Administration Of Phenylephrine Research Articles

Treatment of Hypotension with Phenylephrine Increases Cerebral Microvascular Perfusion in a Rat Model of Acute Hemodilution

Intraoperative blood loss is associated with reduced mean arterial blood pressure (MAP), which may endanger vital organ perfusion, including the brain. Phenylephrine (PE), an α1-receptor agonist, is clinically utilized to treat intraoperative hypotension through vasoconstriction of resistance arterioles. Clinical studies suggest that raising MAP with PE may decrease perfusion to vital organs such as the brain. Experimental studies suggest that lower α-receptor density in the cerebral resistance arteries may lead to preserved brain perfusion after PE administration. We hypothesize that treatment of hypotension with PE will result in preserved brain perfusion due to different microvascular blood flow and tissue oxygen tension (pO2) responses in the brain and skeletal muscle in an experimental rat model. With Animal Care and Use Committee approval in accordance with ARRIVE-2 guidelines, spontaneously breathing anesthetized rats (1.5% isoflurane) underwent hemodilution by exchanging 40-50% estimated blood volume 1:1 with saline over 10 minutes to achieve a 10-20 mmHg drop in MAP. MAP (tail artery) was measured continuously. Hypotension was treated with PE (10-20 μg/kg/min iv) to increase MAP to a target above baseline MAP. Shed blood was re-infused after stopping the PE infusion. Microvascular blood flow (Oxyflo; Oxford Optronix, Oxford, UK, n=7) or microvascular pO2 (OxyLED, Oxyphor G4, Oxygen Enterprises Ltd., Philadelphia, PA, n=6) were measured continuously in the cerebral cortex (burr hole) and biceps femoris muscle simultaneously in each rat. Results were analyzed via one or two-way ANOVA, with significance achieved at p<0.05. Baseline and post-hemodilution MAP values were comparable in both groups. PE infusion increased MAP to a mean level near 100 mmHg in both groups (p<0.05). Microvascular blood flow and tissue pO2 were greater in the brain as compared to the muscle at all time points (p<0.01 for both). PE infusion resulted in an increase in cerebral microvascular blood flow from baseline (1465±689 vs. 687±453 blood perfusion units (BPU); p<0.001) that was sustained after discontinuing PE and during blood reinfusion. No changes in muscle microvascular flow were observed after PE infusion (294±129 vs. 168±113 BPU). A sustained increase in cerebral microvascular pO2 was measured following PE infusion (50.2±8.6 vs. 40.6±4.6 mmHg; p=0.02), whereas muscle tissue pO2 did not change (22.2±5.6 vs. 25.0±2.5 mmHg). A differential blood flow and microvascular pO2 response was observed following PE infusion in brain and skeletal muscle. Both cerebral microvascular blood flow and tissue pO2 demonstrated sustained increases after PE infusion. By contrast, no changes were observed in muscle microvascular blood flow and pO2. These results suggest that treatment of hypotension with PE administration preferentially increased cerebral vs. muscle perfusion in an experimental model of acute blood loss and fluid resuscitation. Canadian Anesthesiologists’ Society and University of Toronto Merit Award Support. 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.

Correlations between heart sound components and hemodynamic variables

Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.

Prediction of preload dependency using phenylephrine-induced peripheral perfusion index during general anaesthesia: a prospective observational study

BackgroundTracking preload dependency non-invasively to maintain adequate tissue perfusion in the perioperative period can be challenging.The effect of phenylephrine on stroke volume is dependent upon preload. Changes in stroke volume induced by phenylephrine administration can be used to predict preload dependency. The change in the peripheral perfusion index derived from photoplethysmography signals reportedly corresponds with changes in stroke volume in situations such as body position changes in the operating room. Thus, the peripheral perfusion index can be used as a non-invasive potential alternative to stroke volume to predict preload dependency. Herein, we aimed to determine whether changes in perfusion index induced by the administration of phenylephrine could be used to predict preload dependency.MethodsWe conducted a prospective single-centre observational study. The haemodynamic parameters and perfusion index were recorded before and 1 and 2 min after administering 0.1 mg of phenylephrine during post-induction hypotension in patients scheduled to undergo surgery. Preload dependency was defined as a stroke volume variation of ≥ 12% before phenylephrine administration at a mean arterial pressure of < 65 mmHg. Patients were divided into four groups according to total peripheral resistance and preload dependency.ResultsForty-two patients were included in this study. The stroke volume in patients with preload dependency (n = 23) increased after phenylephrine administration. However, phenylephrine administration did not impact the stroke volume in patients without preload dependency (n = 19). The perfusion index decreased regardless of preload dependency. The changes in the perfusion index after phenylephrine administration exhibited low accuracy for predicting preload dependency. Based on subgroup analysis, patients with high total peripheral resistance tended to exhibit increased stroke volume following phenylephrine administration, which was particularly prominent in patients with high total peripheral resistance and preload dependency.ConclusionThe findings of the current study revealed that changes in the perfusion index induced by administering 0.1 mg of phenylephrine could not predict preload dependency. This may be attributed to the different phenylephrine-induced stroke volume patterns observed in patients according to the degree of total peripheral resistance and preload dependency.Trial registrationUniversity Hospital Medical Information Network (UMIN000049994 on 9/01/2023).

