Peripheral nerve injury alters the alpha2 adrenoceptor subtype activated by clonidine for analgesia

BACKGROUND: Previous studies suggest that the alpha adrenoceptor subtype is the target for spinally administered alpha -adrenergic agonists, clonidine, for pain relief. However, ST 91, a preferential alpha adrenoceptor subtype agonist, induces antinociception, and intrathecally administered alpha antisense oligodeoxynucleotide decreases antinociception induced by clonidine in the rat, suggesting non-A sites may be important as well. Therefore, the authors examined the subtype of alpha adrenoceptor activated by clonidine and ST 91 in normal rats and those with nerve injury-induced hypersensitivity. METHODS: The same mechanical stimulus was applied to normal rats and those following spinal nerve ligation, and the effect of intrathecal clonidine and ST 91 on withdrawal threshold to the stimulus was determined. To further examine subtypes, animals were spinally pretreated with vehicle, BRL 44408 (an alpha subtype-preferring antagonist), and ARC 239 (an alpha subtype-preferring antagonist). RESULTS: In normal animals, clonidine's effect was diminished by pretreatment with either antagonist, whereas ST 91's antinociceptive effect was solely blocked by pretreatment with ARC 239. In nerve-injured animals, the antihypersensitivity action of both clonidine and ST 91 was blocked by administration of ARC 239, whereas BRL 44408 was ineffective. CONCLUSIONS: These data agree with previous studies supporting that the alpha adrenoceptor is important to the antinociceptive effect of clonidine in normal animals. Nerve injury alters this and results in a total reliance on alpha adrenoceptors.     

Comparison of static and rolling logistic regression models on predicting invasive mechanical ventilation or death from COVID‐19—A retrospective,multicentre study

IntroductionCOVID‐19 virus has undergone mutations, and the introduction of vaccines and effective treatments have changed its clinical severity. We hypothesized that models that evolve may better predict invasive mechanical ventilation or death than do static models.MethodsThis retrospective study of adult patients with COVID‐19 from six Michigan hospitals analysed 20 demographic, comorbid, vital sign and laboratory factors, one derived factor and nine factors representing changes in vital signs or laboratory values with time for their ability to predict death or invasive mechanical ventilation within the next 4, 8 or 24 h. Static logistic regression was constructed on the initial 300 patients and tested on the remaining 6741 patients. Rolling logistic regression was similarly constructed on the initial 300 patients, but then new patients were added, and older patients removed. Each new construction model was subsequently tested on the next patient. Static and rolling models were compared with receiver operator characteristic and precision‐recall curves.ResultsOf the 7041 patients, 534 (7.6%) required invasive mechanical ventilation or died within 14 days of arrival. Rolling models improved discrimination (0.865 ± 0.010, 0.856 ± 0.007 and 0.843 ± 0.005 for the 4, 8 and 24‐h models, respectively; all p < 0.001 compared with the static logistic regressions with 0.827 ± 0.011, 0.794 ± 0.012 and 0.735 ± 0.012, respectively). Similarly, the areas under the precision‐recall curves improved from 0.006, 0.010 and 0.021 with the static models to 0.030, 0.045 and 0.076 for the 4‐, 8‐ and 24‐h rolling models, respectively, all p < 0.001.ConclusionRolling models with contemporaneous data maintained better metrics of performance than static models, which used older data.     

Peripheral Nerve Injury Alters the α2 Adrenoceptor Subtype Activated by Clonidine for Analgesia

Background: Previous studies suggest that the [alpha]2A adrenoceptor subtype is the target for spinally administered [alpha]2-adrenergic agonists, i.e., clonidine, for pain relief. However, ST 91, a preferential [alpha]2 NON-A adrenoceptor subtype agonist, induces antinociception, and intrathecally administered [alpha]2C antisense oligodeoxynucleotide decreases antinociception induced by clonidine in the rat, suggesting non-A sites may be important as well. Therefore, the authors examined the subtype of [alpha]2 adrenoceptor activated by clonidine and ST 91 in normal rats and those with nerve injury-induced hypersensitivity.

Methods: The same mechanical stimulus was applied to normal rats and those following spinal nerve ligation, and the effect of intrathecal clonidine and ST 91 on withdrawal threshold to the stimulus was determined. To further examine subtypes, animals were spinally pretreated with vehicle, BRL 44408 (an [alpha]2A subtype-preferring antagonist), and ARC 239 (an [alpha]2 NON-A subtype-preferring antagonist).

Results: In normal animals, clonidine's effect was diminished by pretreatment with either antagonist, whereas ST 91's antinociceptive effect was solely blocked by pretreatment with ARC 239. In nerve-injured animals, the antihypersensitivity action of both clonidine and ST 91 was blocked by administration of ARC 239, whereas BRL 44408 was ineffective.     

Scopolamine prevents dreams during general anesthesia

BACKGROUND: Dreaming during anesthesia is not a well-understood phenomenon. Anticholinergic drugs are used in anesthesia as premedication, but their use to decrease the incidence of dreams and psychological adverse reactions after anesthesia is not well established. The authors therefore studied the efficacy of intramuscular atropine and scopolamine for the prevention of dreams during general anesthesia with propofol and nitrous oxide. METHODS: Healthy women undergoing minor gynecologic surgery were randomly assigned to receive 2.5 microg/kg scopolamine or 10 microg/kg atropine intramuscularly (n = 50/group). In both groups, anesthesia was induced and maintained with propofol as a 2.5-mg/kg bolus, followed by 12 mg x kg(-1) x h(-1) as a continuous infusion and 70% nitrous oxide in oxygen. Two interviews regarding dreaming activity and characteristics were conducted at 20 min and 6 h after surgery. RESULTS: None of the patients in the scopolamine group and 47% of the patients in the atropine group reported the occurrence of dreams 20 min after recovery. The results were similar at 6 h: 6% of the scopolamine group and 43% of the atropine group reported dream activity. No differences in sedation or anesthetic requirements were found. CONCLUSIONS: Previous studies in animals and humans suggest that dreams are affected by drugs acting on the central cholinergic system. The current results suggest that intramuscular scopolamine prevents dreams or dream recall in healthy young women undergoing short elective surgery with propofol-nitrous oxide anesthesia.