Intravenous Infusion Of Phenylephrine 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.

Comparison of Phenylephrine Infusion Versus Boluses for Management of Blood Pressure in Elective Caesarean Section

Comparison of Phenylephrine Infusion Versus Boluses for Management of Blood Pressure in Elective Caesarean Section

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.

Determination of ED90s of Phenylephrine and Norepinephrine Infusion for Prevention of Spinal Anesthesia-Induced Hypotension in Patients with Preeclampsia During Cesarean Delivery.

Vasopressors remain an important strategy for managing spinal anesthesia-induced hypotension in women with preeclampsia. The aim of this study was to investigate the ED90s and efficacy ratio of phenylephrine and norepinephrine in managing spinal anesthesia-induced hypotension in women with preeclampsia during cesarean delivery. 60 women with preeclampsia, who underwent cesarean delivery, were randomly assigned to receive either a continuous intravenous infusion of phenylephrine or norepinephrine following spinal anesthesia. The initial dosage of phenylephrine or norepinephrine for the first women was 0.5 or 0.05 μg/kg/min, respectively, and subsequent infusion dosages were adjusted based on their efficacy in preventing spinal anesthesia-induced hypotension (defined as a systolic blood pressure less than 80% of the baseline level). The incremental or decremental doses of phenylephrine or norepinephrine were set at 0.1 or 0.01 μg/kg/min. The primary outcomes were the ED90s and efficacy ratio of phenylephrine and norepinephrine infusions for preventing spinal anesthesia-induced hypotension prior to delivery. The results obtained from isotonic regression analysis revealed that the ED90 values of the phenylephrine and norepinephrine group for preventing spinal anesthesia-induced hypotension were 0.597 (95% CI: 0.582-0.628) and 0.054 (95% CI: 0.053-0.056) μg/kg/min, respectively, with an efficacy ratio of 11.1:1. The results of Probit regression analysis revealed that the ED90 values were determined to be 0.665 (95% CI: 0.576-1.226) and 0.055 (95% CI: 0.047-0.109) μg/kg/min, respectively, with an efficacy ratio of 12.1:1. The administration of 0.6 μg/kg/min phenylephrine and 0.05 μg/kg/min norepinephrine has been found to effectively manage a 90% incidence of spinal anesthesia-induced hypotension in women with preeclampsia.

Prophylactic Fixed-Rate Phenylephrine Versus Norepinephrine Infusion in the Prevention of Post-spinal Anesthesia Hypotension During Cesarean Delivery.

Background Maternal hypotension following spinal anesthesia can be actively countered by the use of vasopressors. Prophylactic infusion of vasopressors with a rescue bolus dosing was observed to be more effective for hemodynamic stability when compared to administering a bolus dose alone. Although phenylephrine is the recommended drug to treat spinal hypotension, many recent studies have focussed on the role of norepinephrine infusions during cesarean section. In this study, we compared prophylactic fixed-rate intravenous infusions of phenylephrine and norepinephrine during cesarean delivery under spinal anesthesia and the requirement of intraoperative provider-administered rescue bolus of phenylephrine needed to overcome post-spinal anesthesia hypotension. Methodology A total of 208 patients undergoing elective cesarean section under spinal anesthesia were randomly assigned to two groups (group P and group N). Group N included 104 patients who received norepinephrine infusion at a rate of 2.5 μg/minute (0.04 μg/kg/minute), and group P included 104 patients who received phenylephrine infusion at a rate of 50 μg/minute (0.8 μg/kg/minute)to treat spinal hypotension. The primary outcome of our study was to compare the reduction in the number and total dose of intraoperative provider-administered rescue bolus of phenylephrine needed to maintain systolic blood pressure. The secondary outcome of our study was to compare the neonatal outcome using umbilical venous blood gas sampling and Apgar score at one and five minutes. Results The total number of phenylephrine rescue bolus required to treat hypotension was significantly lower in group N (p = 0.0005) compared to group P. The neonatal outcome was similar between the two groups. Conclusions Prophylactic norepinephrine infusion when compared to prophylactic phenylephrine infusion is associated with a lesser requirement of rescue phenylephrine boluses.

