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1.
Anesthesiology ; 140(5): 963-978, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324729

RESUMO

BACKGROUND: Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults. METHODS: The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid ß (Aß) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls. RESULTS: The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aß, tau, or p-tau levels, or tau/Aß or p-tau/Aß ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (ß, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up. CONCLUSIONS: During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aß) changes or greater cognitive decline.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Peptídeos beta-Amiloides , Proteínas tau , Disfunção Cognitiva/diagnóstico , Cognição , Biomarcadores , Fragmentos de Peptídeos
2.
Can J Anaesth ; 70(12): 1917-1927, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37932648

RESUMO

PURPOSE: Severe acute pain after Cesarean delivery increases the risk of developing persistent pain (~20% incidence) and postpartum depression (PPD) (~15% incidence). Both conditions contribute to maternal morbidity and mortality, yet early risk stratification remains challenging. Neuroinflammation has emerged as a key mechanism of persistent pain and depression in nonobstetric populations. Nevertheless, most studies focus on plasma cytokines, and the relationship between plasma and cerebrospinal fluid (CSF) cytokine levels is unclear. Our primary aim was to compare inflammatory marker levels between patients who developed the composite outcome of persistent pain and/or PPD vs those who did not. METHODS: We recruited term patients with singleton pregnancies undergoing elective Cesarean delivery under neuraxial anesthesia into an exploratory prospective cohort study. We collected baseline demographic, obstetric, and Edinburgh Postnatal Depression Scale information, and performed quantitative sensory tests. Plasma was collected preoperatively and 48 hr postoperatively. In the operating room, 10 mL of CSF was collected, followed by a standardized anesthetic. Intra- and postoperative management were according to standard practice. We obtained Edinburgh Postnatal Depression Scale and pain scores at six weeks and three months after delivery. The primary outcome was persistent pain and/or PPD at three months. We analyzed the difference in inflammatory marker levels between the groups (primary aim) using two-sided Mann-Whitney tests. RESULTS: Eighty participants were enrolled, and 63 patients completed the study; 23 (37%) experienced the primary outcome at three months. Preoperative plasma transforming growth factor beta 1 (TGF-ß1) concentration was higher in patients who developed the primary outcome compared with those who did not (median [interquartile range (IQR)], 2,879 [2,241-5,494] vs 2,292 [1,676-2,960] pg·mL-1; P = 0.04), while CSF IL-1ß concentration was higher in patients who developed the primary outcome than in those who did not (median [IQR], 0.36 [0.29-0.39] vs 0.30 [0.25-0.35] pg·mL-1; P = 0.03). CONCLUSIONS: We observed differential levels of plasma and CSF inflammatory biomarkers in patients who developed persistent pain and PPD compared with those who did not. We showed the feasibility of collecting plasma and CSF samples at Cesarean delivery, which may prove useful for future risk-stratification. STUDY REGISTRATION: ClinicalTrials.gov (NCT04271072); registered 17 February 2020.


RéSUMé: OBJECTIF: La douleur aiguë sévère après un accouchement par césarienne augmente le risque de douleur persistante (~20 % d'incidence) et de dépression post-partum (DPP) (~15 % d'incidence). Ces deux conditions contribuent à la morbidité et à la mortalité maternelles, mais la stratification précoce des risques demeure difficile. La neuroinflammation est apparue comme un mécanisme clé de la douleur persistante et de la dépression dans les populations non obstétricales. Néanmoins, la plupart des études se concentrent sur les cytokines plasmatiques, et la relation entre les taux de cytokines plasmatiques et de liquide céphalorachidien (LCR) n'est pas claire. Notre objectif principal était de comparer les taux de marqueurs inflammatoires entre les patient·es qui ont eu un résultat composite de douleur persistante et/ou de DPP vs les personnes qui n'en ont pas eu. MéTHODE: Nous avons recruté des patient·es à terme avec des grossesses uniques bénéficiant d'une césarienne programmée sous anesthésie neuraxiale dans une étude de cohorte prospective exploratoire. Nous avons recueilli des informations démographiques de base, obstétricales et tirées de l'Échelle de dépression postnatale d'Édimbourg, et effectué des tests sensoriels quantitatifs. Le plasma a été prélevé avant l'opération et 48 heures après l'opération. En salle d'opération, 10 mL de LCR ont été recueillis, suivis d'un anesthésie standardisée. La prise en charge per- et postopératoire était conforme à la pratique courante. Nous avons obtenu les scores sur l'Échelle de dépression postnatale d'Édimbourg et les scores de douleur six semaines et trois mois après l'accouchement. Le critère d'évaluation principal était la douleur persistante et/ou la DPP à trois mois. Nous avons analysé la différence dans les niveaux de marqueurs inflammatoires entre les groupes (objectif principal) en utilisant des tests bilatéraux de Mann-Whitney. RéSULTATS: Quatre-vingts personnes ont été recrutées et 63 patient·es ont terminé l'étude; 23 (37 %) ont rapporté le critère d'évaluation principal à trois mois. Le facteur TGF-ß1 (transforming growth factor beta 1) plasmatique préopératoire était plus élevé chez les patient·es qui ont manifesté le critère d'évaluation principal par rapport aux personnes qui ne l'ont pas manifesté (médiane [écart interquartile (ÉIQ)], 2879 [2241-5494] vs 2292 [1676­2960] pg·mL−1; P = 0,04), tandis que le IL-1ß dans le LCR était plus élevé chez les patient·es qui ont manifesté le critère d'évaluation principal que chez les personnes qui ne l'ont pas manifesté (médiane [ÉIQ], 0,36 [0,29-0,39] vs 0,30 [0,25­0,35] pg·mL−1; P = 0,03). CONCLUSION: Nous avons observé des taux différentiels de biomarqueurs inflammatoires plasmatiques et de LCR chez les patient·es qui ont manifesté une douleur persistante et une DPP par rapport aux personnes qui n'en ont pas manifesté. Nous avons montré la faisabilité de la collecte d'échantillons de plasma et de LCR lors de l'accouchement par césarienne, ce qui pourrait s'avérer utile pour la stratification future des risques. ENREGISTREMENT DE L'éTUDE: clinicaltrials.gov (NCT04271072); enregistrée le 17 février 2020.


