Drop In Mean Arterial Pressure Research Articles

Mechanical Circulatory Support Reduces Directly Recorded Renal Sympathetic Nerve Activity in an Ovine Model of Cardiogenic Shock

Cardiogenic shock (CS) following myocardial infarction carries a high mortality risk despite advancements in management. The use of mechanical circulatory support in CS has become an effective strategy to improve haemodynamics and prevent acute kidney injury. However, the mechanism of how kidney function improves is unclear. We hypothesised that mechanical support would inhibit renal sympathetic nerve activity (RSNA), mediating renal protection in CS. Experiments were conducted in two groups of anaesthetised female sheep. In one group, CS was induced (n=8) using injections of polystyrene microspheres into the left coronary artery under fluoroscopic guidance. After a 30-minute baseline period (post -embolisation), intravenous phenylephrine infusion at incremental doses was used to assess the baroreflex control of RSNA before pump insertion. When the pressures recovered to baseline values, the circulatory assist Impella pump was inserted into the left ventricle and run randomly at different levels (P0 min-P6 max) with two minutes at each pump level. The controls underwent the same protocol without embolisation (n=6). Coronary artery embolisation resulted in a drop in mean arterial pressure (MAP) of 21 ± 4 mmHg compared to baseline values (n=8). This was associated with a 67% increase in renal sympathetic nerve activity (RSNA) from 16 ± 5 to 21 ± 5 spikes/s (p=0.038; n=7). Circulatory support using Impella significantly increased MAP from 55 ± 4 mmHg to 68 ± 5 mmHg at pump level P6 (one-way ANOVA, p<0.001). Incremental pump support resulted in a significant decrease in RSNA (p<0.001). At pump level P6, RSNA was decreased by 25 ± 5 % compared to P0 (p<0.001). Baroreflex curves predicted a 2% reduction in RSNA at P6 equivalent pressures in CS, which was significantly less than that observed with circulatory support (p=0.006). In the control cohort with no CS, the changes in MAP and RSNA from P0 to P6 were qualitatively similar to the CS cohort. MAP increased from 84 ± 9 to 94 ± 8 mmHg (one-way ANOVA, p<0.001) and RSNA decreased by 13 ± 5 % at P6 (one-way ANOVA, p<0.001). The expected reduction in RSNA with baroreflex assessment at equivalent pressures to P6 was 5% in controls, which was not significantly different to what was observed (p=0.065). Our data indicate that the use of Impella pumps in CS reduces RSNA, which may mediate improvements in kidney function. Interestingly, the renal sympathoinhibition with the Impella pump is greater than that with vasoactive agents alone. We gratefully acknowledge the granting support from Abiomed and the University of Auckland Faculty Research Development Fund. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

EFFICACY OF TOLAZOLINE AND VATINOXAN IN REDUCING ADVERSE EFFECTS OF BUTORPHANOL-AZAPERONE-MEDETOMIDINE IMMOBILIZATION IN ROCKY MOUNTAIN ELK (CERVUS CANADENSIS).

A mixture of butorphanol, azaperone, and medetomidine (BAM) is frequently used for immobilization of North American hoofstock. Common adverse effects include respiratory depression, hypoxemia, and bradycardia. In this nonblinded crossover study the efficacy of two a-2 adrenergic antagonists, tolazoline and vatinoxan, were evaluated in alleviating adverse effects of BAM in Rocky Mountain elk (Cervus canadensis). Early administration of these antagonists was hypothesized to cause an increase in heart rate, respiratory rate, partial pressure of oxygen (PaO2) and hemoglobin oxygen saturation (SpO2), as well as reduction in mean arterial blood pressure without affecting sedation levels. Eight captive adult female elk were immobilized on three separate occasions at least 14 d apart with 0.15 mg/kg butorphanol, 0.05 mg/kg azaperone, and 0.06 mg/kg medetomidine. Tolazoline (2 mg/kg IM), vatinoxan (3 mg/mg medetomidine IV) or sterile saline (2 ml IM) were administered 20 min postinduction. The BAM caused hypoxemia, bradycardia, and moderate hypertension, and because of the severe hypoxemia observed, all animals received intratracheal oxygen throughout immobilization. Heart rate, respiratory rate, rectal temperature, SpO2, PaO2, and systolic, diastolic, and mean arterial blood pressure were monitored every 5 min throughout the immobilization. Intramuscular tolazoline caused a brief but significant drop in mean arterial pressure compared with controls and a brief but nonsignificant increase in heart rate. Vatinoxan caused a significant drop in blood pressure and a brief significant increase in heart rate. Changes in respiratory rates and PaO2 were not observed with either antagonist; however, all animals received oxygen, which may have influenced this result. The depth of sedation was unchanged after administration of either drug.

Venoarterial Extracorporeal Membrane Oxygenation Implementation in Septic Shock Rat Model.