A Randomized Controlled Trial Comparing the Effect of Phenylephrine by Intramuscular Route With Intravenous Infusion in Maintaining Haemodynamic Stability During Elective Lower Segment Caesarean Section Under Spinal Anaesthesia.

Background Hypotension is a commonly encountered side effect in patients undergoing spinal anaesthesia, particularly in patients undergoing caesarean section. Phenylephrine is a widely used drug to treat spinal-induced hypotension and to maintain hemodynamic stability. Our aim is to evaluate the effectiveness of phenylephrine given through two different routes prophylactically in prevention of post-spinal hypotension in patients undergoing caesarean section. Methods A total of 150 healthy pregnant women undergoing elective caesarean section were randomly allocated into three groups: Group M (prophylactic intramuscular use of 2 mg phenylephrine), group V (prophylactic intravenous infusion of 30 mcg phenylephrine per minute), and group P (no prophylaxis), rescue phenylephrine 30 mcg IV and atropine 0.6 mg IV were used intraoperatively to treat bradycardia and hypotension in all three groups. The primary outcome was maternal hemodynamic changes. Results There was an insignificant difference in demographic data between the groups. Maternal systolic and diastolic blood pressure were more stable in group M compared to group V and group P. Heart rate was significantly lower only in group V. We did not observe any statistical difference between the groups in the APGAR score or the fetal arterial blood gas values. The incidence of nausea and vomiting was more in group P. Conclusion Preventive intramuscular phenylephrine exhibited a more stable maternal hemodynamics when compared with the prophylactic intravenous infusion of phenylephrine and placebo in elective caesarean under spinal anaesthesia.

A randomised comparative study to compare the prophylactic use of phenylephrine and norepinephrine in caesarean delivery under spinal anaesthesia

Background: To compare the efficacy and safety of prophylactic intravenous infusions of phenylephrine (0.1 mg/kg/min) and norepinephrine (NE) (0.05 mg/kg/min) for the management of maternal hypotension under spinal anesthesia for cesarean delivery. Methods: A prospective randomized comparative interventional study was conducted on 100 pregnant patients who underwent elective/emergency cesarean section under the sub-arachnoid block. The study patients were randomly allocated into two equal groups comprising of Group P (n = 50): who received phenylephrine 0.1 mg/kg/min infusion prophylactically and Group N (n = 50): who received norepinephrine 0.05 mg/kg/min infusion prophylactically. The data of outcome measures were compared among the two groups by SPSS ver 21.0. Results: A significant difference was seen in the incidence of bradycardia between groups P and N (20% vs 4%, P value = 0.028). The blood pressure was significantly higher in Group N (systolic-120.5 vs 104 mm of Hg, P = 0.026; diastolic-66 vs 61 mm of Hg, P = 0.019). Group N patients had no complications whereas Group P patients experienced nausea (8%) and vomiting (4%), P = 0.027. Neonatal outcomes in terms of Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score and umbilical arterial/venous blood gases were similar among the two groups (P > 0.05). Conclusion: In conclusion, the study results show that NE is better in maintaining the hemodynamic parameters (BP and HR) during spinal anesthesia for cesarean delivery with minimal side effects. It can be suggested that NE may be advantageous in pregnancies especially those complicated with pregnancy-induced hypertension.

Prophylactic Phenylephrine Increases the Dose Requirement of Oxytocin to Treat Uterine Atony During Cesarean Delivery: A Double-Blinded, Single-Center, Randomized and Placebo-Controlled Trial.

