Carotid Blood Flow Research Articles

Pharmacokinetic and pharmacodynamic evaluation of various vasopressin doses and routes of administration in a neonatal piglet model

Epinephrine is the only recommended vasopressor during neonatal cardiopulmonary resuscitation. However, there are concerns about the potential adverse effects of epinephrine, which might hamper efficacy during cardiopulmonary resuscitation. An alternative might be vasopressin, which has a preferable adverse effect profile, however, its optimal dose and route of administration is unknown. We aimed to compare the pharmacodynamics and pharmacokinetics of various vasopressin doses administered via intravenous (IV), intraosseous (IO), endotracheal (ETT), and intranasal (IN) routes in healthy neonatal piglets. Forty-four post-transitional piglets (1–3 days of age) were anesthetized, intubated via a tracheostomy, and randomized to receive vasopressin via intravenous (control), IO, ETT, or IN route. Heart rate (HR), arterial blood pressure, carotid blood flow, and cardiac function (e.g., stroke volume, ejection fraction) were continuously recorded throughout the experiment. Blood was collected prior to drug administration and throughout the observation period for pharmacodynamics and pharmacokinetic analysis. Significant changes in hemodynamic parameters were observed following IO administration of vasopressin while pharmacokinetic parameters were not different between IV and IO vasopressin. Administration of vasopressin via ETT or IN did not change hemodynamic parameters and had significantly lower maximum plasma concentrations and systemic absorption compared to piglets administered IV vasopressin (p < 0.05). The IV and IO routes appear the most effective for vasopressin administration in neonatal piglets, while the ETT and IN routes appear unsuitable for vasopressin administration.

Hypoxia evokes a sequence of raphe-pontomedullary network operations for inspiratory drive amplification and gasping.

Hypoxia can trigger a sequence of breathing-related behaviors, from augmentation to apneusis to apnea and gasping. Gasping is an autoresuscitative behavior that, via large tidal volumes and altered intrathoracic pressure, can enhance coronary perfusion, carotid blood flow, and sympathetic activity, and thereby coordinate cardiac and respiratory functions. We tested the hypotheses that hypoxia-evoked gasps are amplified through a disinhibitory microcircuit within the inspiratory neuron chain and that this drive is distributed via an efference copy mechanism. This generates coordinated gasplike discharges concurrently in other circuits of the raphe-pontomedullary respiratory network. Data were obtained from six decerebrate, vagotomized, neuromuscularly blocked, and artificially ventilated adult cats. Arterial blood pressure, phrenic nerve activity, end-tidal CO2, and other parameters were monitored. Hypoxia was produced by ventilation with a gas mixture of 5% O2 in nitrogen. Neuron spike trains were recorded at multiple pontomedullary sites simultaneously and evaluated for firing rate modulations and short-timescale correlations indicative of functional connectivity. Experimental perturbations evoked reconfiguration of raphe-pontomedullary circuits during initial augmentation, apneusis and augmented bursts, apnea, and gasping. Functional connectivity, altered firing rates, efference copy of gasp drive, and coordinated incremental blood pressure increases support a distributed brain stem network model for amplification and broadcasting of inspiratory drive during autoresuscitative gasping. Gasping begins with a reduction in inhibition by expiratory neurons and an initial loss of inspiratory drive during hypoxic apnea and culminates in autoresuscitative efforts. NEW & NOTEWORTHY Severe hypoxia evokes a sequence of breathing-related behaviors culminating in gasping. We report firing rate modulations and short-timescale correlations in spike trains recorded simultaneously in the raphe-pontomedullary respiratory network during hypoxia. Our findings support a disinhibitory microcircuit and a distributed efference copy mechanism for amplification of gasping. Coordinated increments in blood pressure lead to a model for autoresuscitative bootstrapping of peripheral chemoreceptor reflexes, breathing, and sympathetic activity, complementing and extending prior work.

Wall Shear Stress (WSS) Analysis in Atherosclerosis in Partial Ligated Apolipoprotein E Knockout Mouse Model through Computational Fluid Dynamics (CFD).

