Validation of a viable delirium detection test performed by nurses and physicians during routine patient care.

BACKGROUND: Delirium is a frequent mental impairment in geriatric patients hospitalized in acute care facilities. It carries a high risk of complications and is often the first symptom of acute illness. It is clearly important to identify the development of delirium at an early stage, and several short and effective diagnostic tests have been developed and validated for this purpose. Despite this, patients on hospital wards are seldom monitored for signs of emergent delirium, suggesting that compliance with guidelines would be improved by introducing a simpler and more user-friendly test. METHODS: We recently implemented a simple delirium assessment tool, called RMA that can be introduced into the daily routine of ward staff without significantly adding to their workload. The nurses noted their impression of the patient's cognitive state in the electronic medical record, and during the morning round the ward physician administered a short attention test to any patients suspected of new cognitive impairment. In this study, we compared RMA test against the widely used and well validated 4AT. RESULTS: RMA performed daily by the ward staff was found to be non-inferior to 4AT performed by an experienced rater. Compared to 4AT, R&M had a sensitivity of 93.9% and a specificity of 98.3%. An Altman-Bland plot indicated that both tests can be used interchangeably. CONCLUSIONS: The RMA test is reliable, easy to administer, likely to boost compliance with guidelines, and is expected to raise awareness of delirium among the nurses and physicians directly involved in the diagnostic process.

Acupuncture Treatment of Delirium in Older Adults Hospitalized in Internal Medicine Departments: An Open-Label Pragmatic Randomized-Controlled Trial.

BACKGROUND: Acupuncture seems to improve cognitive function in experimental models and to reduce agitation in dementia. The addition of acupuncture to standard-of-care (SOC) may improve clinical outcomes related to delirium in hospitalized older adults. METHODS: This pragmatic open-label randomized-controlled trial evaluated 81 older adults hospitalized in an internal medicine ward and diagnosed with delirium. Fifty were randomized to daily acupuncture combined with SOC and 31 to SOC only for up to 1 week. Delirium was diagnosed using Confusion Assessment Method (CAM) tool, and its severity was assessed by the long CAM-Severity (CAM-S) tool. The primary study outcome was delirium resolution evaluated as time-to-first delirium remission (over 7 days) and the number of days spent delirium-free. RESULTS: Time-to-first delirium remission was shorter in the acupuncture arm as compared to the SOC only arm (p < 0.001). A multivariate Cox regression analysis showed a shorter time-to-first remission of delirium in the acupuncture arm as compared with SOC arm [Hazard Ratio 0.267 (95% CI 0.098-0.726, p = 0.010)]. In the 7 days of evaluation, a significantly higher number of delirium-free days was found in the acupuncture arm compared to the SOC arm (p < 0.001), and CAM-S sum from day 2 to day 7 of evaluation was significantly lower in the acupuncture group compared to the control group (p = 0.002). No adverse safety event was found in the acupuncture group. CONCLUSION: Acupuncture seems to be safe and effective in the treatment of delirium in older patients hospitalized in internal medicine departments.

Peri-pharyngeal muscle response to inspiratory loading: comparison of patients with OSA and healthy subjects.

Upper airway patency to airflow and the occurrence of obstructive sleep apnea involve a complex interplay between pharyngeal anatomy and synergic co-activation of peri-pharyngeal muscles. In previous studies we observed large differences in the response to sleep-associated flow limitation between the genioglossus and other (non-GG) peri-pharyngeal muscles. We hypothesized that similar differences are present also during wakefulness. In the present study we compared the response to inspiratory loading of the genioglossus electromyogram and four other peri-pharyngeal muscles. Studies were performed in eight obstructive sleep apnea patients, seven age-matched healthy subjects and five additional younger subjects. Electromyogram activity was evaluated over a range of negative oesophageal pressures and expressed as % of maximal electromyograms. In healthy subjects, the slope response to inspiratory loading (electromyogram/pressures) was similar for the genioglossus and non-GG muscles studied. However, the electromyogram responses were significantly higher in the young subjects compared with older subjects. In contrast, in the obstructive sleep apnea patients, the electromyogram/pressure response of the non-GG muscles was similar to that of the age-matched healthy subjects, whereas the slope response of the genioglossus electromyogram was significantly higher than non-GG muscles. We conclude that both age and the presence of obstructive sleep apnea affect the response of peri-pharyngeal muscles to inspiratory loading. In patients with obstructive sleep apnea the genioglossus seems to compensate for mechanical disadvantages, but non-GG muscles apparently are not included in this neuromuscular compensatory mechanism. Our current and previous findings suggest that attempts to improve obstructive sleep apnea with myofunctional therapy should put added emphasis on the training of non-GG muscles.

