Antipsychotics and Risks of Cardiovascular and Cerebrovascular Diseases and Mortality in Dwelling Community Older Adults.

This study aims to investigate the effect of antipsychotic agents on cardiovascular and cerebrovascular diseases (CVD/CEV) and mortality risks in the older population living in a community. A cohort of 42,650 new users of antipsychotic agents was built using Quebec healthcare databases (1998-2011). The outcomes were CVD/CEV and mortality incidence in 5 years of follow-up in the total cohort, sub-cohort of patients with no schizophrenia/dementia, sub-cohort with schizophrenia, and sub-cohort with dementia. Comparisons were made between the new users who continued the treatment (adherent level ≥ 60%) vs. those ceasing treatment (adherence level < 60%) using inverse probability of treatment weighting and Cox models. Comparing high adherence vs. low levels, CVD/CEV risk was increased by 36% in the sub-cohort with schizophrenia for atypical antipsychotic users and by 25% in the sub-cohort with dementia for typical antipsychotic users. An increasing mortality risk of 2- to 3-fold was linked with the typical antipsychotic use in all cohorts except the sub-cohort with schizophrenia; in addition, mortality risk is linked with the use of high vs. low doses. Antipsychotics were not linked with CVD/CEV risk, except for atypical antipsychotics in patients with schizophrenia and typical antipsychotics in patients with dementia. The mortality risk was linked with the use of typical antipsychotics and the dose used.

Clinical relevance of transcranial Doppler in a cardiac surgery setting: embolic load predicts difficult separation from cardiopulmonary bypass.

BACKGROUND: During cardiac surgery, transcranial Doppler (TCD) represents a non-invasive modality that allows measurement of red blood cell flow velocities in the cerebral arteries. TCD can also be used to detect and monitor embolic material in the cerebral circulation. Detection of microemboli is reported as a high intensity transient signal (HITS). The importance of cerebral microemboli during cardiac surgery has been linked to the increased incidence of postoperative renal failure, right ventricular dysfunction, and hemodynamic instability. The objective of this study is to determine whether the embolic load is associated with hemodynamic instability during cardiopulmonary bypass (CPB) separation and postoperative complications. METHODS: A retrospective single-centre cohort study of 354 patients undergoing cardiac surgery between December 2015 and March 2020 was conducted. Patients were divided in tertiles, where 117 patients had a low quantity of embolic material (LEM), 119 patients have a medium quantity of microemboli (MEM) and 118 patients who have a high quantity of embolic material (HEM). The primary endpoint was a difficult CPB separation. Multivariate logistic regression was used to determine the potential association between a difficult CPB separation and the number of embolic materials. RESULTS: Patients who had a difficult CPB separation had more HITS compared to patients who had a successful CPB separation (p < 0.001). In the multivariate analysis, patients with MEM decreased their odds of having a difficult CPB weaning compared to patients in the HEM group (OR = 0.253, CI 0.111-0.593; p = 0.001). In the postoperative period patients in the HEM group have a higher Time of Persistent Organ Dysfunction (TPOD), a longer stay in the ICU, a longer duration under vasopressor drugs and a higher mortality rate compared to those in the MEM and LEM groups. CONCLUSION: The result of this study suggests that a high quantity of cerebral embolic material increases the odds of having a difficult CPB separation. Also, it seems to be associated to more complex surgery, a longer CPB time, a higher TPOD and a longer stay in the ICU. Six out of eight patients who died in this cohort were in the HEM group.

Inhaled Epoprostenol and Milrinone Effect on Right Ventricular Pressure Waveform Monitoring.