Atherosclerosis involves an inflammatory response due to plaque formation within the arteries, which can lead to ischemic stroke and heart disease. It is one of the leading causes of death worldwide, with various contributing factors such as hyperlipidemia, hypertension, obesity, diabetes, and smoking. Wall shear stress (WSS) is also known as a contributing factor of the formation of atherosclerotic plaques. Since the causes of atherosclerosis cannot be attributed to a single factor, clearly understanding the mechanisms and causes of its occurrence is crucial for preventing the disease and developing effective treatment strategies. To better understand atherosclerosis and define the correlation between various contributing factors, computational fluid dynamics (CFD) analysis is primarily used. CFD simulates WSS, the frictional force caused by blood flow on the vessel wall with various hemodynamic changes. Using apolipoprotein E knockout (ApoE-KO) mice subjected to partial ligation and a high-fat diet at 1-week, 2-week, and 4-week intervals as an atherosclerosis model, CFD analysis was conducted along with the reconstruction of carotid artery blood flow via magnetic resonance imaging (MRI) and compared to the inflammatory factors and pathological staining. In this experiment, a comparative analysis of the effects of high WSS and low WSS was conducted by comparing the standard deviation of time-averaged wall shear stress (TAWSS) at each point within the vessel wall. As a novel approach, the standard deviation of TAWSS within the vessel was analyzed with the staining results and pathological features. Since the onset of atherosclerosis cannot be explained by a single factor, the aim was to find the correlation between the thickness of atherosclerotic plaques and inflammatory factors through standard deviation analysis. As a result, the gap between low WSS and high WSS widened as the interval between weeks in the atherosclerosis mouse model increased. This finding not only linked the occurrence of atherosclerosis to WSS differences but also provided a connection to the causes of vulnerable plaques.

Mild (34 °C) versus moderate hypothermia (24 °C) in a swine model of extracorporeal cardiopulmonary resuscitation

BackgroundThe role of hypothermia in post-arrest neuroprotection is controversial. Animal studies suggest potential benefits with lower temperatures, but high-fidelity ECPR models evaluating temperatures below 30 °C are lacking. ObjectivesTo determine whether rapid cooling to 24 °C initiated upon reperfusion reduces brain injury compared to 34 °C in a swine model of ECPR. MethodsTwenty-four female pigs had electrically induced VF and mechanical CPR for 30 min. Animals were cannulated for VA-ECMO and cooled to either 34 °C for 4 h (n = 8), 24 °C for 1 h with rewarming to 34 °C over 3 h (n = 7), or 24 °C for 4 h without rewarming (n = 9). Cooling was initiated upon VA-ECMO reperfusion by circulating ice water through the oxygenator. Brain temperature and cerebral and systemic hemodynamics were continuously monitored. After four hours on VA-ECMO, brain tissue was obtained for examination. ResultsTarget brain temperature was achieved within 30 min of reperfusion (p = 0.74). Carotid blood flow was higher in the 24 °C without rewarming group throughout the VA-ECMO period compared to 34 °C and 24 °C with rewarming (p < 0.001). Vasopressin requirement was higher in animals treated with 24 °C without rewarming (p = 0.07). Compared to 34 °C, animals treated with 24 °C with rewarming were less coagulopathic and had less immunohistochemistry-detected neurologic injury. There were no differences in global brain injury score. ConclusionsDespite improvement in carotid blood flow and immunohistochemistry detected neurologic injury, reperfusion at 24 °C with or without rewarming did not reduce early global brain injury compared to 34 °C in a swine model of ECPR.

Ezetimibe protects against Gentamycin-induced ototoxicity in rats by antioxidants, anti-inflammatory mechanisms, and BDNF upregulation

Objective The threat of hearing loss has become a universal reality. Gentamycin (GM) can lead to ototoxicity and may result in permanent hearing loss. This study aimed to elucidate whether the hypolipidemic drug Ezetimibe (EZE) has a possible underlying mechanism for protecting rats from GM-induced ototoxicity. Methods and results 30 male Wister albino rats were separated into three groups, ten in each group: control, GM, and GM + EZE. At the end of the experiment, rats underwent hearing threshold evaluation via auditory brainstem response (ABR), carotid artery blood flow velocity (CBV), and resistance (CVR) measurement, in addition to a biochemical assessment of serum malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), hemeOxygenase-1 (HO-1), and tumor necrosis factor-α (TNF-α). Also, real-time PCR was employed to quantify the levels of brain-derived neurotrophic factor (BDNF). Cochlea was also studied via histological and immunohistochemical methods. GM revealed a significant increase in CVR, MDA, NO, and TNF-α and a significant decrease in ABR, CBV, CAT, HO-1, and cochlear BDNF expression. EZE supplementation revealed a significant rise in ARB in addition to CBV and a decline in CVR and protected cochlear tissues via antioxidant, anti-inflammatory, and antiapoptotic mechanisms via downregulating Caspase-3 immunoreaction, upregulating proliferating cellular nuclear antigen (PCNA) immunoreaction, and upregulating of the cochlear BDNF expression. Correlations were significantly negative between BDNF and MDA, NO, TNF-α, COX 2, and caspase-3 immunoreaction and significantly positive with CAT, HO-1, and PCNA immunoreaction. Discussion EZE can safeguard inner ear tissues from GM via antioxidant, anti-inflammatory, and antiapoptotic mechanisms, as well as upregulation of BDNF mechanisms.