Effect of phenylephrine rescue injection on hypotension after spinal anaesthesia for caesarean delivery when guided by both heart rate and SBP during an early warning window: A randomised controlled trial.

Spinal anaesthesia is now the most common technique for caesarean delivery. However, because of the intermittent nature of noninvasive blood pressure (NIBP) measurements, maternal blood pressure may become hypotensive between the measurements. There is thus an inbuilt delay before the anaesthesiologist can intervene to counteract the hypotension. Based on the principle that changes in blood pressure can induce compensatory changes in the heart rate (HR), combining the NIBP with real-time HR, we designed two warning windows to predict hypotension and hypertension. To evaluate whether phenylephrine administration guided by these warning windows would help maintain haemodynamic stability. A teaching hospital. A randomised controlled trial. One hundred and ten pregnant women scheduled for elective caesarean delivery were enrolled, from which, after exclusions, 86 were eligible for the study. All eligible patients received a continuous intravenous infusion of phenylephrine as soon as spinal anaesthesia was initiated. Thereafter, patients were randomly assigned to two groups. In the test group (Win-Group): rescue phenylephrine administration was triggered by an early warning window of HR above 100 beats per minute (bpm) and SBP 90 to 110 mmHg; pausing the infusion phenylephrine was triggered by a HR lower than 60 bpm and SBP greater than 90 mmHg. In the control group, phenylephrine was guided by BP only when it appeared on the monitor: SBP less than 90 mmHg was the trigger for administering rescue phenylephrine; SBP greater than 110 mmHg was the trigger for pausing the phenylephrine infusion. The primary outcome was incidence of hypotension. Secondary outcomes were the incidence of hypertension and other adverse haemodynamic events. The incidence of hypotension was significantly lower in the Win-Group than in the BP-Group (27.8 vs. 66.7%, P = 0.001). The minimum SBP was significantly higher in Win-Group than in BP-Group (93.9 ± 9.49 vs. 86.7 ± 11.16 mmHg, P = 0.004). There was no significant difference in the incidence of hypertension between groups. After spinal anaesthesia for caesarean delivery, when phenylephrine infusion is guided by HR along with BP from a warning window it effectively reduces the incidence of hypotension without any significant effect on incidence of hypertension. Chictr.org.cn; Identifier: ChiCTR 2100041812.

Tonic noradrenergic input to neurons in the dorsal raphe nucleus mediates food intake in male mice

The dorsal raphe nucleus (DRN) is essential for the control of food intake. Efferent projections from the DRN extend to several forebrain regions that are involved in the control of food intake. However, the neurotransmitters released in the DRN related to the control of food intake are not known. We have previously demonstrated that a tonic α1 action on DRN neurons contributes to satiety in the fed rats. In this study we investigated the participation of norepinephrine (NE) signaling in the DRN in the satiety response. Intra-DRN administration of NE causes an increase in the 2-hour food intake of sated mice, an effect that was blocked by previous administration of yohimbine, an α2 antagonist. Similarly, Intra-DRN administration of clonidine, an α2 agonist, increases food intake in sated mice. This result indicates that in the satiated mice exogenous NE acts on α2 receptors to increase food intake. Furthermore, administration of phenylephrine, an α1 agonist, decreases food intake in fasted mice and prazosin, an α1 antagonist, increases food intake in the sated mice. Taken together these results indicate that, in a satiated condition, a tonic α1 adrenergic action on the DRN neurons inhibits food intake and that exogenous NE administered to the DRN acts on α2 adrenergic receptors to increase food intake. These data reinforce the intricate neuronal functioning of the DRN and its effects on feeding.

Alleviating Hypertension by Selectively Targeting Angiotensin Receptor-Expressing Vagal Sensory Neurons.

