Intraoperative Use of Phenylephrine versus Ephedrine and Postoperative Delirium: A Multicenter Retrospective Cohort Study.

BACKGROUND: The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. The hypothesis was that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium. METHODS: A total of 103,094 hospitalized adults undergoing general anesthesia for noncardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within 7 days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied. RESULTS: Between the two healthcare networks, 78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery; 770 patients (0.8%) developed delirium within 7 days. The median (interquartile range) total intraoperative dose of phenylephrine was 1.0 (0.2 to 3.3) mg and 10.0 (10.0 to 20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within 7 days (adjusted odds ratio, 1.35; 95% CI, 1.06 to 1.71; and adjusted absolute risk difference, 0.2%; 95% CI, 0.1 to 0.3%; P = 0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence, 3.2%; adjusted odds ratio, 1.88; 95% CI, 1.49 to 2.37; P < 0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient, 0.08; 95% CI, 0.02 to 0.14; P = 0.013, per each µg/kg increase in the cumulative phenylephrine dose). CONCLUSIONS: The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on these data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.

Association of Obstructive Sleep Apnea With Postoperative Delirium in Procedures of Moderate-to-High Complexity: A Hospital-Registry Study.

BACKGROUND: Patients suffering from obstructive sleep apnea (OSA) experience chronic sleep disturbances and desaturation, factors that have been associated with postoperative delirium and that can be aggravated after anesthesia for complex procedures. We investigated whether OSA is associated with delirium after anesthesia, and whether this association is modified by procedural complexity. METHODS: Hospitalized patients ≥60 years who underwent general anesthesia or procedural sedation for procedures of moderate-to-high complexity between 2009 and 2020 at a tertiary health care network in Massachusetts were included. The primary exposure was OSA, defined based on International Classification of Diseases ( Ninth/Tenth Revision, Clinical Modification ) ( ICD-9 / 10-CM ) diagnostic codes, structured nursing interviews, anesthesia alert notes, and a validated risk score (BOSTN [body mass index, observed apnea, snoring, tiredness, and neck circumference]). The primary end point was delirium within 7 days after the procedure. Multivariable logistic regression and effect modification analyses adjusted for patient demographics, comorbidities, and procedural factors were applied. RESULTS: A total of 46,352 patients were included, of which 1694 patients (3.7%) developed delirium, 537 (3.2%) with OSA, and 1,157 (4.0%) without OSA. In adjusted analyses, OSA was not associated with postprocedural delirium in the overall cohort (adjusted odds ratio [OR adj ], 1.06; 95% confidence interval [CI], 0.94-1.20; P = .35). However, a high procedural complexity modified the primary association ( P value for interaction = .002). OSA patients had a higher risk of delirium after high-complexity procedures (≥40 work relative value units) such as cardiac (OR adj , 1.33; 95% CI, 1.08-1.64; P = .007, P value for interaction = .005) or thoracic surgery (OR adj , 1.89; 95% CI, 1.19-3.00; P = .007, P value for interaction = .009), but no increased risk after moderate complexity procedures, including general surgery (OR adj , 0.86; 95% CI, 0.55-1.35; P = .52). CONCLUSIONS: Compared to non-OSA patients, a history of OSA is associated with a higher risk after high-complexity procedures such as cardiac or thoracic surgery but not after procedures of moderate complexity.

Dose-dependent relationship between intra-procedural hypoxaemia or hypocapnia and postoperative delirium in older patients.

