Administration Of Phenylephrine Research Articles

Rapid response to the alpha-1 adrenergic agent phenylephrine in the perioperative period is impacted by genomics and ancestry

The emergence of genomic data in biobanks and health systems offers new ways to derive medically important phenotypes, including acute phenotypes occurring during inpatient clinical care. Here we study the genetic underpinnings of the rapid response to phenylephrine, an α1-adrenergic receptor agonist commonly used to treat hypotension during anesthesia and surgery. We quantified this response by extracting blood pressure (BP) measurements 5 min before and after the administration of phenylephrine. Based on this derived phenotype, we show that systematic differences exist between self-reported ancestry groups: European-Americans (EA; n = 1387) have a significantly higher systolic response to phenylephrine than African-Americans (AA; n = 1217) and Hispanic/Latinos (HA; n = 1713) (31.3% increase, p value < 6e−08 and 22.9% increase, p value < 5e−05 respectively), after adjusting for genetic ancestry, demographics, and relevant clinical covariates. We performed a genome-wide association study to investigate genetic factors underlying individual differences in this derived phenotype. We discovered genome-wide significant association signals in loci and genes previously associated with BP measured in ambulatory settings, and a general enrichment of association in these genes. Finally, we discovered two low frequency variants, present at ~1% in EAs and AAs, respectively, where patients carrying one copy of these variants show no phenylephrine response. This work demonstrates our ability to derive a quantitative phenotype suited for comparative statistics and genome-wide association studies from dense clinical and physiological measures captured for managing patients during surgery. We identify genetic variants underlying non response to phenylephrine, with implications for preemptive pharmacogenomic screening to improve safety during surgery.

Whole brain irradiation in mice causes long-term impairment in astrocytic calcium signaling but preserves astrocyte-astrocyte coupling.

Whole brain irradiation (WBI) therapy is an important treatment for brain metastases and potential microscopic malignancies. WBI promotes progressive cognitive dysfunction in over half of surviving patients, yet, the underlying mechanisms remain obscure. Astrocytes play critical roles in the regulation of neuronal activity, brain metabolism, and cerebral blood flow, and while neurons are considered radioresistant, astrocytes are sensitive to γ-irradiation. Hallmarks of astrocyte function are the ability to generate stimulus-induced intercellular Ca2+ signals and to move metabolic substrates through the connected astrocyte network. We tested the hypothesis that WBI-induced cognitive impairment associates with persistent impairment of astrocytic Ca2+ signaling and/or gap junctional coupling. Mice were subjected to a clinically relevant protocol of fractionated WBI, and 12 to 15months after irradiation, we confirmed persistent cognitive impairment compared to controls. To test the integrity of astrocyte-to-astrocyte gap junctional coupling postWBI, astrocytes were loaded with Alexa-488-hydrazide by patch-based dye infusion, and the increase of fluorescence signal in neighboring astrocyte cell bodies was assessed with 2-photon microscopy in acute slices of the sensory-motor cortex. We found that WBI did not affect astrocyte-to-astrocyte gap junctional coupling. Astrocytic Ca2+ responses induced by bath administration of phenylephrine (detected with Rhod-2/AM) were also unaltered by WBI. However, an electrical stimulation protocol used in long-term potentiation (theta burst), revealed attenuated astrocyte Ca2+ responses in the astrocyte arbor and soma in WBI. Our data show that WBI causes a long-lasting decrement in synaptic-evoked astrocyte Ca2+ signals 12-15months postirradiation, which may be an important contributor to cognitive decline seen after WBI.

QA project: Hemodynamic safety of endobronchial administration of phenylephrine for control of airway bleeding by bronchoscopy

BackgroundPhenylephrine has been administered endobronchially for airway bleeding during bronchoscopy as an alternative to epinephrine. Topical phenylephrine, often used in nasal surgery as a vasoconstrictor agent has been linked to cardiovascular morbidity. ObjectiveTo evaluate the safety of bronchoscopic instillation of phenylephrine during bronchoscopy. MethodsWe retrospectively reviewed patients who received endobronchial phenylephrine in our endoscopy suite. We compared the changes in blood pressure and heart rate before and after endobronchial phenylephrine administration. The safety of endobronchial phenylephrine was assessed with regards to the changes in hemodynamics and acute cardiovascular event, and 30-day mortality. Acute cardiovascular complications included acute coronary syndrome, aortic dissection, tachyarrhythmias, pulmonary edema and stroke. ResultsWe identified 30 patients who received endobronchial phenylephrine 100mcg/ml with a mean total volume of 6.5 ± 10.6 ml. They were given mainly for balloon dilation and cryobiopsy procedure (96.7%). On excluding patients who received concurrent IV pressor, there was a statistically significant increase of mean arterial pressure (MAP) by 12 ± 21 mmHg, p = 0.01 within 30 min of endobronchial phenylephrine compared to procedure day MAP baseline. There was 27% of patients with more than 20% increase in their MAP but none of the patients had MAP more than 140 nor the occurrence of acute cardiovascular event. There was no significant change in the patients’ heart rate following endobronchial phenylephrine. ConclusionIn our review, endobronchial phenylephrine with dose comparable to IV administration can cause significant raise in MAP but their absolute levels did not go beyond 180/120 mmHg nor resulted in acute cardiovascular complications.

