Derivation and validation of a novel comorbidity‐based delirium risk index to predict postoperative delirium using national administrative healthcare database

ObjectiveTo derive and validate a comorbidity‐based delirium risk index (DRI) to predict postoperative delirium.Data Source/Study SettingData of 506 438 hip fracture repair surgeries from 2006 to 2016 were collected to derive DRI and perform internal validation from the Premier Healthcare Database, which provided billing information on 20‐25 percent of hospitalizations in the USA. Additionally, data of 1 130 569 knee arthroplasty surgeries were retrieved for external validation.Study DesignThirty‐six commonly seen comorbidities were evaluated by logistic regression with the outcome of postoperative delirium. The hip fracture repair surgery cohort was separated into a training dataset (60 percent) and an internal validation (40 percent) dataset. The least absolute shrinkage and selection operator (LASSO) procedure was applied for variable selection, and weights were assigned to selected comorbidities to quantify corresponding risks. The newly developed DRI was then compared to the Charlson‐Deyo Index for goodness‐of‐fit and predictive ability, using the Akaike information criterion (AIC), Bayesian information criterion (BIC), area under the ROC curve (AUC) for goodness‐of‐fit, and odds ratios for predictive performance. Additional internal validation was performed by splitting the data by four regions and in 4 randomly selected hospitals. External validation was conducted in patients with knee arthroplasty surgeries.Data CollectionHip fracture repair surgeries, knee arthroplasty surgeries, and comorbidities were identified by using ICD‐9 codes. Postoperative delirium was defined by using ICD‐9 codes and analyzing billing information for antipsychotics (specifically haloperidol, olanzapine, and quetiapine) typically recommended to treat delirium.Principal FindingsThe derived DRI includes 14 comorbidities and assigns comorbidities weights ranging from 1 to 6. The DRI outperformed the Charlson‐Deyo Comorbidity Index with better goodness‐of‐fit and predictive performance.ConclusionsDelirium risk index is a valid comorbidity index for covariate adjustment and risk prediction in the context of postoperative delirium. Future work is needed to test its performance in different patient populations and varying definitions of delirium.     

Biochemical investigations into the alcoholic delirium: Alterations of biogenic amines

Summary In eight male patients with alcoholic delirium concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovannilic acid (HVA) in CSF, activity of dopamine--hydroxylase (DBH), and urinary excretion of noradrenaline (NA), adrenaline (A), and dopamine (DA) were measured during the delirium and a drug-free control period.MHPG concentration in CSF, excretion of NA and A as well as activity of serum DBH were significantly elevated during the delirium phase as compared to the control period. Urinary DA excretion and HVA in CSF did not show any constant changes. There was a positive correlation (r=0.64) between DBH activity and the intensity of the delirium (as measured on the delirium rating scale).It is hypothesized that there is a relationship between alcoholic delirium and increased central noradrenergic activity.Parts of this study were presented at the Sixth International Institute on the Prevention and treatment of Drug Dependence (Hamburg, June 28–July 2, 1976)     

Effects of hypnotics on the sleep EEG of healthy young adults: new data and psychopharmacologic implications

Benzodiazepine hypnotics increase NREM sleep and alter its EEG by reducing delta (0.3–3 Hz) and increasing sigma (12–15 Hz) and beta (15–23 Hz) activity. We tested whether the nonbenzodiazepine hypnotic, zolpidem (10 mg), produced the same pattern of sleep and EEG changes as two “classical” benzodiazepines, triazolam (0.25 mg) and temazepam (30 mg). Sleep EEG of 16 subjects was analyzed with period amplitude analysis for 3 nights during drug administration or placebo. The effects of zolpidem were in the same direction but generally of smaller magnitude than those of the classical benzodiazepines. These differences are more likely the result of non-equivalent dosages than different pharmacologic actions. Period amplitude analysis showed that the decreased delta activity resulted mainly from a decrease in wave amplitude. In contrast, the increased sigma and beta activity were produced by increased wave incidence. Delta suppression increased with repeated drug administration but sigma and beta stimulation did not. While these findings have little relevance for the clinical choice of hypnotics they may hold important implications for the brain mechanisms involved in hypnotic tolerance and withdrawal delirium.     

Delirious episodes induced by intravenous administration of clomipramine associated with an acute increase in its plasma concentrations

The aim of this paper is to describe two cases of clomipramine-induced delirium. One 61-year-old and one 67-year-old female depressive patients became delirious after beginning intravenous clomipramine injections in addition to their oral clomipramine administrations. Their plasma levels of both clomipramine and its metabolite, desmethylclomipramine, were acutely increased about twofold during delirium. The intravenous clomipramine administrations were discontinued. Their delirious state was gradually improved after stopping the intravenous clomipramine administrations. These findings suggest that acute increases of plasma levels of clomipramine and desmethylclomipramine after intravenous clomipramine injections might be related to the appearance of the delirious episodes.     

Reducing delirium and cognitive dysfunction after off-pump coronary bypass: A randomized trial

BackgroundNeuropsychiatric complications of surgical coronary revascularization are inconspicuous but frequent and clinically relevant. So far, attempts to reduce their occurrence, such as the introduction of off-pump coronary artery bypass (OPCAB) grafting method, have not brought the desired results. The aim of this trial was to determine whether using any of the 2 selected modifications of OPCAB could decrease the incidence of these undesired sequelae.MethodsIn this single-center, assessor- and patient-blinded, superiority, randomized controlled trial, 192 patients scheduled for elective isolated OPCAB were randomized to 3 parallel arms. The control arm underwent “conventional” OPCAB with vein grafts. The first study arm underwent anaortic OPCAB (ANA) with total arterial revascularization. The second study arm underwent OPCAB with vein grafts using carbon dioxide surgical field flooding (CO₂FF). Outcomes included the incidence of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD).ResultsThe incidence of PD was 35.9% in the control (OPCAB) arm, 32.8% in the CO₂FF arm, and 12.5% in the ANA arm (χ² [2, N = 191] = 10.17; P = .006). Post hoc tests revealed that the incidence of PD in the ANA arm differed from that in the OPCAB arm (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.68; P = .002). The incidence of ePOCD was 34.4% in the OPCAB arm, 28.1% in the CO₂FF arm, and 9.5% in the ANA arm (χ² [2, N = 191] = 11.58; P = .003). Post hoc tests revealed that the incidence of ePOCD differed between the ANA and OPCAB arms (OR, 0.20; 95% CI, 0.06-0.58; P < .001).ConclusionsPerforming ANA significantly decreases the incidence of PD and ePOCD compared with “conventional” OPCAB with vein grafts, whereas CO₂FF is inconsequential in this regard. These results, which probably reflect decreased delivery of embolic load to the brain in ANA, may have practical applicability in daily practice to improve clinical outcomes.     

severe disease complicated by osteoporosis

In this illustrative case, rheumatoid disease changed an active, self-supporting woman into a disabled, dependent and depressed person. When disease activity is continuous, early efforts to prevent severe deformity take on great urgency. It is also important to alleviate the psychosocial impact of the disease, which may well be more than even a highly motivated patient can handle alone.