Association between statin use on delirium and 30-day mortality in patients with chronic obstructive pulmonary disease in the intensive care unit.

BACKGROUND: Delirium occurs frequently in patients with chronic obstructive pulmonary disease in the intensive care unit. Effective prevention and treatment strategies for delirium remain limited. We aimed to assess delirium and 30-day mortality in patients with chronic obstructive pulmonary disease who were statin and non-statin users. METHODS: In this retrospective study, patients with chronic obstructive pulmonary disease were identified from the Medical Information Mart for Intensive Care database (MIMIC-IV). The primary exposure variable was the use of statins 3 days after entering the intensive care unit and the primary outcome measure was the presence of delirium. The secondary outcome measure was 30-day mortality. Since the cohort study was retrospective, we used an inverse probability weighting derived from the propensity score matching to balance different variables. RESULTS: Among a cohort of 2725 patients, 1484 (54.5%) were statin users. Before propensity score matching, the prevalence of delirium was 16% and the 30-day mortality was 18% in patients with chronic obstructive pulmonary disease. Statin use was significantly negatively correlated with delirium, with an odds ratio of 0.69 (95% CI 0.56-0.85, p < 0.001) in the inverse probability weighted cohort and 30-day mortality of 0.7 (95% CI 0.57-0.85, p < 0.001). CONCLUSIONS: Statin use is associated with a lower incidence of delirium and 30-day mortality in patients with chronic obstructive pulmonary disease in the intensive care unit.

Serum anion gap is associated with mortality in intensive care unit patients with diastolic heart failure.

Serum anion gap (AG) is closely related to mortality in critically ill patients with several diseases. We aimed to determine the relationship between serum AG levels and 28-day intensive care unit (ICU) mortality in patients with diastolic heart failure (DHF). This cohort study enrolled critically ill patients with DHF from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Serum AG levels were calculated using the traditional and albumin-adjusted methods. Multivariate Cox proportional hazards regression and restricted cubic spline curves were used to determine the correlation between serum AG levels and 28-day ICU mortality. We used receiver operating characteristic (ROC) curves and area under the curve (AUC) to compare the ability of traditional and albumin-adjusted AG to predict mortality. Overall, 3290 patients were included. Multivariate analysis showed an association of high levels of traditional (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.1-1.98, p = 0.009) and albumin-adjusted AG (HR, 1.36; 95% CI, 1.02-1.79, p = 0.033) with higher risk of 28-day ICU mortality. Restricted cubic spline curves indicated a linear relationship between AG level and 28-day ICU mortality. Comparison of the ROC curves revealed that albumin-adjusted AG had a greater ability to predict 28-day ICU mortality compared with traditional AG (AUCs of 0.569 [95% CI, 0.536-0.601] and 0.619 [95% CI, 0.588-0.649], respectively). In ICU patients with DHF, higher levels of traditional and albumin-adjusted AG were associated with higher 28-day ICU mortality. Albumin-adjusted AG exhibited greater predictive ability for mortality compared with traditional AG.

Association between delirium and statin use in patients with congestive heart failure: a retrospective propensity score-weighted analysis.

Background: The relationship between statin use and delirium remains controversial; therefore, we aimed to study the association between statin exposure and delirium and in-hospital mortality in patients with congestive heart failure. Methods: In this retrospective study, patients with congestive heart failure were identified from the Medical Information Mart for Intensive Care database. The primary exposure variable was statin use 3 days after admission to the intensive care unit, and the primary outcome measure was the presence of delirium. The secondary outcome measure was in-hospital mortality. Since the cohort study was retrospective, we used inverse probability weighting derived from the propensity score to balance various variables. Results: Of 8,396 patients, 5,446 (65%) were statin users. Before matching, the prevalence of delirium was 12.5% and that of in-hospital mortality was 11.8% in patients with congestive heart failure. Statin use was significantly negatively correlated with delirium, with an odds ratio of 0.76 (95% confidence interval: [0.66-0.87]; P < 0.001) in the inverse probability weighting cohort and in-hospital mortality of 0.66 (95% confidence interval: [0.58-0.75]; P < 0.001). Conclusion: Statins administered in the intensive care unit can significantly reduce the incidence of delirium and in-hospital mortality in patients with congestive heart failure.

Melanocortin 4 receptor mediates neuropathic pain through p38MAPK in spinal cord.

BACKGROUND: Neuropathic pain is characterised by spontaneous ongoing or shooting pain and evoked amplified pain responses after noxious or non-noxious stimuli. Neuropathic pain develops as a result of lesions or disease affecting the somatosensory nervous system either in the periphery or centrally. Melanocortin 4 receptor (MC4R) plays an important role in the initiation of neuropathic pain but the underlying mechanisms are still unclear. METHODS: Adult male Wistar rats were given chronic constriction injury (CCI) or sham operations. Part of CCI rats were intrathecally treated with HS014 (MC4R antagonist) or SB203580 (p38MAPK inhibitor). On the third, seventh and fourteenth day, the thermal threshold of operated paws was tested. In addition, the MC4R or phosphorylated p38MAPK (p-p38MAPK) levels of lumbar spinal cord were tested with ELISA (enzyme-linked immunosorbent assay), western blot and immunohistochemistry. RESULTS: Here we demonstrate that (1) both HS014 and SB203580 reduced CCI reduced hyperalgesia (2) p-p38MAPK was increased after CCI with a time course parallel to that of the MC4R change, (3) The p38 activation was prevented by blocking MC4R with an antagonist HS014, but MC4R-IR was not prevented by SB203580. (4) MC4R and p-p38MAPK were located in the same cells. CONCLUSION: The mechanisms of neuropathic pain mediated by MC4R is related to the inhibition of p38MAPK activation. P38MAPK may be a downstream of MC4R.

Melanocortin 4 receptor induces hyperalgesia and allodynia after chronic constriction injury by activation of p38 MAPK in DRG.

Melanocortin 4 receptor (MC4R) is implicated in the initiation and maintenance of neuropathic pain. Although the effect of MC4R on neuropathic pain is known, it remains unclear how MC4R mediates neuropathic pain. In vitro MC4R activates mitogen-activated kinase (MAPK). Accordingly, we investigate whether MC4R activates the p38MAPK cascade in vivo to trigger pain behavior of Wistar rats after chronic constriction injury (CCI). Intrathecal injection of MC4R antagonist HS014 (5 µg/day) at the moment of CCI for seven days attenuated thermal hyperalgesia and mechanical allodynia. Similarly, intrathecal injection of a p38 inhibitor (SB203580, 10 mg/day) at the moment of CCI for seven days was also effective. To assess whether the effects of HS014 were mediated via increased p38MAPK activation, ipsilateral L4 and L5 dorsal root ganglion (DRG) were analyzed for MC4R and phosphorylated p38MAPK (p-p38MAPK) after CCI alone or CCI combined with HS014 treatment or SB203580 treatment. After CCI, DRG p-p38MAPK and MC4R were elevated by three, seven, and 14 days. Treatment with SB203580 blocked p38 activation. Both MC4R and phosphorylated p38 localized in DRG neurons. These data suggest a sequential role for MC4R and p38 in the induction and maintenance of neuropathic pain. MC4R plays an important role in the establishment of neuropathic pain following CCI, seemingly dependent on p38 activation.