Effect of phenylephrine on cerebral oxygen saturation and cardiac output in adults when used to treat intraoperative hypotension: a systematic review.

The objective of this review was to examine the effect of phenylephrine on cerebral oxygen saturation, cardiac output, and middle cerebral artery blood flow velocity when used to treat intraoperative hypotension. While the etiology of postoperative cognitive dysfunction in adults following surgery is likely multifactorial, intraoperative cerebral hypoperfusion is a commonly proposed mechanism. Research evidence and expert opinion are emerging that suggest phenylephrine adversely affects cerebral oxygen saturation and may also adversely affect cerebral perfusion via a reduction in cardiac output or cerebral vascular vasoconstriction. The administration of phenylephrine to treat intraoperative hypotension is common anesthesia practice, despite a lack of evidence to show it improves cerebral perfusion. Therefore, a systematic review of the effect of phenylephrine on cerebral hemodynamics has significant implications for anesthesia practice and future research. Studies of adults 18 years and over undergoing elective, non-neurosurgical procedures involving anesthesia were included. In these studies, participants received phenylephrine to treat intraoperative hypotension. The effect of phenylephrine on cerebral oxygen saturation, cardiac output, or middle cerebral artery blood flow velocity was measured. Key information sources searched included MEDLINE (Ovid), Embase, CINAHL (EBSCO), and Google Scholar. The scope of the search was limited to English-language studies published from 1999 through 2017. The recommended JBI approach to critical appraisal, study selection, data extraction, and data synthesis were used. This systematic review found that phenylephrine consistently decreased cerebral oxygen saturation values despite simultaneously increasing mean arterial pressure to normal range. Results also found that ephedrine and dopamine were superior to phenylephrine in maintaining or increasing values. Phenylephrine was found to be similar to vasopressin in the extent to which both decreased cerebral oxygen saturation values. Results also showed that phenylephrine resulted in statistically significant declines in cardiac output, or failed to improve abnormally low preintervention values. The effect of phenylephrine on middle cerebral artery blood flow velocity was only measured in one study and showed that phenylephrine increased flow velocity by about 20%. Statistical pooling of the study results was not possible due to the gross variation in how the intervention was administered and how effect was measured. This review found that phenylephrine administration resulted in declines in cerebral oxygen saturation and cardiac output. However, the research studies were ineffective in informing phenylephrine's mechanism of action or its impact on postoperative cognitive function. PROSPERO (CRD42018100740).

INFLUENCE OF SUBARACHNOID ANESTHESIA IN THE PRONE POSITION ON THE ENERGY OF CIRCULATION

The energy supply of the body has an energy price, which is paid, in particular, by the myocardium. This price depends on the circulatory conditions, which can also be affected by iatrogenic factors, such as subarachnoid anesthesia (SA) in the prone position. Decreasing of a vascular tone under the influence of SA requires the myocardium to increase energy consumption to maintain an adequate cardiac index (CI). With a resistive type of circulation, autoregulation of blood circulation may become untenable, that requires artificial maintenance of vascular tone with the α1-adrenomimetics, that also contribute to an increase in energy expenditure by the myocardium. All this makes the assessment of blood flow energy relevant.The aim of the study was to study the effect of SA in the prone position on the energy of circulation.65 patients underwent transpedicular stabilization of 1-2 segments under SA in the prone position have been examined. On the eve of the operation, the prognostic index of hemodynamic instability (PIHI) has been determined by the N. Lysohub’s method. At three stages (the position on the back after performing SA, 5 and 20 minutes after turning on the prone position), kinetic (systolic index, ejection fraction, heart rate and SI), dynamic (effective, or average, AP — APe, central venous pressure, the difference between them — systemic perfusion pressure and specific peripheral vascular resistance) and hemic (blood oxygen content) indicators have been determined. Based on these indicators and the energy potential of oxygen (the energy obtained by glucose oxidation by 1 mol of oxygen), the following energy parameters have been calculated: flow power index (FPI), tissue power consumption index (TPCI), oxygen reserve (OR) and circulatory reserve index (CRI). APe was maintained at least 60 mm Hg during anesthesia by infusion and, if necessary, by administration of the α1- adrenomimetic phenylephrine. Patients have been retrospectively divided into 2 groups: patients of the VF1 group (n = 25) needed phenylephrine administration, and patients of the VF2 group (n = 40) did not need it.The following results have been obtained. The minimum PIHI in the VF1 group was 0.1, which made it possible to expect a high probability of hemodynamic instability, while in the VF2 group it was no higher than 0.05. The integral kinetic parameter CI in the groups did not differ significantly, but the energy consumption and their efficiency between the groups significantly differed. FPI in the VF1 group was significantly lower than in the VF2 group, although TPCI did not differ significantly between the groups. TPCI compliance with tissue needs was determined by OR, which was significantly lower in the VF1 group. The final parameter CRI was significantly lower in the VF1 group, although CI did not differ significantly from the VF2 group level. This indicates energy insufficiency of circulation in patients with a resistive type of circulation against the background of SA in the prone position, so with this type, the presence of which is confirmed by a high PIHI, preference should be given to another type of anesthesia.