Dissociation of electromyogram and mechanical response in sleep apnoea during propofol anaesthesia.

Pharyngeal collapsibility during sleep is believed to increase due to a decline in dilator muscle activity. However, genioglossus electromyogram (EMG) often increases during apnoeas and hypopnoeas, often without mechanical effect. 17 patients with obstructive sleep apnoea were anaesthetised and evaluated from termination of propofol administration to awakening. Genioglossus EMG, flow and pharyngeal area (pharyngoscopy) were monitored. Prolonged hypopnoeas enabled evaluation of the relationships between genioglossus EMG and mechanical events, before and after awakening. Additional dilator muscle EMGs were recorded and compared to the genioglossus. Electrical stimulation of the genioglossus was used to evaluate possible mechanical dysfunction. Prolonged hypopnoeas during inspiration before arousal triggered an increase in genioglossus EMG, reaching mean ± SD 62.2 ± 32.7% of maximum. This augmented activity failed to increase flow and pharyngeal area. Awakening resulted in fast pharyngeal enlargement and restoration of unobstructed flow, with marked reduction in genioglossus EMG. Electrical stimulation of the genioglossus under propofol anaesthesia increased the inspiratory pharyngeal area (from 25.1 ± 28 to 66.3 ± 75.5 mm(2); p<0.01) and flow (from 11.5 ± 6.5 to 18.6 ± 9.2 L · min(-1); p<0.001), indicating adequate mechanical response. All additional dilators increased their inspiratory activity during hypopnoeas. During propofol anaesthesia, pharyngeal occlusion persists despite large increases in genioglossus EMG, in the presence of a preserved mechanical response to electrical stimulation.

Early Detection and Intervention for Patients with Delirium Admitted to the Department of Internal Medicine: Lessons from a Pilot Initiative.

INTRODUCTION: Older patients who arrive to the emergency room with delirium have a worse prognosis than others. Early detection and treatment of this problem has been shown to improve outcome. We have launched a project at our hospital to improve the care of patients who arrive delirious to the medical emergency room. The present article describes lessons that can be learned from this pilot initiative. METHODS: All patients older than 70 years admitted to the department of internal medicine were screened for delirium in the emergency room using the 4AT screening tool. Data of patients with a 4AT score ≥5 (or with incomplete score) were transferred to the geriatric unit of the hospital. On the ward, the presence of delirium was confirmed by a geriatric nurse that validated that the patient could walk with support and ordered mobilization and physiotherapy (M&P). RESULTS: Over the 2 and a half years (10 quarters) allocated for the pilot project, 1,078 medical patients with delirium were included in this survey. In 59.3%, the diagnosis of delirium could be confirmed only after admission. Due to budgetary constraints, only 54.7% received the allocated specific intervention - early M&P. Since it was decided that randomization was not appropriate for our initiative, we found that patients who received M&P had lower (better) 4AT scores on admission, and lower mortality. No significant difference was found between the patients who received M&P and the others in length of hospitalization and discharge to nursing homes. Retrospective comparison of the two groups did not enable to determine whether M&P was given to the patients for whom it was most effective. CONCLUSIONS: It is often not possible to verify in the emergency room that the cognitive decline is indeed new, that is, is due to delirium, and measures must be taken to verify this point as soon as possible after admission. Due to numerous constraints, the availability of early M&P is often insufficient. Whenever resources are scarce and randomization is avoided, adequate criteria should be found for allocating existing dedicated staff to patients for whom early mobilization is likely to be most beneficial.

Relationship between the activity of the genioglossus, other peri-pharyngeal muscles and flow mechanics during wakefulness and sleep in patients with OSA and healthy subjects.

