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European Journal of Anaesthesiology Jun 2023Classically, cerebral autoregulation (CA) entails cerebral blood flow (CBF) remaining constant by cerebrovascular tone adapting to fluctuations in mean arterial pressure... (Clinical Trial)
Clinical Trial
BACKGROUND
Classically, cerebral autoregulation (CA) entails cerebral blood flow (CBF) remaining constant by cerebrovascular tone adapting to fluctuations in mean arterial pressure (MAP) between ∼60 and ∼150 mmHg. However, this is not an on-off mechanism; previous work has suggested that vasomotor tone is proportionally related to CA function. During propofol-based anaesthesia, there is cerebrovascular vasoconstriction, and static CA remains intact. Sevoflurane-based anaesthesia induces cerebral vasodilation and attenuates CA dose-dependently. It is unclear how this translates to dynamic CA across a range of blood pressures in the autoregulatory range.
OBJECTIVE
The aim of this study was to quantify the effect of step-wise increases in MAP between 60 and 100 mmHg, using phenylephrine, on dynamic CA during propofol- and sevoflurane-based anaesthesia.
DESIGN
A nonrandomised interventional trial.
SETTING
Single centre enrolment started on 11 January 2019 and ended on 23 September 2019.
PATIENTS
We studied American Society of Anesthesiologists (ASA) I/II patients undergoing noncardiothoracic, nonneurosurgical and nonlaparoscopic surgery under general anaesthesia.
INTERVENTION
In this study, cerebrovascular tone was manipulated in the autoregulatory range by increasing MAP step-wise using phenylephrine in patients receiving either propofol- or sevoflurane-based anaesthesia. MAP and mean middle cerebral artery blood velocity (MCA Vmean ) were measured in ASA I and II patients, anaesthetised with either propofol ( n = 26) or sevoflurane ( n = 28), during 10 mmHg step-wise increments of MAP between 60 and 100 mmHg. Static CA was determined by plotting 2-min averaged MCA Vmean versus MAP. Dynamic CA was determined using transfer function analysis and expressed as the phase lead (°) between MAP and MCA Vmean oscillations, created with positive pressure ventilation with a frequency of 6 min -1 .
MAIN OUTCOMES
The primary outcome of this study was the response of dynamic CA during step-wise increases in MAP during propofol- and sevoflurane-based anaesthesia.
RESULTS
MAP levels achieved per step-wise increments were comparable between anaesthesia regiment (63 ± 3, 72 ± 2, 80 ± 2, 90 ± 2, 100 ± 3 mmHg, and 61 ± 4, 71 ± 2, 80 ± 2, 89 ± 2, 98 ± 4 mmHg for propofol and sevoflurane, respectively). MCA Vmean increased more during step-wise MAP increments for sevoflurane compared to propofol ( P ≤0.001). Dynamic CA improved during propofol (0.73° mmHg -1 , 95% CI 0.51 to 0.95; P ≤ 0.001)) and less pronounced during sevoflurane-based anaesthesia (0.21° mmHg -1 (95% CI 0.01 to 0.42, P = 0.04).
CONCLUSIONS
During general anaesthesia, dynamic CA is dependent on MAP, also within the autoregulatory range. This phenomenon was more pronounced during propofol anaesthesia than during sevoflurane.
TRIAL REGISTRATION
NCT03816072 ( https://clinicaltrials.gov/ct2/show/NCT03816072 ).
Topics: Humans; Sevoflurane; Blood Pressure; Propofol; Methyl Ethers; Anesthesia, General; Homeostasis; Phenylephrine
PubMed: 36655712
DOI: 10.1097/EJA.0000000000001798 -
Anesthesiology Aug 2017
Topics: Blood Pressure; Female; Humans; Phenylephrine; Urogenital Abnormalities; Uterus
PubMed: 28598893
DOI: 10.1097/ALN.0000000000001738 -
British Journal of Anaesthesia Feb 2015
Topics: Adult; Cesarean Section; Female; Fluid Therapy; Humans; Hypotension; Phenylephrine; Postoperative Complications; Pregnancy; Spinal Diseases; Vasoconstrictor Agents
PubMed: 25080429
DOI: 10.1093/bja/aeu267 -
Alternative Therapies in Health and... Oct 2022To investigate the therapeutic effect of phenylephrine combined with goal-directed fluid therapy (GDFT) in elderly patients undergoing total hip arthroplasty. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate the therapeutic effect of phenylephrine combined with goal-directed fluid therapy (GDFT) in elderly patients undergoing total hip arthroplasty.
