Mg Of Phenylephrine Research Articles

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

BackgroundPhenylephrine 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. MethodsSeventy-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. ResultsThe dose of phenylephrine per minute (34.4 ± 7.3 μg·min−1 vs. 40.9 ± 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 ± 217.1 μg vs. 706.2 ± 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. ConclusionsIntermittent 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.

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).

The effect of two dose phenylephrin for preventing hypotension during spinal anesthesia for cesarean delivery

Background: Spinal anesthesia-induced hypotension is one of the most complications which can cause many severe maternal and fetal complications. Therefore, the prevention and treatment of spinal anesthesia-induced hypotension in pregnant women undergoing cesarean delivery play an important role. The use of vasopressors is the most effective method of hypotensive prophylaxis and phenylephrine is currently the first-line vasopressor of choice to prevent this complication. The aim of this study is to evaluate the effectiveness and safety of two-dose phenylephrine for prevention of spinal anesthesia-induced hypotension during cesarean delivery. Materials and methods: In a randommized controlled clinical trial, 150 pregnants undregoing cesarean delivery with spinal anesthesia were randomly divided into three groups: Group I: as a control group without phenylephrine prophylaxis (n = 50), Group II: 50µg intravenously bolus phenylephrine (n = 50), and Group III: 75µg intravenously bolus phenylephrine (n = 50) immediately after induction of spinal anesthesia. Hypotension, defined decreasing systolic blood pressure &gt; 20% of baseline. The incidence of hypotension, levels of hypotension, maternal side effects and neonatal APGAR scores at 1 and 5 minutes. Results: The incidence of hypotension was 44%, the incidence of re-hypotension was 16%. Group III: the incidence of hypotension was 28%, the incidence of re-hypotension was 2%. The neonatal APGAR scores of the two groups at both 1 minute and 5 minutes was the same (p &gt; 0.05), all cases had APGAR &gt; 7. Conclusion: Phenylephrine intravenous bolus at doses of 50 µg and 75 µg are both effective for the prevention spinal anesthesia-induced hypotension for cesarean section. However, the 75 µg phenylephrine dose was more effective than the 50 µg dose because of lower rates of hypotension and recurrent hypotension (28% and 2% vs 44% and 16%, p &lt; 0.05). In addition, both groups of prophylactic phenylephrine didn’t cause detrimental adverses for parturients and their babies. Key words: Hypotensive prophylaxis, cesarean section, phenylephrin.

Evaluating an advanced double intravenous vasopressor automated system to treat hypotension during spinal anesthesia for cesarean delivery: a randomized controlled trial

BackgroundThe optimal treatment of hypotension during spinal anaesthesia is uncertain. A novel double intravenous vasopressor automated (DIVA) system reduces hypotension compared to standard care, and was subsequently modified to an advanced-DIVA (ADIVA) system. The primary objective was to compare ADIVA versus DIVA on incidence of hypotension (systolic BP (SBP) < 80% baseline).MethodsWe conducted a randomized-controlled trial in women undergoing elective cesarean delivery under spinal anesthesia. SBP and heart rate were measured continuously using a Nexfin monitor. ADIVA delivered 25 μg phenylephrine (heart rate > 60 beats.min−1) or 2 mg ephedrine (heart rate < 60 beats.min−1) at SBP 90 to 110% of baseline, 50 μg phenylephrine or 4 mg ephedrine at SBP 80 to 90%, and 75 μg phenylephrine or 6 mg ephedrine at SBP < 80%. ADIVA calculated the trend of SBP; vasopressors were administered rapidly if SBP trended downward, or 30 s if SBP trended upward. In contrast, DIVA delivered 25 μg phenylephrine or 2 mg ephedrine at SBP 90 to 100% of baseline, and 50 μg phenylephrine or 4 mg ephedrine at SBP < 90%. Boluses were followed by a 10-s lockout. Other outcomes included hypertension (SBP > 120% baseline), vasopressor consumption, clinical outcomes, and performance measures from spinal anesthesia to fetal delivery.ResultsWe analyzed 94 parturients (ADIVA: n = 46, DIVA: n = 48), with no difference in the incidence of hypotension between ADIVA (78.3%) and DIVA (83.3%, p = 0.677). ADIVA had significantly higher proportion of hypotensive SBP readings, lower phenylephrine consumption and higher umbilical arterial pH. There was no difference in hypertension, bradycardia, ephedrine consumption, intravenous fluid volume, nausea/vomiting, Apgar scores, and umbilical venous pH or lactate. ADIVA maintained SBP higher above baseline with greater fluctuation than DIVA. ConclusionADIVA was associated with a greater proportion of hypotensive SBP readings, reduced phenylephrine consumption, and increased umbilical arterial pH than DIVA. Further research is needed to determine the optimal method of vasopressor delivery in parturients undergoing cesarean delivery.Trial registrationThis study was registered on Clinicaltrials.gov registry (NCT03620942) on 08/08/2018.