BACKGROUND: Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are major complications in cardiac surgery. This study aimed to evaluate the change in RV pressure waveform in patients receiving a combination of inhaled epoprostenol and inhaled milrinone (iE&iM) before cardiopulmonary bypass (CPB) and to assess the safety of this approach with a matched case-control group. METHODS: A prospective single-centre cohort study of adult patients undergoing cardiac surgery administered iE&iM through an ultrasonic mesh nebulizer. RV pressure waveform monitoring was obtained by continuously transducing the RV port of the pulmonary artery (PA) catheter. RESULTS: The final analysis included 26 patients receiving iE&iM. There was a significant drop in mean PA pressure (MPAP) (-4.8 ± 8.7, P = 0.010), systolic PA pressure (SPAP) (-8.2 ± 12.8, P = 0.003), RV end-diastolic pressure (RVEDP) (-2.1 ± 2.8, P < 0.001) and RV diastolic pressure gradient (RVDPG) (-1.7 ± 1.4, P < 0.001) after 17 ± 9 minutes of iE&iM administration. Patients also had a significant increase in RV outflow tract (RVOT) gradient (3.7 ± 4.7, P < 0.001), RV maximal rate of pressure rise during early systole (dP/dt max) (68.3 ± 144.7, P = 0.024), and left ventricular (LV) dP/dt max (66.4 ± 90.1, P < 0.001). Change in RVOT gradient was only observed in those with a positive pulmonary vasodilator response to treatment. Treatment with iE&iM did not present adverse effects when compared with a matched case-control group. CONCLUSIONS: Coadministration of iE&iM in cardiac surgery patients presenting with PH or signs of RV dysfunction is a safe and effective treatment approach in improving RV function. Appearance of a transient increase in RVOT gradient after iE&iM could be useful to predict response to treatment.

Pulmonary Vasodilator Response of Combined Inhaled Epoprostenol and Inhaled Milrinone in Cardiac Surgical Patients.

BACKGROUND: Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are major complications in cardiac surgery. Intraoperative management of patients at high risk of RV failure should aim to reduce RV afterload and optimize RV filling pressures, while avoiding systemic hypotension, to facilitate weaning from cardiopulmonary bypass (CPB). Inhaled epoprostenol and inhaled milrinone (iE&iM) administered in combination before CPB may represent an effective strategy to facilitate separation from CPB and reduce requirements for intravenous inotropes during cardiac surgery. Our primary objective was to report the rate of positive pulmonary vasodilator response to iE&iM and, second, how it relates to perioperative outcomes in cardiac surgery. METHODS: This is a retrospective cohort study of consecutive patients with PH or RV dysfunction undergoing on-pump cardiac surgery at the Montreal Heart Institute from July 2013 to December 2018 (n = 128). iE&iM treatment was administered using an ultrasonic mesh nebulizer before the initiation of CPB. Demographic and baseline clinical data, as well as hemodynamic, intraoperative, and echocardiographic data, were collected using electronic records. An increase of 20% in the mean arterial pressure (MAP) to mean pulmonary artery pressure (MPAP) ratio was used to indicate a positive response to iE&iM. RESULTS: In this cohort, 77.3% of patients were responders to iE&iM treatment. Baseline systolic pulmonary artery pressure (SPAP) (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.24-2.16 per 5 mm Hg; P = .0006) was found to be a predictor of pulmonary vasodilator response, while a European System for Cardiac Operative Risk Evaluation (EuroSCORE II) score >6.5% was a predictor of nonresponse to treatment (≤6.5% vs >6.5% [reference]: OR, 5.19; 95% CI, 1.84-14.66; P = .002). Severity of PH was associated with a positive response to treatment, where a higher proportion of responders had MPAP values >30 mm Hg (42.4% responders vs 24.1% nonresponders; P = .0237) and SPAP values >55 mm Hg (17.2% vs 3.4%; P = .0037). Easier separation from CPB was also associated with response to iE&iM treatment (69.7% vs 58.6%; P = .0181). A higher proportion of nonresponders had a very difficult separation from CPB and required intravenous inotropic drug support compared to responders, for whom easy separation from CPB was more frequent. Use of intravenous inotropes after CPB was lower in responders to treatment (8.1% vs 27.6%; P = .0052). CONCLUSIONS: A positive pulmonary vasodilator response to treatment with a combination of iE&iM before initiation of CPB was observed in 77% of patients. Higher baseline SPAP was an independent predictor of pulmonary vasodilator response, while EuroSCORE II >6.5% was a predictor of nonresponse to treatment.

Early Detection and Correction of Cerebral Desaturation With Noninvasive Oxy-Hemoglobin, Deoxy-Hemoglobin, and Total Hemoglobin in Cardiac Surgery: A Case Series.