Development of artificial intelligence-driven biosignal-sensitive cardiopulmonary resuscitation robot

Aim of the studyWe evaluated whether an artificial intelligence (AI)-driven robot cardiopulmonary resuscitation (CPR) could improve hemodynamic parameters and clinical outcomes. MethodsWe developed an AI-driven CPR robot which utilizes an integrated feedback system with an AI model predicting carotid blood flow (CBF). Twelve pigs were assigned to the AI robot group (n = 6) and the LUCAS 3 group (n = 6). They underwent 6 min of CPR after 7 min of ventricular fibrillation. In the AI robot group, the robot explored for the optimal compression position, depth and rate during the first 270-second period, and continued CPR with the optimal setup during the next 90-second period and beyond. The primary outcome was CBF during the last 90-second period. The secondary outcomes were coronary perfusion pressure (CPP), end-tidal carbon dioxide level (ETCO2) and return of spontaneous circulation (ROSC). ResultsThe AI model’s prediction performance was excellent (Pearson correlation coefficient = 0.98). CBF did not differ between the two groups [estimate and standard error (SE), −23.210 ± 20.193, P = 0.250]. CPP, ETCO2 level and rate of ROSC also did not show difference [estimate and SE, −0.214 ± 7.245, P = 0.976 for CPP; estimate and SE, 1.745 ± 3.199, P = 0.585 for ETCO2; 5/6 (83.3%) vs. 4/6 (66.7%), P = 1.000 for ROSC). ConclusionThis study provides proof of concept that an AI-driven CPR robot in porcine cardiac arrest is feasible. Compared to a LUCAS 3, an AI-driven CPR robot produced comparable hemodynamic and clinical outcomes.

Glycated Haemoglobin Correlates With Carotid Intima-Media Thickness and Blood Flow Velocity in Carotid Arteries in Nondiabetic Patients—Preliminary Results

Glycated Haemoglobin Correlates With Carotid Intima-Media Thickness and Blood Flow Velocity in Carotid Arteries in Nondiabetic Patients—Preliminary Results

Impaired memory in Sprague-Dawley rats exposed to complex groundwater mixtures of contaminants is associated with reduced cranial blood flow and hippocampal neurotoxicity

Exposure to industrial contaminants has been implicated in neurobehavioral toxicity in humans. To explore this potential risk, we investigated the neurotoxic effects of oral exposure to a complex groundwater mixture containing petroleum hydrocarbons, pesticides, heavy metals, and unknown parent and breakdown products using male and female Sprague Dawley rats. Rats were randomly divided into six groups and orally exposed daily via drinking water to: (i) tap water, (ii) 10 % v/v low impact groundwater, and (iii) 0.01 %, 0.1 %, 1 %, and 10 % high-impact groundwater for 60 days. Medium- and long-term memory (measured using the novel object recognition task) were impaired. However, no gross motor or coordination deficits were observed by the end of the study period (rotarod test). Doppler ultrasound of the middle cerebral and common carotid arteries was performed to examine the hemodynamic changes. The common carotid blood flow decreased in the groundwater-exposed rats compared to that in the control. However, no significant differences in cerebral blood velocity were observed between the exposed and control groups. A significant reduction in hippocampal serotonin levels was observed in groundwater-exposed rats relative to that in the control group. Collectively, these results indicate that impaired recognition memory in rats exposed to groundwater is accompanied by reduced cranial blood flow and hippocampal neurotoxicity, characterized by altered serotonergic signalling. The levels of detected contaminants known to cause neural or vascular damage were of magnitudes lower than the concentrations of contaminants found in the groundwater mixture, meaning the culprit chemical identity remains unknown. This study emphasizes the need to use whole mixture in exposures when dealing with complex contaminated sites rather than the use of individual compounds.

Assessing the influence of abdominal compression on time to return of circulation during resuscitation of asphyxiated newborn lambs: a randomised preclinical study

ObjectiveDuring neonatal resuscitation, the return of spontaneous circulation (ROSC) can be achieved using epinephrine which optimises coronary perfusion by increasing diastolic pressure. Abdominal compression (AC) applied during resuscitation could potentially...