Efficacy of fixed-dose phenylephrine bolus for treating post-spinal hypotension: Comparison between pre-eclamptics and normotensives.

Pre-eclamptic parturients may have an exaggerated response to vasopressors. This study compares the efficacy of a 50 μg fixed bolus of phenylephrine for treatment of post-spinal hypotension in pre-eclamptic versus normotensive parturients. After written informed consent and ethics committee approval, 30 normotensive and 30 pre-eclamptic parturients between 18 and 40 years with singleton term pregnancy about to undergo cesarean section (CS) under spinal anesthesia were included. Post-spinal hypotension was treated with a 50 μg fixed bolus of phenylephrine. The cumulative dose of phenylephrine, the number of boluses, and the median dose required to treat the first hypotensive episode, total number of hypotensive episodes, maternal side effects, neonatal appearance, pulse, grimace, activity, and respiration (APGAR) scores, and umbilical arterial cord blood pH were noted. Statistical analysis was done using Student's t-test, Mann-Whitney U-test, Chi-square test/Fisher's exact test as appropriate. A P <0.05 was considered significant. The cumulative dose and number of boluses of phenylephrine required to treat post-spinal hypotension were comparable. The median dose required to treat the first episode of post-spinal hypotension was also similar (p = 0.792). The time to develop the first hypotensive episode was significantly earlier for group N (p = 0.002). The efficacy of a single fixed bolus of 50 μg phenylephrine was similar in both groups (p = 1.000). Neonatal median APGAR scores at 1 min after birth were significantly higher for group N (p = 0.016). A fixed-dose bolus of 50 μg phenylephrine is safe and effective in treating post-spinal hypotension in pre-eclampsia. The efficacy of phenylephrine is comparable in pre-eclamptic and normotensive parturients.

Arterial Stiffness Predicts General Anesthesia–Induced Vasopressor-Resistant Hypotension in Patients Taking Angiotensin-Converting Enzyme Inhibitors

Patients chronically treated with angiotensin-converting enzyme inhibitors (ACEIs) may develop hypotension after induction of general anesthesia. A fraction of these patients are resistant to therapeutic doses of vasopressors, which poses serious concerns for hemodynamic management. The authors hypothesized that the patients who develop refractory hypotension, compared with those who do not, show lower central arterial stiffness due to the profound effect of ACEIs. Prospective observational study. Single tertiary center. Fifty surgical patients chronically treated with ACEIs were enrolled. Prior to surgery, all the patients had central arterial stiffness assessment measured by carotid-femoral pulse-wave velocity. Patients were categorized into 2 groups according to the systolic blood pressure response during the first 10 minutes after induction of general anesthesia: a vasopressor-resistant hypotension group requiring more than 200 µg phenylephrine, or a control group requiring no more than 200 µg of phenylephrine to maintain systolic blood pressure above 90 mmHg during the study period. Carotid-femoral pulse-wave velocity was significantly lower in the vasopressor-resistant hypotension group compared to the control group (7.6 [7.2-8.3] m/s v 9.9 [8.7-12.0] m/s, p = 0.001 [Hodges-Lehman median difference 2.2, 95% confidence interval = 1.1-4.4]). These findings suggested that preoperative measurement of carotid-femoral pulse-wave velocity in patients chronically treated with ACEIs could help identify patients at increased risk of developing hypotension refractory to vasopressors after induction of general anesthesia.

