To: Delirium and sleep quality in the intensive care unit: the role of melatonin

To the Editor

The interesting article by Soares et al. on delirium and sleep hygiene in the intensive care unit (ICU) and the role of melatonin(¹) raises concerns that should be discussed.

The first point is that sleep hygiene and the risk of delirium in the ICU depend not only on age, comorbidities, disease severity, environment, and therapeutic interventions,(¹) but also on the type of ICU, reason for admission, history, and genetic factors. Regarding the ICU type, the risk of sleep deprivation or delirium may depend primarily on whether the patient is, for example, in a neurological ICU or a cardiac ICU. Patients with cerebral disease are more likely to experience sleep disturbances and develop delirium compared to patients in a cardiac ICU. Patients with a history of psychiatric disease (e.g., depressive or psychotic episodes, social withdrawal, Hikikamori) may be at higher risk of poor sleep quality or delirium in the ICU than patients without. Patients with hereditary hyperammonemia, trisomy 21, spinocerebellar ataxia, Niemann-Pick disease, and several other genetic disorders may be at higher risk of developing delirium or sleep deprivation than patients without a genetic disease.(²)

The second point is that sleep can be disturbed not only by the external influences of light and noise but also by temperature, humidity, diet, fluid intake, number of probes attached to the patient, and the amount of electrosmog.(³) Since ICUs are equipped with numerous electronic devices and nurses, doctors, and patients carry their mobile phones, laptops, and tablets with them 24 hours a day, everyone in the ICU, including patients, is exposed to these external stressors, which can inevitably and severely affect biorhythms. Catheters, probes, and sensors attached to the patient can prevent relaxation due to permanent haptic disturbances.

The third point is that internal causes of sleep deprivation, such as overstimulation due to increased secretion of cortisol or adrenaline, can lead to patients being unable to fall asleep and stay asleep. Stress with the consecutive secretion of stress hormones can arise not only from external stressors but also from internal stress factors, such as pain, fear, insecurity, depression, hopelessness, unpleasant physical sensations, discomfort with the situation, delusions, or lack of information about the current situation, and being torn away from familiar surroundings.

A fourth point that has not been considered as affecting sleep quality and the likelihood of developing delirium is medication withdrawal. There is a high risk of sleep deprivation and delirium, particularly in patients weaned from mechanical ventilation. Withdrawal of analgesics, sedatives (especially benzodiazepines), relaxants, antiepileptics, hypnotics, or adrenergics can result in withdrawal syndromes, which in turn lead to sleep disorders and delirium.

The fifth point is that delirium can be easily missed in the ICU.(⁴) Particularly in sedated and relaxed patients, the typical manifestations of delirium may not occur unless mechanical ventilation, sedation, and muscle relaxation are stopped. Even more challenging to diagnose is hypoactive delirium, in which there are no motor symptoms or hyperactivity but vegetative overstimulation, which nevertheless leads to disorientation and confusion.

The sixth point is that hyperactive or hypoactive delirium is a severe psychiatric disease that should not be treated with melatonin but with neuroleptics (e.g., risperidone, haloperidol) and, if necessary, benzodiazepines or propofol.(⁵,⁶)

It is highly questionable whether improving sleep hygiene with melatonin can prevent the development of delirium. All external and internal risk factors must be eliminated to prevent delirium, and if delirium becomes manifest, it must be treated acutely by a psychiatrist. Delirium is an emergency.

• Publisher's note

REFERENCES

• ¹ Soares PHR, Serafim RB. Delirium and sleep quality in the intensive care unit: the role of melatonin. Crit Care Sci. 2024;36:e20240083en.
• ² Quirós-Mata M, Delaney J, Russell R, Sabapathy C, Stankova J, Traube C. Delirium in a patient with trisomy 21 undergoing chemotherapy for high-risk acute lymphoblastic leukemia. Pediatr Blood Cancer. 2023;70(5):e30176.
• ³ Wesselius HM, van den Ende ES, Alsma J, Ter Maaten JC, Schuit SC, Stassen PM, et al.; "Onderzoeks Consortium Acute Geneeskunde" Acute Medicine Research Consortium. Quality and quantity of sleep and factors associated with sleep disturbance in hospitalized patients. JAMA Intern Med. 2018;178(9):1201-8.
• ⁴ Tuomisto A, Kennedy P. Improving the recognition and assessment of ICU delirium. J Contin Educ Nurs. 2024;55(11):530-4.
• ⁵ Prendergast NT, Tiberio PJ, Girard TD. Treatment of delirium during critical illness. Annu Rev Med. 2022;73(1):407-21.
• ⁶ Bandyopadhyay A, Yaddanapudi LN, Saini V, Sahni N, Grover S, Puri S, et al. Efficacy of melatonin in decreasing the incidence of delirium in critically ill adults: a randomized controlled trial. Crit Care Sci. 2024;36:e20240144en.

Publication Dates

• Publication in this collection
  16 June 2025
• Date of issue
  2025

History

• Received
  09 Sept 2024
• Accepted
  13 Sept 2024