Impact of arginine-vasopressin on regional perfusions in a porcine model of post-resuscitation syndrome

BackgroundPost-cardiac arrest (CA) shock is associated with multiple organ failure, including acute kidney injury, and is the leading cause of early death among patient successfully resuscitated from CA. Arginine-vasopressin (AVP) may be an interesting therapeutic alternative or complement to noradrenaline (NAD) to both control shock and preserve regional, especially renal, organ perfusions. Methods18 swine (24–39 kg) were submitted to 14 min of ventricular fibrillation and cardio-pulmonary resuscitation. After return of spontaneous circulation (ROSC), animals randomly received either AVP, NAD or AVP-NAD combination for maintaining a targeted mean arterial pressure of 70 ± 5 mmHg for 6 h. Haemodynamic and biological parameters, including kidney function biomarkers and diuresis, were monitored throughout the follow-up. ResultsTargeted mean arterial pressure was successfully obtained in the NAD (n = 6) and the AVP-NAD (n = 6) groups, but not in the AVP group (n = 6), where 4 animals died. As compared to NAD alone, renal blood flow (2.9 ± 1.15 vs 4.36 ± 0.64 mL//kg/min in NAD and AVP-NAD groups) and diuresis were higher in the AVP-NAD group. This was associated with a reduction of carotid blood flow and a more severe metabolic acidosis during the first 3 h of follow-up in the AVP-NAD group as compared to NAD group. ConclusionCombination of AVP and NAD improved renal perfusion and diuresis but reduced carotid blood flow as compared to NAD alone in a porcine model of post-resuscitation syndrome. AVP alone failed to manage shock and led to mortality.

Pulsatile Perfusion Therapy at 0.1 Hz Improves Survival Following Severe Hemorrhage in Rats

Oscillations in arterial pressure and blood flow at 0.1 Hz are associated with protection of tissue oxygenation during conditions of reduced tissue perfusion. Pulsatile Perfusion Therapy (PPT) is a method we have developed to induce these oscillations, and has been associated with increased tolerance to simulated hemorrhage via lower body negative pressure in humans. However, it is unknown how effective this therapy would be in an actual hemorrhage model. The aim for this study was to test the effcacy of PPT in a rat model of severe hemorrhage. We hypothesized that PPT at 0.1 Hz would protect arterial pressure and cerebral blood flow following severe hemorrhage in rats, subsequently improving survival. Eleven adult Sprague-Dawley rats (six female, five male) were anesthetized via isoflurane, then underwent bilateral carotid artery catheterization for assessment of arterial pressure and carotid artery blood flow, while heart rate was assessed via lead II ECG. Following a 15-min baseline period, all animals were hemorrhaged to 50% of their estimated blood volume over 30-min. Rats were then randomly assigned to the PPT group (3 female, 3 male) or the control group (CON; 3 female, 2 male). PPT was administered via inflatable cuffs attached to both hind limbs, oscillating between 0 mmHg and 250 mmHg every 5-s (10-s cycles or 0.1 Hz) for 30-min immediately following hemorrhage. For the CON group, the leg cuffs were also attached but were not inflated for this 30-min period. All animals were then monitored for an additional 150-min recovery period post-hemorrhage, or until death — defined as the absence of ventricular function on the ECG. Survival time and peak mean arterial pressure (MAP), carotid blood flow, and heart rate were assessed to determine the effectiveness of PPT in protecting hemodynamic responses following hemorrhage. PPT increased survival time ( P = 0.02), with 3 of 6 (50%) rats in the PPT group and 0 of 5 (0%) rats in the CON group surviving the entire 180-min recovery period following hemorrhage. During recovery, PPT protected MAP (PPT: −46.5 ± 12.9% vs. CON: −72.6 ± 19.5% from baseline; P = 0.07) and carotid blood flow (PPT: −61.5 ± 17.7% vs. CON: −83.7 ± 6.7% from baseline; P = 0.04), but did not affect heart rate (PPT: 0.11 ± 6.58% vs. CON: −18.70 ± 29.34% from baseline, P = 0.20), although responses were highly variable between subjects. PPT protected arterial pressure and carotid blood flow in rats following severe hemorrhage, subsequently improving survival. These data add further evidence for the use of 0.1 Hz hemodynamic oscillations as a therapeutic intervention for the treatment of hemorrhage. Physiology and Anatomy Department Seed Grant. 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.

Questioning the Role of Carotid Artery Ultrasound in Assessing Fluid Responsiveness in Critical Illness: A Systematic Review and Meta-Analysis.

