Despite technological advances in surgery and anesthesia during the last few decades, the incidence of postoperative cognitive dysfunction remains a relatively common complication in surgical patients. After surgery, elderly patients in particular often exhibit a transient reversible state of cerebral cognitive alterations. Anesthetics administered as part of a surgical procedure may alter the patient's behavioral state by influencing brain activity. This concise report will address the scientific evidence on the relationship between postoperative cognitive dysfunctions and the most common inhalational agents currently used in anesthesia (volatile anesthetics: isoflurane, desflurane and sevoflurane, gaseous nitrous oxide). The available literature does not allow definitive conclusions to be drawn on the possible differences between anesthetics in relation to the subsequent occurrence of cognitive dysfunction. However, such information is crucial to improve anesthesia performance and patient safety, as well as outcomes.

The cholinergic system is one of the most important modulatory neurotransmitter systems in the brain. Alterations of the transmission communicators are accompanied by reduction of the cortical activity, which is associated with a learning and memory deficit. Down's syndrome is a pathological condition characterized by a high number of abnormalities that involve the brain. The cholinergic system is involved in alterations of the neurological system such as severe learning difficulties. To explain these alterations, important results are obtained from studies about murine trisomy 16 (animal model of Down's syndrome). The results obtained provide useful elements in the improvement of knowledge about the neurological and neurotransmissional alterations that are responsible for the neurobiological characteristics of Down's syndrome. These data potentially justify, in these patients, the therapeutic use of drugs that are principally administered to improve the severe learning difficulties of people with Alzheimer's disease, and suggest a trend which generates a hypothesis worthy of further exploration.

Hypothyroidism and hyperthyroidism are commonly present conditions in adults, leading to neurological symptoms, affecting the central and peripheral nervous system, and to neurocognitive impairment. Several studies investigated a possible association between Alzheimer's disease (AD) and thyroid dysfunctions. Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in AD. Moreover, thyroid hormones negatively regulate expression of the amyloid-β protein precursor (AβPP), which plays a key role in the development of AD. A condition, the so called euthyroid sick syndrome (ESS), characterized by reduced serum T3 and T4 concentrations without increased serum thyroid stimulation hormone secretion, occurs within hours after major surgery. After surgery, elderly patients often exhibit a transient, reversible state of cognitive alterations. Delirium occurs in 10-26% of general medical patients over 65, and it is associated with a significant increase in morbidity and mortality. Modifications in thyroid hormone functioning may take place as a consequence of psycho-physical stress caused by surgery, and probably as a consequence of reduced conversion of T4 into T3 by the liver engaged in metabolizing anesthetic drugs. Therefore, modifications of thyroid hormones post-surgery, might play a role in the pathogenesis of postoperative cognitive dysfunction.

Opioids are used in clinical practice for sedation, anesthesia, and analgesia. Their effects depend on their pharmacokinetic and pharmacodynamic characteristics. The liver is the major site for the biotransformation of most opioids. The major metabolic pathway is oxidation. Metabolism influences distribution, clearance, onset, and offset of opioid drugs. Action also depends on the coupling of opioids with the class of receptors involved and on localization of specific receptors. Three major types of opioid receptors, designated as μ, ẟ, and ϰ, present in the central nervous system, are coupled to G proteins and inhibit adenylyl cyclase. Down’s syndrome is a congenital condition characterized by mental retardation and particular physical features. Neurotransmission alterations are important. Alteration in the concentration of opioids in the cortex of these patients has been demonstrated. Neurobiological abnormalities and, in some, abnormalities in the neurotransmission systems, anxiety, and, in particular, nociception all suggest that structural and functional alterations of opioid receptors may be present. A clear knowledge of these multiple abnormalities is essential for skillful management of the perioperative period and for a good outcome for patients with Down’s syndrome.

Pain is a homeostatic mechanism that intervenes to protect the organism from harmful stimuli that could damage its integrity. It is made up of two components: the sensory-discriminative component, which identifies the provenance and characteristics of the type of pain; and the affective-motivational component, on which emotional reflexes, following the painful sensation, depend.There is a system for pain control at an encephalic and spinal level, principally made up of the periaqueductal grey matter, the periventricular area, the nucleus raphe magnus, and the pain-inhibition complex situated in the posterior horns of the spinal cord. Through the activation of these pain-control systems, the nervous system suppresses the afference of pain signals. Endogenous opioids represent another analgesic system.In the course of various studies on pain transmission in Down patients, the reduced tolerance of pain and the incapacity to give a qualitative and quantitative description emerged in a powerful way. All of these aspects cause difficulty in evaluating pain. This is linked to several learning difficulties. However, it cannot be excluded that in these anomalies of pain perception, both the anatomical and the neurotransmitter alteration, typical of this syndrome, may hold a certain importance.This fact may have important clinical repercussions that could affect the choice of therapeutic and rehabilitative schemes for treatment of pathologies in which pain is the dominant symptom, such as postoperative pain. It could influence research on analgesics that are more suitable for these patients, the evaluation of the depth of analgesia during surgical operation, and ultimately, absence of obvious pain manifestations. In conclusion, alterations of the central nervous system, neurotransmitters, pain transmission, and all related problems should be considered in the management of pain in patients with Down's syndrome, especially by algologists and anesthesiologists.