without a focus on patient comfort, sleep, and rest and often lack access to appropriate natural daylight. To add to this problem, critical illness, particularly sepsis, disrupts circadian rhythms and sleep patterns, and disruption of circadian rhythms, in turn, impairs immunity and contributes to delirium. In a randomized controlled trial in the previous issue of Critical Care, Van Rompaey and colleagues have intervened to reduce noise, which is a key factor in this disruption, by having patients use earplugs at night. Delirium was assessed by using the NEECHAM (Neelon and Champagne) confusion scale, and sleep perception was assessed by patients' responses to a set of five questions. After the first night, patients reported a better sleep perception and the occurrence of delirium was reduced (hazard ratio of 0.47 for the development of delirium) or was delayed. The study did not quantify adequacy of pain control in post-surgical patients and used patient reporting to assess sleep. Whether patients were receiving respiratory or other organ support was not reported. The potential benefit of earplugs is an important practical finding that could be implemented in most intensive care units.     

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.     

Bench-to-bedside review: Delirium in ICU patients - importance of sleep deprivation

Delirium occurs frequently in critically ill patients and has been associated with both short-term and long-term consequences. Efforts to decrease delirium prevalence have been directed at identifying and modifying its risk factors. One potentially modifiable risk factor is sleep deprivation. Critically ill patients are known to experience poor sleep quality with severe sleep fragmentation and disruption of sleep architecture. Poor sleep while in the intensive care unit is one of the most common complaints of patients who survive critical illness. The relationship between delirium and sleep deprivation remains controversial. However, studies have demonstrated many similarities between the clinical and physiologic profiles of patients with delirium and sleep deprivation. This article aims to review the literature, the clinical and neurobiologic consequences of sleep deprivation, and the potential relationship between sleep deprivation and delirium in intensive care unit patients. Sleep deprivation may prove to be a modifiable risk factor for the development of delirium with important implications for the acute and long-term outcome of critically ill patients.     

Sedative and analgesic medications: risk factors for delirium and sleep disturbances in the critically ill

Sedatives and analgesics are routinely used in critically ill patients, although they have the potential for side effects, such as delirium and sleep architecture disruption. Although it should be emphasized that these medications are extremely important in providing patient comfort, health care professionals must also strive to achieve the right balance of sedative and analgesic administration through greater focus on reducing unnecessary or overzealous use. Ongoing clinical trials should help us to understand whether altering the delivery strategy, via daily sedation interruption, or protocolized target-based sedation or changing sedation paradigms to target different central nervous system receptors can affect cognitive outcomes and sleep preservation in our critically ill patients.     

Sleep deprivation in critical illness: its role in physical and psychological recovery

Critically ill patients frequently experience poor sleep, characterized by frequent disruptions, loss of circadian rhythms, and a paucity of time spent in restorative sleep stages. Factors that are associated with sleep disruption in the intensive care unit (ICU) include patient-ventilator dysynchrony, medications, patient care interactions, and environmental noise and light. As the field of critical care increasingly focuses on patients' physical and psychological outcomes following critical illness, understanding the potential contribution of ICU-related sleep disruption on patient recovery is an important area of investigation. This review article summarizes the literature regarding sleep architecture and measurement in the critically ill, causes of ICU sleep fragmentation, and potential implications of ICU-related sleep disruption on patients' recovery from critical illness. With this background information, strategies to optimize sleep in the ICU are also discussed.     

Use of complementary and alternative therapies to promote sleep in critically ill patients