Septic shock, a global health concern, boasts high mortality rates. Research exploring the efficacy of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in septic shock remains limited. Our study aimed to establish a rodent model employing VA-ECMO in septic shock rats, assessing the therapeutic impact of VA-ECMO on septic shock. Nineteen Sprague-Dawley rats were randomly assigned to sham, septic shock, and (septic shock + VA-ECMO; SSE) groups. Septic shock was induced by intravenous lipopolysaccharides, confirmed by a mean arterial pressure drop to 25-30% of baseline. Rats in the SSE group received 2 hours of VA-ECMO support and 60 minutes of post-weaning ventilation. Sham and septic shock groups underwent mechanical ventilation for equivalent durations. Invasive mean arterial pressure monitoring, echocardiographic examinations, and blood gas analysis revealed the efficacy of VA-ECMO in restoring circulation and ensuring adequate tissue oxygenation in septic shock rats. Post-experiment pathology exhibited the potential of VA-ECMO in mitigating major organ injury. In summary, our study successfully established a stable septic shock rat model with the implementation of VA-ECMO, offering a valuable platform to explore molecular mechanisms underlying VA-ECMO's impact on septic shock.

Abstract Number ‐ 54: First Fully Automated Robotic Transcranial Doppler Optimization of Cerebral Blood Flow During Cardiac Revascularization Surgery

Introduction Current technologies including EEG and near infrared pulse oximetry for non‐invasive monitoring of cerebral blood flow during cardiac surgery have proven inadequate for perioperative stroke risk mitigation. Cerebral arterial flow velocity is an excellent indicator of cerebral blood flow making transcranial doppler ultrasound (TCD) an excellent alternative technology for operating room continuous cerebral monitoring. To date, TCD utilization in the operating room has been limited due to frequent movement‐related loss of signal requiring nearly continuous manual probe readjustment. The recent development of fully autonomous robotic TCD (aTCD) has overcome these technical limitations, opening the door for real‐time continuous noninvasive cerebral blood flow monitoring with simultaneous emboli detection. Methods A 47‐year‐old female patient was found to have preoperative complete occlusion of the proximal brachiocephalic artery producing a double cerebral steal phenomenon with retrograde flow in the right internal carotid and vertebral arteries into the subclavian. A preoperative aTCD study disclosed baseline markedly diminished blood flow in the right middle cerebral artery (MCA) fed exclusively by small‐diameter collaterals via the circle of Willis.Intraoperatively, robotic aTCD was used to continuously monitor blood flow in the bilateral MCAs and perform emboli detection. In response to movement‐related signal loss, the robotic aTCD autonomously adjusted the probe position to maintain continuous MCA insonation. Results Shortly after intubation, a small drop in mean arterial pressure led to a near‐total loss of cerebral perfusion to the entire right hemisphere. This perfusion decrease was detected by aTCD, triggering the anesthesiologist to rapidly correct blood pressure to ensure adequate cerebral perfusion as confirmed by the robotic system. The patient was then placed on bypass pump with deployment of a temporary Y‐graft from the pump to the subclavian artery distal to the vertebral branch point and to the aorta to temporarily reverse the double cerebral steal. Coronary bypass was then performed, throughout which cerebral flow velocities were monitored continuously with aTCD and maintained in the safe cerebral perfusion range by adjusting pump pressures. Following a three‐vessel coronary bypass graft, permanent brachiocephalic artery bypass grafts were placed from the proximal aorta to the right subclavian and the proximal common carotid artery.Postoperative aTCD disclosed correction of the previously diminished blood flow detected in the right MCA preoperatively. Brain MRI postoperatively confirmed the absence of acute stroke. Conclusions This case represents the first use of robotic aTCD for real time continuous cerebral blood flow monitoring and optimization during complex cardiac surgery. Our experience suggests that aTCD may improve patient outcomes, particularly during high‐risk cardiac surgical and interventional procedures. Further studies of this promising technology are now needed.

Comparison of effect of prophylactic administration of ondansetron and placebo on prevention of post induction hypotension in elderly patients undergoing surgery in general anesthesia

Background: Post-induction hypotension is a frequently encountered complication seen particularly in elderly population. Hypotension, by impairing vital organ perfusion, increases the morbidity and mortality of the patients. prophylactic use of ondansetron in preventing hypotension after induction of general anaesthesia in elderly patients , hence getting the benefit of preventing both hypotension and postoperative nausea and vomiting by the use of a single drug.
 Subjects and method: This randomized controlled clinical trial was carried out in the operation theaters of general surgery, Mayo Hospital, Lahore, from 09-09-2017 to 09-09-2018. A total of 80 patients who were to undergo general anaesthesia for elective general surgical procedures were recruited for this study. After taking informed consent, the patients were randomly divided into two groups. Patients in group A received ondansetron and those in group B received placebo prior to the induction of anaesthesia. Efficacy was labeled in terms of absence of hypotension i.e. a drop in mean arterial pressure of no more than 25% of baseline at 1, 3, 5, 9 and 11 minutes after induction of anaesthesia. The data was recorded on a predesigned proforma. Statistical analysis was done using SPSS version 21.
 Results: Both groups were comparable in terms of age, gender, ASA status, BMI and weight. Efficacy was seen in 19 (47.50%) cases managed by ondansetron vs. 10 (25%) in placebo group (p = 0.03). There was significant difference of efficacy in patients with age between 60 to 70 years where 63.63% patients in the Group A effectively maintained their blood pressure (p=0.02). Patients having age 70 years or above did not show statistically significant difference. History of hypertension made no impact on the efficacy of ondansetron for maintaining blood pressure after induction (p=0.53)
 Keywords: 
 Ondansetron, Efficacy, Hypotension

