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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Comparison of Prophylactic Phenylephrine Infusion and Rescue Bolus Administration for Maintaining Blood Pressure During Spinal Anaesthesia for Caesarean Delivery in Obese Parturient: A Randomised Control Trial.

Background: Phenylephrine (PE) is one of the vasopressor used to treat hypotension during anaesthesia. The primary aim of this study was to compare the effect of prophylactic infusion and rescue bolus of PE on the haemodynamic changes during spinal anaesthesia (SA) for Caesarean section (CS) in obese parturients. Methods: A total of 74 obese parturients scheduled for elective CS under SA were randomised into two groups; Group A (n = 37) received prophylactic PE infusion starting at 50 µg min-1 and adjusted according to the given algorithm and Group B (n = 37) received 100 µg PE bolus to treat hypotension. The measured parameters were systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), the total requirement of PE and neonatal Apgar score. Results: Six patients were excluded from the analysis due to missing data and only 68 were analysed. Group A showed significantly higher SBP, DBP and MAP than Group B (P < 0.05). The requirement of PE was higher in Group A than Group B [817.7 (265.7) µg versus 360.6 (156.0) µg; P = < 0.05]. Both groups had no difference in terms of the neonatal Apgar score. Conclusion: Prophylactic PE infusion provided better haemodynamic control than therapeutic boluses in obese parturients undergoing CS under SA.

The effect of three different mydriatic eye drops on retinal vessel diameters.

PURPOSE: To investigate the effects of topically applied 1% tropicamide, 2.5% phenylephrine and 1% cyclopentolate on retinal vessel calliper (VC) using optical coherence tomography (OCT). METHODS: Patients who came to the ophthalmology clinic for routine examination and whose OCT films were taken before dilatation and after 30 min of last dilatation drop were included in the study. 90 ophthalmologically healthy subjects were divided into 3 groups of 30 subject each according to the application of the drops as follows: Tropicamide group (Group 1), Phenylephrine group (Group 2), Cyclopentolate group (Group 3). The right eyes of the subjects were dilated with drops and the left eyes were taken as the control group. VC of retinal artery and vein passing through an area one-half to one-disc diameter from the optic disc margin were measured from OCT films. The mean of the sum of superior retinal artery (SRA) and inferior retinal artery (IRA) VC and the mean of the sum of superior retinal vein (SRV) and inferior retinal vein (IRV) VC before and after the drop were compared. RESULTS: There was no statistically significant change in the mean sum of SRA and IRA VC and the mean sum of SRV and IRV VC before and after dilatation drops in all three groups. CONCLUSION: Dilatation drops have no statistically significant effect on retinal artery and vein VC.

Effect of norepinephrine and phenylephrine on prothrombotic response in patients undergoing cesarean section under spinal anesthesia: protocol for a randomized, double-blind, controlled study.

BACKGROUND: Norepinephrine and phenylephrine are commonly used vasoactive drugs to treat hypotension during the perioperative period. The increased release of endogenous norepinephrine elicits prothrombotic changes, while parturients are generally in a hypercoagulable state. Therefore, this trial aims to investigate whether there is a disparity between equivalent doses of prophylactic norepinephrine infusion and phenylephrine infusion on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. METHODS: Sixty-six eligible parturients will be recruited for this trial and randomly assigned to the norepinephrine or phenylephrine group. The "study drug" will be administered at a rate of 15 ml/h starting from the intrathecal injection. The primary outcome are plasma coagulation factor VIII activity (FVIII: C), fibrinogen, and D-dimer levels. The secondary outcomes include hemodynamic variables and umbilical artery blood pH value. DISCUSSION: Our study is the first trial comparing the effect of norepinephrine and phenylephrine on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. Positive or negative results will all help us better understand the impact of vasoactive drugs on patients. If there are any differences, this trial will provide new evidence for maternal choice of vasoactive medications in the perioperative period. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300077164. Registered on 1 November 2023. https://www.chictr.org.cn/ .

Vasoconstriction with phenylephrine increases cardiac output in preload dependent patients.