A noninvasive and accurate method of identifying fluid responsiveness in hemodynamically unstable patients has long been sought by physicians. Carotid ultrasound (US) is one such modality previously canvassed for this purpose. The aim of this novel systematic review and meta-analysis is to investigate whether critically unwell patients who are requiring intravenous (IV) fluid resuscitation (fluid responders) can be identified accurately with carotid US. The protocol was registered with PROSPERO on the 30/11/2022 (ID number: CRD42022380284). Studies investigating carotid ultrasound accuracy in assessing fluid responsiveness in hemodynamically unstable patients were included. Studies were identified through searches of six databases, all run on 4 November 2022, Medline, Embase, Emcare, APA PsycInfo, CINAHL, and Cochrane Library. Risk of bias was assessed using the QUADAS-2 and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines. Results were pooled, meta-analysis was conducted where amenable, and hierarchical summary receiver operating characteristic models were established to compare carotid ultrasound measures. Seventeen studies were included (n = 842), with 1048 fluid challenges. 441 (42.1%) were fluid responsive. Four different carotid US measures were investigated, including change in carotid doppler peak velocity (∆CDPV), carotid blood flow (CBF), change in carotid artery velocity time integral (∆CAVTI), and carotid flow time (CFT). Pooled carotid US had a pooled sensitivity, specificity, and AUROC with 95% confidence intervals (CI) of 0.73 (0.66-0.78), 0.82 (0.72-0.90), and 0.81 (0.78-0.85), respectively. ∆CDPV had sensitivity, specificity, and AUROC with 95% CI of 0.72 (0.64-0.80), 0.87 (0.73-0.94), and 0.82 (0.78-0.85), respectively. CBF had sensitivity, specificity, and AUROC with 95% CI of 0.70 (0.56-0.80), 0.80 (0.50-0.94), and 0.77 (0.78-0.85), respectively. Risk of bias and assessment was undertaken using the QUADAS-2 and GRADE tools. The QUADAS-2 found that studies generally had an unclear or high risk of bias but with low applicability concerns. The GRADE assessment showed that ∆CDPV and CBF had low accuracy for sensitivity and specificity. It appears that carotid US has a limited ability to predict fluid responsiveness in critically unwell patients. ∆CDPV demonstrates the greatest accuracy of all measures analyzed. Further high-quality studies using consistent study design would help confirm this.

Haemodynamic implications of VA-ECMO vs. VA-ECMO plus Impella CP for cardiogenic shock in a large animal model.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with profound left ventricular (LV) failure is associated with inadequate LV emptying. To unload the LV, VA-ECMO can be combined with Impella CP (ECMELLA). We hypothesized that ECMELLA improves cardiac energetics compared with VA-ECMO in a porcine model of cardiogenic shock (CS). Land-race pigs (weight 70kg) were instrumented, including a LV conductance catheter and a carotid artery Doppler flow probe. CS was induced with embolization in the left main coronary artery. CS was defined as reduction of ≥50% in cardiac output or mixed oxygen saturation (SvO2) or a SvO2<30%. At CS VA-ECMO was initiated and embolization was continued until arterial pulse pressure was <10mmHg. At this point, Impella CP was placed in the ECMELLA arm. Support was maintained for 4h. CS was induced in 15 pigs (VA-ECMO n=7, ECMELLA n=8). At time of CS MAP was <45mmHg in both groups, with no difference at 4h (VA-ECMO 64mmHg±11 vs. ECMELLA 55mmHg±21, P=0.08). Carotid blood flow and arterial lactate increased from CS and was similar in VA-ECMO and ECMELLA [239mL/min±97 vs. 213mL/min±133 (P=0.6) and 5.2±3.3 vs. 4.2±2.9mmol/ (P=0.5)]. Pressure-volume area (PVA) was significantly higher with VA-ECMO compared with ECMELLA (9567±1733 vs. 6921±5036mmHg×mL/min×10-3, P=0.014). Total diureses was found to be lower in VA-ECMO compared with ECMELLA [248mL (179-930) vs. 506mL (418-2190); P=0.005]. In a porcine model of CS, we found lower PVA, with the ECMELLA configuration compared with VA-ECMO, indicating better cardiac energetics without compromising systemic perfusion.