The efficacy of complementary and alternative therapies for sleep promotion in critically ill patients is largely unexamined. We found only seven studies (three on environmental interventions and one each on massage, music therapy, therapeutic touch, and, melatonin) that examined the effect of complementary and alternative therapies. A number of studies, however, have shown that massage, music therapy. and therapeutic touch promote relaxation and comfort in critically ill patients, which likely leads to improved sleep. Massage, music therapy, and therapeutic touch are safe for critically ill patients and should be routinely applied by ICU nurses who have received training on how to administer these specialized interventions. Environmental interventions, such as reducing noise, playing white noise such as ocean sounds, and decreasing interruptions to sleep for care, also are safe and logical interventions that ICU nurses should use to help patients sleep. Progressive muscle relaxation has been extensively studied and shown to be efficacious for improving sleep in persons with insomnia; however, progressive muscle relaxation requires that patients consciously attend to relaxing specific muscle groups and practice these techniques, which may be difficult for critically 11 patients. We do not currently recommend aromatherapy and alternative sedatives, such as valerian and melatonin, for sleep promotion in critically ill patients because the safety of these substances is unclear. In summary, we recommend that ICU nurses implement music therapy, environmental interventions, therapeutic touch, and relaxing massage to promote sleep in critically ill patients. These interventions are safe and may improve patient sleep, although randomized controlled trials are needed to test their efficacy. Aromatherapy and alternative sedatives require further investigation to determine their safety and efficacy.     

Sleep in the intensive care unit

Abnormalities of sleep are extremely common in critically ill patients, but the mechanisms are poorly understood. About half of total sleep time occurs during the daytime, and circadian rhythm is markedly diminished or lost. Judgments based on inspection consistently overestimate sleep time and do not detect sleep disruption. Accordingly, reliable polygraphic recordings are needed to measure sleep quantity and quality in critically ill patients. Critically ill patients exhibit more frequent arousals and awakenings than is normal, and decreases in rapid eye movement and slow wave sleep. The degree of sleep fragmentation is at least equivalent to that seen in patients with obstructive sleep apnea. About 20% of arousals and awakenings are related to noise, 10% are related to patient care activities, and the cause for the remainder is not known; severity of underlying disease is likely an important factor. Mechanical ventilation can cause sleep disruption, but the precise mechanism has not been defined. Sleep disruption can induce sympathetic activation and elevation of blood pressure, which may contribute to patient morbidity. In healthy subjects, sleep deprivation can decrease immune function and promote negative nitrogen balance. Measures to improve the quantity and quality of sleep in critically ill patients include careful attention to mode of mechanical ventilation, decreasing noise, and sedative agents (although the latter are double-edged swords).     

Melatonin as a regulator of human sleep and circadian systems

Melatonin(N-acetyl-5-methoxytryptamine) is synthesized from tryptophan and is intensively secreted into the blood only in darkness (nighttime) by the pineal gland. Melatonin is not only the most reliable marker of internal circadian phase but also a potent sleep-promoting and circadian phase regulatory agent in humans. There is evidence that daytime administered melatonin is able to exhibit short-acting hypnagogic effect and phase-shifting of the circadian rhythms such that sleep timing and associated various physiological functions realign at a new desired phase. Under favor of these properties, melatonin and melatonin receptor agonists have been shown to be potent therapeutic agents for the treatment of circadian rhythm sleep disorders and some type of insomnia.     

Sedation and paralysis during mechanical ventilation

Treatment of anxiety and delirium, provision of adequate analgesia, and, when necessary, amnesia in critically ill patients is humane and may reduce the incidence of post-traumatic stress disorders. Injudicious use of sedatives and paralytics to produce a passive and motionless patient, however, may prolong weaning and length of stay in the intensive care unit. This report reviews indications and choices for pharmacologic treatment of anxiety, delirium, agitation, and provision of anesthesia in critically ill patients. The choice of pharmacologic agents is made difficult by complex or poorly understood pharmacokinetics, drug actions, and adverse effects in critically ill patients. Advantages, adverse effects, and limitations of drug treatment, including use of neuromuscular blocking drugs and use of sedatives and analgesia during the withdrawal of life-sustaining measures are reviewed.     

Circadian rhythm sleep disorders

Individuals who have circadian rhythm sleep disorders present with symptoms of insomnia or excessive sleepiness and complain of an inability to sleep at their desired time. Although the primary etiology of these disorders is a misalignment between the endogenous circadian clock and the external environment, social and behavioral factors can also play important roles in perpetuating or exacerbating these disorders. Currently, the management of circadian rhythm disorders is limited to the use of bright light and melatonin to realign the circadian clock with the desired sleep time.However, as the understanding of the physiologic and genetic basis of sleep and circadian rhythm regulation advances, even more practical and effective treatments should become available.     