METHODS
From June 2018 to May 2019, a total of 80 patients, age > 70 years, scheduled for total hip arthroplasty at Guangzhou Red Cross Hospital in China were consecutively included in this prospective randomized controlled trial. The patients were divided into 2 groups of 40 patients each by the random number table method. Patients in the control group were given GDFT alone, and patients in the experimental group were given phenylephrine combined with GDFT. The duration of surgery, blood loss, intraoperative urine output, and fluid input were analyzed. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI) and stroke volume variation (SVV) were compared in the 2 groups at different times: before surgery (T0), after induction (T1), before bone cement placement (T2), after bone cement placement (T3) and after surgery (T4). Lactate, oxygenation index and cerebral oxygen uptake rate were compared perioperatively. Meanwhile, the incidence of abdominal distension, nausea and vomiting, pulmonary infection and cognitive dysfunction within 7 days after surgery were compared.
RESULTS
The intraoperative fluid input in the experimental group was significantly lower than in the control group (P < .05). In T1 and T3, heart rate (HR) and stroke volume variability (SVV) in the control group were significantly higher than in the experimental group (P < .05), but mean arterial pressure (MAP) and cardiac index (CI) were significantly lower than in the experimental group (P < .05). The intraoperative lactic acid in the control group was significantly higher than in the experimental group (P < .05). In addition, we found that the intraoperative oxygenation index and the postsurgical oxygenation index in the control group decreased by 86.86% and 87.49%, respectively, compared with the preoperative values (P < .05). In addition, at T1 and T3, HR and SVV in the control group were significantly higher than T0 (P < .05), while MAP and CI were significantly lower than T0 (P < .05). In the experimental group, there was no significant difference in HR, SVV, MAP or CI at any time points compared with those of T0 (P < .05). The oxygenation index in the control group was lower than before surgery (P < .05). There was no significant difference in urine volume or brain oxygen uptake between the 2 groups (P < .05).
CONCLUSION
Phenylephrine combined with GDFT can be used in elderly patients undergoing hip arthroplasty to reduce fluid input and improve intraoperative hemodynamic stability, to reduce the occurrence of postoperative related complications.
Topics: Aged; Arthroplasty, Replacement, Hip; Bone Cements; Fluid Therapy; Goals; Humans; Lactic Acid; Oxygen; Phenylephrine; Postoperative Complications; Prospective Studies
PubMed: 35839108
DOI: No ID Found -
Revista Brasileira de Anestesiologia 2009Hypotension during spinal block for cesarean section is secondary to the sympathetic blockade and aorto-caval compression by the uterus and it can be deleterious to both... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Hypotension during spinal block for cesarean section is secondary to the sympathetic blockade and aorto-caval compression by the uterus and it can be deleterious to both the fetus and the mother. Ephedrine and phenylephrine improve venous return after sympathetic blockade during the spinal block. The objective of this study was to compare the efficacy of ephedrine and phenylephrine in the prevention and treatment of maternal hypotension during spinal block and to evaluate their side effects and fetal changes.
METHODS
Sixty patients undergoing spinal block with bupivacaine and sufentanil for cesarean section were randomly divided in two groups to receive prophylactic ephedrine (Group E, n = 30, dose = 10 mg) or phenylephrine (Group P, n = 30, dose = 80 microg). Hypotension (blood pressure equal or lower than 80% of baseline values) was treated with bolus administration of the vasoconstrictor at 50% of the initial dose. The incidence of hypotension, reactive hypertension, bradycardia, and vomiting, and Apgar scores on the 1st and 5th minutes, and blood gases of the umbilical cord blood were evaluated.
RESULTS
The mean dose of ephedrine used was 14.8 +/- 3.8 mg and of phenylephrine was 186.7 +/- 52.9 microg. Demographic parameters and the incidence of vomiting, bradycardia, and reactive hypertension were similar in both groups. Hypotension had an incidence of 70% in Group E and 93% in Group P (p < 0.05). The mean arterial pH of the umbilical cord blood and the Apgar score in the 1st minute were lower in Group E (p < 0.05). Differences in the Apgar score in the 5th minute were not observed.