Immediate inflammatory response to mechanical circulatory support in a porcine model of severe cardiogenic shock

BackgroundIn selected cases of cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is combined with trans valvular micro axial flow pumps (ECMELLA). Observational studies indicate that ECMELLA may reduce mortality but exposing the patient to two advanced mechanical support devices may affect the early inflammatory response. We aimed to explore inflammatory biomarkers in a porcine cardiogenic shock model managed with V-A ECMO or ECMELLA.MethodsFourteen landrace pigs had acute myocardial infarction-induced cardiogenic shock with minimal arterial pulsatility by microsphere embolization and were afterwards managed 1:1 with either V-A ECMO or ECMELLA for 4 h. Serial blood samples were drawn hourly and analyzed for serum concentrations of interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha, and serum amyloid A (SAA).ResultsAn increase in IL-6, IL-8, and SAA levels was observed during the experiment for both groups. At 2–4 h of support, IL-6 levels were higher in ECMELLA compared to V-A ECMO animals (difference: 1416 pg/ml, 1278 pg/ml, and 1030 pg/ml). SAA levels were higher in ECMELLA animals after 3 and 4 h of support (difference: 401 ng/ml and 524 ng/ml) and a significant treatment-by-time effect of ECMELLA on SAA was identified (p = 0.04). No statistical significant between-group differences were observed in carotid artery blood flow, urine output, and lactate levels.ConclusionsLeft ventricular unloading with Impella during V-A ECMO resulted in a more extensive inflammatory reaction despite similar end-organ perfusion.

Steady Flow Left Ventricle Unloading Is Superior to Pulsatile Pressure Augmentation Venting During Venoarterial Extracorporeal Membrane Oxygenation Support.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) shunts venous blood to the systemic arterial circulation to provide end-organ perfusion while increasing afterload that may impede left ventricle (LV) ejection and impair cardiac recovery. To maintain flow across the aortic valve and reduce risk of lethal clot formation, secondary mechanical circulatory support (MCS) devices are increasingly used despite limited understanding of their effects on cardiac function. This study sought to quantify the effects of VA-ECMO and combined with either intraaortic balloon pump (IABP) or percutaneous ventricular assist device (pVAD) on LV physiologic state and perfusion metrics in a porcine model of acute cardiogenic shock. Shock was induced through serial left anterior descending artery microbead embolization followed by initiation of VA-ECMO support and then placement of either IABP or pVAD. Hemodynamic measurements, LV pressure-volume loops, and carotid artery blood flow were evaluated before and after institution of combined MCS. The IABP decreased LV end-diastolic pressure by a peak of 15% while slightly increasing LV stroke work compared with decreases of more than 60% and 50% with the pVAD, respectively. The pVAD also demonstrated increased coronary perfusion and systemic pressure gradients in comparison to the IABP. Combined support with VA-ECMO and pVAD improves cardiovascular state in comparison to IABP.

The Reliability of Carotid Artery Doppler Ultrasonography Indices in Predicting Fluid Responsiveness during Surgery for Geriatric Patients: A Prospective, Observational Study.

The reliability of determining fluid responsiveness during surgery in geriatric patients is challenging. Our primary outcome was to determine the reliability of Corrected Flow Time (FTc) in predicting fluid responsiveness. Elderly patients undergoing major surgery under general anesthesia were included. Measurements of common carotid artery diameter, velocity time integral, and systolic flow time (FT) were performed before and after a fluid challenge. FTc and carotid blood flow (CBF) were subsequently calculated. The median change in carotid diameter was significantly higher in the fluid-responder (R) compared to the non-responder (NR) (6.51% vs. 0.65%, p = 0.049). The median change in CBF was notably higher in R compared to NR (30.04% vs. 9.72%, p = 0.024). Prior to the fluid challenge, systolic FT was significantly shorter in R than NR (285 ms vs. 315 ms, p = 0.027), but after the fluid challenge, these measurements became comparable among the groups. The change in systolic FT was higher in R (15.38% vs. 7.49%, p = 0.027). FTc and the change in FTc exhibited similarities among the groups at all study time points. Receiver operating characteristic analysis demonstrated an area under the curve of 0.682 (95% CI: 0.509-0.855, p = 0.039) for carotid diameter, 0.710 (95% CI: 0.547-0.872, p = 0.011) for CBF, 0.706 (95% CI: 0.540-0.872, p = 0.015) for systolic FT, and 0.580 (95% CI = 0.389-0.770, p = 0.413) for FTc. In geriatric patients, potential endothelial changes in the carotid artery may influence the dynamic markers of fluid responsiveness. Despite the demonstrated effectiveness of FTc in predicting fluid responsiveness in the general population, this study underscores the limited reliability of carotid Doppler ultrasonography indices for prediction in a geriatric patient population.