Assuntos
Depressão Pós-Parto , Gravidez , Feminino , Humanos , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/etiologia , Estudos Prospectivos , Cesárea , Dor/etiologia
4.
Ann Clin Transl Neurol ; 9(2): 155-170, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35104057

RESUMO

OBJECTIVE: Numerous investigators have theorized that postoperative changes in Alzheimer's disease neuropathology may underlie postoperative neurocognitive disorders. Thus, we determined the relationship between postoperative changes in cognition and cerebrospinal (CSF) tau, p-tau-181p, or Aß levels after non-cardiac, non-neurologic surgery in older adults. METHODS: Participants underwent cognitive testing before and 6 weeks after surgery, and lumbar punctures before, 24 h after, and 6 weeks after surgery. Cognitive scores were combined via factor analysis into an overall cognitive index. In total, 110 patients returned for 6-week postoperative testing and were included in the analysis. RESULTS: There was no significant change from before to 24 h or 6 weeks following surgery in CSF tau (median [median absolute deviation] change before to 24 h: 0.00 [4.36] pg/mL, p = 0.853; change before to 6 weeks: -1.21 [3.98] pg/mL, p = 0.827). There were also no significant changes in CSF p-tau-181p or Aß over this period. There was no change in cognitive index (mean [95% CI] 0.040 [-0.018, 0.098], p = 0.175) from before to 6 weeks after surgery, although there were postoperative declines in verbal memory (-0.346 [-0.523, -0.170], p = 0.003) and improvements in executive function (0.394, [0.310, 0.479], p < 0.001). There were no significant correlations between preoperative to 6-week postoperative changes in cognition and CSF tau, p-tau-181p, or Aß42 changes over this interval (p > 0.05 for each). INTERPRETATION: Neurocognitive changes after non-cardiac, non-neurologic surgery in the majority of cognitively healthy, community-dwelling older adults are unlikely to be related to postoperative changes in AD neuropathology (as assessed by CSF Aß, tau or p-tau-181p levels or the p-tau-181p/Aß or tau/Aß ratios). TRIAL REGISTRATION: clinicaltrials.gov (NCT01993836).


Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Doenças Neurodegenerativas , Complicações Cognitivas Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/líquido cefalorraquidiano , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/fisiopatologia , Período Pré-Operatório
5.
JAMA Surg ; 157(1): e215856, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34787647

RESUMO

Importance: Inhaled nitric oxide (iNO) is commonly administered for selectively inhaled pulmonary vasodilation and prevention of oxidative injury after lung transplant (LT). Inhaled epoprostenol (iEPO) has been introduced worldwide as a cost-saving alternative to iNO without high-grade evidence for this indication. Objective: To investigate whether the use of iEPO will lead to similar rates of severe/grade 3 primary graft dysfunction (PGD-3) after adult LT when compared with use of iNO. Design, Setting, and Participants: This health system-funded, randomized, blinded (to participants, clinicians, data managers, and the statistician), parallel-designed, equivalence clinical trial included 201 adult patients who underwent single or bilateral LT between May 30, 2017, and March 21, 2020. Patients were grouped into 5 strata according to key prognostic clinical features and randomized per stratum to receive either iNO or iEPO at the time of LT via 1:1 treatment allocation. Interventions: Treatment with iNO or iEPO initiated in the operating room before lung allograft reperfusion and administered continously until cessation criteria met in the intensive care unit (ICU). Main Outcomes and Measures: The primary outcome was PGD-3 development at 24, 48, or 72 hours after LT. The primary analysis was for equivalence using a two one-sided test (TOST) procedure (90% CI) with a margin of 19% for between-group PGD-3 risk difference. Secondary outcomes included duration of mechanical ventilation, hospital and ICU lengths of stay, incidence and severity of acute kidney injury, postoperative tracheostomy placement, and in-hospital, 30-day, and 90-day mortality rates. An intention-to-treat analysis was performed for the primary and secondary outcomes, supplemented by per-protocol analysis for the primary outcome. Results: A total of 201 randomized patients met eligibility criteria at the time of LT (129 men [64.2%]). In the intention-to-treat population, 103 patients received iEPO and 98 received iNO. The primary outcome occurred in 46 of 103 patients (44.7%) in the iEPO group and 39 of 98 (39.8%) in the iNO group, leading to a risk difference of 4.9% (TOST 90% CI, -6.4% to 16.2%; P = .02 for equivalence). There were no significant between-group differences for secondary outcomes. Conclusions and Relevance: Among patients undergoing LT, use of iEPO was associated with similar risks for PGD-3 development and other postoperative outcomes compared with the use of iNO. Trial Registration: ClinicalTrials.gov identifier: NCT03081052.


Assuntos
Epoprostenol/administração & dosagem , Transplante de Pulmão , Óxido Nítrico/administração & dosagem , Vasodilatadores/administração & dosagem , Administração por Inalação , Adulto , Feminino , Rejeição de Enxerto , Humanos , Masculino , Prognóstico
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