Effects of dobutamine and phenylephrine on cerebral perfusion in patients undergoing cerebral bypass surgery: a randomised crossover trial

BackgroundPatients undergoing cerebral bypass surgery are prone to cerebral hypoperfusion. Currently, arterial blood pressure is often increased with vasopressors to prevent cerebral ischaemia. However, this might cause vasoconstriction of the graft and cerebral vasculature and decrease perfusion. We hypothesised that cardiac output, rather than arterial blood pressure, is essential for adequate perfusion and aimed to determine whether dobutamine administration resulted in greater graft perfusion than phenylephrine administration. MethodsThis randomised crossover study included 10 adult patients undergoing cerebral bypass surgery. Intraoperatively, patients randomly and sequentially received dobutamine to increase cardiac index or phenylephrine to increase mean arterial pressure (MAP). An increase of >10% in cardiac index or >10% in MAP was targeted, respectively. Before both interventions, a reference phase was implemented. The primary outcome was the absolute difference in graft flow between the reference and intervention phase. We compared the absolute flow difference between each intervention and constructed a random-effect linear regression model to explore treatment and carry-over effects. ResultsGraft flow increased with a median of 4.1 (inter-quartile range [IQR], 1.7–12.0] ml min−1) after dobutamine administration and 3.6 [IQR, 1.3–7.8] ml min−1 after phenylephrine administration (difference –0.6 ml min−1; 95% confidence interval [CI], –14.5 to 5.3; P=0.441). There was no treatment effect (0.9 ml min−1; 95% CI, 0.0–20.1; P=0.944) and no carry-over effect. ConclusionsBoth dobutamine and phenylephrine increased graft flow during cerebral bypass surgery, without a preference for one method over the other. Clinical trial registrationNetherlands Trial Register, NL7077 (https://www.trialregister.nl/trial/7077).

Hypotension after spinal anaesthesia is not always the rule in parturients undergoing caesarean section

Background General anaesthesia is a real challenge for the anaesthetist when anaesthetizing obstetric patients due its well-known complications of difficult intubation and thereby increasing morbidity and mortality of pregnant women. These risks can be easily avoided by regional anaesthesia. Spinal anaesthesia is frequently associated with hypotension which can have detrimental effects both on the mother and the neonate. Prophylactic phenylephrine administration had been widely practiced to prevent post-spinal hypotension during caesarean section. The goal of this study is to prove and determine that it is not always necessary to use a vasoconstrictor to avoid hypotension after spinal anesthesia for parturients undergoing caesarean section.Method We enrolled 100 patients in this randomized controlled study who were having elective caesarean delivery. Spinal anaesthesia was performed under aseptic conditions. Immediately following spinal blockade, patients were randomly allocated to receive either a single bolus of phenylephrine 100 μg in a volume of 10 ml, or equivalent volume of normal saline 0.9%. Incidence of post-spinal hypotension was used as the primary outcome. Maternal haemodynamic parameters, intraoperative nausea and vomiting, the need for phenylephrine or glycopyrrolate administration, neonatal Apgar score at 1, 5 minutes, and base excess (BE) value of the neonatal umbilical venous blood were all recorded and reflected the secondary outcomes.Results There was no significant difference regarding the incidence of post-spinal hypotension in phenylephrine and placebo group. There was no difference in neonatal Apgar score at 1, 5 minutes, and base excess in both groups.ConclusionThe present study demonstrated that it is not necessary to provide a vasoconstrictor to avoid hypotension that results from spinal anaesthesia in caesarean sections.