The cerebral and cardiac effects of Norepinephrine in an experimental cardiac arrest model

IntroductionEpinephrine has been the main drug recommended for decades during cardiopulmonary resuscitation (CPR). But epinephrine’s ß-adrenergic effects might increase myocardial oxygen consumption and may cause arrythmias after ROSC. Norepinephrine has a weaker ß-adrenergic effect and could be useful during CPR. Studies on norepinephrine’s effect on hemodynamic parameters and cerebral perfusion are scarce. This study aimed to assess norepinephrine's hemodynamic impact in an experimental model of cardiac arrest. MethodsAfter an initial dose study to determine the optimal dose, we conducted a prospective randomized study with 19 pigs. After 3 minutes of untreated ventricular fibrillation, animals received boluses of 0.5 mg Epinephrine (EPI) or 1 mg Norepinephrine (NE) every 5 minutes during CPR. Coronary perfusion pressure (CPP), carotid blood flow (CBF) and cerebral perfusion pressure (CePP) were evaluated. ResultsAt baseline, hemodynamic parameters did not differ between the two groups. During CPR, CPP and CBF were similar: 17.3 (12.8; 31.8) in the EPI group vs 16.0 (11.1; 37.7) in the NE group, p = 0.9 and 28.4 (22.0; 54.8) vs 30.8 (12.2; 56.3) respectively, p = 0.9. CePP was not significantly lower during resuscitation in the NE group compared to the EPI group: 12.2 (−8.2; 42.2) vs 7.8 (−2.0; 32.0) p = 0.4. Survival rate was low with only one animal in the EPI group and 2 in the NE group. ConclusionCerebral perfusion pressure, coronary perfusion pressure and carotid blood flow during CPR did not significantly differ between the norepinephrine group and the epinephrine group. Further investigations should evaluate different options such as a continuous NE infusion.

Carotid Blood Flow as a Surrogate for Pulse Contour Analysis in Assessment of Fluid Responsiveness: A Prospective, Observational, Single-Centre Study (Contour Study).

Background and objectives The quest for an accurate and reliable non-invasive method of assessing cardiac output in critically ill patients is still ongoing. Carotid artery Doppler is a promising non-invasive, reproducible, and feasible bedside monitor. So we compared the change in cardiac output derived from arterial pressure waveforms (pulse contour analysis) with that from carotid artery Doppler-derived measurements, in post-major elective abdominal surgery patients. Materials and methods We conducted a prospective observational study in 30 adult post-major elective abdominal surgery patients admitted to the Gastroenterology and Liver Transplant intensive care unit postoperatively on mechanical ventilator support, who were found to be fluid responsive clinically on passive leg raise (PLR) test. Demographics and vasopressor support were recorded. Hemodynamic parameters including heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), cardiac output (CO) using arterial pulse contour analysis (Vigileo monitor/FloTrac® sensor; Edwards Lifesciences, Irvine, California, United States), and carotid blood flow(CBF) were recorded on the baseline, pre- and post- PLR, and post fluid bolus administration. Balanced salt solution at the rate of 6ml/kg over 20 minutes was given as a fluid bolus. Results Of the 30 patients who were included in the study, 16 patients (53.3%) were on vasopressor support, mean (± SD)age of the patients was 52.93 (± 8.13) years. There was a significant increase in the SBP (mmHg) pre- to post-PLR, that is,112.2±15.57 and 118.7±14.96, respectively (p-value = 0.001). Also from pre-PLR to post-fluid bolus administration, the increase in SBP was significant, 112.2±15.57 and121.93±13.96, respectively (p-value = 0.001). The change in cardiac output measured using Vigileo and CBF from pre- to post-PLR (7.66±1.45 to 9.14±1.76, p< 0.001 for Vigileo and 8.10±1.66 to 9.72±1.99, p<0.001 for CBF) and pre-PLR to post fluid administration (7.66±1.45 to 9.39±1.77, p< 0.001for Vigileo and 8.10±1.66to 10.31±2.26, p< 0.001 for CBF) were significant. There was a positive correlation between the change in cardiac output as measured from arterial pulse contour analysis technique (Vigileo) and that measured from CBF (r=0.884) pre- and post-PLR. There was a significant correlation between cardiac output measurements derived from two techniques, before PLR, after PLR, and after fluid expansion (p< 0.001 for each variable). The change in cardiac output before PLR and after fluid expansion was also correlated by both the techniques (correlation coefficient being, r=0.781). Conclusion There was a significant positive correlation of the CO (absolute and change) measurements pre- and post-interventions (that is, PLR and fluid bolus administration) as made by pulse contour analysis (Vigileo) and by CBF in post-surgical patients. Pulse wave Doppler of CBF could be used as a surrogate for invasive measures of CO measurement for prediction of fluid responsiveness in this subgroup. Further larger studies can be performed to validate the same.

