Delirium in the intensive care unit: an under-recognized syndrome of organ dysfunction

The intensivist should think of delirium, or acute central nervous system dysfunction, as the brain's form of "organ dysfunction.' Delirium is extremely common in intensive care unit (ICU) patients due to factors such as comorbidity, critical illness, and iatrogenesis. This complication of hospital stay is extremely hazardous in older persons and is associated with prolonged hospital stays, institutionalization, and death. Neurologic dysfunction compromises patients' ability to be removed from mechanical ventilation or achieve full recovery and independence. Yet ICU nurses and physicians are usually unaware of the presence of hypoactive delirium and only recognize this disturbance in agitated patients (hyperactive delirium). More importantly, there are few studies that have included ICU patients in the assessment or prevention of delirium. This article reviews the definition and salient features of delirium, its primary risk factors, a newly validated instrument for delirium assessment that is being developed for ICU nurses and physicians, and pharmacological agents associated with the development of delirium and used in its management.     

Chronic lithium treatment decreases neuronal activity in the nucleus accumbens and cingulate cortex of the rat.

Although the efficacy of lithium as a mood stabilizer is well documented, the mechanism of its therapeutic effect associated with prolonged treatment remains unknown. Identifying discrete brain regions and neural pathways that are functionally altered following long-term lithium treatment is central to elucidating a psychotherapeutic mechanism. We have used a sensitive and quantitative histochemical assay for the determination of cytochrome oxidase (CO) activity, a mitochondrial marker of neuronal activity, to determine the effect of repeated lithium treatment on regional neuronal activity in the rat brain. Oral lithium treatment (21 days) selectively decreased cytochrome oxidase activity in the cingulate cortex and regions of the nucleus accumbens. These decreases were not seen after 5 days of lithium administration, although serum lithium concentrations were similar after both 5 and 21 days of treatment. The analysis of interregional correlations further suggests a role for amygdala pathways in the effects of lithium following 21 days of treatment. The implications of these data for understanding the mechanisms of action of lithium are discussed.     

Effects of early treatment with antiserum to ovine follicle-stimulating hormone and luteinizing hormone on gonadal development in the rat.

Neonatal rats secrete considerable amounts of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) between 5 and 15 days of age. Antisera to LH and FSH were injected during this 11-day period in an attempt to study the importance of gonadotropins for functional development of the gonads. Autopsies at 15 days of age revealed normal ovarian follicular histology after either antiserum treatment, but antiserum to LH significantly retarded differentiation of interstitial tissue. Uterine weights were increased, and some of the serum samples showed elevated FSH levels following the antiserum treatments. The testes of antiserum-treated rats were heavier at 15 days of age, while accessory sex organ weights were unchanged. Vaginal opening after antiserum treatment was more variable than in controls, but tended to be earlier. The first appearance of penile serum was not significantly changed. Both males and females were fertile as adults. Important limitations to the use of chronic antiserum injections were found in immature rats. The antisera were present for at least 34 days after injection. The ways in which this pool of antiserum might have influenced the results are discussed.     

Role of the pulvinar-lateral posterior nucleus complex in turning behavior

The behavioral response to electrical stimulation of the pulvinar-lateral posterior complex (P-LP) was studied in 11 adult cats with chronically implanted electrodes. The EEG of P-LP, caudate nucleus, superior colliculus, dorsal hippocampus and cerebral cortex was recorded during the stimulation sessions. Three cats had a cannula implanted in one P-LP through which drugs were microinjected. Threshold currents evoked contralateral head turning and conjugate eye deviation, and suprathreshold currents induced contralateral circling. Ninety-four percent of 456 stimulations in P-LP elicited contralateral head movements. P-LP EEG did not differ from controls during head turning induced by threshold currents, but it was desynchronized with slightly suprathreshold currents and occasionally showed after-discharges, concomitant with circling, with higher currents. Microinjections of ACh, KCl (25%), and penicillin into P-LP also induced contralateral circling, which was usually followed by a generalized epileptic seizure. This would support the postulate that the behavioral responses observed through electrical stimulation were mediated by synaptic activities within the P-LP. These results indicate that P-LP is involved in turning and circling behavior.     