General Anaesthesia (GA) is accompanied by a marked decrease in sympathetic outflow and thus loss of vasomotor control of cardiac preload. The use of vasoconstriction during GA has mainly focused on maintaining blood pressure. Phenylephrine (PE) is a pure α1-agonist without inotropic effects widely used to correct intraoperative hypotension. The potential of PE for augmenting cardiac stroke volume (SV) and -output (CO) by venous recruitment is controversial and no human studies have explored the effects of PE in preload dependent circulation using indicator dilution technique. We hypothesized that PE-infusion in patients with cardiac stroke volume limited by reduced preload would restore preload and thus augment SV and CO. 20 patients undergoing GA for gastrointestinal surgery were monitored with arterial catheter and LiDCO unity monitor. Upon stable haemodynamics after induction patients were placed in head-up tilt (HUT). All patients became preload responsive as verified by a stroke volume variation (SVV) of > 12%. PE-infusion was then started at 15-20mikrg/min and adjusted until preload was restored (SVV < 12%). Li-dilution cardiac output (CO) was initially measured after induction (baseline), again with HUT in the preload responsive phase, and finally when preload was restored with infusion of PE.At baseline SVV was 10 ± 3% (mean ± st.dev.), CI was 2,6 ± 0,4 L/min*m2, and SVI 43 ± 7mL/m2. With HUT SVV was 19 ± 4%, CI was 2,2 ± 0,4 L/min*m2, SVI 35 ± 7mL/m2. During PE-infusion SVV was reduced to 6 ± 3%, CI increased to 2,6 ± 0,5 L/min*m2, and SVI increased to 49 ± 11mL/m2. All differences p < 0,001. In conclusion: Infusion of phenylephrine during preload dependency increased venous return abolishing preload dependency as evaluated by SVV and increased cardiac stroke volume and -output as measured by indicator-dilution technique. (ClinicalTrials.gov NCT05193097).

Norepinephrine or phenylephrine for the prevention of post-spinal hypotension after caesarean section: A double-blinded, randomized, controlled study of fetal heart rate and fetal cardiac output.

STUDY OBJECTIVE: Spinal anesthesia often causes hypotension, with consequent risk to the fetus. The use of vasopressor agents has been highly recommended for the prevention of spinal anesthesia-induced hypotension during caesarean delivery. Many studies have shown that norepinephrine can provide more stable maternal hemodynamics than phenylephrine. We therefore tested the hypothesis that norepinephrine preserves fetal circulation better than phenylephrine when used to treat maternal hypotension consequent to spinal anesthesia. DESIGN: Prospective, randomized, double-blinded study. SETTING: Operating room. PATIENTS: We recruited 223 parturients with uncomplicated singleton pregnancies who were scheduled for elective caesarean section under combined spinal-epidural anesthesia. INTERVENTIONS: The patients received prophylactic intravenous infusion of either 0.08 µg/kg/min norepinephrine or 0.5 µg/kg/min phenylephrine for prevention of spinal anesthesia-induced hypotension. MEASUREMENTS: Changes in fetal heart rate and fetal cardiac output before and after spinal anesthesia were measured using noninvasive Doppler ultrasound. MAIN RESULTS: 90 subjects who received norepinephrine infusion and 93 subjects who received phenylephrine infusion were ultimately analyzed in the present study. The effects of norepinephrine and phenylephrine on the change of fetal heart rate and fetal cardiac output at 3 and 6 min after spinal block were similar. Although there was a statistically significant decrease in fetal cardiac output at 6 min after subarachnoid block initiation in both the norepinephrine group (mean difference 0.02 L/min; 95% CI, 0-0.04 L/min; P = 0.03) and the phenylephrine group (mean difference 0.02 L/min; 95% CI, 0-0.04 L/min; P = 0.02), it remained within the normal range. CONCLUSIONS: Prophylactic infusion of comparable doses of phenylephrine or norepinephrine has similar effects on fetal heart rate and cardiac output changes after spinal anesthesia. Neither phenylephrine nor norepinephrine has meaningful detrimental effects on fetal circulation or neonatal outcomes.

Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns.