A total closed chest swine model of acute myocardial infarction-related cardiogenic shock: A critical double coronary sub-occlusion approach

The management of acute myocardial infarction-related cardiogenic shock (AMICS) represents a significant challenge, with mortality rates remaining high (40–60%), despite recent advances. Current animal models of myocardial infarction are either associated with a very high rate of per-procedure malignant arrhythmia, or with very low impairment of hemodynamic parameters, or with the inability to have complete coronary reperfusion. We sought to develop a closed chest and clinically relevant large animal model of severe AMICS, with high survival rate. Adult pigs were anaesthetized and mechanically ventilated. Percutaneous cardiac catheterization was performed under fluoroscopy. Advanced left ventricular dysfunction was induced by 120 minutes of critical sub-occlusion of the proximal left anterior descending coronary artery and the mid circumflex artery. A thorough hemodynamic assessment was obtained by invasive and non-invasive monitoring devices. Repeated blood samples were obtained to determine blood gas parameters, lactate, and haemoglobin concentration. After death, the heart was retrieved for further histological analyses. All animals (n = 12) developed significant circulatory failure associated with AMICS upon reperfusion and beyond. No animal died during the ischemia process. However, all animals that did not benefited from vasopressor support (“sham” group, n = 4) spontaneously died within 30 minutes of reperfusion, confirming the severity of the model. Cardiogenic shock was characterized by a drop in mean arterial pressure below 60 mmHg (58 ± 5 mmHg at 120 min of ischemia), a significant decrease in mean cardiac output (−44% from 5.7 ± 0.4 at baseline to 3.2 ± 0.4 at 120 minutes of ischemia) and SvO2 (−32% from 57 ± 8 at baseline to 39 ± 6 at 120 minutes of ischemia) and a significant increase in left ventricle end-diastolic pressure (LVEDP) (+110% from 10 ± 3 at baseline to 21 ± 3 at 120 minutes of ischemia). CO2 gap and coronary sinus venous oxygen saturation increased significantly upon ischemia and reperfusion and remained elevated throughout (P ≤ 0.001 for all comparisons). Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. We present, for the first time, a stable and clinically relevant model of severe AMICS obtained by critical double coronary sub-occlusion. The greater severity of the model did not lead to an increase in the frequency of malignant arrythmias and per-procedure mortality.

Construction of an Early Alert System for Intradialytic Hypotension before Initiating Hemodialysis Based on Machine Learning

Introduction: Intradialytic hypotension (IDH) is prevalent and associated with high hospitalization and mortality rates. The purpose of this study was to explore the risk factors for IDH and use artificial intelligence to establish an early alert system before hemodialysis sessions to identify patients at high risk of IDH. Materials and Methods: We obtained data on 314,534 hemodialysis sessions conducted at Sichuan Provincial People’s Hospital from the renal disease treatment information system. IDH was defined as a systolic blood pressure drop ≥20 mm Hg, a mean arterial pressure drop ≥10 mm Hg during dialysis, or the occurrence of clinical hypotensive events requiring nursing intervention. After pre-processing, the data were randomly divided into training (80%) and testing (20%) sets. Four interpolation methods, three feature selection methods, and 18 machine learning algorithms were used to construct predictive models. The area under the receiver operating characteristic curve (AUC) was the main indicator for evaluating the performance of the models, while Shapley Additive ExPlanation was used to explain the contribution of each variable to the best predictive model. Results: A total of 3,906 patients and 314,534 dialysis sessions were included, of which 142,237 cases showed IDH (incidence rate, 45.2%). Nineteen parameters were identified through artificial intelligence feature screening. They included age, pre-dialysis weight, dry weight, pre-dialysis blood pressure, heart rate, prescribed ultrafiltration, blood cell counts (neutrophil, lymphocyte, monocyte, eosinophil, lymphocyte, and platelet counts), hematocrit, serum calcium, creatinine, urea, glucose, and uric acid. Random forest, gradient boosting, and logistic regression were the three best models, and the AUCs were 0.812 (95% confidence interval [CI], 0.811–0.813), 0.748 (95% CI, 0.747–0.749), and 0.743 (95% CI, 0.742–0.744), respectively. Conclusion: Our dialysis software-based artificial intelligence alert system can be used to predict IDH occurrence, enabling the initiation of relevant interventions.