CONCLUSIONS
Ephedrine was more effective than phenylephrine in the prevention of hypotension. Both drugs had similar incidence of side effects. Fetal repercussions were less frequent with phenylephrine and were transitory with the use of ephedrine.
Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Cesarean Section; Double-Blind Method; Ephedrine; Female; Fetus; Humans; Hypotension; Phenylephrine; Pregnancy; Prospective Studies; Vasoconstrictor Agents
PubMed: 19374211
DOI: 10.1590/s0034-70942009000100003 -
American Journal of Physiology.... Apr 2023Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signaling, the primary mechanism mediating sympathetic...
Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signaling, the primary mechanism mediating sympathetic vasoconstriction at sea level (SL), has not been examined at HA. In nine male lowlanders, we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (ΔFVC) during ) incremental intra-arterial infusion of phenylephrine to assess α-adrenergic receptor responsiveness and ) combined intra-arterial infusion of β-adrenergic and α-adrenergic antagonists propranolol and phentolamine (α-β-blockade) to assess adrenergic vascular restraint at rest and during exercise-induced sympathoexcitation (cycling; 60% peak power). Experiments were performed near SL (344 m) and after 3 wk at HA (4,383 m). HA abolished the vasoconstrictor response to low-dose phenylephrine (ΔFVC: SL: -34 ± 15%, vs. HA; 3 ± 18%; < 0.0001) and markedly attenuated the response to medium (ΔFVC: SL: -45 ± 18% vs. HA: -28 ± 11%; = 0.009) and high (ΔFVC: SL: -47 ± 20%, vs. HA: -35 ± 20%; = 0.041) doses. Blockade of β-adrenergic receptors alone had no effect on resting FVC ( = 0.500) and combined α-β-blockade induced a similar vasodilatory response at SL and HA ( = 0.580). Forearm vasoconstriction during cycling was not different at SL and HA ( = 0.999). Interestingly, cycling-induced forearm vasoconstriction was attenuated by α-β-blockade at SL (ΔFVC: Control: -27 ± 128 vs. α-β-blockade: +19 ± 23%; = 0.0004), but unaffected at HA (ΔFVC: Control: -20 ± 22 vs. α-β-blockade: -23 ± 11%; = 0.999). Our results indicate that in healthy males, altitude acclimatization attenuates α-adrenergic receptor responsiveness; however, resting α-adrenergic restraint remains intact, due to concurrent resting sympathoexcitation. Furthermore, forearm vasoconstrictor responses to cycling are preserved, although the contribution of adrenergic receptors is diminished, indicating a reliance on alternative vasoconstrictor mechanisms.
Topics: Male; Humans; Adrenergic Agents; Vasoconstriction; Vasoconstrictor Agents; Phenylephrine; Regional Blood Flow; Muscle, Skeletal; Hypoxia
PubMed: 36717165
DOI: 10.1152/ajpregu.00230.2022 -
Academic Emergency Medicine : Official... Feb 1996To evaluate glucagon and phenylephrine in combination as a treatment for the hemodynamic effects of verapamil overdose. (Comparative Study)
Comparative Study
OBJECTIVE
To evaluate glucagon and phenylephrine in combination as a treatment for the hemodynamic effects of verapamil overdose.
METHODS
Pentobarbital-anesthetized and instrumented dogs were overdosed using a previously developed verapamil overdose model (15 mg/kg IV over 30 minutes). The animals were maintained and observed for 90 minutes or until death. Cardiac output (CO), heart rate (HR), and mean arterial pressure (MAP) were monitored. Following the 30-minute verapamil infusion (toxicity), the control animals received no treatment; the glucagon animals received a 5-mg glucagon bolus and a drip of 5 mg/90 minutes; and the glucagon/phenylephrine animals received the same glucagon therapy plus a phenylephrine drip titrated to 180 micrograms/min over 15 minutes. The groups were compared using analysis of variance: the experimental variables were group and time; the response variables were changes from toxicity for the hemodynamic parameters. Post-hoc comparisons were done with alpha set at 0.05.
RESULTS
A significant change in CO was seen in the glucagon group (delta = 2.6 L/min) and the glucagon/phenylephrine group (delta = 1.9 L/min) compared with the control group (delta = 0.8 L/min). The change in CO was significantly larger for the glucagon animals compared with the glucagon/phenylephrine animals. The change in MAP for the glucagon/phenylephrine group (delta = 24 mm Hg) was significant compared with the control group (delta = 14 mm Hg). The MAP change for the glucagon group (delta = 19 mm Hg) was not significantly different from that of either the control or the glucagon/phenylephrine group. The change in glucagon HR (delta = 6 beats/min) was significant compared with the control group (delta = -4 beats/min) and the glucagon/phenylephrine group (delta = -4 beats/min).