Cardiovascular homeostasis is maintained, in part, by neural signals arising from arterial baroreceptors that apprise the brain of blood volume and pressure. Here, we test whether neurons within the nodose ganglia that express angiotensin type-1a receptors (referred to as NGAT1aR) serve as baroreceptors that differentially influence blood pressure (BP) in male and female mice. Using Agtr1a-Cre mice and Cre-dependent AAVs to direct tdTomato to NGAT1aR, neuroanatomical studies revealed that NGAT1aR receive input from the aortic arch, project to the caudal nucleus of the solitary tract (NTS), and synthesize mechanosensitive ion channels, Piezo1/2 To evaluate the functionality of NGAT1aR, we directed the fluorescent calcium indicator (GCaMP6s) or the light-sensitive channelrhodopsin-2 (ChR2) to Agtr1a-containing neurons. Two-photon intravital imaging in Agtr1a-GCaMP6s mice revealed that NGAT1aR couple their firing to elevated BP, induced by phenylephrine (i.v.). Furthermore, optical excitation of NGAT1aR at their soma or axon terminals within the caudal NTS of Agtr1a-ChR2 mice elicited robust frequency-dependent decreases in BP and heart rate, indicating that NGAT1aR are sufficient to elicit appropriate compensatory responses to vascular mechanosensation. Optical excitation also elicited hypotensive and bradycardic responses in ChR2-expressing mice that were subjected to deoxycorticosterone acetate (DOCA)-salt hypertension; however, the duration of these effects was altered, suggestive of hypertension-induced impairment of the baroreflex. Similarly, increased GCaMP6s fluorescence observed after administration of phenylephrine was delayed in mice subjected to DOCA-salt or chronic delivery of angiotensin II. Collectively, these results reveal the structure and function of NGAT1aR and suggest that such neurons may be exploited to discern and relieve hypertension.

Norepinephrine versus phenylephrine for managing maternal hypotension during cesarean delivery under spinal anesthesia: a meta-analysis of maternal and neonatal outcomes

Norepinephrine or phenylephrine administration to prevent and treat hypotension during spinal anesthesia for cesarean section has been a significant topic of discussion. This meta-analysis aimed to update existing evidence and provide further insights into neonatal and maternal outcomes associated with norepinephrine and phenylephrine. Review of randomized controlled trials (RCTs) was performed to assess the effectiveness of norepinephrine and phenylephrine in managing maternal hypotension during cesarean delivery under spinal anesthesia. Neonatal umbilical cord blood pH and maternal hypotension were the primary outcomes. Based on the analysis of 26 RCTs with 2984 participants, we found no significant difference between the norepinephrine and phenylephrine groups in umbilical artery pH in neonates (mean difference (MD) 0.00; 95% confidence interval (CI) −0.00 to 0.01, p = 0.20). Neonates Apgar scores did not differ between both groups. Norepinephrine was associated with lower incidences of bradycardia (risk ratio (RR) 0.44; 95% CI 0.37 to 0.51, p &lt; 0.001) and reactive hypertension (RR 0.53; 95% CI 0.39 to 0.72, p &lt; 0.001) in parturient women than phenylephrine. In neither group did umbilical cord blood levels of partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2) and base excess (BE) levels of neonates differ significantly, nor did maternal hypotension, nausea or vomiting incidence during delivery. For maternal hypotension after spinal anesthesia, norepinephrine and phenylephrine did not significantly differ in neonatal acidemia. Despite similarities to phenylephrine in managing hypotension and maintaining maternal hemodynamic stability, norepinephrine is a promising alternative.

N-Acetylcysteine Alleviates Phenylephrine-Induced Cardiomyocyte Dysfunction via Engaging PI3K/AKT Signaling Pathway.

Increased reactive oxygen species (ROS) and oxidative stress response lead to cardiomyocyte hypertrophy and apoptosis, which play crucial roles in the pathogenesis of heart failure. The purpose of current research was to explore the role of antioxidant N-acetylcysteine (NAC) on cardiomyocyte dysfunction and the underlying molecular mechanisms. Compared with control group without NAC treatment, NAC dramatically inhibited the cell size of primary cultured neonatal rat cardiomyocytes (NRCMs) tested by immunofluorescence staining and reduced the expression of representative markers associated with hypertrophic, fibrosis and apoptosis subjected to phenylephrine administration examined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Moreover, enhanced ROS expression was attenuated, whereas activities of makers related to oxidative stress response examined by individual assay Kits, including total antioxidation capacity (T-AOC), glutathione peroxidase (GSH-Px), and primary antioxidant enzyme Superoxide dismutase (SOD) were induced by NAC treatment in NRCMs previously treated with phenylephrine. Mechanistically, we noticed that the protein expression levels of phosphorylated phosphatidylinositol 3-kinase (PI3K) and AKT were increased by NAC stimulation. More importantly, we identified that the negative regulation of NAC in cardiomyocyte dysfunction was contributed by PI3K/AKT signaling pathway through further utilization of PI3K/AKT inhibitor (LY294002) or agonist (SC79). Collected, NAC could attenuate cardiomyocyte dysfunction subjected to phenylephrine, partially by regulating the ROS-induced PI3K/AKT-dependent signaling pathway.