BACKGROUND: Previous studies indicated an association between impaired cerebral perfusion and post-procedural neurological disorders. We investigated whether intra-procedural hypoxaemia or hypocapnia are associated with delirium after surgery. METHODS: Inpatients ≥60 yr of age undergoing anaesthesia for surgical or interventional procedures between 2009 and 2020 at an academic healthcare network in the USA (Massachusetts) were included in this hospital registry study. The primary exposure was intra-procedural hypoxaemia, defined as peripheral oxygen saturation <90% for >2 cohering min. The co-primary exposure was hypocapnia during general anaesthesia, defined as end-tidal carbon dioxide pressure ≤25 mm Hg for >5 cohering min. The primary outcome was delirium within 7 days after surgery. RESULTS: Of 71 717 included patients, 1702 (2.4%) developed postoperative delirium, and hypoxaemia was detected in 2532 (3.5%). Of 42 894 patients undergoing general anaesthesia, 532 (1.2%) experienced hypocapnia. The occurrence of either hypoxaemia (adjusted odds ratio [ORadj]=1.71; 95% confidence interval [CI], 1.40-2.07; P<0.001) or hypocapnia (ORadj=1.77; 95% CI, 1.30-2.41; P<0.001) was associated with a higher risk of delirium within 7 days. Both associations were dependent on the magnitude, and increased with event duration (ORadj=1.03; 95% CI, 1.02-1.04; P<0.001 and ORadj=1.01; 95% CI, 1.00-1.01; P=0.005, for each minute increase in the longest continuous episode, respectively). There was no association between occurrence of hypercapnia and postoperative delirium (ORadj=1.24; 95% CI, 0.90-1.71; P=0.181). CONCLUSIONS: Intra-procedural hypoxaemia and hypocapnia were dose-dependently associated with a higher risk of postoperative delirium. These findings support maintaining normal gas exchange to avoid postoperative neurological disorders.

Cognitive function in older patients and their stress challenge using different anesthesia regimes: a single center observational study.

BACKGROUND: With increasing age older patients are at higher risk for cognitive decline after surgery. Even tailored anesthesia procedures in older patients remain a high risk for postoperative cognitive disorder. Additional stress derived from anxiety and anesthesia itself can negatively impact postoperative cognitive outcomes. The objective of this study was to evaluate the impact of general versus regional anesthesia on postoperative cognitive disorder and indicators of perioperative stress in elderly undergoing surgery. METHODS: In this single center prospective study between December 2014 and November 2015, 46 patients aged 50 to 85 years undergoing dermatology surgery were enrolled. Patients were stratified by receiving general versus regional nerve anesthesia. On three consecutive days, saliva cortisol levels were analyzed three times per day. Cognitive function was assessed on the day before and the day after surgery using comprehensive neuropsychological testing of multiple cognitive functions including memory, executive function, attention and processing speed. RESULTS: Comparing the regional anesthesia group (RAG, n = 28) with the general anesthesia group (GAG, n = 18) no significant difference in the postoperative cognitive function was observed. However, patients in the GAG had significantly higher postoperative cortisol levels when compared to patients in the RAG. In both groups, a peak of cortisol value was detected on the day of surgery, which was higher in the GAG in comparison to the RAG. CONCLUSIONS: We did not observe a difference in postoperative cognitive function between patients undergoing regional or general anesthesia for dermatology surgery. However, we found lower cortisol level in the RAG. Based on these findings, future studies should investigate alternatives to reduce stress in a general anesthesia setting. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02505815.

Short term cognitive function after sevoflurane anesthesia in patients suspect to obstructive sleep apnea syndrome: an observational study.