824 HEMODYNAMIC EFFECTS OF LEVOSIMENDAN IN PATIENTS WITH ACUTE HEART FAILURE AND SEVERE RENAL FAILURE

Abstract Background The inodilator levosimendan has shown improved outcomes in acute heart failure (AHF) and cardiac surgery. Its hemodynamic effect is persistent, owing to a long (70-80 hours) elimination half-life of its active metabolites. No robust data is available of the use of levosimendan in patients with severe renal failure (SRF), thus its use is contraindicated in patients with estimated glomerular filtration rate (eGFR≤30 mL/min). Hypothesis Different pharmacokinetics due to renal failure may alter levosimendan active metabolites elimination, causing more pronounced hemodynamic effects. We aimed to characterize the hemodynamic effect of levosimendan in a real-world cohort of SRF patients. Methods We reviewed patients who received levosimendan (12.5 mg) for AHF or cardiogenic shock in our CICU (N=132), excluding those without invasive hemodynamics (n=85), and those without data before and during levosimendan infusion (n=11), a total of 36 patients were finally included in this analysis. We compared hemodynamics before and during levosimendan infusion in the study cohort with CKD-EPI eGFR≤30 mL/min/1.73 m2 or CRRT and those without. Results Patients with low eGFR (n=11) were older, they had similar LVEF and invasive hemodynamics before levosimendan infusion to the higher eGFR cohort. Visual inspection of the LOESS regression plots (Figure) revealed an higher drop in mean arterial pressure (MAP) and diastolic arterial pressure (DAP) in the low eGFR cohort. The maximum drop was observed at day 4 from levosimendan initiation, invasive hemodynamics at this timepoint revealed a lower DAP (44.6±8.8 vs 62.6±11.9 mmHg; p=0.014) and a tendentially lower MAP (73.6±5.5 vs 84.4±11.5 mmHg; p=0.079) while systolic arterial pressure (125.0±24.6 vs 121.3±21.8 mmHg; p=0.779), cardiac index (2.1±0.5 vs 2.5±0.7 L/m2; p=0.211), and mean pulmonary arterial pressure (25.8±8.3 vs 24.8±9.6 mmHg; p=0.844) did not differ between groups. In-hospital death was not different in the two cohorts (27.3 vs 16.0%; p=0.650). Conclusions Patient with eGFR≤30 mL/min/1.73 m2 demonstrated a higher drop in DAP and MAP four days after levosimendan infusion start, without impact on hospital mortality. These findings may suggest a more pronounced hemodynamic effect of levosimendan in patients with SRF, possibly due to altered pharmacokinetics of its active metabolites.

Invasive and non-invasive assessment of macro- and micro-circulatory effects of vasopressors during sevoflurane anesthesia in a pediatric experimental model: A randomized trial.

While non-invasive assessment of macro- and micro-circulation has the promise to optimize anesthesia management, evidence is lacking for the relationship between invasive and non-invasive measurements of cardiac output and microcirculatory indices. We aimed to compare the abilities of non-invasive techniques to detect changes in macro- and micro-circulation following deep anesthesia and subsequent restoration of the compromised hemodynamic by routinely used vasopressors in a randomized experimental study. A 20%-25% drop in mean arterial pressure was induced by sevoflurane in anesthetized mechanically ventilated just-weaned piglets (n=12) prior to the administration of vasopressors in random order (dopamine, ephedrine, noradrenaline, and phenylephrine). Simultaneous transpulmonary thermodilution cardiac output assessment with the invasive pulse index continuous contour (PiCCO) method was compared with non-invasive estimates obtained with electrical conductivity (ICON) and echo Doppler (Cardio Q). Changes in microcirculation were characterized by sublingual red blood cell velocity, jugular cerebral venous oxygen saturation, and arterial lactate. Cardiac output indices obtained by invasive and non-invasive methods. Changes in cardiac output measured invasively and non-invasively correlated significantly after sevoflurane (r=.78, p=.003 and r=.76, p=.006 between PiCCO and ICON or Cardio Q, respectively). Following the administration of vasopressors, invasive and non-invasive cardiac output assessments were unrelated with significant correlations observed only between PiCCO and ICON after dopamine and ephedrine. Sevoflurane-induced hypotension decreased jugular cerebral venous oxygen saturation significantly and was recovered by all vasopressors. Sevoflurane and vasopressors had no effect on red blood cell velocity, which increased only after dopamine. No consistent changes in lactate were observed during the study period. The results of this study suggest that non-invasive cardiac output measurements may not accurately reflect changes in macrocirculation after hemodynamic optimization by vasopressors. Due to the incoherence between macro- and micro-circulation, monitoring microcirculation is essential to guide patient management.

Lower body muscle preactivation and tensing mitigate symptoms of initial orthostatic hypotension in young females.

Initial orthostatic hypotension (IOH) is a form of orthostatic intolerance defined by a transient decrease in blood pressure upon standing. Current clinical recommendations for managing IOH includes standing up slowly or lower body muscle tensing (TENSE) after standing. Considering that IOH is likely due to a large muscle activation response resulting in excessive vasodilation with a refractory period (<2 minutes), we hypothesized that preactivating lower body muscles (PREACT) before standing would reduce the drop in mean arterial pressure (MAP) upon standing and improve presyncope symptoms. The purpose of this study was to provide IOH patients with effective symptom management techniques. Study participants completed 3 sit-to-stand maneuvers, including a stand with no intervention (Control), PREACT, and TENSE. Continuous heart rate and beat-to-beat blood pressure were measured. Stroke volume and cardiac output were then estimated from these waveforms. A total of 24 female IOH participants (mean ± SD: 32 ± 8 years) completed the study. The drops in MAP following PREACT (-21 ± 8 mm Hg; P <.001) and TENSE (-18 ± 10 mm Hg; P <.001) were significantly reduced compared to Control (-28 ± 10 mm Hg). The increase in cardiac output was significantly larger following PREACT (2.6 ± 1 L/min; P <.001) but not TENSE (1.9± 1 L/min; P = .2) compared to Control (1.4 ± 1 L/min). The Vanderbilt Orthostatic Symptom Score following PREACT (9±8 au; P = .033) and TENSE (8 ± 8 au; P = .046) both were significantly reduced compared to Control (14 ± 9 au). Both the drop in MAP and symptoms upon standing improved with either PREACT or TENSE. These maneuvers provide novel symptom management techniques for patients with IOH.