Performance of closed-loop systems for intravenous drug administration: a systematic review and meta-analysis of randomised controlled trials.

Closed-loop drug delivery systems are autonomous computers able to administer medication in response to changes in physiological parameters (controlled variables). While limited evidence suggested that closed-loop systems can perform better than manual drug administration in certain settings, this technology remains a research tool with an uncertain risk/benefit profile. Our aim was comparing the performance of closed-loop systems with manual intravenous drug administration in adults. We searched MEDLINE, CENTRAL, and Embase from inception until November 2022, without restriction to language. We assessed for inclusion randomised controlled trials comparing closed-loop and manual administration of intravenous drugs in adults, intraoperatively or in the Intensive Care Unit. We identified 32 studies on closed-loop administration of propofol, noradrenaline, phenylephrine, insulin, neuromuscular blockers, and vasodilators. Most studies were at moderate or high risk of bias. The results showed that closed-loop systems reduced the duration of blood pressure outside prespecified targets during noradrenaline (MD 14.9%, 95% CI 9.6-20.2%, I2 = 66.6%) and vasodilators administration (MD 7.4%, 95% CI 5.2-9.7%, I2 = 62.3%). Closed-loop systems also decreased the duration of recovery after propofol (MD 1.3min, 95% CI 0.4-2.1min, I2 = 58.6%) and neuromuscular blockers (MD 9.0min, 95% CI 7.9-10.0min, I2 = 0%). The certainty of the evidence was low or very low for most outcomes. Automatic technology may be used to improve the hemodynamic profile during noradrenaline and vasodilators administration and reduce the duration of postanaesthetic recovery.Registration: This systematic review was registered with PROSPERO (CRD42022336950) on the 7th of June 2022.

Phenylephrine and norepinephrine increase blood pressure through opposing physiologic mechanisms in isoflurane-anesthetized dogs receiving acepromazine.

To elucidate the cardiovascular effects of escalating doses of phenylephrine and norepinephrine in dogs receiving acepromazine and isoflurane. 8 beagles aged 1 to 2 years (7.4 to 11.2 kg). All dogs received acepromazine 0.01 mg/kg, propofol 4 to 5 mg/kg, and isoflurane and were mechanically ventilated. Mean arterial pressure (MAP) from a femoral artery catheter and continuous electrocardiogram were recorded. Cardiac output (CO) was measured with transpulmonary thermodilution. Systemic vascular resistance (SVR), global end-diastolic volume (GEDV), and global ejection fraction (GEF) were subsequently calculated. Phenylephrine and norepinephrine were infused in random order at 0.07, 0.3, 0.7, and 1.0 μg/kg/min. All variables were measured after 15 minutes of each infusion rate. The effects of dose, agent, and their interaction on the change of each variable were evaluated with mixed-effect models. A P < .05 was used for significance. Atrial premature complexes occurred in 3 dogs during norepinephrine infusion at doses of 0.3, 0.7, and 1 μg/kg/min; no dysrhythmias were seen with phenylephrine administration. MAP increased during dose escalation (P < .0001) within each agent and did not differ between agents (P = .6). The decrease in HR was greater for phenylephrine (P < .0001). Phenylephrine decreased CO and GEF and increased GEDV and SVR (all P < .03). Norepinephrine decreased the SVR and increased CO, GEDV, and GEF (all P < .03). Our results confirm that phenylephrine increases arterial pressures mainly through vasoconstriction in acepromazine-premedicated dogs while norepinephrine, historically considered a vasopressor, does so primarily through an increase in inotropism.

Comparative study on analgesia duration with bupivacaine-buprenorphine combination vs. bupivacaine alone for cesarean delivery