Regional cerebral oxygen saturation (rS o2 ) obtained from near-infrared spectroscopy (NIRS) provides valuable information during cardiac surgery. The rS o2 is calculated from the proportion of oxygenated to total hemoglobin in the cerebral vasculature. Root O3 cerebral oximetry (Masimo) allows for individual identification of changes in total (ΔcHbi), oxygenated (Δ o2 Hbi), and deoxygenated (ΔHHbi) hemoglobin spectral absorptions. Variations in these parameters from baseline help identify the underlying mechanisms of cerebral desaturation. This case series represents the first preliminary description of Δ o2 Hbi, ΔHHbi, and ΔcHbi variations in 10 cardiac surgical settings. Hemoglobin spectral absorption changes can be classified according to 3 distinct variations of cerebral desaturation. Reduced cerebral oxygen content or increased cerebral metabolism without major blood flow changes is reflected by decreased Δ o2 Hbi, unchanged ΔcHbi, and increased ΔHHbi Reduced cerebral arterial blood flow is suggested by decreased Δ o2 Hbi and ΔcHbi, with variable ΔHHbi. Finally, acute cerebral congestion may be suspected with increased ΔHHbi and ΔcHbi with unchanged Δ o2 Hbi. Cerebral desaturation can also result from mixed mechanisms reflected by variable combination of those 3 patterns. Normal cerebral saturation can occur, where reduced cerebral oxygen content such as anemia is balanced by a reduction in cerebral oxygen consumption such as during hypothermia. A summative algorithm using rS o2 , Δ o2 Hbi, ΔHHbi, and ΔcHbi is proposed. Further explorations involving more patients should be performed to establish the potential role and limitations of monitoring hemoglobin spectral absorption signals.

Impact of Processed Electroencephalography in Cardiac Surgery: A Retrospective Analysis.

OBJECTIVE: The use of brain function monitoring with processed electroencephalography (pEEG) during cardiac surgery is gaining interest for the optimization of hypnotic agent delivery during the maintenance of anesthesia. The authors sought to determine whether the routine use of pEEG-guided anesthesia is associated with a reduction of hemodynamic instability during cardiopulmonary bypass (CPB) separation and subsequently reduces vasoactive and inotropic requirements in the intensive care unit. DESIGN: This is a retrospective cohort study based on an existing database. SETTING: A single cardiac surgical center. PARTICIPANTS: Three hundred patients undergoing cardiac surgery, under CPB, between December 2013 and March 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred and fifty patients had pEEG-guided anesthesia, and 150 patients did not have a pEEG-guided anesthesia. Multiple logistic regression demonstrated that pEEG-guided anesthesia was not associated with a successful CPB separation (p = 0.12). However, the use of pEEG-guided anesthesia reduced by 57% the odds of being in a higher category for vasoactive inotropic score compared to patients without pEEG (odds ratio = 0.43; 95% confidence interval: 0.26-0.73; p = 0.002). Duration of mechanical ventilation, fluid balance, and blood losses were also reduced in the pEEG anesthesia-guided group (p < 0.003), but there were no differences in organ dysfunction duration and mortality. CONCLUSION: During cardiac surgery, pEEG-guided anesthesia allowed a reduction in the use of inotropic or vasoactive agents at arrival in the intensive care unit. However, it did not facilitate weaning from CPB compared to a group where pEEG was unavailable. A pEEG-guided anesthetic management could promote early vasopressor weaning after cardiac surgery.

Downregulation of low-density lipoprotein receptor mRNA in lymphatic endothelial cells impairs lymphatic function through changes in intracellular lipids.