Purpose: Studies involving mouse models and human uterine smooth muscle cells have shown that phenylephrine inhibits uterine contractions in non-pregnant mice and human in vitro cell via cyclic adenosine monophosphate (cAMP) signaling. However, there has been no limited exploration to date of the effect of phenylephrine on uterine contractions in clinical practice. This study aimed to compare the dose requirement of oxytocin with or without the infusion of prophylactic phenylephrine to prevent post spinal hypotension during cesarean delivery under combined spinal and epidural anesthesia. Methods: This was a double-blinded, single-center, randomized, control study. One hundred and sixty pregnant patients provided informed consent and were randomly allocated to the phenylephrine (phenylephrine infusion) and control (saline infusion) groups. Patients randomized to the phenylephrine group received an intravenous prophylactic phenylephrine infusion at a fixed rate of 0.5 μg/kg/min. The control group received a saline placebo at the same rate and used the same apparatus for delivery. After neonatal delivery and clamping of the umbilical cord, patients received a standard institutional oxytocin protocol. The primary outcome measure was the total dose of oxytocin administered during CD. Secondary outcomes including the proportion (%) of patients requiring a secondary uterotonic agent and estimated blood loss (EBL) in the first 24 h after surgery. Results: The median oxytocin dose administered was significantly higher in the phenylephrine group than in the control group [6.9 ± 2.5 international standardized units (IU) vs. 5.4 ± 2.4 IU, p = 0.0004]. The number of patients that required a secondary uterotonic agent was significantly higher in the phenylephrine group than in the control group (24.2% vs. 9.1%; p = 0.034). The EBL in the first 24-h postoperatively was similar between the two groups (467 ± 47 ml vs. 392 ± 38 ml; p = 0.22). Conclusions: Prophylactic infusion of phenylephrine used to prevent post-spinal hypotension during CD was associated with a higher dose of oxytocin. This has important clinical implications, as the suboptimal use of oxytocin is associated with an increased risk of postpartum hemorrhage and increased maternal morbidity and mortality. Further studies are now needed to confirm these findings.

A Study of Phenylephrine Administration for the Prevention and Treatment of Hypotension in Cesarean Section during Spinal Anaesthesia

Background: Hypotension remains the most common complication following spinal anesthesia in cesarean sections. Despite using various preventive measures, hypotension occurs in most cases; vasopressors are often required. The current study evaluated the safety and efficacy of prophylactic phenylephrine infusion in preventing spinal anesthesia-induced hypotension in the Cesarean Section. Materials and Methods: A total of 50 parturients aged 20-35 years with American Society of Anesthesiologists (ASA) grade II, scheduled for elective cesarean sections were randomly allocated into one of the two groups. Group A (n=25) received intravenous prophylactic phenylephrine infusion at 100μg/min for 3min after spinal anesthesia using a syringe pump. Each minute, systolic arterial pressure (SAP) was measured, and infusion stopped if SAP > baseline and continued if less than or equal to baseline systolic arterial pressure. Intravenous phenylephrine bolus 100μg was given when SAP decreased to <80% of baseline. Group B (n=25) received only intravenous phenylephrine bolus 100μg when SAP decreased to <80% of baseline. After 1 minute of spinal anesthesia, Heart Rate (HR), SAP, and diastolic blood pressure (DBP) were recorded every minute until the baby's extraction. After the delivery of the baby, APGAR scores at 1 minute and 5 minutes were noted. Umbilical artery blood was sent for analysis of the pH. The total volumes of study solutions given up to the time of delivery of the baby were recorded. Results: Phenylephrine infusion decreased the incidence and frequency of hypotension compared with control and the phenylephrine dose was much higher in the infusion group than in the control group (p=0.0001). None of the patients had any incidence of nausea or vomiting. There was no significant difference in umbilical artery blood pH and no reduction in the APGAR scores. HR was significantly slower in the infusion group compared with the control group. Conclusion: A prophylactic infusion of phenylephrine100 μg/min in patients receiving spinal anesthesia for elective cesarean delivery decreased the incidence of hypotension and without any deleterious neonatal outcome.

Interstitial Fibrosis in HFpEF Attenuates Diastolic Circumferential Strain and the Transcriptional Response to Left Ventricular Pressure Overload