BACKGROUND: Spinal anesthesia has been the preferred type of anesthesia for cesarean sections and other obstetric operations. Bupivacaine has been used for this purpose being long acting. Lately various narcotic analgesics have been added to prolong the analgesia and reduce the expected toxicity of bupivacaine alone. We evaluated the duration of analgesia achieved with the combination of bupivacaine-buprenorphine versus bupivacaine alone in cesarean delivery under spinal anesthesia.&#x0D; Methods: A comparative study was conducted at a tertiary care teaching healthcare center in Karachi, Pakistan. One hundred patients scheduled for elective cesarean section were enrolled and divided into two groups. Group A received 10 mg of hyperbaric bupivacaine 0.5% along with normal saline, while Group B received the same dose of bupivacaine along with buprenorphine 75 µg. Preoperative assessment, intraoperative procedures, and postoperative management were performed following standard protocols of our institution. Statistical analysis was conducted using independent t-tests and chi-square tests.&#x0D; Results: The findings revealed significantly longer mean time to request for analgesia in Group B compared to Group A (825.33 min vs. 166.78 min; P = 0.182), Only 14 patients in Group B (28%) required analgesia within 24 h, while all patients in Group A requested analgesia within that time frame (P = 0.0001). Moreover, an insignificantly lower incidence of hypotension and reduced need for phenylephrine administration was observed in Group B compared to Group A (P = 0.585). Group B also demonstrated a lower incidence of nausea (P = 0.380) and vomiting (P = 0.370) compared to Group A, but the difference was statistically not significant.&#x0D; Conclusion: This study suggests that the addition of buprenorphine to bupivacaine in spinal anesthesia for cesarean delivery provides prolonged analgesia, reduces the incidence of nausea and vomiting, and decreases the need for vasopressor administration. These findings support the potential benefits of using the bupivacaine-buprenorphine combination in cesarean deliveries.&#x0D; Key words: Cesarean Delivery; Opioids, Intrathecal; Anesthesia, Spinal; Bupivacaine; Buprenorphine; Analgesia, Duration&#x0D; Citation: Saleh M, Malik S, Memon GN, Rehman M. Comparative study on analgesia duration with bupivacaine-buprenorphine combination vs. bupivacaine alone for cesarean delivery. Anaesth. pain intensive care 2023;27(5):501−505; DOI: 10.35975/apic.v27i5.2303&#x0D; Received: July 29, 2023; Reviewed: August 10, 2023; Accepted: August 10, 2023

Incidence of bradycardia during noradrenaline or phenylephrine bolus treatment of postspinal hypotension in cesarean delivery: A randomized double-blinded controlled trial.

The treatment of choice for spinal anesthesia-induced hypotension during cesarean section is phenylephrine. As this vasopressor can cause reflex bradycardia, noradrenaline is a suggested alternative. This randomized double-blinded controlled trial included 76 parturients undergoing elective cesarean delivery under spinal anesthesia. Women received noradrenaline in bolus doses of 5mcg or phenylephrine in bolus doses of 100 mcg. These drugs were used intermittently and therapeutically to maintain systolic blood pressure ≥ 90% of its baseline value. The primary study outcome was bradycardia incidence (<60 bpm) with intermittent bolus administration of these drugs. Secondary outcomes included extreme bradycardia (<40 bpm), number of bradycardia episodes, hypertension (systolic blood pressure > 120% of baseline value), and hypotension (systolic blood pressure < 90% of baseline value and requiring vasopressor use). Neonatal outcomes per the Apgar scale and umbilical cord blood gas analysis were also compared. The incidence of bradycardia in both groups (51.4% and 70.3%, respectively; p=0.16) were not significantly different. No neonates had umbilical vein or artery pH values below 7.20. The noradrenaline group required more boluses than phenylephrine group (8 vs. 5; p=0.01). There was no significant intergroup difference in any of the other secondary outcomes. When administered in intermittent bolus doses for the treatment of postspinal hypotension in elective cesarean delivery, noradrenaline, and phenylephrine have a similar incidence of bradycardia. When treating hypotension related to spinal anesthesia in obstetric cases, strong vasopressors are commonly administered, thought these can also have side effects. This trial assessed bradycardia after bolus administration of noradrenaline or phenylephrine, and found no difference in risk for clinically meaningful bradycardia.

Regional Differences in Human Skin Responses to Receptor Agonists: Implications for Differing Facial vs. Forearm Innervation

There is not yet consensus on the precise differences between non-glabrous and facial skin characteristics. Our lab identified similar responses to local heat stress in forearm and facial skin, while others identified differing responses to autonomic stressors within facial regions. Anatomical differences, such as the thinner nature of facial skin and specifically its thinner stratum corneum, may also impact facial autonomic responses. Considering this layer is a protective barrier, facial skin may be more sensitive to perturbations like drug administration. While non-glabrous skin is innervated by spinal nerves, facial skin is innervated by cranial nerves. Because of these anatomical and physiological differences between non-glabrous and facial skin, it is possible that their differing neural and receptor characteristics impact a key autonomic end-organ response: cutaneous blood flow. In this pilot experiment, we investigated possible regional differences between the forehead and forearm in response to adrenergic and cholinergic agonists. We hypothesized that drugs targeting adrenergic (phenylephrine, clonidine, and isoproterenol) and cholinergic (acetylcholine) cutaneous receptors would elicit similar vasomotor effects in both locations. One female subject underwent forearm and forehead iontophoresis of each agonist using adaptations of published protocols, as well as a control protocol using deionized water (vehicle) alone. We recorded blood flow via laser-Doppler flowmetry (Moor Instruments) and beat-by-beat arterial blood pressure via finger photoplethysmography (ADInstruments). We calculated baseline cutaneous vascular conductance (CVC) and plateau 43°C CVC to determine the change in skin blood flow resulting from drug administration. Our results indicate that while phenylephrine administration caused vasodilation, opposing our hypothesis, administration of all other drugs caused responses in agreement with our expectations. Thus, these pilot data suggest that facial and non-glabrous skin may respond similarly to adrenergic or cholinergic agonists. These findings imply a potential use for topical dermatological drug treatments utilized on the trunk/extremities to benefit cutaneous facial diseases.