Rationale: Impairment in lymphatic transport is associated with the onset and progression of atherosclerosis in animal models. The downregulation of low-density-lipoprotein receptor (LDLR) expression, rather than increased circulating cholesterol level per se, is involved in early atherosclerosis-related lymphatic dysfunction. Enhancing lymphatic function in Ldlr-/- mice with a mutant form of VEGF-C (VEGF-C 152s), a selective VEGFR-3 agonist, successfully delayed atherosclerotic plaque onset when mice were subsequently fed a high-fat diet. However, the specific mechanisms by which LDLR protects against lymphatic function impairment is unknown. Methods and results: We have thus injected wild-type and Pcsk9-/- mice with an adeno-associated virus type 1 expressing a shRNA for silencing Ldlr in vivo. We herein report that lymphatic contractility is reduced upon Ldlr dowregulation in wild-type mice only. Our in vitro experiments reveal that a decrease in LDLR expression at the mRNA level reduces the chromosome duplication phase and the protein expression of VEGFR-3, a membrane-bound key lymphatic marker. Furthermore, it also significantly reduced the levels of 18 lipid subclasses, including key constituents of lipid rafts as well as the transcription of several genes involved in cholesterol biosynthesis and cellular and metabolic processes. Exogenous PCSK9 only reduces lymphatic endothelial-LDLR at the protein level and does not affect lymphatic endothelial cell integrity. This puts forward that PCSK9 may act upon lymphatic muscle cells to mediate its effect on lymphatic contraction capacity in vivo. Conclusion: Our results suggest that treatments that specifically palliate the down regulation of LDLR mRNA in lymphatic endothelial cells preserve the integrity of the lymphatic endothelium and sustain lymphatic function, a prerequisite player in atherosclerosis.

Intra-abdominal pressure during and after cardiac surgery: a single-centre prospective cohort study.

PURPOSE: While intra-abdominal hypertension (IAH) has been associated with adverse outcomes in multiple settings, the epidemiology and clinical implications of IAH in the context of cardiac surgery are less known. In this study, we aimed to describe the prevalence of IAH in patients undergoing cardiac surgery and determine its association with patient characteristics and postoperative outcomes. METHODS: We conducted a single-centre prospective cohort study in which intra-abdominal pressure was measured in the operating room after general anesthesia (T1), after the surgical procedure (T2), and two hours after intensive care unit (ICU) admission (T3) in a subset of patients. Intra-abdominal hypertension was defined as intra-abdominal pressure (IAP) ≥ 12 mm Hg. Postoperative outcomes included death, acute kidney injury (AKI), and length of stay in the ICU and hospital. RESULTS: A total of 513 IAP measurements were obtained from 191 participants in the operating room and 131 participants in the ICU. Intra-abdominal hypertension was present in 105/191 (55%) at T1, 115/191 (60%) at T2, and 31/131 (24%) at T3. Intra-abdominal pressure was independently associated with body mass index, central venous pressure, and mean pulmonary artery pressure but was not associated with cumulative fluid balance. Intraoperative IAH was not associated with adverse outcomes including AKI. CONCLUSIONS: Intra-abdominal hypertension is very common during cardiac surgery but its clinical implications are uncertain.

RéSUMé: OBJECTIF: Bien que l'hypertension intra-abdominale (HIA) ait été associée à des issues indésirables dans de multiples contextes, l'épidémiologie et les implications cliniques de l'HIA dans le contexte de la chirurgie cardiaque sont moins connues. Dans cette étude, nous avons cherché à décrire la prévalence de l'HIA chez les patients bénéficiant d'une chirurgie cardiaque et à déterminer son association avec les caractéristiques des patients et les issues postopératoires. MéTHODE: Nous avons mené une étude de cohorte prospective monocentrique dans laquelle la pression intra-abdominale a été mesurée en salle d'opération après une anesthésie générale (T1), après l'intervention chirurgicale (T2) et deux heures après l'admission à l'unité de soins intensifs (USI) (T3) dans un sous-ensemble de patients. L'hypertension intra-abdominale a été définie comme une pression intra-abdominale (PIA) ≥ 12 mmHg. Les issues postopératoires comprenaient le décès, l'insuffisance rénale aiguë (IRA), et la durée du séjour à l'USI et à l'hôpital. RéSULTATS: Au total, 513 mesures de la PIA ont été obtenues auprès de 191 participants en salle d'opération et de 131 participants à l'USI. L'hypertension intra-abdominale était présente chez 105/191 patients (55 %) à T1, 115/191 (60 %) à T2 et 31/131 (24 %) à T3. La pression intra-abdominale était indépendamment associée à l'indice de masse corporelle, à la pression veineuse centrale et à la pression artérielle pulmonaire moyenne, mais n'était pas associée à un bilan hydrique cumulatif. L'HIA peropératoire n'était pas associée à des issues indésirables, y compris à l'IRA. CONCLUSION: L'hypertension intra-abdominale est très fréquente lors d'une chirurgie cardiaque, mais ses implications cliniques sont incertaines.