BACKGROUND: The obstructive sleep apnea syndrome (OSAS) is characterized by intermittent cerebral hypoxia which can cause cognitive alterations. Likewise, hypoxia induced neurocognitive deficits are detectable after general anesthesia using volatile anesthetics. The objective of this study was to evaluate the association between a moderate to high risk patients of OSAS and postoperative cognitive dysfunction after volatile anesthesia. METHODS: In this single center prospective, observational study between May 2013 and September 2013, 46 patients aged 55 to 80 years with an estimated hospital stay of at least 3 days undergoing surgery were enrolled. Patients were screened using the STOP-BANG test with score of 3 or higher indicating moderate to high risk of OSAS. The cognitive function was assessed using a neuropsychological assessment battery, including the DemTect test for cognitive impairment among other tests e.g. SKT memory, the day before surgery and within 2 days after extubation. RESULTS: Twenty-three of the 46 analyzed patients were identified with a moderate to high risk of OSAS. When comparing post- to preoperative phase a significant better performance for the SKT was found for both groups (p <  0.001). While the moderate to high risk group scores increased postoperative in the DemTect test, they decreased in the low risk group (p <  0.003). When comparing the changes between groups, the moderate to high risk patients showed significant better test result for DemTect testing after anaesthesia. This effect remained robust when adjusting for potential confounding variables using a two-factor ANOVA. CONCLUSION: Compared to low risk, a moderate to high risk of OSAS based on the STOP-BANG score was associated with improved postoperative cognitive function measured by the DemTect test. TRIAL REGISTRATION: The study was approved by the local Ethics committee (Ethikkommission der Medizinischen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany) (reference number: 87_12 B ) on 19.04.2012.

A high risk of sleep apnea is associated with less postoperative cognitive dysfunction after intravenous anesthesia: results of an observational pilot study.

BACKGROUND: The obstructive sleep apnea syndrome (OSAS) is characterized by temporary cerebral hypoxia which can cause cognitive dysfunction. On the other hand, hypoxia induced neurocognitive deficits are detectable after general anesthesia. The objective of this study was to evaluate the impact of a high risk of OSAS on the postoperative cognitive dysfunction after intravenous anesthesia. METHODS: In this single center trial between June 2012 and June 2013 43 patients aged 55 to 80 years with an estimated hospital stay of at least 3 days undergoing surgery were enrolled. Patients were screened for a high risk of OSAS using the STOP-BANG test. The cognitive function was assessed using a neuropsychological test battery, including the DemTect test for cognitive impairment and the RMBT test for memory, the day before surgery and within 36 h after extubation. RESULTS: Twenty-two of the 43 analyzed patients were identified as patients with a high risk of OSAS. Preoperatively, OSAS patients showed a significant worse performance only for the DemTect (p = 0.0043). However, when comparing pre- and postoperative test results, the OSAS patients did not show a significant loss in any test but significantly improved in RMBT test, whereas the control group showed a significant worse performance in three of eight tests. In five tests, we found a significant difference between the two groups with respect to the change from pre- to postoperative cognitive function. CONCLUSION: Patients with a high risk of OSAS showed a less impairment of memory function and work memory performance after intravenous anesthesia. This might be explained by a beneficial effect of intrinsic hypoxic preconditioning in these patients.

Coronary artery bypass surgery and acute kidney injury--impact of the off-pump technique.

BACKGROUND: Acute kidney injury (AKI) is a serious and frequent complication after coronary artery bypass grafting (CABG). Cardiopulmonary bypass (CPB) was identified as a major AKI risk factor after CABG. Our aim was to assess the impact of the off-pump coronary artery bypass (OPCAB) compared to the on-pump coronary artery bypass (ONCAB) technique on the rate and severity of AKI, while taking other risk factors for AKI into account. METHODS: An observational study of 201 consecutive adult patients was conducted; 100 were operated by the OPCAB and 101 by the ONCAB technique. All patients in each group were operated by a single, experienced surgeon. Fifteen pre-, intra- and postoperative variables that were repeatedly identified in previous studies as independent AKI risk factors were included in this analysis. AKI was defined as an increase of serum creatinine >/=50% or >/=0.3 mg/dL within 48 h and AKI severity was classified, according to current AKIN definitions. RESULTS: Significantly fewer OPCAB patients developed AKI compared to ONCAB (14.0 versus 27.7%; P = 0.03). OPCAB was associated with milder stages of AKI, whereas ONCAB patients had more severe AKI. Congestive heart failure and chronic kidney disease were independent risk factors for AKI. The OPCAB technique for CABG was identified as the only independent factor associated with lower incidence of AKI. CONCLUSIONS: Using current AKI definitions and classifications, the OPCAB technique for CABG, which avoids CPB; was associated with a significantly lower rate and less severe AKI compared to ONCAB. The OPCAB technique was identified as the only modifiable and potentially protective factor against postoperative AKI.