Transesophageal echocardiography for cardiac herniation occurring during robotic-assisted mitral valve repair: a case report

BackgroundCardiac herniation has been reported in thoracic trauma and after pneumonectomy; however, it is sporadic in cardiac surgery.Case presentationA 35-year-old male patient underwent an elective totally endoscopic robotic-assisted mitral valve repair (TERMVR). His hemodynamics were stable after weaning from cardiopulmonary bypass, and no residual mitral valve regurgitation was observed. However, during suturing of the port wound, the patient developed hypotension, which improved with phenylephrine administration. Four-chamber transesophageal echocardiography (TEE) images showed cardiac deformity, and postoperative chest radiography confirmed the dextrocardia. The cardiac herniation was repaired by deflating the left lung and over-inflating the right lung using a double-lumen tube, allowing selective ventilation without re-thoracotomy. The patient was discharged on the sixth postoperative day without complications.ConclusionsThis was a very unusual case of cardiac herniation during TERMVR visualized using distinct TEE images. The cardiac herniation was successfully repaired using a double-lumen tube without re-thoracotomy.

PS-BPB04-5: SELECTIVE ACTIVATION OF GLUTAMATERGIC NEURONS WITHIN THE SFO EVOKES A PRESSOR RESPONSE THAT IS DEPENDENT ON THE PVN

Objective: An overactive glutamatergic projection from the subfornical organ (SFO) to the paraventricular nucleus (PVN) is associated with the development of hypertension. Despite this, the functional relationship of this pathway under normotensive conditions remains poorly defined within the literature. Without this knowledge, it remains unknown if a dysfunction of this pathway is the underlying cause of hypertension or rather simply a consequence of the underlying hypertensive disease pathology. As such, the aim of this study is to identify the short-term function of the SFO and PVN pathway under normotensive conditions. Design and Methods: An optogenetic viral vector (pAAV-CaMKIIa-hChR2 (H134R)-EYFP) was microinjected into the SFO of Lewis rats (n = 5). Three weeks later, rats were anaesthetised and instrumented to record blood pressure and sympathetic nerve activity, administer intravenous drugs and to photo-stimulate glutamatergic SFO neurons. Results: Photostimulation of glutamatergic SFO neurons produced a pressor response that was abolished by inhibition of neuronal transmission within the PVN (9 ± 1mmHg vs 3 ± 1mmHg peak change from baseline, baseline vs PVN inhibition, n = 2 rats, 3 replicates per rat). In a separate cohort (n = 3 rats, 5 replicates per rat), we determined if the pressor response elicited was dependant on the sympathetic nervous system and/or the release of the vasoactive hormone vasopressin. Blockade of sympathetic vasomotor outflow attenuated the pressor response by 76%, whereas combined inhibition of sympathetic outflow and vasopressin 1a receptors attenuated the pressor response by 88%. Finally, photostimulation of glutamatergic SFO neurons led to a peak increase in sympathetic nerve activity (n = 2) that was abolished by phenylephrine administration, suggesting that the neuronal circuitry underpinning this response is barosensitive. Conclusions: This study demonstrates that the pressor response elicited by glutamatergic SFO neurons is dependent on the PVN and is largely mediated by the sympathetic nervous system via barosensitive neuronal circuitry. Chronic activation of this pathway will be undertaken to determine if an overactivation of this neuronal pathway induces hypertension in normotensive animals.

Phenylephrine and Ephedrine for Prevention of Hypotension in Women during Lower Segment Caesarean Section under Spinal Anaesthesia: A Randomised Clinical Study