Pulsatile Femoral Vein Doppler and Congestive Delirium, What Is the Relationship?: A Case Report.

Delirium is common in patients undergoing cardiac surgery, and venous congestion has been reported as an important risk factor. We report a 69-year-old patient who developed postoperative delirium in the intensive care unit following aortic valve replacement surgery. The postoperative course was complicated by delirium for which echographic signs of venous congestion on the portal and the renal but also the femoral veins and their resolution correlated with the course of delirium. The use of common femoral vein Doppler as a simple bedside technique to predict and identify congestive delirium has not been reported before.

Right Ventricular Outflow Tract Obstruction in Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Right ventricular outflow tract obstruction (RVOTO) is a cause of hemodynamic instability that can occur in several situations, including cardiac surgery, lung transplantation, and thoracic surgery, and in critically ill patients. The timely diagnosis of RVOTO is important because it requires specific considerations, including the adverse effects of positive inotropes, and depending on the etiology, the requirement for urgent surgical intervention. METHODS: The objective of this systematic review and meta-analysis was to determine the prevalence of RVOTO in adult patients, and the distribution of all reported cases by etiology. RESULTS: Of 233 available reports, there were 229 case reports or series, and 4 retrospective cohort studies, with one study also reporting a prospective cohort. Of 291 reported cases of RVOTO, 61 (21%) were congenital, 56 (19%) were iatrogenic, and 174 (60%) were neither congenital nor iatrogenic (including intracardiac tumour). The mechanism of RVOTO was an intrinsic obstruction in 169 cases (58%), and an extrinsic obstruction in 122 cases (42%). A mechanical obstruction causing RVOTO was present in 262 cases (90%), and 29 cases of dynamic RVOTO (10%) were reported. In the 5 included cohorts, with a total of 1122 patients, the overall prevalence was estimated to be 4.0% (1%-9%). CONCLUSIONS: RVOTO, though rare, remains clinically important, and therefore, multicentre studies are warranted to better understand the prevalence, causes, and consequences of RVOTO.

CONTEXTE: L'obstruction de la chambre de chasse du ventricule droit (OCCVD) est une cause d'instabilité hémodynamique qui peut survenir dans plusieurs situations, y compris une chirurgie cardiaque, une transplantation pulmonaire ou une chirurgie thoracique, ou encore chez des patients en phase critique. Il est important que le diagnostic d'OCCVD soit posé rapidement, car d'une part cette affection exige la prise en compte d'éléments particuliers, y compris les effets indésirables des agents inotropes positifs et, d'autre part, en fonction de l'étiologie, une intervention chirurgicale d'urgence pourrait être nécessaire. MÉTHODOLOGIE: L'objectif de cette revue systématique associée à une méta-analyse était de déterminer la prévalence de l'OCCVD chez les patients adultes ainsi que la distribution de tous les cas rapportés en fonction de leur étiologie. RÉSULTATS: Sur les 233 rapports disponibles, on comptait 229 études ou séries de cas, et quatre études de cohortes rétrospectives, dont une qui présentait également les résultats d'une cohorte prospective. Sur 291 cas d'OCCVD rapportés, 61 (21 %) étaient d'origine congénitale, 56 (19 %) étaient d'origine iatrogène et 174 (60 %) avaient une origine qui n'était ni congénitale ni iatrogène (dont une tumeur intracardiaque). Le mécanisme de l'OCCVD était une obstruction intrinsèque dans 169 cas (58 %), et une obstruction extrinsèque dans 122 cas (42 %). Une obstruction mécanique causant l'OCCVD était présente dans 262 cas (90 %), et 29 cas d'OCCVD dynamique (10 %) ont été rapportés. Dans les 5 cohortes incluses, comptant au total 1 122 patients, la prévalence globale était estimée à 4,0 % (de 1 % à 9 %). CONCLUSIONS: L'OCCVD, malgré sa rareté, n'en est pas moins importante sur le plan clinique; la réalisation d'études multicentriques serait donc justifiée pour permettre de mieux comprendre la prévalence, les causes et les conséquences de cette affection.

Effect of electroencephalography-guided anesthesia on neurocognitive disorders in elderly patients undergoing major non-cardiac surgery: A trial protocol The POEGEA trial (POncd Elderly GEneral Anesthesia).