Understanding the intricate relationship between cancer clinicopathological features and anesthetics dosage is crucial for optimizing patient outcomes and safety during surgery. This retrospective study investigates this relationship in patients with non-small cell lung cancer (NSCLC) undergoing video-assisted thoracic surgery (VATS). A comprehensive analysis of medical records was undertaken for NSCLC patients who underwent VATS with intravenous compound inhalation general anesthesia. Patients were categorized based on histological, chemotherapy, radiotherapy, and epidural anesthesia factors. Statistical analysis was performed to compare the differences between the groups. The results revealed compelling insights. Specifically, patients with lung adenocarcinoma (LUAD) undergoing VATS exhibited higher dosages of rocuronium bromide and midazolam during general anesthesia, coupled with a shorter post-anesthesia care unit (PACU) stay compared to those with squamous cell carcinoma (sqCL). Furthermore, chemotherapy patients undergoing VATS demonstrated diminished requirements for phenylephrine and remifentanil in contrast to their non-chemotherapy counterparts. Similarly, radiotherapy patients undergoing VATS demonstrated a decreased necessity for rocuronium bromide compared to non-radiotherapy patients. Notably, patients who received epidural anesthesia in combination with general anesthesia manifested reduced hydromorphone requirements and prolonged hospital stays compared to those subjected to general anesthesia alone. In conclusion, the findings from this study indicate several important observations in diverse patient groups undergoing VATS. The higher dosages of rocuronium bromide and midazolam in LUAD patients point to potential differences in drug requirements among varying lung cancer types. Additionally, the observed shorter PACU stay in LUAD patients suggests a potentially expedited recovery process. The reduced anesthetic requirements of phenylephrine and remifentanilin chemotherapy patients indicate distinct responses to anesthesia and pain management. Radiotherapy patients requiring lower doses of rocuronium bromide imply a potential impact of prior radiotherapy on muscle relaxation. Finally, the combination of epidural anesthesia with general anesthesia resulted in reduced hydromorphone requirements and longer hospital stays, suggesting the potential benefits of this combined approach in terms of pain management and postoperative recovery. These findings highlight the importance of tailoring anesthesia strategies for specific patient populations to optimize outcomes in VATS procedures.

Effect of pneumatic leg compression on phenylephrine dose for hypotension prophylaxis via variable rate infusion at cesarean delivery: an unblinded randomized controlled trial.

BACKGROUND: Phenylephrine infusion is recommended to prevent spinal hypotension during cesarean delivery (CD) but may be associated with dose-dependent side effects. We hypothesized that adding intermittent pneumatic compression (IPC) of the lower legs to a variable-rate phenylephrine infusion will reduce the dose of phenylephrine required during CD. METHODS: Seventy-six healthy women undergoing elective CD under combined spinal-epidural anesthesia were randomly assigned to IPC or control groups (n = 38 per group). After spinal anesthesia, IPC of the lower legs was initiated in the IPC group, and all women received a phenylephrine infusion starting at 25 µg·min-1 and increasing by 16.7 µg·min-1 for systolic blood pressure (SAP) < 90% baseline. If hypotension (SAP < 80% baseline) occurred, 100 µg phenylephrine bolus was administered. The primary outcome was the dose of phenylephrine per minute. RESULTS: The dose of phenylephrine per minute (34.4 ±â€¯7.3 µg·min-1 vs. 40.9 ±â€¯9.5 µg·min-1, P = 0.001; mean difference -6.6 µg·min-1, 95% CI -10.5 to -2.7 µg·min-1) and the incidence of hypotension (24% vs. 55%, P = 0.005) were lower in the IPC group than in the control group. There were no significant differences between the two groups in the total dose of phenylephrine (603.2 ±â€¯217.1 µg vs. 706.2 ±â€¯247.5 µg, P = 0.058; mean difference -102.9 µg, 95% CI -209.4 to 3.5 µg), maternal side effects, or neonatal outcomes. CONCLUSIONS: Intermittent pneumatic compression combined with a variable-rate phenylephrine infusion reduced the phenylephrine dose per minute and the incidence of hypotension during CD under spinal anesthesia.

Assessing changes in regional cerebral hemodynamics in adults with a high-density full-head coverage time-resolved near-infrared spectroscopy device.