Spinal cord autoregulation using near-infrared spectroscopy under normal, hypovolemic, and post-fluid resuscitation conditions in a swine model: a comparison with cerebral autoregulation

BackgroundFew studies have investigated spinal cord autoregulation using near-infrared spectroscopy (NIRS). Here, we assessed spinal cord autoregulation under normal, hypovolemic, and post-fluid resuscitation conditions compared with cerebral autoregulation.MethodsTen pigs (36.1 ± 1.1 kg) were anesthetized with 2.5% isoflurane, before phenylephrine administration at 0.5, 1, 2, and 5 μg kg−1 min−1 in a stepwise fashion at 10-min intervals (baseline), followed by similar administration of sodium nitroprusside (SNP). Hypovolemia was induced by a 600-ml bleed (25% estimated total blood volume). Only phenylephrine was readministered (same protocol). Hypovolemia was reversed by infusing 600 ml hydroxyethyl starch, before readministering phenylephrine and SNP. The relationships between mean arterial pressure (MAP) and cerebral, thoracic, and lumbar spinal cord tissue oxygenation indices (TOIs) were evaluated.ResultsThoracic and lumbar spinal cord TOIs were approximately 15% and 10% lower, respectively, than the cerebral TOI at similar MAPs. The average relationship between MAP and each TOI showed an autoregulatory pattern, but negative correlations were observed in the cerebral TOI during phenylephrine infusion. A 600-ml bleed lowered each relationship < 5% and subsequent fluid resuscitation did not change the relationship. Individual oxygenation responses to blood pressure indicated that the spinal cord is more pressure-passive than the cerebrum. Paradoxical responses (an inverse relationship of tissue oxygenation to MAP) were observed particularly in cerebrum during phenylephrine infusion and were rare in the spinal cord.ConclusionsSpinal cord autoregulation is less robust than cerebral autoregulation and more pressure-dependent. Similar to cerebral oxygenation, spinal cord oxygenation is volume-tolerant but is more sensitive to hypotension.

Adverse Cardiovascular Effects of Phenylephrine Eye Drops Combined with Intravenous Atropine

Background: Phenylephrine and atropine can cause serious adverse effects, when applied in combination. We investigated the effect of phenylephrine eye drops combined with intravenous atropine on the cardiovascular system in patients under general anaesthesia undergoing intraocular surgery. Methods: Thirteen patients undergoing intraocular surgery under general anaesthesia were observed in this study; all were injected intravenously with atropine due to the oculocardiac reflex during surgery. Fifty-four SD rats that received phenylephrine eye drops and intravenous atropine treatment under general anaesthesia were assessed, of which 24 treated with these drugs simultaneously were administered normal saline or antagonists. Blood pressure and heart rate were recorded and analysed. Findings: In patients, topical ocular application of 5% phenylephrine and intravenous atropine treatment led to a significant heart rate increase ten minutes after intravenous atropine treatment; the increase lasted 20 minutes. The significant increase in diastolic blood pressure (DBP) and systolic blood pressure (SBP) lasted 20 and 25 minutes, respectively. From five to 25 minutes after intravenous atropine treatment, SBP and DBP were both more than 20% higher than the at baseline. In rats, the blood pressure and heart rate changes were independent of the phenylephrine and atropine administration sequence but were related to the administration time interval. The variations in blood pressure and heart rate reached their peak when phenylephrine and atropine were administered simultaneously. The urapidil and neostigmine groups showed a significant decrease in blood pressure after the increase from the administration of phenylephrine and atropine. After neostigmine treatment, the heart rate was significantly lower than that associated with normal saline treatment. Interpretation: Phenylephrine eye drops combined with intravenous atropine treatment have obvious cardiovascular effects, which can be reversed by neostigmine. These drugs combination should be used carefully for ophthalmic surgery, especially in patients with cardiocerebrovascular diseases. Funding Statement: This work was supported by the Science and Technology Program of Guangzhou of Wei Chi (No. 201804010415). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: The use of experimental animals in this study complied with the animal ethics principles, and the protocol was approved by the laboratory animal ethics committee (No. 00201878).

Does α1-adrenergic receptor blockade modulate sweating during incremental exercise in young endurance-trained men?