Mean arterial pressure drop is an independent risk factor of hepatorenal syndrome in patients with HBV-ACLF.

Background/aimsIn patients with acute-on-chronic liver failure (ACLF), type 1 hepatorenal syndrome (HRS) is a critical organ failure complication that resulted in rapid mortality. There are no efficient parameters to predict HRS in hepatitis B virus (HBV)-related ACLF. To assess HBV-ACLF risk factors and evaluate the association between mean arterial pressures (MAP), HRS and survival in patients with HBV-ACLF.MethodsA total of 420 ACLF patients were screened from June 2015 to June 2016, and 57 HBV-ACLF patients were included in the study. Clinical data and MAP measurements of these patients were collected. Multivariate analyses, Cox proportional hazards regression and receiver operator characteristic (ROC) curves were used to analyze.ResultsIn a 30-day study period, 43 (75.44%) patients survived. Patients in the HRS group were older and had higher Model for End-Stage Liver Disease (MELD) scores than patients in the non-HRS group. A MAP drop of ≥9.5 mmHg was an independent predictor of HRS with a sensitivity and specificity of 92.86 and 69.77%, respectively. The baseline MELD score was also an independent risk factor of HRS. MAP drop (OR, 1.582; P = 0.000), prothrombin time, HRS, MELD and FIB were independent prognostic factors for 30-day mortality. The area under the ROC curve of MAP drop was 0.808 (P = 0.001).ConclusionA decrease in MAP was a valuable predictor of HRS in patients with HBV-related ACLF. MAP drop ≥9.5 mmHg may be useful for predicting patient prognosis and exploring new treatment measures in patients with HBV-related ACLF.

Resuscitation of hemorrhagic shock using normal saline does not damage the glycocalyx in the immediate resuscitation phase.

OBJECTIVES:The objectives were to study the effect of aggressive resuscitation using normal saline on hemodynamics, serum atrial natriuretic peptide (ANP), syndecan-1 (marker of endothelial glycocalyx shedding), and extravascular lung water index (ELWI) following hemorrhagic shock.METHODS:Eleven male piglets (Sus scrofa) underwent blood drawing to create 20% drop in mean arterial pressure (MAP). Two-phase resuscitation was performed: Phase 1 using normal saline of an equal volume of blood drawn to create shock and Phase 2 using 40 ml/kg BW of normal saline to simulate hypervolemia and hemodilution. Heart rate, MAP, cardiac index (CI), systemic vascular resistance index, oxygen delivery (DO2), global end-diastolic volume index, ELWI, hemoglobin (Hb), lactate, ANP, and syndecan-1 at each phase and up to 60 min following Phase 2 resuscitation were recorded.RESULTS:Phase 2 resuscitation significantly decreased Hb concentration (P = 0.006), however, DO2 was maintained (P = 1.000). CI increased from shock to Phase 1 (P = 0.029) and further increase in Phase 2 resuscitation (P = 0.001). Overall, there was a transient increase of ANP following Phase 1 resuscitation, from 85.20 ± 40.86 ng/L at baseline to 106.42 ± 33.71 ng/L (P = 0.260). Serum syndecan-1 and ELWI change at all phases were not significant.CONCLUSIONS:We demonstrate compensatory protective mechanism despite overzealous fluid resuscitation. Compensatory increased CI despite decreased Hb maintained DO2. In the absence of inflammation, serum ANP did not increase significantly, no glycocalyx shedding occurred, subsequently no change in ELWI. We show that factors other than volume overload are more dominant in causing glycocalyx shedding.

Feasibility and postoperative opioid sparing effect of an opioid-free anaesthesia in adult cardiac surgery: a retrospective study

BackgroundNo previous study investigated the dexmedetomidine-based opioid-free anesthesia (OFA) protocol in cardiac surgery. The main objective of this study was to evaluate the feasibility and the postoperative opioid-sparing effect of dexmedetomidine-based OFA in adult cardiac surgery patients.MethodsWe conducted a single-centre and retrospective study including 80 patients above 18 years old who underwent on-pump cardiac surgery between November 2018 and February 2020. Patients were divided into two groups: OFA (lidocaine, ketamine, dexmedetomidine, MgSO4) or opioid-based anaesthesia (remifentanil and anti-hyperalgesic medications such as ketamine and/or MgSO4 and/or lidocaine at the discretion of the anesthesiologist). The primary endpoint was the total amount of opioid consumed in its equivalent of intravenous morphine during the first 48 postoperative hours. Secondary outcomes included perioperative hemodynamics, post-operative maximal pain at rest and during coughing and adverse outcomes. Data are expressed as median [interquartile range].ResultsPatients in the OFA-group had a higher EuroSCORE II, with more diabetes, more dyslipidemia and more non-elective surgery but fewer smoking history. In the OFA group, the median loading dose of dexmedetomidine was 0.6 [0.4–0.6] μg.kg− 1 while the median maintenance dose was 0.11 μg.kg− 1.h− 1 [0.05–0.20]. In 10 (25%) patients, dexmedetomidine was discontinued for a drop of mean arterial pressure below 55 mmHg. The median total amount of opioid consumed in its equivalent of intravenous morphine during the first 48 postoperative hours was lower in the OFA group (15.0 mg [8.5–23.5] versus 30.0 mg [17.3–44.3], p < 0.001). While no differences were seen with rest pain (2.0 [0.0–3.0] versus 0.5 [0.0–5.0], p = 0.60), the maximal pain score during coughing was lower in OFA group (3.5 [2.0–5.0] versus 5.5 [3.0–7.0], p = 0.04). In OFA group the incidence of atrial fibrillation (18% versus 40%, p = 0.03) and non-invasive ventilation use (25% versus 48%, p = 0.04) were lower. The incidence of bradycardia and the intraoperative use of norepinephrine were similar between both groups.ConclusionDexmedetomidine-based OFA in cardiac surgery patients is feasible and could be associated with a lower postoperative morphine consumption and better postoperative outcomes. Further randomized studies are required to confirm these promising results and determine the optimal associations, dosages, and infusion protocols during cardiac surgery.Graphical abstract