Introduction: Hypotension is the most common serious adverse event associated with Spinal Anaesthesia (SA) and is associated with nausea and vomiting leading to pulmonary aspiration, respiratory depression and cardiac arrest. Phenylephrine (PE) and Ephedrine (EP) are vasopressors commonly used for prevention of hypotension associated with SA. Aim: To compare the efficacy and safety of PE and EP in prevention of hypotension induced by SA in women during Lower Segment Caesarean Section (LSCS) surgery. Materials and Methods: The present randomised clinical study was conducted on 60 women, between 18-36 years of age and a Heart Rate (HR) of 60-100 per minute randomised to receive either 100 mcg Intravenous (i.v.) bolus of PE, or 12 mg i.v. of EP during intrathecal block. Women having intraoperative hypotension were injected additional doses of vasopressor. Cardiovascular parameters were recorded at baseline (before block) and then at 1, 5, 10, 15, 30, 40 and 60 minutes. Further, safety was also assessed based on hypotension events and adverse events reported during immediate postoperative period. Data analysis was done using IBM SPSS 17 and a p-value &lt;0.05 was considered statistically significant. Results: The mean age of the study participants in PE and EP group was 26.67±5.40 and 26.23±4.59 years, respectively. Significant differences were observed between PE and EP groups for change in Systolic Blood Pressure (SBP) after 1, 10, 30, 40 and 60 minutes. Overall, there was a slight fall in SBP with PE, whereas, with EP there was a slight rise in SBP. Also, the Diastolic Blood Pressure (DBP) was maintained with EP throughout the 60 minute period, whereas with PE there was an initial rise in DBP followed by a slight fall in DBP. The Mean Arterial Pressure (MAP) was well maintained with PE throughout, whereas with EP there was a fall in MAP after 15 minutes. However, these changes were not clinically significant. The Pulse Rate (PR) was lower with PE compared to EP group at time points of 1, 5, 15 and 20 minutes. The mean respiratory rates and blood oxygen saturation were similar with PE and EP administration (p&gt;0.05). A total of 13 (43.3%) patients in the PE group and 14 (46%) in the EP group had adverse events excluding hypotensive patients. Conclusion: According to the findings of the present study, the i.v. bolus of 100 mcg PE and 12 mg EP administered immediately after SA are equally effective in prevention of maternal hypotension and do not cause any significant cardiovascular and respiratory effects.

Influence of continuous administration of phenylephine versus dobutamine on paraspinal oxygen saturation

Introduction: This randomized controlled trial evaluates the effect of continuous administration of phenylephrine versus dobutamine on paraspinal oxygenation, measured by near-infrared spectroscopy (NIRS). Paraspinal NIRS-monitoring evaluates the spinal oxygenation in an indirect, continuous and real-time manner. The influence of these drugs on the paraspinal oxygenation is unknown, but can be highly relevant during major aortic repair. Methods: This dissertation discusses a preliminary data analysis concerning the first twenty patients included. Phenylephrine or dobutamine were administered continuously during elective arterial dilation procedures of the lower limb. Adhering to a predefined protocol, drug administration was titrated to maintain normotension. The primary outcome variable is the NIRS-measured paraspinal oxygen saturation (rS psO2), this at three distinct paraspinal levels (T3T4 – T9T10 – L1L2), and additionally at the deltoid muscle (rSdO2). A linear mixed modelling approach was used for statistical analysis. This manuscript adheres to the applicable CONSORT guidelines. Results: Estimated mean relative NIRS-values (e.g. changes from baseline) were calculated at the different locations. We observed an overall positive effect on these oximetry values in the dobutamine administered group, this in contrast with an overall negative effect with phenylephrine administration. Significant differences in estimated mean relative values between the groups were observed at the lumbar level (-0.67% vs 2.97%) and at the deltoid muscle (-2.63% vs 2.01%), with significantly higher values during dobutamine administration. Conclusion: By means of a mixed modelling approach to estimate mean relative values of rSpsO2 and rSdO2, we compared the effects of the administration of phenylephrine or dobutamine. Noticeable differences between the two groups were observed and seem to favour the use of dobutamine. Besides an overall positive effect of dobutamine administration, significant differences between the two interventions were observed at the lumbar level, in favour of dobutamine administration. Limitations of this analysis are the rather complex modelling, and the lack of implementation of cardiac output variables in the model.

Ephedrine vs. phenylephrine effect on sublingual microcirculation in elderly patients undergoing laparoscopic rectal cancer surgery.

BackgroundThe effects of anesthesia administration on sublingual microcirculation are unknown. It is unclear how sublingual microcirculation responds to ephedrine or phenylephrine administration. We hypothesized that microvascular perfusion is impaired under anesthesia.Materials and methodsWe randomly divided 100 elderly patients undergoing laparoscopic rectal cancer surgery into phenylephrine and ephedrine groups in a 1:1 ratio. Ephedrine or phenylephrine was administered when MAP was < 80% for > 1 min. The heart rate (HR) and mean arterial pressure (MAP) were recorded every 5 min. Lactic acid was tested both pre- and postoperatively. The sublingual microcirculation characteristics of the microvascular flow index, the percentage of perfused vessels, the density of perfused vessels, and the heterogeneity index were monitored using a sidestream dark field imaging device.ResultsTheir MAP showed an evident decrease of > 20%. At this point, the HR, microvascular flow index, perfused vessel density, and proportion of perfused vessels decreased similarly in ephedrine and phenylephrine groups. Conversely, the heterogeneity index increased in both groups. After phenylephrine and ephedrine administration, ephedrine treatment significantly increased the proportion of perfused vessels, microvascular flow index, and HR compared with phenylephrine treatment.ConclusionGeneral anesthesia was associated with reduced MAP, HR, and sublingual microcirculation in elderly patients undergoing laparoscopic rectal cancer surgery. The results of ephedrine treatment were better than those of phenylephrine treatment in terms of HR, increased the proportion of perfused vessels, and microvascular flow index of sublingual microcirculation.Clinical trial registration[www.ClinicalTrials.gov], identifier [ChiCTR-2000035959].