Significance: Cerebral oximeters have the potential to detect abnormal cerebral blood oxygenation to allow for early intervention. However, current commercial systems have two major limitations: (1) spatial coverage of only the frontal region, assuming that surgery-related hemodynamic effects are global and (2) susceptibility to extracerebral signal contamination inherent to continuous-wave near-infrared spectroscopy (NIRS). Aim: This work aimed to assess the feasibility of a high-density, time-resolved (tr) NIRS device (Kernel Flow) to monitor regional oxygenation changes across the cerebral cortex during surgery. Approach: The Flow system was assessed using two protocols. First, digital carotid compression was applied to healthy volunteers to cause a rapid oxygenation decrease across the ipsilateral hemisphere without affecting the contralateral side. Next, the system was used on patients undergoing shoulder surgery to provide continuous monitoring of cerebral oxygenation. In both protocols, the improved depth sensitivity of trNIRS was investigated by applying moment analysis. A dynamic wavelet filtering approach was also developed to remove observed temperature-induced signal drifts. Results: In the first protocol (28±5 years; five females, five males), hair significantly impacted regional sensitivity; however, the enhanced depth sensitivity of trNIRS was able to separate brain and scalp responses in the frontal region. Regional sensitivity was improved in the clinical study given the age-related reduction in hair density of the patients (65±15 years; 14 females, 13 males). In five patients who received phenylephrine to treat hypotension, different scalp and brain oxygenation responses were apparent, although no regional differences were observed. Conclusions: The Kernel Flow has promise as an intraoperative neuromonitoring device. Although regional sensitivity was affected by hair color and density, enhanced depth sensitivity of trNIRS was able to resolve differences in scalp and brain oxygenation responses in both protocols.

Epinephrine vs. phenylephrine infusion for prophylaxis against maternal hypotension after spinal anesthesia for cesarean delivery: a randomized controlled trial.

BACKGROUND: The hemodynamic effects of relatively low-dose epinephrine and phenylephrine infusions during cesarean delivery under spinal anesthesia were compared. METHODS: This randomized controlled trial included full-term pregnant women who underwent elective cesarean delivery. After spinal anesthesia, participants received either epinephrine (0.03 mcg/kg/min) or phenylephrine (0.4 mcg/kg/min) infusion that continued until 5 min after delivery. The primary outcome was a composite outcome of the occurrence of any of hypotension, hypertension, bradycardia, and/or tachycardia. Neonatal outcomes, including umbilical artery blood gas and Apgar scores, were assessed. RESULTS: In total, 98 patients in each group were analyzed, and the number of patients with the composite outcome was comparable between the epinephrine and phenylephrine groups (30/98 [31%] vs. 31/98 [32%], respectively; P = 0.877). However, the incidence of hypotension was likely lower in the epinephrine group than in the phenylephrine group (P = 0.066), and the number of hypotensive episodes per patient was lower in the epinephrine group than in the phenylephrine group. On the other hand, the incidence of tachycardia was higher in the epinephrine group than that in the phenylephrine group. The incidence of hypertension was comparable between the two groups and none of the participants developed bradycardia. Neonatal outcomes were comparable between the two groups. CONCLUSIONS: Epinephrine and phenylephrine infusion produced comparable maternal hemodynamics and neonatal outcomes. Epinephrine was associated with a higher incidence of maternal tachycardia and likely lower incidence of maternal hypotension than phenylephrine. IRB number: MD-245-2022. CLINICAL TRIAL REGISTRATION: This study was registered on May 31, 2023 at clinicaltrials.gov registry, NCT05881915, URL: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05881915term=NCT05881915&draw=2&rank=1.

Dose-Response Study of Phenylephrine for Preventing Spinal-Induced Hypotension During Cesarean Delivery with Combined Spinal-Epidural Anesthesia Under the Effect of Prophylactic Intravenous Ondansetron.

Background: Ondansetron reduces the median effective dose (ED50) of prophylactic phenylephrine to prevent spinal-induced hypotension (SIH) during cesarean delivery. However, the exact dose response of phenylephrine in combination with prophylactic ondansetron for preventing SIH is unknown. Therefore, this study aimed to determine the dose-response of phenylephrine to prevent SIH in cesarean delivery when 4 mg of ondansetron was used as a preventive method. Methods: A total of 80 parturients were enrolled and divided randomly into four groups (n = 20 in each group) who received either 0.2, 0.3, 0.4, or 0.5 µg/kg/min of prophylactic phenylephrine. Ten minutes before the initiation of spinal induction, 4 mg prophylactic ondansetron was administered. The effective dose of prophylactic phenylephrine was defined as the dose required to prevent hypotension after the period of intrathecal injection and up to neonatal delivery. The ED50 and ED90 of prophylactic phenylephrine and 95% confidence intervals (95% CI) were calculated using probit analysis. Results: The ED50 and ED90 for prophylactic phenylephrine to prevent SIH were 0.25 (95% CI, 0.15 to 0.30), and 0.45 (95% CI, 0.39 to 0.59) µg/kg/min, respectively. No significant differences were observed in the side effects and neonatal outcomes between the four groups. Conclusion: The administration of 4 mg of prophylactic ondansetron was associated with an ED50 of 0.25 (95% CI, 0.15~0.30) and ED90 of 0.45 (95% CI, 0.39~0.59) µg/kg/min for phenylephrine to prevent SIH.