Hypothalamic regulation of histidyl-proline diketopiperazine binding sites in the rat liver

The effects of hypothalamic hormones and electrolytic lesioning of the ventromedial hypothalamic nuclei (VMH) on histidyl-proline diketopiperazine (cyclo(His-Pro] binding in the rat liver were studied. VMH-lesioning markedly decreased cyclo(His-Pro) binding in the liver. Scatchard analysis revealed that the loss of cyclo(His-Pro) binding induced by VMH lesioning was due to a decrease in the number and affinity of binding sites. Somatostatin (SS) administration decreased cyclo(His-Pro) binding. The SS-induced changes in cyclo(His-Pro) binding were due to changes in the binding affinity. On the other hand, the administration of TRH or LH-RH did not affect cyclo(His-Pro) binding in the liver, although cyclo(His-Pro) has been proposed to be a metabolite of TRH. These findings suggest that the hypothalamus may regulate the cyclo(His-Pro) binding sites in the liver probably by controlling pancreatic SS secretion, since a VMH-lesion is reported to cause hypersecretion of pancreatic SS.     

Increased activation of the fear neurocircuitry in children exposed to violence

Most studies investigating the effect of childhood trauma on the brain are retrospective and mainly focus on maltreatment, whereas different types of trauma exposure such as growing up in a violent neighborhood, as well as developmental stage, could have differential effects on brain structure and function. The current magnetic resonance imaging study assessed the effect of trauma exposure broadly and violence exposure more specifically, as well as developmental stage on the fear neurocircuitry in 8‐ to 14‐year‐old children and adolescents (N = 69). We observed reduced hippocampal and increased amygdala volume with increasing levels of trauma exposure. Second, higher levels of violence exposure were associated with increased activation in the amygdala, hippocampus, and ventromedial prefrontal cortex during emotional response inhibition. This association was specifically observed in children younger than 10 years. Finally, increased functional connectivity between the amygdala and brainstem was associated with higher levels of violence exposure. Based on the current findings, it could be hypothesized that trauma exposure during childhood results in structural changes that are associated with later risk for psychiatric disorders. At the same time, it could be postulated that growing up in an unsafe environment leads the brain to functionally adapt to this situation in a way that promotes survival, where the long‐term costs or consequences of these adaptations are largely unknown and an area for future investigations.     

DEET insect repellent: effects on thermoregulatory sweating and physiological strain

Insect repellents (e.g. N,N-diethyl-m-toluamide or DEET) applied to the skin can potentially interfere with sweat production and evaporation, thus increasing physiological strain during exercise-heat stress. The purpose was to determine the impact of 33% DEET lotion on sweating responses, whole body thermoregulation and thermal sensation during walking exercise in the heat. Nine volunteers (2 females, 7 males; 22.1 ± 4.9 years; 176.4 ± 10.0 cm; 79.9 ± 12.9 kg) completed 5 days of heat acclimation (45°C, 20% rh; 545 watts; 100 min/day) and performed three trials: control (CON); DEET applied to forearm (DEET_LOC, 12 cm²); and DEET applied to ~13% body surface area (DEET_WB,). Trials consisted of 30 min walking (645 watts) in 40°C, 20% rh environment. Local sweat rate (SR), onset and skin wettedness were measured in DEET_LOC, and heart rate (HR), rectal temperature (T _re), skin temperature (T _sk), RPE, and thermal sensations (TS) were measured during DEET_WB. No differences (p > 0.05) were observed between DEET_LOC versus CON, respectively, for steady state SR (1.89 ± 0.44 vs. 2.09 ± 0.84 mg/cm²/min), SR area under the curve (46.9 ± 11.7 vs. 55.0 ± 20.8 mg/cm²), sweating onset, or skin wettedness. There were no differences (p > 0.05) in HR, T _re, T _sk, Physiological Strain Index, RPE or TS between DEET_WB versus CON. DEET did not impact measures of local forearm sweating and when applied according to military doctrine, did not adversely impact physiological responses during exercise-heat stress. DEET can be safely worn during military, occupational and recreational activities in hot, insect infested environments.