Endocardial TRPC-6 Channels Act as Atrial Mechanosensors and Load-Dependent Modulators of Endocardial/Myocardial Cross-Talk.

Mechanoelectrical feedback may increase arrhythmia susceptibility, but the molecular mechanisms are incompletely understood. This study showed that mechanical stretch altered the localization, protein levels, and function of the cation-selective transient receptor potential channel (TRPC)-6 in atrial endocardial cells in humans, pigs, and mice. In endocardial/myocardial cross-talk studies, addition of media from porcine atrial endocardium (AE) cells altered the calcium (Ca2+) transient characteristics of human-induced pluripotent stem cell-derived cardiomyocytes. These changes did not occur with media from stretched AE cells. Our data suggested that endocardial TRPC-6-dependent paracrine signaling may modulate myocardial Ca2+ homeostasis under basal conditions and protect against stretch-induced atrial arrhythmias.

Mechano-regulation of the beating heart at the cellular level--mechanosensitive channels in normal and diseased heart.

The heart as a contractile hollow organ finely tunes mechanical parameters such as stroke volume, stroke pressure and cardiac output according to filling volumes, filling pressures via intrinsic and neuronal routes. At the cellular level, cardiomyocytes in beating hearts are exposed to large mechanical stress during successive heart beats. Although the mechanisms of excitation-contraction coupling are well established in mammalian heart cells, the putative contribution of mechanosensitive channels to Ca²âº homeostasis, Ca²âº signaling and force generation has been primarily investigated in relation to heart disease states. For instance, transient receptor potential channels (TRPs) are up-regulated in animal models of congestive heart failure or hypertension models and seem to play a vital role in pathological Ca²âº overload to cardiomyocytes, thus aggravating the pathology of disease at the cellular level. Apart from that, the contribution of mechanosensitive channels (MsC) in the normal beating heart to the downstream force activation cascade has not been addressed. We present an overview of the current literature and concepts of mechanosensitive channel involvement in failing hearts and cardiomyopathies and novel data showing a likely contribution of Ca²âº influx via mechanosensitive channels in beating normal cardiomyocytes during systolic shortening.

Regulation of murine cardiac contractility by activation of α(1A)-adrenergic receptor-operated Ca(2+) entry.

AIMS: Sympathetic regulation of cardiac contractility is mediated in part by α(1)-adrenergic receptors (ARs), and the α(1A)-subtype has been implicated in the pathogenesis of cardiac hypertrophy. However, little is known about α(1A)-AR signalling pathways in ventricular myocardium. The aim of this study was to determine the signalling pathway that mediates α(1A)-AR-coupled cardiac contractility. METHODS AND RESULTS: Using a transgenic model of enhanced cardiac α(1A)-AR expression and signalling (α(1A)-H mice), we identified a receptor-coupled signalling pathway that enhances Ca(2+) entry and increases contractility. This pathway involves α(1A)-AR-activated translocation of Snapin and the transient receptor potential canonical 6 (TRPC6) channel to the plasma membrane. In ventricular cardiomyocytes from α(1A)-H and their non-transgenic littermates (or WTs), stimulation with α(1A)-AR-specific agonists resulted in increased [Ca(2+)](i), which was dose-related and proportional to the level of α(1A)-AR expression. Blockade of TRPC6 inhibited the α(1A)-AR-mediated increase in [Ca(2+)](i) and contractility. External Ca(2+) entry, underlying the [Ca(2+)](i) increase, was not due to store-operated Ca(2+) entry but to a receptor-operated mechanism of Ca(2+) entry resulting from α(1A)-AR activation. CONCLUSION: These findings indicate that Ca(2+) entry via the α(1A)-AR-Snapin-TRPC6-pathway plays an important role in physiological regulation of cardiac contractility and may be an important target for augmenting cardiac performance.