Left-lateral position versus phenylephrine prophylactic treatment for hypotension following combined spinal epidural anesthesia during elective cesarean section.

Backgroud: Hypotension is one of the most common and dangerous complications following combined spinal epidural anesthesia during elective cesarean delivery. Many methods are used to prevent or treat the hypotension with pharmacological or non-pharmacological measures. Our aim was to assess left-lateral position and phenylephrine prophylactic treatment for the prevention or treatment of maternal hypotension. Methods: A total of 127 pregnant women were enrolled to be analyzed. The primary outcome measure was the incidence of maternal hypotension and secondary outcome measures included maternal demographic characteristics, anesthesia-to-incision time interval, birthweight and Apgar scores. Results: The incidence of hypotension was 65.4 % in sequential reactive treatment and only 11.3 % achieved complete anesis after left-lateral position, significantly higher than 17.4 % in left-lateral position combined phenylephrine prophylactic treatment (P < 0.001). The increasing in gestational age may decrease the hypotension risk (P < 0.001). There were no significantly differences with maternal age, gravidity, parity, BMI before pregnancy, BMI before cesarean section, anesthesia-to-incision time interval, birthweight and Apgar scores (P > 0.05). The univariate logistic regression analysis revealed a significant association between treatment and hypotension (OR 0.11, 95 % CI 0.05-0.27). After adjusting for confounding variables, the risk of hypotension was decreased in subjects with treatment (OR 0.1, 95 % CI 0.04-0.25; OR 0.15, 95 % CI 0.05-0.43; OR 0.16, 95 % CI 0.05-0.46). The results of stratified and interaction analyses of the association between treatment revealed no interactive role from maternal age, gravidity and BMI before cesarean section (P > 0.05). Conclusions: Single use of left-lateral position had limited effective and left-lateral position combined prophylactic phenylephrine used may be much better to prevent or treat hypetension, but larger studies with more robust data are needed to confirm these findings.

Use of vasopressors to manage spinal anesthesia-induced hypotension during cesarean delivery.

Cesarean sections are commonly performed under spinal anesthesia, which can lead to hypotension, adversely affecting maternal and fetal outcomes. Hypotension following spinal anesthesia is generally defined as a blood pressure of 80-90% below the baseline value. Various strategies have been implemented to reduce the incidence of spinal anesthesia-induced hypotension. The administration of vasopressors is a crucial method for preventing and treating hypotension. In the past decade, phenylephrine, a primarily alpha-adrenergic agonist, has been the preferred vasopressor for cesarean sections. Recently, norepinephrine, a potent alpha-agonist with modest beta-agonist activity, has gained popularity owing to its advantages over phenylephrine. Vasopressors can be administered via a bolus or continuous infusion. Although administering boluses alone is simpler in a clinical setting, continuous prophylactic infusion initiated immediately after spinal anesthesia is more effective in reducing the incidence of hypotension. Tailoring the infusion dose based on the patient's body weight and adjusting the rate in response to blood pressure changes, in addition to using a prophylactic or rescue bolus, helps reduce blood pressure variability during cesarean sections under spinal anesthesia until neonatal delivery.

Comparison of the effect of intravenous phenylephrine and norepinephrine boluses for post-spinal hypotension on neonatal outcome in elective caesarean section: A randomised controlled trial.