Bolus norepinephrine and phenylephrine for maternal hypotension during elective cesarean section with spinal anesthesia: a randomized, double-blinded study

Background:In recent years, norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia. Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China. Thus, in this randomized, double-blinded study, we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension.Methods:In a tertiary women's hospital in Nanjing, China, 102 women were allocated with computer derived randomized number to receive prophylactic 8 μg norepinephrine (group N; n = 52) or 100 μg phenylephrine (group P; n = 50) immediately post-spinal anesthesia, followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80% of the baseline. Our primary outcome was standardized maternal cardiac output (CO) reading from spinal anesthesia until delivery analyzed by a two-step method. Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes. Maternal side effects and neonatal outcomes were collected as well.Results:Compared to group P, women in group N had a higher CO (standardized CO 5.8 ± 0.9 vs. 5.3 ± 1.0 L/min, t = 2.37, P = 0.02) and stroke volume (SV, standardized SV 73.6 ± 17.2 vs. 60.0 ± 13.3 mL, t = 4.52, P < 0.001), and a lower total peripheral resistance (875 ± 174 vs. 996 ± 182 dyne·s/cm5, t = 3.44, P < 0.001). Furthermore, the incidence of bradycardia was lower in group N than in group P (2% vs. 14%, P = 0.023), along with an overall higher standardized heart rate (78.8 ± 11.6 vs. 75.0 ± 7.3 beats/min, P = 0.049). Other hemodynamics, as well as maternal side effects and neonatal outcomes, were similar in two groups (P > 0.05).Conclusions:Compared to equivalent phenylephrine, intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia; however, no obvious maternal or neonatal clinical advantages were observed for norepinephrine.

Evaluation of the bioequivalence of two formulations containing the combination of 400 mg of acetaminophen (paracetamol), 4 mg of phenylephrine and 4 mg of chlorpheniramine in capsules: open-label, three-way crossover study, partially replicated in healthy volunteers of both sexes

This study was carried out in order to compare the relative bioavailability of two different formulations containing 400 mg of acetaminophen + 4 mg of phenylephrine hydrochloride + 4 mg of chlorpheniramine maleate, Test formulation (Cimegripe®) and Reference formulation (Resfenol®) in 84 healthy volunteers of both sexes under fasting conditions. The study was conducted in a single dose, randomized, open-label, crossover 3-way and partially replicated. The tolerability was evaluated by the monitoring of adverse events and vital signs, results of clinical and laboratory tests. Plasma concentrations were quantified by validated bioanalytical methods using the ultra-performance liquid chromatography coupled to tandem mass spectrometry. The Cmax, Tmax, AUC0-t, AUC0-inf, T1/2 and Kel pharmacokinetic parameters were calculated from these obtained concentrations. The 90% confidence intervals were constructed for the ratio reference/test from the geometric average of the Cmax and AUC parameters which were comprised between 80% and 125%. Only the Cmax parameter of the phenylephrine was applied the scaled average bioequivalence due to the intraindividual coefficient of variation > 30% obtained, thus extending the acceptance limits of the interval. It can be concluded that the two formulations were bioequivalent in terms of rate and absorption extent and thus interchangeable.

Prophylactic phenylephrine and fluid co-administration to reduce spinal hypotension during elective caesarean section in a resource-limited setting: a prospective alternating intervention study.

Spinal hypotension is a common and clinically important problem during caesarean section. Current consensus recommendations for resource-rich settings suggest the use of a titrated phenylephrine infusion, in combination with fluid coloading, for prevention of maternal hypotension. In resource-limited settings, where syringe drivers are unavailable, these recommendations advise the addition of 500μg phenylephrine to the first 1l of intravenous fluid given after initiation of spinal anaesthesia, with additional vasopressor boluses as required. This prospective, alternating intervention study compared the use of a conventional phenylephrine rescue bolus strategy for prevention of hypotension, defined as systolic arterial pressure <90mmHg, with a phenylephrine infusion given according to the consensus recommendation. We studied 300 women having elective caesarean section. There were 77 (51%) women who developed hypotension in the bolus group vs. 55 (37%) in the phenylephrine infusion group (p=0.011). This represented a 29% reduction in hypotension, with a number needed to treat of 6.8. The six highest systolic arterial pressure readings occurred in the phenylephrine infusion group (range 166-188mmHg), and there were four instances of bradycardia (heart rate <50 beats.min-1 ) with preserved systolic arterial pressure in each group. There were no adverse clinical sequelae, and no differences in neonatal Apgar scores in either group. The consensus recommendation for phenylephrine and fluid co-administration in resource-limited settings appears effective in preventing maternal hypotension, but at the cost of sporadic systolic hypertension.