Loss of Female Sex Hormones Does Not Induce a Mechanistic Switch for Development of Hypertension in Obese Female Mice

Hypertension is a leading risk factor for cardiovascular disease (CVD), affecting more than 75% of postmenopausal women. Obesity, a significant risk factor for developing hypertension and CVD, is present in approximately 40% of postmenopausal women. Despite extensive studies on the mechanisms of hypertension, the mechanisms whereby obesity and menopause interact to elevate blood pressure (BP) in women remain unknown. Previous studies from our laboratory have demonstrated that obesity-associated hypertension is dependent on leptin in both males and females but involves sex-specific mechanisms: leptin-mediated sympatho-activation in males and leptin-induced aldosterone production in females. As estrogen blunts sympathetic activity, we hypothesized that loss of female sex hormones with ovariectomy (OVX) induces a switch in the mechanisms of hypertension from aldosterone to sympatho-mediated in obese mice. Obese yellow agouti mice (Ay) on a KK background underwent OVX or sham surgery at 12 weeks of age. BP recording via radiotelemetry revealed no elevation in BP (Sham: 119±2.9 vs. OVX: 116±7.7 mmHg) or heart rate (HR, Sham: 622±17 vs. OVX: 592±17 bpm) in response to OVX. To investigate the effects of OVX on sympatho-activation, we measure BP and HR responses to ganglionic blockade (hexamethonium) as well as to atropine and propranolol. Surprisingly, we observed no alteration in the drop in mean arterial pressure (MAP) and the increase in HR in response to hexamethonium, propranolol and atropine respectively after OVX. Mice then underwent seven days treatment with Allo-Aca, a leptin receptor antagonist (0.05mg/kg/day s.c. osmotic minipump). Allo-Aca decreased BP to a similar extent in sham and OVX mice, though not significantly. BP data was again recorded in response to ganglionic blockade and atropine but neither OVX nor leptin receptor antagonist treatment elicited significant differences on HR or MAP responses. Endothelial function was experimentally measured by wire myography concentration response curves to acetylcholine in mouse thoracic aorta. Endothelial function in OVX mice (n=3) showed a trend to being impaired compared to sham mice (n=4) (2-way ANOVA, P<0.17). Relaxation responses to acetylcholine in the presence of LNAME indicated that endothelial dysfunction in OVX mice was not attributable to reduction in nitric oxide activity. Collectively, this preliminary data suggest that obese ovariectomized mice may not undergo a mechanistic shift for the development of hypertension in response to the absence of female sex hormones and may continue to develop endothelial dysfunction via aldosterone-dependent mechanisms.

Neonatal maternal separation decreases mean arterial blood pressure in adult female rats

Introduction The prevalence of depression is higher in adult women than in men. Interestingly, a decrease in arterial blood pressure is commonly observed in patients affected by this mood disorder. This association raises the possibility that low blood pressure could distinguish a subgroup of the population that are at higher risk to develop this psychiatric disorder. In rats, exposure to neonatal maternal separation (NMS) leads to depressive-like behaviors in adult animals, thus offering a simple translational model for pre-clinic studies. In addition, a variety of studies showed that during the premenstrual period a high number of women at reproductive-age present symptoms of irritability, emotional hypersensitivity, increased anxiety as well as depression. The impact of hormonal fluctuations on psychiatric disorders is well established, yet there are only a few studies regarding blood pressure control during different phases of the menstrual cycle. While the link between stress (including NMS) and hypertension has been well documented in males, the effects of hormonal fluctuations in pre-clinical studies in female animals have not been explored. Based on that, we developed two main hypotheses: 1) by comparison with undisturbed (control) rats, NMS decreases arterial blood pressure in adult females. 2) NMS will increase the impact of the estrous cycle on blood pressure. Methodology Rat pups were either undisturbed (control) or subjected to NMS during which pups were placed in individual spaces into a temperature-controlled incubator 3h/day from postnatal day 3 to 12. Once they reached adulthood, (8 weeks of age) cardiovascular parameters were measured in females using the tail cuff method. To cover all phases of the estrous cycle, we did our measurements once a week during 7 weeks, (between 8-14 weeks of animal's life), during the morning (9-12h) period. The data were analyzed using the two-way ANOVA test, comparing the treatment (CTRL vs NMS) and the phases of the estrous cycle. Results We showed that the diastolic and systolic pressures of NMS females were 5% less than controls (diastolic: CTRL: 84 mmHg, NMS: 79 mmHg, p=0.0015, systolic: CTRL: 121 mmHg, NMS: 116 mmHg, p=0.02). This resulted in a significant drop in mean arterial pressure (CTRL: 96 mmHg, NMS: 91 mmHg, p=0.02). The heart rate was similar between the groups. Surprisingly, we observed no effects of the estrous cycle on the blood pressure neither in NMS nor in control animals. Discussion This demonstrates that the NMS decreases the blood pressure of our female animals in adult life as observed in humans with anxiety and depressive behaviors. This observation further validates our model and justifies new studies exploring the mechanisms by which early life stress leads to physiological and psychiatric changes in adulthood. Ultimately, this research can help us develop more precise therapies for specific groups. For instance, Licht et al 2009 demonstrated that the use of antidepressant from patients that exhibited decreased blood pressure increases their risk to present hypertension.