Background and Aims: There is limited data on the effects of norepinephrine on neonatal outcomes and maternal complications relative to other vasopressors. The study aimed to compare neonatal outcomes and maternal complications after bolus intravenous doses of phenylephrine and norepinephrine for post-spinal hypotension in elective caesarean section women. Methods: This randomised study was done on 100 elective caesarean section women under spinal anaesthesia. Block randomisation divided women into two groups to receive intravenous phenylephrine 50 µg bolus (Group A) or norepinephrine 5 µg bolus (Group B) following post-spinal hypotension. Groups were evaluated and compared for umbilical arterial blood gas analysis, birth weight, APGAR (appearance, pulse, grimace, activity, and respiration) score, maternal haemodynamics, and complications. Kolmogorov-Smirnov and Shapiro-Wilk tests were used to verify data normality. Independent samples t-test or Mann-Whitney U test was employed to compare continuous variables based on data normality, and the Chi-square test was used to determine categorical variable associations. Results: Demographic characteristics of women were found to be comparable between groups. Umbilical arterial potential of hydrogen, partial pressure of oxygen, partial pressure of carbon dioxide, base excess, bicarbonate, birth weight, and APGAR scores were comparable across groups, showing no significant differences (P > 0.05). Groups had similar maternal haemodynamic characteristics and episodes of nausea, vomiting, and chest pain across groups without statistical significance (P > 0.05). Conclusion: No notable distinction was found between neonatal outcomes and maternal complications between phenylephrine and norepinephrine bolus regimens. Norepinephrine can be used as an alternative to phenylephrine post-spinal hypotension in women undergoing elective caesarean section.

Phenylephrine alters phase synchronization between cerebral blood velocity and blood pressure in ME/CFS with orthostatic intolerance.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CBV) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.8 yr). All patients with ME/CFS had postural tachycardia syndrome (POTS). A 10-min 60° head-up tilt (HUT) significantly increased heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decreased end-tidal CO2 (ETCO2; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, P < 0.05) in ME/CFS versus control. In ME/CFS, HUT significantly decreased CBV compared with control (-22.5% vs. -8.7%, P < 0.005). To mitigate the orthostatic CBV reduction, we administered supplemental CO2, phenylephrine, and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct n = 4 N-back during HUT in ME/CFS similar to control (ME/CFS = 38.5 ± 5.5 vs. ME/CFS + PE= 65.6 ± 5.7 vs. Control 56.9 ± 7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. Although CO2 and acetazolamide had no effect on PhSI in ME/CFS, phenylephrine caused a significant reduction in PhSI (ME/CFS = 0.80 ± 0.03 vs. ME/CFS + PE= 0.69 ± 0.04, P < 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in patients with ME/CFS, perhaps related to improved neurovascular coupling, cerebral autoregulation, and maintenance of CBV.NEW & NOTEWORTHY We evaluated cognitive function before and after CO2, acetazolamide, and phenylephrine, which mitigate orthostatic reductions in cerebral blood velocity. Neither CO2 nor acetazolamide affected N-back testing (% correct answers) during an orthostatic challenge. Only phenylephrine improved upright N-back performance in ME/CFS, as it both blocked hyperventilation and increased CO2 significantly compared with those untreated. And only phenylephrine resulted in improved PSI values in both ME/CFS and control while upright, suggesting improved cerebral autoregulation.

Estrogen-receptor status determines differential regulation of α1- and α2-adrenoceptor-mediated cell survival, angiogenesis, and intracellular signaling responses in breast cancer cell lines.

Psychosocial stress promotes cancer pathogenesis involving angiogenesis through alterations in neuroendocrine-immune functions that may involve adrenoceptor (AR)-dependent signaling mechanisms in the brain, lymphoid organs, and cancerous cells. Various concentrations of α1- and α2- AR-specific agonists and antagonists were incubated in vitro with estrogen receptor-positive (ER +) MCF-7, and ER (-) MDA MB-231 cells to examine the secretions of VEGF-A, VEGF-C, and nitric oxide (NO), and expression of signaling molecules- p-ERK, p-CREB, and p-Akt on the proliferation of breast cancer cell lines. Cellular proliferation, VEGF-A and NO secretion, expression of p-ERK, p-CREB, and p-Akt were enhanced in MCF-7 cells treated with α1-AR agonist while VEGF-C secretion alone was enhanced in MDA MB-231 cells. Treatment of MCF-7 and MDA MB-231 cells with α2- AR agonist similarly enhanced proliferation and decreased NO production and p-CREB expression while VEGF-C secretion was decreased in MCF-7 cells and p-Akt expression was decreased in MDA MB-231 cells. α1-AR inhibition reversed cellular proliferation and VEGF-A secretion by MCF-7 cells while α2-AR inhibition reversed the proliferation of MCF-7 and MDA MB-231 cells and VEGF-C secretion by MCF-7 cells. Taken together, breast cancer pathogenesis may be influenced by distinct α-AR-mediated signaling mechanisms on angiogenesis and lymphangiogenesis that are dependent on estrogen receptor status.