Preventive intramuscular phenylephrine in elective cesarean section under spinal anesthesia: A randomized controlled trial

BackgroundPhenylephrine is the first-line vasoactive drug in the cesarean section under spinal anesthesia. The rate of hypotension remains high after intravenous preventive use of phenylephrine. However, few studies have investigated the effect of preventive intramuscular phenylephrine via a longer period of usage on fetal and maternal outcomes. MethodsA total of 99 healthy parturients undergoing elective cesarean delivery were randomly allocated into three groups: M group (preventive intramuscular use of 5 mg phenylephrine), V group (preventive intravenous use of 100 μg phenylephrine), and P group (0.9% normal saline placebo). Rescue phenylephrine, ephedrine and atropine were used intraoperatively to adjust blood pressure and heart rate. The primary outcome was umbilical artery pH. ResultsSignificant differences in umbilical artery pH (M group: 7.32 ± 0.05 versus V group: 7.25 ± 0.04 versus P group: 7.21 ± 0.03, P < 0.05), fetal acidosis (M group: 3% [n = 33] versus V group: 15% [n = 33] versus P group: 30% [n = 33], P = 0.01) and maternal intraoperative hypotension (M group: 12% [33] versus V group: 39% [33] versus P group: 73% [33], P < 0.0001) were identified among the groups. Multiple linear regression analysis demonstrated that treating arms, neonatal birthweight and the interval from the end of anesthesia to baby delivery were associated with umbilical artery pH. ConclusionCompared with the preventive intravenous use of phenylephrine and placebo, preventive intramuscular phenylephrine exhibited a better neonatal acid-base status and more stable maternal hemodynamics in elective cesarean under spinal anesthesia.

Comparison of the potency of phenylephrine and norepinephrine bolus doses used to treat post-spinal hypotension during elective caesarean section

BackgroundPhenylephrine, although considered the vasopressor of choice, can cause reflex bradycardia and a fall in cardiac output. Norepinephrine, due to its direct positive chronotropic and reflex negative chronotropic actions, is expected to overcome this problem. However, limited information about its effective dose for management of post-spinal hypotension, and its potency compared to phenylephrine, is available. MethodsOne hundred consecutive patients who developed post-spinal hypotension were treated with a predetermined dose of either phenylephrine or norepinephrine. Correction of hypotension after one minute was considered ‘success’. The starting dose for the first patient and testing interval (the incremental or decremental dosing) were 100 μg and 10 μg in the phenylephrine group, and 6 μg and 0.5 μg in the norepinephrine group. Doses for subsequent patients were determined by the responses of previous patients according to the Narayana rule for up-down sequential allocation. ED95 and ED50 of phenylephrine and norepinephrine boluses and their potency ratio were calculated. ResultsUsing Probit analysis, ED95 and ED50 values were 43.1 µg (95% CI 39.5 to 65.0 µg) and 33.2 µg (95% CI 5.1 to 37.0 µg) for phenylephrine, and 3.7 µg (95% CI 3.5 to 4.7 µg) and 3.2 µg (95% CI 1.8 to 3.4 µg) for norepinephrine. The relative potency ratio of norepinephrine and phenylephrine was 11.3 (95% CI 8.1 to 16.9). ConclusionBased on the results of this study, norepinephrine is about 11 times more potent than phenylephrine. When used as bolus doses for treatment of hypotension, 100 μg phenylephrine should be approximately equivalent to 9 μg norepinephrine.

A Case Report of Hypertensive Emergency and Intracranial Hemorrhage Due to Intracavernosal Phenylephrine.