Objective We previously demonstrated thattransient repetitive pressure overload (RPO) in swine leads to myocardial interstitial fibrosis and reduced diastolic left ventricular (LV) compliance. While this phenotype is similar to that found in some patients with heart failure with preserved ejection fraction (HFpEF), it occurs in the absence of anatomic LV hypertrophy, persistent hypertension, or comorbidities. The present study was designed to determine if reduced LV diastolic distensibility alters the acute transcriptional response to transient pressure overload. Methods A total of 21 swine were studied. Hemodynamic assessment, echocardiography, and blood sampling were performed before and after a 60 minute intravenous infusion of phenylephrine (PE; 300 μg/min) to elevate LV end-diastolic pressure (EDP) to ~30 mmHg. Myocardial RNA from control animals (n=7) was compared to tissue isolated 24 hours after a single episode of pressure overload (n=6) or after 14 days of RPO (n=8). We assessed LV diastolic strain and compliance via echocardiography and quantified interstitial fibrosis with picrosirius red staining. Genes previously demonstrated to be altered after pressure overload including natriuretic peptides (ANP and BNP), inflammatory mediators (CD68 and CCR2) and pro-fibrotic factors (LOXL2 and Fibronectin) were assessed with quantitative PCR and normalized to β2 microglobulin. Results Transient PE infusion increased LV EDP from 14 ± 1 to 30 ± 1 mmHg and systolic arterial pressure from 120 ± 6 to 205 ± 6 mmHg (both p<0.01). The hemodynamic response to PE was similar during a single episode of pressure overload and after 14 days of RPO. There was concentric LV remodeling (LV mass/EDV: 1.3 ± 0.1 vs. 1.1 ± 0.1 g/mL; p<0.05) without anatomic hypertrophy after RPO (LV mass/body mass: 2.4 ± 0.1 vs. 2.3 ± 0.1 g/kg; p=0.37), yet interstitial fibrosis increased from 6.6 ± 0.7% to 12.9 ± 1.8% (p<0.05) and LV diastolic compliance (∆EDV/∆EDP) decreased from 1.7 ± 0.2 to 0.6 ± 0.2 mL/mmHg (p<0.05). As a result, myocardial diastolic circumferential strain after RPO was markedly reduced in comparison to a single episode of pressure overload in the normal heart (1.5 ± 2.7% after RPO vs. 11.1 ± 3.0% in controls; p<0.05). The reduction in diastolic circumferential strain after RPO markedly attenuated the transcriptional response to acute pressure overload (Figure). In normal myocardium, transient pressure overload upregulated natriuretic peptides (ANP 26-fold and BNP 12-fold; both p<0.01), pro-inflammatory genes (CD68 2.3-fold and CCR2 4-fold; p=0.06), and pro-fibrotic genes (LOXL2 3.4-fold and fibronectin 3.9-fold; p<0.05). In contrast, the reduction in diastolic strain after RPO prevented any increase in gene expression despite a similar magnitude of transient pressure overload. Conclusions These results dissociate the effects of myocardial strain from systolic and end-diastolic pressure on the transcriptional response to LV pressure overload. The dependence of gene expression on diastolic strain rather than LV pressure may explain observations such as the frequent absence of natriuretic peptide elevation in patients with HFpEF.

Ventromedial prefrontal cortex CRF1 receptors modulate the tachycardic activity of baroreflex.

Ventral medial prefrontal cortex (vMPFC) glutamatergic neurotransmission has a facilitatory role on cardiac baroreflex activity which is mediated by NMDA receptors activation. Corticotrophin releasing factor receptors type1 and 2 (CRF1 and CRF2), present in the vMPFC, are colocalized in neurons containing glutamate vesicles, suggesting that such receptors may be involved in glutamate release in this cortical area. Therefore, our hypothesis is that the CRF1 and CRF2 receptors can modulate the baroreflex bradycardic and tachycardic responses. In order to prove this assumption, male Wistar rats had bilateral stainless steel guide cannula implanted into the vMPFC, and baroreflex was activated by intravenous infusion of phenylephrine or sodium nitroprusside through a vein catheter. A second catheter was implanted into the femoral artery for cardiovascular measurements. The CRF1 receptor antagonist administration in either infralimbic cortex (IL) or prelimbic cortex (PL), vMPFC regions, was unable to change the bradycardic responses but increased the slope of the baroreflex tachycardic activity. Microinjection of the CRF2 receptor antagonist into the IL and PL did not alter ether bradycardic nor tachycardic baroreflex responses. The administration of the non-selective CRF receptors agonist, urocortin in these areas, did not modify bradycardic responses but decreased tachycardia slope of the baroreflex. CRF1 receptor antagonist administration prior to non-selective CRF agonist in vMPFC prevented the tachycardic responses reduction. However, CRF2 receptor antagonism could not prevent the effect of CRF receptors agonist. These results suggest that IL and PL CRF1 but not CRF2 receptors have an inhibitory role on the baroreflex tachycardic activity. Furthermore, they have no influence on baroreflex bradycardic activity.