INTRODUCTION: In patients with OSA, substantial increases in genioglossus (GG) activity during hypopneas/apneas usually fail to restore normal airflow. The present study was undertaken to evaluate if this phenomenon can be explained by reduced activation of other peri-pharyngeal muscles. METHODS: We recorded EMGs of the GG and four other peri-pharyngeal muscles (accessory dilators, AD), in 8 patients with OSA and 12 healthy subjects, during wakefulness and sleep. Repetitive events of flow limitation were induced during sleep. The events with the highest increases in AD activity were evaluated, to assess if combined activation of both the GG and AD to levels higher than while awake ameliorate airflow reduction during sleep. RESULTS: Flow limitation triggered large increases in GG-EMG, but only modest augmentation in AD activity. Nevertheless, phasic EMG activity was present in 40 % of the ADs during sleep. In multiple events, increases of both GG and AD activity to levels substantially higher than while awake were not associated with improvement in airflow. CONCLUSIONS: We conclude that sleep-induced reduction in AD response to airway obstruction cannot completely explain the failure of upper airway dilators to maintain pharyngeal patency. We speculate that reduction in dilator muscle efficacy may be due to the alterations in motor units recruitment patterns during sleep.

Interacting effects of genioglossus stimulation and mandibular advancement in sleep apnea.

Both mandibular advancement (MA) and stimulation of the genioglossus (GG) have been shown to improve upper airway patency, but neither one achieves the effect of continuous positive airway pressure (CPAP) treatment. In the present study we assessed the combined effect of MA and GG stimulation on the relaxed pharynx in patients with obstructive sleep apnea (OSA). We evaluated responses of upper airway pressure-flow relationships and endoscopically determined pharyngeal cross-sectional area to MA and electrical stimulation of the GG in 14 propofol-anesthetized OSA patients. Measurements were undertaken at multiple levels of CPAP, enabling calculation of the critical closing pressure (Pcrit), upstream resistance (Rus), and pharyngeal compliance. GG stimulation, MA, and the combination of both shifted the pressure:flow relationships toward higher flow levels, resulting in progressively lower Pcrit (from baseline of 2.9 +/- 2.2 to 0.9 +/- 2.5, -1.4 +/- 2.9, and -4.2 +/- 3.3 cmH(2)O, respectively), without significant change in Rus. DeltaPcrit during GG stimulation was significantly larger during MA than under baseline conditions (-2.8 +/- 1.4 vs. -2.0 +/- 1.4 cmH(2)O, P = 0.011). Combining the effect of GG stimulation with MA lowered Pcrit below 0 in all patients and restored pharyngeal patency to a level that enabled flow above the hypopnea level in 10/14 of the patients. Velopharyngeal compliance was not affected by either manipulation. We conclude that the combined effect of MA and GG stimulation is additive and may act in synergy, preventing substantial flow limitation of the relaxed pharynx in most OSA patients.

[Electrical stimulation of the genioglossus to improve pharyngeal patency in obstructive sleep apnea: comparison of results obtained during sleep and anesthesia].

Contraction of the geniogtossus (GG) has been shown to improve upper airway patency in patients with sleep apnea during sleep and anesthesia. However, a large variability in response exists, requiring selection of adequate patients if GG stimulation should be used as a treatment modality. In the present study, we compared responses in upper airway pressure-flow relationships to electrical stimulation of the GG in patients with obstructive sleep apnea during sleep and mild anesthesia. Nine patients studied during sleep were matched with 9 patients evaluated during propofol anesthesia. Stimulation was performed with fine wire electrodes inserted near the mandibular insertion of the GG. Airflow was measured at muLtiple levels of CPAP, and upper airway collapsibility was defined by the pressure below which airflow ceased (the "critical" pressure, Pcrit). ELectrical stimulation shifted the pressure-flow reLationships toward higher flow Levels in all patients over the entire range of CPAP applied. Pcrit decreased significantly during stimulation-induced contraction of the GG, and similarly in the patients evaluated during sleep and during anesthesia (from 1.6 +/- 2.0 to -1.6 +/- 2.5, and from 1.8 +/- 1.8 to -0.2 +/- 1.8 cmH2O, during steep and anesthesia, respectively, p < 0.01, without a significant change in upstream resistance. Our findings imply that responses in Pcrit to electrical stimulation of the main tongue protrusor during propofoL anesthesia may reflect those observed during sleep, and evaluation of the response of sleep apnea patients to GG stimulation can be evaluated during short anesthesia.

Spectral analysis of peri-pharyngeal muscles' EMG in patients with OSA and healthy subjects.