Background: Intracavernosal injection of phenylephrine is a commonly used therapy for ischemic priapism and is typically well tolerated with few severe adverse side effects. We report a case of intracranial hemorrhage related to hypertensive emergency due to intracavernosal phenylephrine. Case Report: A 43-year-old Caucasian man with history of hypertension, diabetes mellitus type I, end-stage renal disease status post a combination kidney-pancreas transplant, and recurrent idiopathic priapism presented to emergency department with an episode of priapism. His home medications were lisinopril, metoprolol tartrate, mycophenolate mofetil, prednisone, sulfamethoxazole-trimethoprim, and tacrolimus. After local injection of 2 rounds (1 hour apart) of 100 µg phenylephrine into each corpus cavernosa, priapism resolved. Within 5 minutes, the patient had headaches, dyspnea, and excruciating chest pain. His blood pressure (BP) was noted to be 240/130 mm Hg but normalized spontaneously within few minutes. During this period, he developed new-onset right arm and leg weakness and found to have intracranial hemorrhage in the midbrain. Conclusion: A careful review for pharmacologic interactions should be performed prior to intracavernosal phenylephrine administration, and close monitoring should occur after its administration.

Maternal cardiac output response to colloid preload and vasopressor therapy during spinal anaesthesia for caesarean section in patients with severe pre‐eclampsia: a randomised, controlled trial

We examined the haemodynamic effects of colloid preload, and phenylephrine and ephedrine administered for spinal hypotension, during caesarean section in 42 women with severe early onset pre-eclampsia. Twenty patients with pre-delivery spinal hypotension were randomly allocated to receive an initial dose of either 50 μg phenylephrine or 7.5 mg ephedrine; the primary outcome was percentage change in cardiac index. After a 300-ml colloid preload, mean (SD) cardiac index increased from 4.9 (1.1) to 5.6 (1.2) l.min-1 .m-2 (p < 0.01), resulting from an increase in both heart rate, from 81.3 (17.2) to 86.3 (16.5) beats.min-1 (p = 0.2), and stroke volume, from 111.8 (19.0) to 119.8 (17.9) ml (p = 0.049). Fourteen (33%) and 23 (54.8%) patients exhibited a stroke volume response > 10% and > 5%, respectively; a significant negative correlation was found between heart rate and stroke volume changes. Spinal hypotension in 20 patients was associated with an increase from baseline in cardiac index of 0.6 l.min-1 .m-2 (mean difference 11.5%; p < 0.0001). After a median [range] dose of 50 [50-150] μg phenylephrine or 15 [7.5-37.5] mg ephedrine, the percentage change in cardiac index during the measurement period of 150 s was greater, and negative, in patients receiving phenylephrine vs. ephedrine, at -12.0 (7.3)% vs. 2.6 (6.0)%, respectively (p = 0.0001). The percentage change in heart rate after vasopressor was higher in patients receiving phenylephrine, at -9.1 (3.4)% vs. 5.3 (12.6)% (p = 0.0027), as was the change in systemic vascular resistance, at 22.3 (7.5) vs. -1.9 (10.5)% (p < 0.0001). Phenylephrine effectively reverses spinal anaesthesia-induced haemodynamic changes in severe pre-eclampsia, if left ventricular systolic function is preserved.

Intravenous ephedrine, phenylephrine, and ketamine for attenuation of hypotension associated with induction of general anesthesia with propofol