Melatonin, the pineal gland and their implications for headache disorders

There is now evidence that melatonin may have a role in the biological regulation of circadian rhythms, sleep, mood, and ageing. Altered melatonin levels in cluster headache and migraine have been documented. Melatonin mechanisms are related to headache pathophysiology in many ways, including its anti-inflammatory effect, toxic free radical scavenging, reduction of proinflammatory cytokine up-regulation, nitric oxide synthase activity and dopamine release inhibition, membrane stabilization, GABA and opioid analgesia potentiation, glutamate neurotoxicity protection, neurovascular regulation, serotonin modulation, and the similarity of chemical structure to that of indomethacin. Treatment of headache disorders with melatonin and other chronobiotic agents is promising. A double-blind, placebo-controlled trial shows melatonin is effective in cluster headache prevention, other studies also show benefit in other disorders. Melatonin plays an important role in headache disorders, offering new avenues for studying their pathophysiology and treatment.     

Improving Sleep Hygiene to Decrease Delirium Among Critically Ill Patients

A sleep hygiene protocol to reduce risks for delirium among critically ill patients in a transplant intensive care unit was implemented in an urban hospital in the Upper Midwest. The project occurred over a 1-month time frame. The project evaluated the number of hours of uninterrupted sleep, overall participation in therapies and activity, agitation, and confusion scores using standard, validated tools. Staff education was provided pre- and postproject implementation. Pre- and postimplementation surveys were used to assess the knowledge of staff and evaluation of the project. Project results demonstrated effectiveness in reducing sleep disturbance and the risk for delirium.     

Clinical update: melatonin and sleep disorders

The hormone melatonin is increasingly used for the treatment of certain sleep disorders, particularly those related to disturbed biological rhythms. This article summarises current knowledge of its mechanism of action and identifies situations where there is good evidence for its efficacy. The authors provide advice, based on their own experience and consistent published data, concerning the dose range of melatonin to be used and the critically important question of the timing of treatment. Anecdotal evidence for the use of melatonin needs to be replaced by data from well-controlled, preferably multi-centre, randomised clinical trials.     

Identification and management of delirium in the critically ill patient with cancer

Rather than a specific entity, delirium is at the midpoint on a spectrum of potential mental status changes that ranges from full consciousness to deep coma. The extremes are relatively easy to recognize, but other points along the spectrum may go unrecognized or be misdiagnosed. If recognized and treated expeditiously, delirium may be reversed in some patients. It is imperative that those caring for critically ill patients with cancer have the knowledge and tools necessary to identify and manage delirium appropriately. Although all critically ill patients are at risk for delirium, cancer presents additional assaults to the central nervous system via direct tumor invasion or iatrogenic provocations. This article describes delirium in cancer, and addresses diagnostic and management issues across the course of the disease.     

Oxidative stress and role of antioxidant supplementation in critical illness

Sepsis or systemic inflammatory response (SIRS) to infection or to non-infectious stimuli such as trauma, surgery, pancreatitis or ischemia, is an increasingly common cause of morbidity and mortality in patients on intensive therapy unit (ITU). In critically ill patients, this accounts for 10% to 50% of all deaths. Oxidative stress has an important role in the development and manifestations of SIRS. Oxidative stress is an imbalance between the free radical production and the antioxidant defense. In critical illness, overwhelming inflammatory mediator response to infective or non-infective stimuli results in excessive production of free radicals (FR). The action of FR is normally limited by the antioxidant defense system of the body, but in critically ill patients the antioxidant capacity is likely to be compromised. Hence, provision of antioxidants to critically ill patients may help in removing the FR and therefore improving the clinical outcome. However, no study has yet provided conclusive evidence of the beneficial effect of antioxidant supplementation in critically ill patients. The clinical evidence provided so far shows that there are several factors which might determine the efficacy of antioxidant supplementation in critically ill patients. There is a need for large multicentre prospective randomized control trials to assess the effects of different types and doses of antioxidant supplementation in selected groups of patients with different types of critical illness.