INTRODUCTION: In addition to dyscoordination of upper airway dilator muscles activity, sleep may also alter the pattern of intra-muscular activation of single motor units (SMUs). Such changes should be identifiable by a state dependent change in EMG power spectrum, i.e., a shift in centroid frequency (ƒc) during sleep. METHODS: EMGs of the genioglossus and four other peri-pharyngeal muscles were recorded in OSA patients (n = 8), age-matched healthy subjects (n = 7), and 5 young healthy subjects, and ƒc was calculated for wakefulness and sleep periods. RESULTS: ƒc decreased with the onset of sleep and returned to baseline levels after arousal. ƒc of all muscles decreased similarly and significantly during sleep in the OSA and the age-matched healthy subjects, but not in the young subjects. CONCLUSIONS: The pattern of decrease in ƒc is compatible with altered synchronization of SMUs during sleep. We speculate that these changes may contribute to the failure of dilator muscles to improve flow limitation during sleep in older subjects.

The study protocol for a randomized, controlled trial of acupuncture versus a sham procedure versus standard care alone for the treatment of delirium in acutely hospitalized older adults with a medical illness.

BACKGROUND: Many hospitalized older adults experience delirium, but treatment options are limited. Acupuncture has been shown to improve cognitive function and reduce agitation in dementia. We hypothesize that acupuncture, when compared with a sham intervention, will reduce the duration and severity of delirium, normalize delirium biomarkers, and improve clinical outcomes related to delirium in acutely hospitalized older adults with a medical illness. METHODS: This three-arm, prospective, randomized, clinical trial will evaluate adults aged over 65 years who are acutely hospitalized to an internal-medicine ward and diagnosed with delirium or subsyndromal delirium. The 288 patients (96 in each of three groups) will be randomly allocated to receive either daily true acupuncture with usual care, a daily sham procedure with usual care, or usual care only in a 1:1:1 distribution for up to one week or until the patient is delirium-free for over 48 h. Other delirium and clinical interventions will remain unchanged. Delirium will be diagnosed using DSM-5 criteria and its severity will be assessed using the long Confusion Assessment Method Severity (CAM-S) tool. OUTCOMES: The primary study outcome will be the daily CAM-S score over 7 days between the three groups. Secondary outcomes will include time to first resolution of the delirium (over 7 days), the proportion of days spent delirium-free, daily antipsychotic use, daily pain scores, sleep quality, morning serum cortisol and T3 levels, and midnight urinary cortisol/creatinine ratio, all determined twice a week, and delirium-related complications. Hospital mortality, duration of hospital stay and functional status at discharge will also be compared between the three groups. Adverse events potentially related to acupuncture will be evaluated daily. The cost-effectiveness of acupuncture will be estimated. CONCLUSION: This novel randomized study will evaluate both the specific and the non-specific effects of acupuncture on delirium, and related outcomes, and its safety. Potential mechanism(s) of action for acupuncture in reducing delirium will be explored and healthcare-related costs estimated. Positive study results may prove pivotal in facilitating a multimodal, non-pharmacologic, integrative approach to delirium treatment among older, medical inpatients.

Alteration in upper airway dilator muscle coactivation during sleep: comparison of patients with obstructive sleep apnea and healthy subjects.

In patients with obstructive sleep apnea (OSA), substantial increases in genioglossus (GG) activity during hypopneas/apneas usually fail to restore normal airflow. We have previously suggested that sleep-induced alteration in tongue muscle coordination may explain this finding, as retractor muscle coactivation was reduced during sleep compared with wakefulness. The present study was undertaken to evaluate whether these alterations in dilator muscle activation during sleep play a role in the pathogenesis of OSA and whether coactivation of additional peripharyngeal muscles (non-GG muscles: styloglossus, geniohyoid, sternohyoid, and sternocleidomastoid) is also impaired during sleep. We compared GG and non-GG muscle electromyographic (EMG) activity in 8 patients with OSA and 12 healthy subjects during wakefulness while breathing through inspiratory resistors with the activity observed during sleep toward the end of flow limitation, before arousal, at equivalent esophageal pressures. During wakefulness, resistive breathing triggered increases in both GG and non-GG muscle activity. During sleep, flow limitation was associated with increases in GG-EMG that reached, on average, >2-fold the level observed while awake. In contrast, EMGs of the non-GG muscles, recorded simultaneously, reached, on average, only ~2/3 the wakefulness level. We conclude that during sleep GG activity may increase to levels that substantially exceed those sufficient to prevent pharyngeal collapse during wakefulness, whereas other peripharyngeal muscles do not coactivate during sleep in both patients with OSA and healthy subjects. We speculate that upper airway muscle dyssynchrony during sleep may explain why GG-EMG activation fails to alleviate flow limitation and stabilize airway patency during sleep. NEW & NOTEWORTHY Pharyngeal obstruction during sleep may trigger genioglossus activity to levels substantially exceeding those observed during wakefulness, without ameliorating flow limitation. In contrast, other peripharyngeal muscles exhibit a much lower activity during sleep in both patients with obstructive sleep apnea and healthy subjects. Coordinated muscular synergy stabilizes the pharynx despite relatively low activity while awake, yet even higher genioglossal activity allows the pharynx to obstruct when simultaneous activity of other dilator muscles is inadequate during sleep.