Background and objective Hypotension and bradycardia remain the major adverse effects of propofol during induction of general anesthesia. Several drugs were studied to prevent these adverse effects. In our study, we compare the effect of mixing ephedrine, phenylephrine, or ketamine with propofol to attenuate its hypotensive effect during induction of general anesthesia. Materials and methods A total of 120 patients of both sexes between 20 and 50 years of age and ASA I–II physical status undergoing elective ambulatory surgeries under general anesthesia were included in our study. Patients were randomly allocated into four groups (30 patients each): group C (the control group), which received plain propofol; group E (the ephedrine group), which received 15 mg of ephedrine premixed with propofol; group Ph (the phenylephrine group), which received 100 μg of phenylephrine premixed with propofol; and group K (the ketamine group), which received 30 mg of ketamine premixed with propofol. In all groups, mean arterial blood pressure (MABP) and heart rate (HR) were recorded at baseline (before induction) and then every 1 min until 6 min after induction. Results Addition of ephedrine, phenylephrine, or ketamine to propofol during general anesthesia induction can significantly attenuate hypotension and bradycardia. In the control group, the MABP dropped from 91.96±3 mmHg just before induction to 75.6±8.7 mmHg at 6 min after induction. HR in the control group dropped from 83.76±7.29/min just before induction to 75.3±12/min at 6 min after induction. The drop in MABP and HR were nonsignificant in the other three groups. Conclusion Mixing propofol with ketamine, ephedrine, or phenylephrine before induction can attenuate its hypotensive and bradycardic effects.

Short-Term Angiotensin Subtype 1 Receptor Blockade Does Not Alter the Circulatory Responses to Sympathetic Nervous System Modulation in Healthy Volunteers Before and During Sevoflurane Anesthesia: Results of a Pilot Study

The mechanism of perioperative hypotension in patients taking an angiotensin-receptor blocker up to the time of surgery remains unclear. This study tested the hypothesis that short-term angiotensin-receptor blocker treatment attenuated the sympathetic and vascular responses to autonomic stimuli in volunteers undergoing anesthesia. Randomized, crossover, blinded, pilot design. Zablocki Veterans Affairs Medical Center, Milwaukee, WI. The study comprised 8 male and 6 female healthy, young volunteers (age 23±1.2 years [mean±standard error of the mean]). Volunteers were studied after receiving oral placebo or 50 mg of losartan (angiotensin-receptor blocker) for 3 days before each test day. The effectiveness of angiotensin-receptor blocker treatment was confirmed using the mean arterial blood pressure response to intravenous angiotensin II (1-µg bolus). Eight volunteers underwent direct mean arterial pressure and forearm bloodflow measurements during conscious baseline, a cold pressor test, induction of anesthesia, tracheal intubation, maintenance of anesthesia with 1 minimum alveolar concentration of sevoflurane, and airway irritation with 12% desflurane. Six volunteers experienced mean arterial pressure responses to 0.1 mg of phenylephrine at baseline and during 1 minimum alveolar concentration of sevoflurane. Comparisons were made over time and across groups. Angiotensin-receptor blocker treatment significantly reduced-mean arterial pressure and forearm vascular resistance (forearm blood flow/mean arterial pressure) over time and blocked the mean arterial pressure response to angiotensin-II challenge. The changes in mean arterial pressure and forearm vascular resistance in response to all stressors did not differ between treatments. Mean arterial pressure increases from phenylephrine were preserved. In healthy, young volunteers, sympathetically-mediated responses from the short-term use of an angiotensin-receptor blocker were not altered and most likely did not contribute to perioperative hypotension during the intraoperative period.

Comparing prophylactic effect of phenylephrine and ephedrine on hypotension during spinal anesthesia for hip fracture surgery.

Background:Spinal anesthesia is an accepted technique in hip fracture surgery and prevention of this complication by sympathomimetic agents is of potential clinical significance. The aim of this study is to compare the effect of prophylactic phenylephrine versus ephedrine in the prevention of hypotension during spinal anesthesia in hip fracture surgery.Materials and Methods:Ninety-two patients undergoing hip fracture surgery with the American Society of Anesthesiologists I and II were randomized to receive prophylaxis with ephedrine or phenylephrine immediately before the spinal anesthesia. Patients in the ephedrine group received an intravenous (IV) bolus of 10 mg ephedrine, and patients in the phenylephrine group received an IV bolus of 50 μg phenylephrine. We recorded mean arterial pressure (MAP), systolic and diastolic blood pressure, heart rate every 3 min in the first 10 min and then every 5 min until 30 min after spinal anesthesia, nausea and vomiting, additional vasopressor, and atropine administration.Results:The frequency of hypotension was significantly lower in MAP, systolic and diastolic pressure in group phenylephrine in 3, 6, and 9 min after spinal anesthesia (P = 0.002, P = 0.001). There were no significant differences between two groups in heart rate at different time of study. In the phenylephrine group, lower additional vasopressor was used (8.7% and 23.9%) (P = 0.04). There were no significant differences between two groups in the use of atropine (P = 0.24), nausea and vomiting.Conclusion:At the doses of ephedrine and phenylephrine administered in this trial, phenylephrine was better to prevent hypotension during hip fracture surgery with spinal anesthesia. Higher frequency of hypotension was observed in the ephedrine group.