CONCLUSION
The glucagon/phenylephrine therapy improved MAP compared with the control, but reduced CO and HR compared with glucagon alone. Glucagon/phenylephrine therapy is not as effective as glucagon alone in reversing the hemodynamic effects of experimental verapamil overdose.
Topics: Adrenergic alpha-Agonists; Analysis of Variance; Animals; Antidotes; Calcium Channel Blockers; Dogs; Drug Overdose; Drug Therapy, Combination; Evaluation Studies as Topic; Glucagon; Phenylephrine; Receptors, Glucagon; Verapamil
PubMed: 8808371
DOI: 10.1111/j.1553-2712.1996.tb03398.x -
The Journal of Sexual Medicine Nov 2017The internal pudendal arteries (IPAs) supply blood to the penis and are highly susceptible to vascular remodeling in rodent models of diabetes, hypertension, aging, and...
BACKGROUND
The internal pudendal arteries (IPAs) supply blood to the penis and are highly susceptible to vascular remodeling in rodent models of diabetes, hypertension, aging, and chronic kidney disease, thus contributing to erectile dysfunction. Interestingly, vascular remodeling primarily occurs in the distal and not in the proximal IPA, suggesting distinct local physiologic signaling differences within the IPA.
AIM
To examine the role of purinergic signaling and neurotransmitter release by electrical field stimulation (EFS) in the regulation of proximal and distal IPA vascular tone.
METHODS
Proximal and distal IPAs were mounted in wire myographs and vascular responses to phenylephrine, acetylcholine, and 2-(N,N-diethylamino)-diazenolate-2-oxide, diethyl-ammonium salt (DEA NONOate) were measured. EFS-mediated contraction and non-adrenergic non-cholinergic (NANC) relaxation were evaluated in the absence and presence of a nitric oxide synthase antagonist. Purinergic agonist and NANC relaxation responses were assessed in the presence and absence of P2X1 and P2Y1 antagonists. Protein expression of P2X1 and P2Y1 receptors was measured by western blot.
MAIN OUTCOME MEASURES
Proximal and distal IPA contraction and relaxation were measured during increasing agonist administration and EFS in the presence and absence of antagonists.
RESULTS
Proximal and distal IPA concentration response curves to phenylephrine, acetylcholine, and DEA NONOate did no differ. Interestingly, distal IPA exhibited greater EFS-mediated contraction and NANC relaxation compared with proximal IPA. Nitric oxide synthase inhibition completely inhibited distal IPA NANC relaxation but did not affect proximal IPA relaxation. P2X1 or P2Y1 receptor antagonism during NANC relaxation increased distal IPA relaxation but decreased proximal IPA relaxation. Combined P2X1 and P2Y1 receptor antagonism had no effect on proximal IPA relaxation but significantly increased distal IPA NANC relaxation.
CLINICAL TRANSLATION
Understanding neurovascular regulation of IPA vascular tone through nitrergic and purinergic mechanisms could yield new therapeutic targets to improve IPA blood flow and treat vasculogenic erectile dysfunction.
STRENGTHS AND LIMITATIONS
This study is the first to illustrate the differences in mechanisms responsible for regulating vascular tone in the proximal and distal IPAs. All presented findings are currently limited to ex vivo vascular function.
CONCLUSION
The regulation of vascular tone differs regionally in the IPA. The distal IPA is controlled through neurotransmitter-mediated NO-dependent mechanisms and increased sensitivity to purinergic P2X1 and P2Y1 receptor inhibition. Odom MR, Pak ES, Brown DA, Hannan JL. Enhanced Electrical Field Stimulated Nitrergic and Purinergic Vasoreactivity in Distal vs Proximal Internal Pudendal Arteries. J Sex Med 2017;14:1285-1296.