Blunt Pulmonary Injury Induces Profound Pulmonary Hypertension in a Porcine Polytrauma Model

Traumatic blunt pulmonary injuries, while typically appearing mild on initial exam, notoriously progress into cases of pulmonary hypertension (PHT) and pulmonary edema often worsened with the fluid resuscitation necessitated by such injuries. Increased hypoxemia in acute lung injury is believed to cause pulmonary vasoconstriction which further increases pulmonary arterial pressure, and worsens hypoxemia in a vicious cycle of persistent PHT. The relationship between pulmonary hemodynamics and pulmonary edema, however is not well understood. We hypothesize that the initial increase in pulmonary vasoconstriction occurs to isolate damaged lung tissue and prevent pulmonary infiltration due to traumatic disruption of the alveolar air-liquid interface. In this study, we tested this hypothesis by examining the development of extravascular lung water in relation to pulmonary vasoconstriction in a porcine polytrauma model of acute lung injury. Pulmonary function and hemodynamics were examined before and after localized blunt right chest injury trauma in anesthetized, mechanically ventilated Yorkshire cross pigs (26+/- 1 kg, n=9). Acute grade II-III lung injury was verified at the end of the experiment. Cardiac output was measured via thermodilution with a SwanGanz catheter and extravascular lung water index (ELWI) and pulmonary capillary permeability were assessed in real time using the Pulse Ion Contour Cardiac Output (PiCCO) method (Getinge). Pulmonary arterial pressure increased within 60 minutes of initial lung injury (19 +/- 1 mm Hg at baseline vs 23 +/- 2 mm Hg) despite a drop in mean arterial pressure (60 +/- 1 mm Hg at baseline to 48 +/- 4 mm Hg after trauma). The ratio of pulmonary vascular resistance to systemic vascular resistance (PVR/SVR), indicated a selective pulmonary vasoconstriction(0.23 +/- 0.01 to 0.41 +/- 0.05, p = 0.054). ELWI was negatively correlated with the PVR/SVR ratio (r=0.44, p=0.010). Central venous pressure was lowest (6 +/- 0.6 mm Hg) right after trauma and increased (8 +/- 0.4 mm Hg) 2 hours after trauma along with the increase in PVR/SVR post trauma. Results suggests that traumatic pulmonary edema was limited via autoregulatory vasoconstriction. While effective in preventing pulmonary fluid extravasation, pulmonary hypertension resulted in a marked increase in heart afterload and accumulation of fluid in the right heart. The magnitude of this effect was such that even a moderate degree of fluid resuscitation risked precipitating florid congestive heart failure. Our data suggest that great caution must be exercised during fluid resuscitation of the blunt pulmonary trauma patient. The views expressed are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.

Blood pressure in the chronically hypoxaemic fetus is regulated by α-adrenergic receptors on the peripheral vasculature.

Blood pressure in the chronically hypoxaemic fetus is regulated by α-adrenergic receptors on the peripheral vasculature.

S0524 Safety Profile of Endoscopist-Directed Balanced Propofol Sedation for Procedural Sedation: An Experience at a Hospital-Based Endoscopy Unit

INTRODUCTION: Nurse administered propofol sedation was widely used for endoscopic procedures until 2009 when its use was restricted to anesthesiologists per CMS guidelines, a practice that has led to increases in healthcare costs. Aim was to evaluate the safety of endoscopist-directed balanced propofol sedation (EDBPS) for endoscopy. METHODS: We identified patients who underwent endoscopic procedures with EDBPS from Jan to Jun 2017. Medical records were abstracted for data on procedure indication, medication doses, time to induction of sedation, duration of procedure and recovery time. Adverse events (AEs) included: Hypoxia - oxygen saturation (SPO₂) 50 mm Hg, c) Drop in mean arterial pressure (MAP) > 30%; Bradycardia (heart rate < 40 beats/minute). Major complications include death, neurologic sequelae (CVA, permanent cognitive impairment), and need for hospitalization or endotracheal intubation. RESULTS: A total of 1897 patients received EDBPS during the study period. Mean age was 55 (SD 11.4) years and 43.6% were men. Patients received median doses of 50 mcg fentanyl and 2 mg of midazolam and a mean propofol dose of 160 ± 99 mg (range 20–960). Mean time for sedation induction was 3.4 (SD 1.9) and mean recovery was 14 (SD 10.2) min. There were no major complications (0%; 95% CI, 0–0.19%). Three hundred thirty-four patients (17.6%) experienced an AE, all of which were managed with simple measures (chin-lift, jaw thrust and increasing flow of O₂ and IV fluids): 65 (3.4%) had transient hypoxia, 277 (14.6%) had hypotension. In bivariate analysis, a 5-yr increase in patient age was associated with in increased risk of hypotension. A 50 mg increase in propofol dose was associated with a statistically significant risk of transient hypoxia. A 10-min increase in procedure duration was associated with statistically significant risk of both transient hypoxia and hypotension (Table 1). Age, weight, BMI, propofol dose and procedure length were associated with AEs (Table 2). Gender had no association with AEs. In multivariate analysis, only procedure length was independently associated with AEs. CONCLUSION: EDBPS is safe for endoscopic procedural sedation, as AEs occurred infrequently. Given the much higher cost of anesthesia-administered propofol for routine endoscopic procedures, endoscopists should re-instate EDBPS by revising institutional sedation policies.Table 1Table 2