Assessment of an updated double-vasopressor automated system using Nexfin for the maintenance of haemodynamic stability to improve peri-operative outcome during spinal anaesthesia for caesarean section.

Hypotension occurs commonly during spinal anaesthesia for caesarean section, associated with maternal and fetal adverse effects. We developed a double-vasopressor automated system with a two-step algorithm and continuous non-invasive haemodynamic monitoring using the Nexfin device. The system delivered 25 μg phenylephrine every 30 s when systolic blood pressure was between 90% and 100% of baseline, or 2 mg ephedrine at this blood pressure range and heart rate < 60 beats.min(-1) ; and 50 μg phenylephrine or 4 mg ephedrine when systolic blood pressure was < 90% of baseline with the same heart rate criterion. Fifty-seven women received standardised spinal anaesthesia. Twenty-seven (47.4%) had at least one reading of hypotension defined as systolic blood pressure < 80% baseline. Systolic blood pressure was within 20% of the baseline in a mean (SD) of 79.8 (20.9)% of measurements. Fifty-three (93.0%) women required phenylephrine before delivery while 10 (17.5%) required ephedrine. Six women (10.5%) experienced nausea and three (5.3%) vomited. The system was able to achieve a low incidence of maternal hypotension with good maternal and fetal outcomes.

Effect of Different Phenylephrine Bolus Doses for Treatment of Hypotension during Spinal Anaesthesia in Patients Undergoing Elective Caesarean Section

The efficacy of phenylephrine might be improved by giving doses higher than that traditionally used (100 µg). This study compared the effects of three initial bolus doses of intravenous phenylephrine; 100 µg (group P100), 125 µg (group P125) and 150 µg (group P150), for the treatment of post-spinal hypotension in patients undergoing elective caesarean delivery. If hypotension was not corrected by this dose, additional boluses of 25 µg were given every minute. Further hypotensive episodes were treated with half the initial bolus dose, followed by 25 µg boluses, as required. Umbilical arterial and venous blood samples were obtained for blood gas analysis and Apgar scores recorded. One hundred and twenty subjects (40 per group) who developed post-spinal hypotension (75%) were included in this randomised, double blind trial. Although systolic blood pressure was higher at certain time-points after 150 µg phenylephrine, there were no statistically significant differences in the effectiveness of the first bolus of phenylephrine to treat hypotension (85%, 95% and 95% in groups P100, P125 and P150, respectively, P=0.215); the additional dose of phenylephrine after the first bolus (P=0.810); the number of additional boluses (P=0.318) or of hypotensive episodes (P=0.118). There were no significant differences in the number of patients developing reactive hypertension or bradycardia, in maternal side-effects or in neonatal outcomes. Although the study may have been underpowered, initial phenylephrine bolus doses of 100 µg, 125 µg and 150 µg did not significantly differ in efficacy to treat post-spinal hypotension in these patients.

Development of the method for quantitative determination of phenylephrine hydrochloride in the combined drops