INTRODUCTION: The number of elderly patients undergoing major surgery is rapidly increasing. They are particularly at risk of developing postoperative neurocognitive disorders (NCD). Earlier studies suggested that processed electroencephalographic (EEG) monitors may reduce the incidence of postoperative NCD. However, none of these studies controlled for intraoperative nociception levels or personalized blood pressure targets. Their results remain unclear if the reduction in the incidence of postoperative NCD relates to avoidance of any electroencephalographic pattern suggesting excessive anesthesia depth. OBJECTIVE: The objective of this trial is to investigate-in patients ≥ 70 years old undergoing major non-cardiac surgery-the effect of EEG-guided anesthesia on postoperative NCD while controlling for intraoperative nociception, personalized blood pressure targets, and using detailed information provided by the EEG monitor (including burst suppression ratio, density spectral array, and raw EEG waveform). MATERIAL AND METHODS: This prospective, randomized, controlled trial will be conducted in a single Canadian university hospital. Patients ≥ 70 years old undergoing elective major non-cardiac surgery will be included in the trial. The administration of sevoflurane will be adjusted to maintain a BIS index value between 40 and 60, to keep a Suppression Ratio (SR) at 0%, to keep a direct EEG display without any suppression time and a spectrogram with most of the EEG wave frequency within the alpha, theta, and delta frequencies in the EEG-guided group. In the control group, sevoflurane will be administered to achieve an age-adjusted minimum alveolar concentration of [0.8-1.2]. In both groups, a nociception monitor will guide intraoperative opioid administration, individual blood pressure targets will be used, and cerebral oximetry used to tailor intraoperative hemodynamic management. The primary endpoint will be the incidence of NCD at postoperative day 1, as evaluated by the Montreal Cognitive Assessment (MoCA). Secondary endpoints will include the incidence of postoperative NCD at different time points and the evaluation of cognitive trajectories up to 90 days after surgery among EEG-guided and control groups. STUDY REGISTRATION: NCT04825847 on ClinicalTrials.gov.

Femoral Vein Pulsatility: What Does It Mean?

In this report, the clinical evolution of a 72-year-old patient transferred to the surgical intensive care unit after cardiac surgery is described. The presence of a pulsatile Doppler signal of the common femoral vein was noted after surgery. On postoperative day 5, diuretics in addition to a combination of inhaled epoprostenol and milrinone were associated with normalization of femoral vein pulsatility. The observations seen in peripheral venous flow reinforce the hypothesis that pulsatility of the common femoral vein represents an associated echocardiographic sign of right ventricular dysfunction and may be used to monitor systemic venous congestion. Pulsatility in the venous system may be improved by reducing volume overload and improving right ventricular function.

Doppler Interrogation of the Femoral Vein in the Critically Ill Patient: The Fastest Potential Acoustic Window to Diagnose Right Ventricular Dysfunction?

OBJECTIVES: To report the use of common femoral vein Doppler interrogation as a simple technique to diagnose right ventricular dysfunction. DESIGN: Case report. SETTING: Cardiac surgical ICU. PATIENTS: Postoperative cardiac surgical patients. INTERVENTIONS: Common femoral pulsed-wave and color Doppler examination associated with hepatic, portal, and renal venous Doppler measurement were obtained in both patients and before and after treatment in patient number 1. In addition, right ventricular pressure waveform examination was obtained in patient number 2. MEASUREMENTS AND MAIN RESULTS: The technique to obtain common femoral venous Doppler is described. Two cases of patients presenting with right ventricular dysfunction and fluid overload with portal and renal venous congestion in the perioperative period undergoing complex multivalvular cardiac surgery are presented. Hemodynamic waveform monitoring was performed alongside echocardiographic, hepatic, and renal venous flow Doppler assessment, and spectral Doppler profiles of the common femoral veins were examined. Those findings were useful in confirming our diagnosis and guiding our response to treatment. An algorithm was developed and tested on two additional hemodynamically unstable patients. CONCLUSIONS: Doppler examination of the common femoral vein is a simple, fast, and noninvasive technique that could be useful to rule in the presence of right ventricular dysfunction with venous congestion and help guide the management of such patients.