A randomized, double-blinded comparative study of phenylephrine infusion and norepinephrine infusion for the prevention and treatment of spinal anesthesia-induced hypotension in elective and emergency cesarean deliveries

Context and Aims: Among vasopressors used to treat postspinal hypotension (PSH) in cesarean sections (CS), phenylephrine (PE) is the preferred drug at present but reflex bradycardia and thus reduction in cardiac output still pose a concern. Norepinephrine (NE), with its better pharmacological properties, may be a better alternative to overcome this risk. Hence, we did this study intending to compare both the drugs. Materials and Methods: A double-blinded, randomized, controlled trial (RCT) was carried out on 70 patients, 35 in each group-group P (PE) and group N (NE) undergoing CS, to compare and evaluate the efficacy of both drugs for preventing and treating PSH. Patients in Group P and Group N were given intravenous infusion of PE at the rate of 50 μg/min and NE at the rate of 2.5 μg/min, respectively, after the intrathecal injection of bupivacaine. The number of intermittent bolus doses required, heart rate, and mean arterial pressure (MAP) at predefined intervals were noted. Results: The incidence of hypotension calculated from the number of bolus doses required was lower in Group N than in Group P for the initial 15 min (P Conclusion: This study suggests that NE infusion is superior to PE infusion when used in the potency ratio of 20:1, to prevent and treat PSH in CS, with a lesser number of side effects.

Nitric oxide in the insular cortex modulates baroreflex responses in a cGMP-independent pathway

Insular cortex is a brain structure involved in the modulation of autonomic activity and cardiovascular function. The nitric oxide/cyclic guanosine-3′,5′-monophosphate pathway is a prominent signaling mechanism in the central nervous system, controlling behavioral and physiological responses. Nevertheless, despite evidence regarding the presence of nitric oxide-synthesizing neurons in the insular cortex, its role in the control of autonomic and cardiovascular function has never been reported. Thus, the present study aimed to investigate the involvement of nitric oxide/cyclic guanosine-3′,5′-monophosphate pathway mediated by neuronal nitric oxide synthase (nNOS) activation within the insular cortex in the modulation of baroreflex responses in unanesthetized rats. For this, we evaluated the effect of bilateral microinjection of either the nitric oxide scavenger carboxy-PTIO, the selective neuronal nitric oxide synthase inhibitor Nω-Propyl-l-arginine or the soluble guanylate cyclase inhibitor ODQ into the insular cortex on the bradycardia evoked by blood pressure increases in response to intravenous infusion of phenylephrine, and the tachycardia caused by blood pressure decreases evoked by intravenous infusion of sodium nitroprusside. Bilateral microinjection of either NPLA or carboxy-PTIO into the insular cortex increased the reflex bradycardic response, whereas the reflex tachycardia was decreased by these treatments. Bilateral microinjection of the soluble guanylate cyclase inhibitor into the insular cortex did not affect any parameter of baroreflex function evaluated. Overall, our findings provide evidence that insular cortex nitrergic signaling, acting via neuronal nitric oxide synthase, plays a prominent role in control of baroreflex function. However, control of reflex responses seems to be independent of soluble guanylate cyclase activation.

Effect of phenylephrine infusion on hypotension induced by the beach chair position: A prospective randomized trial.

Background:The beach chair position (BCP), used during shoulder surgery, is associated with hypotension, bradycardia, and risk of cerebral hypoperfusion. Phenylephrine is commonly used as a first treatment of choice of intraoperative hypotension during surgery. We evaluated the hemodynamic effects of 2 doses of intravenous phenylephrine infusion administered before being placed in BCP for arthroscopic shoulder surgery. The primary endpoint was the incidence of hypotension after positional change.Methods:Sixty-six patients were randomized to receive either intravenous normal saline (group NS) or intravenous phenylephrine infusion (0.5 μg/kg/min, group LP or 1.0 μg/kg/min, group HP) for 5 minutes before being placed in the BCP. Mean arterial pressure(MAP), heart rate, stroke volume variation, and cardiac index were measured before and after positional change.Results:The total incidence of hypotension after the BCP was 93.65%, but was not significantly different among the 3 groups. However, there was a significant difference in trends between the groups for MAP for 5 minutes after BCP (P = .028). Comparison of changes in MAP at 1 minute compared to post-induction MAP was significantly different between group HP and group NS (P = .014).Conclusion:Infusion of 0.5 and 1.0 μg/kg/min of phenylephrine for 5 minutes before the BCP has no preventive effect for incidence of hypotension. However, this study showed that 1.0 μg/kg/min of phenylephrine infusion for 5 minutes can attenuate the severity of hypotension.