Human eccrine sweat glands respond to α1-adrenergic receptor agonists. We recently reported that adrenergic mechanisms contribute to sweating in endurance-trained men during an incremental exercise to volitional fatigue. However, it remains unclear if this response is mediated by α1-adrenergic receptor activation. Twelve endurance-trained men performed an incremental cycling bout until exhaustion while wearing a water-perfused suit to clamp skin temperature at ~ 34°C. Bilateral forearm sweat rates were measured wherein the distal area was treated with either 1% terazosin (α1-adrenergic receptor antagonist) or saline solution on the opposite limb (Control) via transdermal iontophoresis. We also measured proximal bilateral forearm sweat rate in untreated sites to confirm that no between-limb differences in forearm sweat rate occurred. Once sweat rate returned to pre-exercise resting levels at ~ 20min postexercise, 0.25% phenylephrine (α1-adrenergic receptor agonist) was iontophoretically administered to skin to verify α1-adrenergic receptor blockade. Sweat rates at the proximal untreated right and left forearm sites were similar during exercise (interaction, P = 0.581). Similarly, no effect of terazosin on sweat rate was measured relative to control site (interaction, P = 0.848). Postexercise administration of phenylephrine increased sweat rate at the control site (0.08 ± 0.09mgcm-2min-1), which was suppressed by ~ 90% at the terazosin-treated site (0.01 ± 0.02mgcm-2min-1) (P = 0.026), confirming that α1-adrenergic receptor blockade was intact. Our findings demonstrate that α1-adrenergic receptors located at eccrine sweat glands do not contribute to eccrine sweating during incremental exercise in young endurance-trained men.

Experimental validation of the prestretch-strain relationship as a non-invasive index of left ventricular myocardial contractility.

BackgroundThe slope of the relationship between segmental PreS and total systolic shortening (S) has been proposed as a non-invasive index of left ventricular contractility. The aim of this study was to correlate this novel parameter to invasive gold standard measurements of contractility and to investigate how it is influenced by afterload.MethodsIn domestic pigs, afterload was increased by either balloon inflation in the aorta or by administration of phenylephrine while contractility was increased by dobutamine infusion. During all interventions, left ventricular pressure-volume measurements and trans-diaphragmatic two-dimensional echocardiographic images were acquired. The PreS-S slope was constructed from 18 segmental strain curves obtained by speckle tracking analysis and compared to the slope of the end systolic PV relationship (Emax) and the pre-load recruitable stroke work (PRSW).ResultsSixteen datasets of increased contractility and afterload were analyzed. During dobutamine infusion, the LV volumes decreased (p<0.05) while ejection fraction increased (p<0.05). Emax, PRSW and the slope of the intra-ventricular PreS-S relation increased significantly during dobutamine infusion. Afterload increase led to increase in systolic blood pressure (105±16mmHg vs. 138±25mmHg; p<0.01) and decrease of LV stroke volume and ejection fraction (p<0.01). The PreS-S slope was not influenced by loading conditions in concordance with the PRSW findings. The absolute values of the PreS-S slope did not correlate with Emax or PRSW. However, the change of the PreS-S slope in relation with different interventions demonstrated good correlation with changes in PRSW or Emax, (r = 0.66, p<0.05 and r = 0.69, p<0.05).ConclusionsThe slope of the PreS-S relationship is sensitive to changes in inotropy and is less load-dependent than conventional non-invasive parameters of left ventricular function. The magnitude of the change of this slope correlates well with changes in invasive contractility measurements making it an attractive parameter to assess contractile reserve or contractile changes during longitudinal follow-up of patients.

Cerebrovascular Response to Phenylephrine in Traumatic Brain Injury: A Scoping Systematic Review of the Human and Animal Literature.

Intravenous phenylephrine (PE) is utilized commonly in critical care for cardiovascular support. Its impact on the cerebrovasculature is unclear and its use may have important implications during states of critical neurological illness. The aim of this study was to perform a scoping review of the literature on the cerebrovascular/cerebral blood flow (CBF) effects of PE in traumatic brain injury (TBI), evaluating both animal models and human studies. We searched MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and the Cochrane Library from inception to January 2020. We identified 12 studies with various animal models and 4 studies in humans with varying TBI pathology. There was a trend toward a consistent increase in mean arterial pressure (MAP) by the injection of PE systemically, and by proxy, an increase of the cerebral perfusion pressure (CPP). There was a consistent constriction of cerebral vessels by PE reported in the small number of studies documenting such a response. However, the heterogeneity of the literature on the CBF/cerebral blood volume (CBV) response makes the strength of the conclusions on PE limited. Studies were heterogeneous in design and had significant limitations, with most failing to adjust for confounding factors in cerebrovascular/CBF response. This review highlights the significant knowledge gap on the cerebrovascular/CBF effects of PE administration in TBI, calling for further study on the impact of PE on the cerebrovasculature both in vivo and in experimental settings.