Effect of coactivation of tongue protrusor and retractor muscles on pharyngeal lumen and airflow in sleep apnea patients.

The present study evaluated the effect of coactivation of tongue protrusors and retractors on pharyngeal patency in patients with obstructive sleep apnea. The effect of genioglossus (GG), hyoglossus (HG), and coactivation of both on nasal pressure (Pn):flow relationships was evaluated in a sleep study (SlS, n = 7) and during a propofol anesthesia study (AnS, n = 7). GG was stimulated with sublingual surface electrodes in SlS and with intramuscular electrodes in AnS, while HG was stimulated with surface electrodes in both groups. In the AnS, the cross-sectional area (CSA):Pn relationships was measured with a pharyngoscope to estimate velopharyngeal compliance . In the SlS, surface stimulation of GG had no effect on the critical pressure (Pcrit), HG increased Pcrit from 2.8 +/- 1.7 to 3.7 +/- 1.6 cmH(2)O, but coactivation lowered Pcrit to 0.2 +/- 1.9 cmH(2)O (P < 0.01 for both). In the AnS, intramuscular stimulation of GG lowered Pcrit from 2.6 +/- 1.3 to 1.0 +/- 2.8 cmH(2)O, HG increased Pcrit to 6.2 +/- 2.5 cmH(2)O (P < 0.01), and coactivation had a similar effect to that of GG (Pcrit = 1.2 +/- 2.4 cmH(2)O, P < 0.05). None of the interventions affected significantly velopharyngeal compliance. We conclude that the beneficial effect of coactivation depends on the pattern of GG fiber recruitment: although surface stimulation of GG failed to protrude the tongue, it prevented the occlusive effect of the retractor, thereby improving pharyngeal patency during coactivation. Stimulation of deeper GG fibers with intramuscular electrodes enlarged the pharynx, and coactivation had no additive effect.

Mechanical parameters determining pharyngeal collapsibility in patients with sleep apnea.

The relative impact of mechanical factors on pharyngeal patency in patients with obstructive sleep apnea is poorly understood. The present study was designed to evaluate parameters of the "tube law" on pharyngeal pressure-flow relationships and collapsibility in patients with obstructive sleep apnea. We developed a mathematical model that considered the collapsible segment of the pharynx to represent an orifice of varying diameter. The model enabled us to assess the effects of pharyngeal compliance (C), neutral cross-sectional area (A(o)), external peripharyngeal pressure (P(ex)), and the resistance proximal to the site of collapse on flow mechanics and pharyngeal collapsibility [critical pressure (P(crit))]. All parameters were measured in 15 patients with obstructive sleep apnea under propofol anesthesia, both at rest and during mandibular advancement and electrical stimulation of the genioglossus. The data was used both to confirm the validity of the model and to compare expected and actual relationships between the tube-law parameters and the pharyngeal pressure-flow relationship and collapsibility. We found a close correlation between predicted and measured P(crit) (R = 0.98), including changes observed during pharyngeal manipulations. C and A(o) were closely and directly interrelated (R = 0.93) and did not correlate with P(crit). A significant correlation was found between P(ex) and P(crit) (R = 0.77; P < 0.01). We conclude that the pharynx of patients with obstructive sleep apnea can be modeled as an orifice with varying diameter. Pharyngeal compliance and A(o) are closely interrelated. Pharyngeal collapsibility depends primarily on the surrounding pressure.