93 A hemodynamic challenge in assessment of echocardiographic mitral regurgitation severity

Abstract Mitral regurgitation severity is, in accordance to current recommendations, typically evaluated by echocardiography. Several hemodynamic factors may influence this evaluation, especially systemic arterial blood pressure at the time of echocardiographic evaluation. A 71-year-old woman was admitted in our Cardiology ward with acute decompensated heart failure. She had been previously admitted about 3 months earlier by acute decompensated heart failure, and at that time, admission transthoracic echocardiography (TTE) demonstrated mitral regurgitation, which was evaluated as severe. Systolic systemic arterial blood pressure at the time of that TTE was registered as 135mmHg. For further evaluation of mitral regurgitation mechanism, the patient underwent transoesophageal echocardiography (TEE), and in that exam mitral regurgitation was assessed as only moderate. For that exam, patient was sedated with 5mg of intravenous Midazolam, a drug with known secondary hypotensive effect. Although systemic arterial blood pressure was not described in the TEE report, retrospective analysis of nursery blood pressure records showed that patient was hypotensive during exam with systolic arterial blood pressure of 80-90mmHg. Patients was discharged, and in actual admission, concern was raised that mitral regurgitation could have been underestimated in previous TEE due to reduced afterload caused by the hypotensive effect of sedation. It was then decided to repeat TEE, and, in order to counterpose the hypotensive effect of Midazolam, TEE was performed under intravenous continuous infusion of Phenylephrine, a selective α-1 receptor antagonist with a significant vasopressor effect and minimal effect on cardiac contractility. Systolic systemic arterial blood pressure during this exam was recorded as 135-140mmHg. In this exam mitral regurgitation was confirmed as severe and patient was patient was oriented for mitral valve surgery. DIscussion This case illustrates the importance of assessment of hemodynamic status of the patient during echocardiographic evaluation of mitral regurgitation severity, and presents a pharmacological strategy to compensate hypotensive effects of sedative agents used during TEE.

Complex effects of continuous vasopressor infusion on fluid responsiveness during liver resection

Fluid responsiveness is an important factor to consider for fluid volume loading during major surgery. The effect of continuous vasopressor infusion on fluid responsiveness during prolonged major surgery is a concern. We hypothesised that continuous vasopressor infusion during major surgery might not exert significant effects on changes in stroke volume variation (SVV) following fluid bolus infusion, and thereby on fluid responsiveness. Randomised controlled trial. University hospital from April 2014 to August 2016. Patients undergoing liver resection who were randomised to receive continuous intravenous infusion of phenylephrine (P group), norepinephrine (N group), or no vasopressor (C group) (n=17/group). Exclusion criteria were cardiac arrhythmia and severe cardiac, pulmonary or renal dysfunction. Patients received 4 ml kg fluid boluses of 6% hydroxyethyl starch solution when SVV was at least 12%. Vasopressors were administered continuously to maintain the systemic vascular resistance index at more than 1900 dyn s cm m. Cardiac index and SVV were measured using the FloTrac/Vigileo system (Version 4.00). The number of fluid boluses with fluid responsiveness (i.e. >15% increase in cardiac index) was compared between groups using multilevel logistic regression analysis. Numbers of fluid responsive boluses in the C, P and N groups were 12 (14%), 22 (34%) and 19 (27%), respectively. Odds ratios on fluid responsiveness for phenylephrine and norepinephrine compared with the control were 3.65 (97.5% confidence interval, 1.15 to 11.6; P = 0.012) and 2.56 (97.5% confidence interval, 0.82 to 8.00; P = 0.064), respectively. Decreases in SVV after fluid bolus infusion for the P and N groups were comparable with the C group (P = 0.23 and 0.53, respectively). Continuous administration of phenylephrine increased fluid responsiveness during liver resection, suggesting complex effects of continuous vasopressor infusion involving changes in cardiac preload and afterload. UMIN000011024.