Effect of Phenylephrine and Ephedrine on Cerebral (Tissue) Oxygen Saturation During Carotid Endarterectomy (PEPPER): A Randomized Controlled Trail

Introduction - Adequate blood pressure during carotid endarterectomy (CEA) is essential to preserve cerebral perfusion. To achieve and maintain adequate blood pressure intraoperative, short-acting vasopressor agents like phenylephrine or ephedrine can be used. Previous studies in healthy subjects revealed that besides a systemic hemodynamic effect, these vasopressors also affected frontal lobe cerebral tissue oxygenation (ScO2) showing a decrease after administration of phenylephrine.1,2 This decrease in ScO2 after phenylephrine administration is unwarranted in patients with jeopardized cerebral perfusion, like CEA patients. The aim of this study was to evaluate the impact of both phenylephrine and ephedrine on ScO2 during CEA. Methods - In this double blinded randomized controlled trial 29 patients underwent CEA under general anesthesia for > 70% symptomatic or asymptomatic stenosis. This number of patients matches the number of subjects required according to the power calculation, which suggested 14 patients for each vasopressor study arm.3 Patients were preoperative allocated randomly (1:1) by computer-generated randomization for receiving either phenylephrine or ephedrine in case intraoperative hypotension occurs. During CEA mean arterial pressure (MAP) was measured by radial artery line, placed on the arm with the highest preoperative systolic blood pressure. In case of a decreased MAP ³20% compared to (awake) baseline, patients received a bolus of either phenylephrine (50μg; N=14) or ephedrine (5mg; N=15). After administration the MAP, cardiac output, heart rate, stroke volume and ScO2 were measured. The chosen timeframe for data analysis was 120 seconds before, until 300 seconds after administration. Results - Both phenylephrine (70±9 to 99±22 mmHg; P<0.001; mean±SD) and ephedrine (75±11 mmHg to 109±19 mmHg; P<0.01) adequately restored the MAP. Heart rate did not change significantly after infusion of both vasopressors. However cardiac output was raised after administration of both, 15% and 14% for phenylephrine and ephedrine respectively. ScO2 did not change significantly after administration of either phenylephrine or ephedrine (from 73% to 71% and 72% to 71% respectively). Conclusion - Within this randomized prospective study, we did not observe a different response in ScO2 when MAP was corrected by either phenylephrine or ephedrine in patients who underwent CEA.

Safety and Feasibility of Phenylephrine Administration Through a Peripheral Intravenous Catheter in a Neurocritical Care Unit.

Blood pressure optimization and maintenance of cerebral and spinal perfusion pressure are mainstays in the treatment of a neurocritically ill patient. Traditionally, central venous access has been required for vasopressor administration, with risk of inherent complications. The authors have previously reported pilot data on the safety of peripheral administration of phenylephrine in a neurocritical care unit. In this follow-up, we report the safety, feasibility, and potential efficacy of peripheral administration of low-concentration phenylephrine in a more robust cohort. A retrospective chart review was conducted on all consecutive patients who received peripheral phenylephrine in a tertiary care hospital neurocritical care unit. A cohort of 125 patients were identified and included in the final analysis. The average age was 59.3 years, with an average intensive care unit (ICU) length of stay of 7.61 days. The most common indication for phenylephrine use was spinal perfusion (both with/without neurogenic shock) in 38.4% of cases, followed by postsurgical/anesthesia resuscitation in 16.8% of cases; 25.6% of patients in our cohort required escalation to central venous access (central venous catheter + peripherally inserted central catheter). A total of 2880 patient-hours were recorded with peripheral phenylephrine infusion, of which 73.9% were at goal blood pressure (either systolic or mean arterial pressure). Only one major complication of thrombophlebitis and 8 minor complications were recorded. Protocol-driven peripheral administration of lower concentration phenylephrine in an ICU setting is safe and feasible. This strategy is potentially effective at achieving hemodynamic targets in the majority of patients avoiding the need for central venous access.

Anesthesia During Positive-pressure Myelogram: A New Role for Cerebral Oximetry.