Safety and Efficacy of Phenylephrine Administration for the Treatment of Ischemic Priapism: An Opportunity for Quality Improvement in Periprocedural Safety Assessment

To determine the safety and efficacy of hourly, high dose phenylephrine (>1000 μg) for acute ischemic priapism (AIP) through monitoring adverse hemodynamic events amongst risk profiles. An IRB-approved retrospective review of patients with AIP from 2010 to 2020. Patients were stratified to a low or high dose phenylephrine group based on cumulative, hourly dose of ≤1000 μg and > 1000 μg respectively and examined for successful resolution of their AIP. The safety profile of phenylephrine for patients at risk for adverse hemodynamic events was examined. A total of 123 patients were identified with a median age of 40 (range: 7-76) years with median time from AIP onset to presentation of 11 (2-168) hours. A total of 97 men received phenylephrine (78.9%) and detumescence was achieved nonoperatively in 62 of these men (63.9%) with a mean priapism duration of 8.7 hours. Those resolving with phenylephrine administration had a mean duration of 8.8 ± 5.6 vs 57.3 ± 37.1 hours without resolution P < .001. Among low and high dose phenylephrine groups (500 and 2000 μg respectively), the median duration of AIP was 10 and 12 hours respectively without a difference in AIP resolution (P > .05). Twenty-one patients (17.1%) were deemed at risk for phenylephrine complication of which 4 (4.1%) had phenylephrine discontinued due to hemodynamic changes. Nonoperative resolution of AIP with phenylephrine does not appear to be dose-dependent and hemodynamic changes secondary to phenylephrine administration may be underreported. Future work should utilize standardized risk assessment and periprocedural monitoring for hemodynamic change.

Abstract P2007: Bmal1 Drives Postnatal Cardiac Hypertrophy Via Circadian Chromatin Remodeling Of The Pro-hypertrophic Gene Sik1

Background: During neonatal cardiac development, myocytes integrate cues such as changes in blood pressure and circulating hormones to execute a temporal genetic response that drives physiological cardiac hypertrophy. Chromatin remodeling precedes the adult heart’s response to growth stimuli, yet the temporal nature of neonatal chromatin remodeling is unclear. In other tissues, genes regulated by the master circadian rhythm factor BMAL1 display circadian oscillations in histone acetylation and nucleosome and RNAP II occupancy. We hypothesized that BMAL1 regulates temporal chromatin remodeling and expression of genes critical for neonatal cardiac hypertrophy. Methods: BMAL1 chromatin immunoprecipitation sequencing (ChIP-Seq) and assay for transposase-accessible chromatin and sequencing (ATAC-Seq) data from murine hearts were analyzed to identify genes at which BMAL1 may drive chromatin remodeling. To interrogate myocyte time-of-day dependent response to growth stimuli, neonatal rat ventricular myocytes (NRVM) were subjected to serum shock synchronization to drive oscillatory BMAL1 expression, followed by treatment with the growth stimulus phenylephrine (PE) at the peak and trough of BMAL1 expression. BMAL1 was knocked down via siRNA and hypertrophy was assessed by measurement of cell size and of RT-PCR of fetal genes (Nppa and Nppb). Results: BMAL1 ChIP-Seq data revealed myocyte-specific BMAL1 localization to regions exhibiting an open chromatin signature based on ATAC-seq, including the pro-hypertrophic gene salt-inducible kinase 1 ( Sik1 ). Serum shock induced oscillations of BMAL1 and histone H3.3: administration of PE at the peak of BMAL1 expression induced a 30% increase in cell size and 2-fold increase in fetal gene expression. PE given at the trough of BMAL1 expression affected neither cell size nor fetal genes, demonstrating a critical role for the circadian clock in myocyte growth. BMAL1 knockdown: decreased expression of its known target and partner clock gene, Per2 , as well as expression of Sik1, Nppa , and Nppb ; decreased myocyte size by 30%; and increased expression of histone H3.3. Conclusions: These data indicate that BMAL1 temporally regulates myocyte growth by modulating histone stoichiometry and expression of Sik1 .