Dual Admittance Catheter‐Derived Biventricular Pressure‐Volume Analysis in Swine: Comparison with Contrast‐Enhanced Computed Tomography During Transient Pressure Overload

ObjectiveAdmittance catheter‐derived pressure‐volume (PV) analysis offers the ability to assess dynamic changes in ventricular performance. The present study was designed to evaluate the feasibility and accuracy of biventricular PV analysis by comparing admittance catheter‐derived measurements of left (LV) and right ventricular (RV) volumes with data obtained from simultaneous contrast‐enhanced cardiac computed tomography (CT) before, during, and after transient pressure overload in swine.\MethodsClosed‐chest propofol‐anesthetized swine (n=5) were instrumented with admittance catheters in the LV and RV for continuous biventricular PV analysis (ADV500; Transonic SciSense, Inc.). Multi‐detector CT with iodinated contrast (1 mL/kg at 4 mL/s) was performed before, during, and 30‐minutes after transient pressure overload elicited by a 1‐hour intravenous infusion of phenylephrine (PE; 18 mg/hour). Right and left ventricular end‐diastolic volume, end‐systolic volume, and stroke volume were calculated simultaneously with each modality.ResultsPE elicited a significant rise in LV pressure (110±6/4±1 to 208±9/25±3 mmHg; p&lt;0.01) and RV pressure (25±2/3±1 to 44±2/8±2 mmHg; p&lt;0.05) that normalized 30‐minutes after the end of the infusion period (LV: 99±8/8±2 mmHg; RV: 25±2/3±1 mmHg). Biventricular PV analysis demonstrated a significant increase in LV and RV end‐diastolic volume and end‐systolic volume during PE that normalized in the RV, but not LV, 30‐minutes after cessation of PE (Table). These changes were confirmed by contrast‐enhanced cardiac CT‐derived measurement of ventricular volumes, with no significant differences between PV and CT at any timepoint. Persistent LV dilatation after PE was accompanied by a reduction in LV contractility (LV dP/dtmax: 1288±110 mmHg/sec vs. 2023±89 mmHg/sec at baseline, p&lt;0.05) that reflected stretch‐induced stunning following a ~6‐fold rise in LV end‐diastolic pressure during PE. This was not observed in the RV, as RV contractility was preserved following PE (from 369±42 mmHg/sec at baseline to 352±26 mmHg/sec after PE; p=0.77).ConclusionsBiventricular PV analysis is feasible in swine and provides reasonably accurate measurements of ventricular volumes compared with contrast‐enhanced cardiac CT. Employing this approach during transient PE infusion demonstrated persistent chamber dilatation and systolic dysfunction in the LV, but not RV, consistent with stretch‐induced stunning caused by an acute elevation in preload.Support or Funding InformationThe National Heart Lung and Blood Institute (HL‐061610), the American Heart Association (17SDG33660200), the National Center for Advancing Translational Sciences (UL1TR001412), the Department of Veterans Affairs (1IO1BX002659), and the Albert and Elizabeth Rekate Fund in Cardiovascular Medicine.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Differential roles of hippocampal nNOS and iNOS in the control of baroreflex function in conscious rats

The baroreflex is a prominent moment-to-moment mechanism regulating the blood pressure. The hippocampus is a limbic structure in which has been pointed out as part of central network regulating baroreflex. However, the local neurochemical mechanisms involved in control of baroreflex function are not completely understood. Thus, this study aimed to investigate the involvement of nitrergic neurotransmission present in the dorsal hippocampus in baroreflex control of heart rate in conscious rats. For this, we evaluated the effect of bilateral microinjection into the dorsal hippocampus of either the nitric oxide (NO) scavenger carboxy-PTIO, the selective neuronal nitric oxide synthase (nNOS) inhibitor Nω-Propyl-l-arginine (NPLA) or the selective inducible nitric oxide synthase (iNOS) inhibitor 1400 W in bradycardia evoked by blood pressure increases in response to intravenous infusion of phenylephrine, and tachycardia caused by blood pressure decreases evoked by intravenous infusion of sodium nitroprusside. Bilateral microinjection of carboxy-PTIO into the dorsal hippocampus decreased the baroreflex tachycardic response without affecting the reflex bradycardia. Hippocampus treatment with NPLA increased the baroreflex bradycardia gain without affecting the reflex tachycardia. Bilateral hippocampal treatment with 1400 W decreased the reflex tachycardia and increased the baroreflex bradycardic response. Overall, these findings provide evidence that hippocampal nitrergic mechanisms acting in a NOS isoform-specific manner plays a prominent role in control of baroreflex function. Indeed, the results indicate that nNOS and iNOS exerts an inhibitory influence on reflex bradycardia, whereas iNOS mediates the reflex tachycardia.