A remote-controlled automatic chest compression device capable of moving compression position during CPR: A pilot study in a mannequin and a swine model of cardiac arrest.

Recently, we developed a chest compression device that can move the chest compression position without interruption during CPR and be remotely controlled to minimize rescuer exposure to infectious diseases. The purpose of this study was to compare its performance with conventional mechanical CPR device in a mannequin and a swine model of cardiac arrest. A prototype of a remote-controlled automatic chest compression device (ROSCER) that can change the chest compression position without interruption during CPR was developed, and its performance was compared with LUCAS 3 in a mannequin and a swine model of cardiac arrest. In a swine model of cardiac arrest, 16 male pigs were randomly assigned into the two groups, ROSCER CPR (n = 8) and LUCAS 3 CPR (n = 8), respectively. During 5 minutes of CPR, hemodynamic parameters including aortic pressure, right atrial pressure, coronary perfusion pressure, common carotid blood flow, and end-tidal carbon dioxide partial pressure were measured. In the compression performance test using a mannequin, compression depth, compression time, decompression time, and plateau time were almost equal between ROSCER and LUCAS 3. In a swine model of cardiac arrest, coronary perfusion pressure showed no difference between the two groups (p = 0.409). Systolic aortic pressure and carotid blood flow were higher in the LUCAS 3 group than in the ROSCER group during 5 minutes of CPR (p < 0.001, p = 0.008, respectively). End-tidal CO2 level of the ROSCER group was initially lower than that of the LUCAS 3 group, but was higher over time (p = 0.022). A Kaplan-Meier survival analysis for ROSC also showed no difference between the two groups (p = 0.46). The prototype of a remote-controlled automated chest compression device can move the chest compression position without interruption during CPR. In a mannequin and a swine model of cardiac arrest, the device showed no inferior performance to a conventional mechanical CPR device.

Predicting fluid responsiveness in spontaneously breathing parturients undergoing caesarean section via carotid artery blood flow and velocity time integral measured by carotid ultrasound: a prospective cohort study

BackgroundPresent evidence suggests that the Doppler ultrasonographic indices, such as carotid artery blood flow (CABF) and velocity time integral (VTI), had the ability to predict fluid responsiveness in non-obstetric patients. The purpose of this study was to assess their capacity to predict fluid responsiveness in spontaneous breathing parturients undergoing caesarean section and to determine the effect of detecting and management of hypovolemia (fluid responsiveness) on the incidence of hypotension after anaesthesia.MethodsA total of 72 full term singleton parturients undergoing elective caesarean section were enrolled in this study. CABF, VTI, and hemodynamic parameters were recorded before and after fluid challenge and assessed by carotid artery ultrasonography. Fluid responsiveness was defined as an increase in stroke volume index (SVI) of 15% or more after the fluid challenge.ResultsThirty-one (43%) patients were fluid responders. The area under the ROC curve to predict fluid responsiveness for CABF and VTI were 0.803 (95% CI, 0.701–0.905) and 0.821 (95% CI, 0.720–0.922). The optimal cut-off values of CABF and VTI for fluid responsiveness was 175.9 ml/min (sensitivity of 74.0%; specificity of 78.0%) and 8.7 cm/s (sensitivity of 67.0%; specificity of 90.0%). The grey zone for CABF and VTI were 114.2-175.9 ml/min and 6.8–8.7 cm/s. The incidence of hypotension after the combined spinal-epidural anaesthesia (CSEA) was significantly higher in the Responders group 25.8% (8/31) than in the Non-Responders group 17.1(7/41) (P < 0.001). The total incidence of hypotension after CSEA of the two groups was 20.8% (15/72).ConclusionsUltrasound evaluation of CABF and VTI seem to be the feasible parameters to predict fluid responsiveness in parturients undergoing elective caesarean section and detecting and management of hypovolemia (fluid responsiveness) could significantly decrease incidence of hypotension after anaesthesia.Trial registrationThe trial was registered at the Chinese Clinical Trial Registry (ChiCTR) (www.chictr.org), registration number was ChiCTR1900022327 (The website link: https://www.chictr.org.cn/showproj.html?proj=37271 ) and the date of trial registration was in April 5, 2019. This study was performed in accordance with the Declaration of Helsinki and approved by the Research Ethics Committee of Women’s Hospital, Zhejiang University School of Medicine (20,180,120).