Topics: Acetylcholine; Animals; Arteries; Blotting, Western; Electric Stimulation; Enzyme Inhibitors; Erectile Dysfunction; Male; Muscle Relaxation; Penis; Phenylephrine; Synaptic Transmission
PubMed: 29110801
DOI: 10.1016/j.jsxm.2017.09.013 -
Regulatory Toxicology and Pharmacology... Jun 2018Phenylephrine hydrochloride (HCl) is a decongestant available in over-the-counter (OTC) medicines. Previously marketed prescription products contained phenylephrine... (Randomized Controlled Trial)
Randomized Controlled Trial
Phenylephrine hydrochloride (HCl) is a decongestant available in over-the-counter (OTC) medicines. Previously marketed prescription products contained phenylephrine tannate, an extended-release salt, which allowed dosing every 8-12 h. Given the regulatory history that cold medicines marketed before 1962 had limited supporting clinical data, and with widespread replacement of pseudoephedrine by phenylephrine in OTC products over the last ten years, the need for contemporary studies grew. This exploratory crossover study evaluated effects of salt form, acetaminophen, and food on phenylephrine pharmacokinetics and metabolites in healthy adults. Test treatments were 25 mg phenylephrine tannate (equivalent to 10 mg phenylephrine HCl) combined with 200 mg guaifenesin, fasted; 10 mg phenylephrine HCl combined with 650 mg acetaminophen, fasted; and 10 mg phenylephrine HCl, fed. The reference treatment was 10 mg phenylephrine HCl, fasted. Plasma phenylephrine pharmacokinetics and urine metabolites were determined. Although the tannate salt slowed phenylephrine absorption compared with the HCl salt, terminal concentrations were similar, suggesting that products containing the tannate salt should not be dosed less frequently than those containing the HCl salt. The premise that acetaminophen increases phenylephrine bioavailability by competition for presystemic sulfation was corroborated by increased phenylephrine sulfate in urine. Food delayed phenylephrine absorption, but not the total amount absorbed.
Topics: Acetaminophen; Adult; Analgesics; Cross-Over Studies; Drug Interactions; Fasting; Female; Food; Humans; Intestinal Absorption; Male; Middle Aged; Nasal Decongestants; Phenylephrine; Salts; Young Adult
PubMed: 29635061
DOI: 10.1016/j.yrtph.2018.04.008 -
Journal of Visualized Experiments : JoVE Apr 2011Lymph nodes (LN's), located throughout the body, are an integral component of the immune system. They serve as a site for induction of adaptive immune response and...
Lymph nodes (LN's), located throughout the body, are an integral component of the immune system. They serve as a site for induction of adaptive immune response and therefore, the development of effector cells. As such, LNs are key to fighting invading pathogens and maintaining health. The choice of LN to study is dictated by accessibility and the desired model; the inguinal lymph node is well situated and easily supports studies of biologically relevant models of skin and genital mucosal infection. The inguinal LN, like all LNs, has an extensive microvascular network supplying it with blood. In general, this microvascular network includes the main feed arteriole of the LN that subsequently branches and feeds high endothelial venules (HEVs). HEVs are specialized for facilitating the trafficking of immune cells into the LN during both homeostasis and infection. How HEVs regulate trafficking into the LN under both of these circumstances is an area of intense exploration. The LN feed arteriole, has direct upstream influence on the HEVs and is the main supply of nutrients and cell rich blood into the LN. Furthermore, changes in the feed arteriole are implicated in facilitating induction of adaptive immune response. The LN microvasculature has obvious importance in maintaining an optimal blood supply to the LN and regulating immune cell influx into the LN, which are crucial elements in proper LN function and subsequently immune response. The ability to study the LN microvasculature in vivo is key to elucidating how the immune system and the microvasculature interact and influence one another within the LN. Here, we present a method for in vivo imaging of the inguinal lymph node. We focus on imaging of the microvasculature of the LN, paying particular attention to methods that ensure the study of healthy vessels, the ability to maintain imaging of viable vessels over a number of hours, and quantification of vessel magnitude. Methods for perfusion of the microvasculature with vasoactive drugs as well as the potential to trace and quantify cellular traffic are also presented. Intravital microscopy of the inguinal LN allows direct evaluation of microvascular functionality and real-time interface of the direct interface between immune cells, the LN, and the microcirculation. This technique potential to be combined with many immunological techniques and fluorescent cell labelling as well as manipulated to study vasculature of other LNs.
Topics: Acetylcholine; Animals; Inguinal Canal; Lymph Nodes; Mice; Microscopy; Phenylephrine
PubMed: 21490584
DOI: 10.3791/2551