Efficiency of Percutaneous Stent Angioplasty in Renal Artery Stenosis - 15 Years of Experience at a Single Center.

To determine the therapeutic efficiency of percutaneous revascularization in renal artery stenosis (RAS), as well as the role of comprehensive factors such as patient selection and degree of artery stenosis, on clinical outcome. 101 patients with hemodynamically relevant RAS underwent percutaneous angioplasty (PTA). 65.7 % were male (mean age: 64 years; range: 18-84). The clinical data was retrospectively analyzed. The serum creatinine (Cr), glomerular filtration rate (GFR), and blood pressure (BP) levels pre- and postprocedural, between 6 months and 1year, were retrospectively collected and statistically analyzed. Follow-up data was available in 34 (33.7 %) and 28patients (27.7 %) for Cr and MAP, respectively. A significant drop in mean arterial pressure (MAP) was observed on follow-up (mean -5.27 mmHg). Higher baseline Cr and MAP values showed a more pronounced drop in the follow-up (Cr: p0.002; difference to baseline -0.25 mg/dL, 95 %CI:-0.36, -0.07 and BP p < 0.001; diff. to baseline -0.72 mmHg; 95 %CI: -1.4, -0.40). There was no association between comorbidities, gender, and degree of stenosis with renal and BP outcome. No significant improvement in renal function was observed on follow-up (mean Cr drop: -0.015 mg/dL). The age group 51-60 years showed a significant improvement in BP (p 0.030; diff. to baseline -19.2 mmHg; 95 %CI: -34, -4.3). There was a slight reduction in antihypertensive medication following angioplasty (0.2 fewer). Minor complications were recorded in five procedures (4.9 %). Percutaneous renal artery revascularization in the presence of atherosclerotic RAS is a safe procedure associated with a significant drop in post-procedural BP. No significant improvement in renal function was observed. Further prospective studies focused on patient selection are necessary. · Percutaneous stent angioplasty in renal artery stenosis is associated with a significant improvement in post-procedural blood pressure control.. · There is no improvement in renal function after percutaneous stent angioplasty for renal artery stenosis (RAS).. · Percutaneous stent angioplasty is a safe procedure.. · Guerreiro H, Avanesov M, Dinnies S et al. Efficiency of Percutaneous Stent Angioplasty in Renal Artery Stenosis - 15Years of Experience at a Single Center. Fortschr Röntgenstr 2021; 193: 298 - 304.

Chronic elevation of renal venous pressure induces extensive renal venous collateral formation and modulates renal function and cardiovascular stability in rats.

Acutely increased renal venous pressure (RVP) impairs renal function, but the long-term impact is unknown. We investigated whether chronic RVP elevation impairs baseline renal function and prevents exacerbation of renal dysfunction and cardiovascular instability upon further RVP increase. RVP elevation (20-25 mmHg) or sham operation (sham) was performed in rats. After 1 wk (n = 17) or 3 wk (n = 22), blood pressure, RVP, renal blood flow (RBF), renal vascular conductance (RVC), and glomerular filtration rate (GFR) were measured at baseline and during superimposed RVP increase. Chronic RVP elevation induced extensive renal venous collateral formation. RVP fell to 6 ± 1 mmHg at 1 wk and 3 ± 1 mmHg at 3 wk. Baseline blood pressure and heart rate were unaltered compared with sham. RBF, RVC, and GFR were reduced at 1 wk but normalized by 3 wk. Upon further RVP increase, the drop in mean arterial pressure was attenuated at 3 wk compared with 1 wk (P < 0.05), whereas heart rate fell comparably across all groups; the mean arterial pressure-heart rate relationship was disrupted at 1 and 3 wk. RBF fell to a similar degree as sham at 1 wk (-2.3 ± 0.7 vs. -3.9 ± 1.2 mL/min, P = 0.066); however, at 3 wk, this was attenuated compared with sham (-1.5 ± 0.5 vs. -4.2 ± 0.7 mL/min, P < 0.05). The drop in RVC and GFR was attenuated at 1 and 3 wk (P < 0.05). Thus, chronic RVP elevation induced by partial renal vein ligation elicits extensive renal venous collateral formation, and although baseline renal function is impaired, chronic RVP elevation in this manner induces protective adaptations in kidneys of healthy rats, which attenuates the hemodynamic response to further RVP increase.