Randomized Double-Blinded Comparison of Intermittent Boluses Phenylephrine and Norepinephrine for the Treatment of Postspinal Hypotension in Patients with Severe Pre-Eclampsia During Cesarean Section.

Background: Norepinephrine has fewer negative effects on heart rate (HR) and cardiac output (CO) for treating postspinal hypotension (PSH) compared with phenylephrine during cesarean section. However, it remains unclear whether fetuses from patients with severe pre-eclampsia could benefit from the superiority of CO. The objective of this study was to compare the safety and efficacy of intermittent intravenous boluses of phenylephrine and norepinephrine used in equipotent doses for treating postspinal hypotension in patients with severe pre-eclampsia during cesarean section. Methods: A total of 80 patients with severe pre-eclampsia who developed PSH predelivery during cesarean section were included. Eligible patients were randomized at a 1:1 ratio to receive either phenylephrine or norepinephrine for treating PSH. The primary outcome was umbilical arterial pH. Secondary outcomes included other umbilical cord blood gas values, Apgar scores at 1 and 5 min, changes in hemodynamic parameters including CO, mean arterial pressure (MAP), HR, stroke volume (SV), and systemic vascular resistance (SVR), the number of vasopressor boluses required, and the incidence of bradycardia, hypertension, nausea, vomiting, and dizziness. Results: No significant difference was observed in umbilical arterial pH between the phenylephrine and norepinephrine groups (7.303±0.38 vs 7.303±0.44, respectively; P=0.978). Compared with the phenylephrine group, the overall CO (P=0.009) and HR (P=0.015) were greater in the norepinephrine group. The median [IQR] total number of vasopressor boluses required was comparable between the two groups (2 [1 to 3] and 2 [1 to 3], respectively; P=0.942). No significant difference was found in Apgar scores or the incidence of maternal complications between groups. Conclusion: A 60 µg bolus of phenylephrine and a 4.5 µg bolus of norepinephrine showed similar neonatal outcomes assessed by umbilical arterial pH and were equally effective when treating PSH during cesarean section in patients with severe pre-eclampsia. Norepinephrine provided a higher maternal CO and a lower incidence of bradycardia.

Novel HPTLC method for simultaneous estimation from ternary mixture of chlorpheniramine maleate, dextromethorphan hydrobromide and phenylephrine hydrochloride in syrup formulations.

OBJECTIVES: A synergic antihistamine, cough suppressant, and decongestant combination of chlorpheniramine, dextromethorphan, and phenylephrine is used to treat acute respiratory infections caused by seasonal viruses. The effective qualitative and quantitative methods require the simultaneous measurement of a ternary combination in the pharmaceutical syrup dosage form. Therefore, a new, simple, fast and robust high performance thin layer chromatographic (HPTLC) method has been developed and validated for chlorpheniramine maleate (CPM), dextromethorphan hydrobromide (DEXO) and phenylephrine hydrochloride (PE). MATERIAL AND METHODS: The chromatographic separation was carried out on precoated aluminium plates with silica gel 60 F254 as the stationary phase. Mobile phase used was chloroform: methanol: ammonia (2.5:7.5:0.3, v/v/v) for proper separation. The detection was carried out at 270nm wavelength in absorbance mode. Developed method was validated as per International Council for Harmonization (ICH) Q2 (R1) guideline. RESULTS: The linearity range is 400 to 1400ng/band for CPM, 3000 to 11500ng/band for DEXO and 1000 to 3500ng/band for PE with correlation coefficient ≥ 0.995. The consistent lower values of relative standard deviation (RSD, %) for precision and robustness study indicate the method reliability. The percent recovery ranged from 97.82 to 102.03% indicates the good accuracy of the method. CONCLUSION: The proposed method was complying for the analytical method validation parameters suggested by the ICH Q2 (R1) guideline. The method was found to be simple, rapid and reliable for the simultaneous estimation of CPM, DEXO and PE from its pharmaceutical syrup dosage form. The method was successfully applied to quantify these analytes from the several pharmaceutical syrup dosage form.