Positive-pressure myelogram (PPM) is an emerging radiologic study used to localize spinal dural defects. During PPM, cerebrospinal fluid pressure (CSFp) is increased by injecting saline with contrast into the cerebrospinal fluid. This has the potential to increase intracranial pressure and compromise cerebral perfusion. We performed a retrospective chart review and analysis of 11 patients. The aim was to describe the periprocedural anesthetic management of patients undergoing PPM. All patients underwent PPM with general anesthesia and intra-arterial blood pressure and near-infrared spectroscopy monitoring of regional cerebral tissue oxygen saturation. Mean±SD maximum lumbar CSFp was 58±12 mm Hg. Upon intrathecal injection, mean systolic blood pressure increased from 115±21 to 142±32 mm Hg (P<0.001), diastolic blood pressure from 68±12 to 80±20 mm Hg (P≤0.001), and mean blood pressure from 87±10 to 98±14 mm Hg (P=0.02). Ten of 11 patients received blood pressure augmentation with phenylephrine to minimize the risk of reduced cerebral perfusion secondary to increased CSFp after intrathecal injection. The mean heart rate before and following injection was similar (68±15 vs. 70±15 bpm, respectively; P=0.16). There was a decrease in regional cerebral oxygen saturation after positioning from supine to prone position (79±10% to 74±9%, P=0.02) and a further decrease upon intrathecal injection (75±10% to 69±9%, P≤0.01). Systemic blood pressure increased following intrathecal injection during PPM, possibly due to a physiologic response to intracranial hypertension/reduced cerebral perfusion or administration of phenylephrine. Regional cerebral oxygen saturation decreased with the change to prone position and further decreased upon intrathecal injection. Cerebral near-infrared spectroscopy has a potential role to monitor the adequacy of cerebral perfusion and guide adjustment of systemic blood pressure during PPM.

Pharmacologically versus endogenously induced changes in tissue oxygenation, measured by near infrared spectroscopy (NIRS)

Introduction Near-infrared spectroscopy (NIRS) enables continuous estimation of regional tissue oxygen saturation (rStO2). Ensuring adequate tissue oxygenation in patients undergoing general anaesthesia is of paramount importance to prevent post-procedural end-organ dysfunction. During endotracheal intubation, laryngoscopy elicits an endogenous stress response, resulting in an increased mean arterial pressure (MAP). Intraoperatively, vasopressors are routinely used to counter anaesthesia-related hypotension. Since rStO2 is MAP-dependent, we aimed to study whether changes in rStO2 differ depending on the origin of increased MAP. Methods After ethical approval and written informed consent, we randomly assigned 28 patients undergoing arterial dilation of the lower limb. Phenylephrine or ephedrine were administered according to a predefined scheme, when MAP dipped below 20% from baseline. Cerebral (rScO2) and paravertebral (rSpvO2, measured at T3, T9 and lumbar) rStO2 were measured. Differences in changes in rScO2 and rSpvO2 following MAP increase obtained by vasopressor administration or laryngoscopy, were compared. After rigorous selection of fixed effects to minimize risk of multicollinearity, a linear mixed model was used to determine predicted effects of each intervention on rStO2, with intervention, rStO2-location and their two way interaction as fixed effects. Results We observed a significant increase in rScO2 (+6.27% [CI 5.19, 7.36]) following laryngoscopy, compared to ephedrine (-0.15% [CI -0.86, +0.56]) and phenylephrine (-1.57% [CI -2.27, -0.87]). rSpvO2 showed a decrease following laryngoscopy of -2.91% [CI -3.78, -2.03], whereas no changes were noted after administration of ephedrine (-0.65% [CI -1.36, +0.06]) or phenylephrine +0.35% ([CI -0.36, +1.05]). Discussion MAP increase following tracheal intubation resulted in a significantly higher rise in rScO2 and a significant lower rSpvO2 compared to changes in rStO2 following pharmacologically induced MAP increases.

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

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

A 1D computer model of the arterial circulation in horses: An important resource for studying global interactions between heart and vessels under normal and pathological conditions.

Arterial rupture in horses has been observed during exercise, after phenylephrine administration or during parturition (uterine artery). In human pathophysiological research, the use of computer models for studying arterial hemodynamics and understanding normal and abnormal characteristics of arterial pressure and flow waveforms is very common. The objective of this research was to develop a computer model of the equine arterial circulation, in order to study local intra-arterial pressures and flow dynamics in horses. Morphologically, large differences exist between human and equine aortic arch and arterial branching patterns. Development of the present model was based on post-mortem obtained anatomical data of the arterial tree (arterial lengths, diameters and branching angles); in vivo collected ultrasonographic flow profiles from the common carotid artery, external iliac artery, median artery and aorta; and invasively collected pressure curves from carotid artery and aorta. These data were used as input for a previously validated (in humans) 1D arterial network model. Data on terminal resistance and arterial compliance parameters were tuned to equine physiology. Given the large arterial diameters, Womersley theory was used to compute friction coefficients, and the input into the arterial system was provided via a scaled time-varying elastance model of the left heart. Outcomes showed plausible predictions of pressure and flow waveforms throughout the considered arterial tree. Simulated flow waveform morphology was in line with measured flow profiles. Consideration of gravity further improved model based predicted waveforms. Derived flow waveform patterns could be explained using wave power analysis. The model offers possibilities as a research tool to predict changes in flow profiles and local pressures as a result of strenuous exercise or altered arterial wall properties related to age, breed or gender.