Hospital discharges due to traumatic brain injuries in children and adolescents in 30 European countries

The medial amygdaloid nucleus (MeA) is involved in cardiovascular control. In the present study we report the effect of MeA pharmacological ablations caused by bilateral microinjections of the nonselective synaptic blocker CoCl2 on cardiac baroreflex responses in rats. MeA synaptic inhibition evoked by local bilateral microinjection of 100 nL of CoCl2 (1 mM) did not affect blood pressure or heart rate baseline, suggesting no tonic MeA influence on resting cardiovascular parameters. However, 10 min after CoCl2 microinjection into the MeA of male Wistar rats, the reflex bradycardic response evoked by intravenous infusion of phenylephrine was significantly enhanced when compared with the reflex bradycardic response observed before CoCl2. The treatment did not affect the tachycardic responses to the intravenous infusion of sodium nitroprusside (SNP). Baroreflex activity returned to control values 60 min after CoCl2 microinjections, confirming a reversible blockade. The present results indicate an involvement of the MeA in baroreflex modulation, suggesting that synapses in the MeA have an inhibitory influence on the bradycardic component of the baroreflex in conscious rats.

Involvement of CRF1 receptors in bed nucleus of stria terminalis (BNST) on baroreflex responses in chronically stressed rats

INTRODUCTIONStudies suggest the involvement of CRF receptors in bed nucleus of the stria terminalis (BNST) on cardiovascular responses in acute stress. Data from our group had demonstrated that the expression of CRF1 receptors within the BNST is decreased in animals exposed to chronic variable stress (CVS). Nevertheless, an involvement of BNST CRF neurotransmission on cardiovascular changes evoked by CVS has never been investigated.AIMTo evaluate the involvement of CRF1 receptor in the BNST on baroreflex changes evoked by CVS in rats.METHODOLOGYMale Wistar rats (250g) were submitted to stereotaxic surgery for implantation of cannulas into the BNST. After 4 days of recovery, the animals were exposed to a CVS protocol for 10 days. After the last session, the rats had the femoral artery and vein cannulated for cardiovascular record and drug infusion, respectively. Twenty‐four hours later, the experiments were performed. Baroreflex function was assessed by evoking changes on arterial pressure throughout intravenous infusions of phenylephrine and sodium nitroprusside, which evoke pressor and depressor effects, respectively. Baroreflex activity was evaluated in both control rats and animals subjected to ECV protocol before and after bilateral microinjection of the selective CRF1 antagonist CP376395 (5nmol/100nL) into the BNST.RESULTSComparison of values before BNST treatment revealed that ECV decreased the bradycardiac response evoked by blood pressure increase (−48±10 vs −114±23 bpm, P&lt;0.03). Moreover, bilateral microinjection of CP376395 into the BNST decreased reflex bradycardia in control group (−51±13 vs −114±23 bpm, P&lt;0.02), but not in animals subjected to ECV (−51±10 vs −48±10 bpm, P&gt;0.05). The tachycardia evoked by blood pressure decrease was also decreased following ECV (57±5 vs 97±11 bpm, P&lt;0.05). The BNST treatment with CP376395 decreased the tachycardiac response in control animals (50±9 vs 97±11 bpm, P&lt;0.001), but without affecting this response in CVS rats (52±5 vs 57±5 bpm, P&gt;0.05).CONCLUSIONThe impairment of baroreflex function evoked by CVS is related to decreased control of this reflex cardiovascular by CRF1 receptor in the BNST.Support or Funding InformationFINANCIAL SUPPORT: FAPESPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.