The work is devoted to development of the method for quantitative determination of phenylephrine hydrochloride in the combined nasal drops Gripocitron Rinis. Combination of phenylephrine hydrochloride possessing the vasoconstrictor action with dimetindene maleate having the antihistaminic action formulated into drops decreases nasal discharge and helps to clear the nasal passages without disturbing physiological functions of the ciliated epithelium and mucous membrane. It has been found that the quantitative content of phenylephrine hydrochloride in the combined nasal drops can be determined by spectrophotometry in the ultraviolet spectrum at the wavelength of 296 nm. The method proposed demonstrates the possibility of phenylephrine hydrochloride determination in combined drops in the presence of another active pharmaceutical ingredient – dimetindene maleate, which has the absorption minimum in sodium hydroxide solution at this wavelength. The influence of the additional ingredient – benzalkonium chloride drops on the nature of the absorption spectrum of phenylephrine hydrochloride is recommended to eliminate by the action of potassium dichromate solution. The optimal amount and concentration of solutions of sodium hydroxide and potassium dichromate, the analytical band have been determined. Validation of the given method has been carried out according to the following validation characteristics: linearity (a = 4.34 ≤ maxa 5.10%, b = 1.04), accuracy (0.52 ≤ maxδ 1.02%), convergence (1.07% ≤ max Δas 3.20%) and the correlation coefficient r, which is 0.9997. It has been found that the method suggested for determination of phenylephrine hydrochloride in nasal drops is precise, accurate, reproducible and linear, and it allows recommending it for using in pharmaceutical analysis. Phenylephrine hydrochloride is a known sympathomimetic providing a selective stimulating effect mainly on postsynaptic α-adrenergic receptors [4, 5]. Being a decongestant with a moderate vasoconstrictor action phenylephrine contains in a number of nasal drugs for local application, such as Nasol Baby (phenylephrine hydrochloride), Nasol Kids (phenylephrine hydrochloride with eucalyptol and benzalkonium chloride), Vibrocil and Gripocitron Rinis (phenylephrine hydrochloride with dimetindene maleate and benzalkonium chloride), which are used for symptomatic treatment of nasal congestion, acute and chronic rhinitis, allergic rhinitis, sinusitis, acute otitis. The search of safe and effective monocomponent and combined decongestant nasal drops for local application with phenylephrine hydrochloride actualizes development and standardization of methods for quality control of this substance in the presence of other active pharmaceutical ingredients (API) [3, 6, 7, 9]. Materials and Methods The object of the research was Gripocitron Rinis, nasal drops, 15 ml. The active substances were phenylephrine hydrochloride equivalent to 2.5 mg of phenylephrine, dimetindene maleate 0.25 mg; excipients were citric acid, monohydrate; anhydrous sodium hydrogen phosphate; sorbitol (Е 420); benzalkonium chloride; peppermint oil; purified water as needed. The reference standard (RS) of the substance of phenylephrine hy

Middle cerebral O2 delivery during the modified Oxford maneuver increases with sodium nitroprusside and decreases during phenylephrine

The modified Oxford maneuver is the reference standard for assessing arterial baroreflex function. The maneuver comprises a systemic bolus injection of 100 μg sodium nitroprusside (SNP) followed by 150 μg phenylephrine (PE). On the one hand, this results in an increase in oxyhemoglobin and total hemoglobin followed by a decrease within the cerebral sample volume illuminated by near-infrared spectroscopy (NIRS). On the other hand, it produces a decrease in cerebral blood flow velocity (CBFv) within the middle cerebral artery (MCA) during SNP and an increase in CBFv during PE as measured by transcranial Doppler ultrasound. To resolve this apparent discrepancy, we hypothesized that SNP dilates, whereas PE constricts, the MCA. We combined transcranial Doppler ultrasound of the right MCA with NIRS illuminating the right frontal cortex in 12 supine healthy subjects 18-24 yr old. Assuming constant O₂ consumption and venous saturation, as estimated by partial venous occlusion plethysmography, we used conservation of mass (continuity) equations to estimate the changes in arterial inflow (ΔQa) and venous outflow (ΔQv) of the NIRS-illuminated area. Oxyhemoglobin and total hemoglobin, respectively, increased by 13.6 ± 1.6 and 15.2 ± 1.4 μmol/kg brain tissue with SNP despite hypotension and decreased by 6 ± 1 and 7 ± 1 μmol/kg with PE despite hypertension. SNP increased ΔQa by 0.36 ± .03 μmol·kg(-1)·s(-1) (21.6 μmol·kg(-1)·min(-1)), whereas CBFv decreased from 71 ± 2 to 62 ± 2 cm/s. PE decreased ΔQa by 0.27 ± .2 μmol·kg(-1)·s(-1) (16.2 μmol·kg(-1)·min(-1)), whereas CBFv increased to 75 ± 3 cm/s. These results are consistent with dilation of the MCA by SNP and constriction by PE.