Selective denervation of the aortic and carotid baroreceptors in rats.

What is the central question of this study? The traditional surgical approach for sino-aortic denervation in rats leads to simultaneous carotid baroreceptor and chemoreceptor deactivation, which does not permit their individual study in different situations. What is the main finding and its importance? We have described a new surgical approach capable of selective denervation of the arterial (aortic and carotid) baroreceptors, keeping the carotid bodies (chemoreceptors) intact. It is understood that this technique might be a useful tool for investigating the relative role of the baro- and chemoreceptors in several physiological and pathophysiological conditions. Studies have demonstrated that the traditional surgical approach for sino-aortic denervation in rats leads to simultaneous carotid baroreceptor and chemoreceptor deactivation. The present study reports a new surgical approach to denervate the aortic and the carotid baroreceptors selectively, keeping the carotid bodies (peripheral chemoreceptors) intact. Wistar rats were subjected to specific aortic and carotid baroreceptor denervation (BAROS-X) or sham surgery (SHAM). Baroreflex activation was achieved by i.v. administration of phenylephrine, whereas peripheral chemoreflex activation was produced by i.v. administration of potassium cyanide. The SHAM and BAROS-X rats displayed significant hypertensive responses to phenylephrine administration. However, the reflex bradycardia following the hypertensive response caused by phenylephrine was remarkable in SHAM, but not significant in the BAROS-X animals, confirming the efficacy of the surgical procedure to abolish the baroreflex. In addition, the baroreflex activation elicited by phenylephrine increased carotid sinus nerve activity only in SHAM, but not in the BAROS-X animals, providing support to the notion that the baroreceptor afferents were absent. Instead, the classical peripheral chemoreflex hypertensive and bradycardic responses to potassium cyanide were similar in both groups, suggesting that the carotid body chemoreceptors were preserved after BAROS-X. In summary, we describe a new surgical approach in which only the baroreceptors are eliminated, while the carotid chemoreceptors are preserved. Therefore, it is understood that this procedure is potentially a useful tool for examining the relative roles of the arterial baroreceptors versus the chemoreceptors in several pathophysiological conditions, for instance, arterial hypertension and heart failure.

Antihypotensive effect of oxytocin mini-dose at the beginning of spinal anaesthesia for elective caesarean section

Oxytocin is widely used after child delivery for preventing postpartum haemorrhage. Rather high level of spinal block for for Caesarean section has a disadvantage of frequent arterial hypotension. The aim of our study was to assess maternal circulation after mini-dose (0.5 IU) oxytocin administered before, not after, delivery.Methods. Spinal anaesthesia (L3, hyperbaric 0.5% bupivacaine, 13.5 mg) for Caesarean section was performed in 80 women, randomly divided into study (n=40) and control (n=40) groups. In the study group, oxytocin (0.5 IU, slow intravenous bolus) was administered immediately after anaesthesia performance. In both groups, after delivery the slow oxytocin bolus was administered (4.5 IU in study and 5 IU in control group), then another 5 IU were infused in normal saline over 20-25 min.Results. During anaesthesia, minimal systolic arterial pressure (M±SD) in the study group (107±11 Torr) was significantly (p&lt;0.0001) higher than in the control group (88±10 Torr). Phenylephrine administration before delivery was needed in the study group (28 of 40) significantly (Fisher exact p = 0.0015) more rarely than in the control group (39 of 40); whereas during the whole surgery the difference was insignificant (36 of 40 vs 40 of 40, Fisher exact p = 0.1156). Time to first phenylephrine administration in the study group (10.7±4.0 min) was significantly (p&lt;0.0001) longer than in the control group (1.8±1.0 min). Cumulative phenylephrine dose before delivery (Median: min–max) in the study group (1.25: 1,25–2,5 mg) was significantly (p=0.00424) less than in the control group (5: 2.5–6.25 mg). Cumulative phenylephrine dose during the whole surgery in the study group (3.625: 1.25–7.5 mg) was significantly (p&lt;0.00001) less than in the control group (10: 5–12.5 mg). Our results can be explained by blood mobilization from uterine vasculature. Conclusions. Oxytocin mini-dose (0.5 u), administered at the beginning of spinal anaesthesia for Caesarean section, attenuates arterial hypotension and allows less phenylephrine use.