The Anaesthetic Efficacy of Tetracaine and Oxymetazoline Compared With Co-Phenylcaine in Healthy Individuals.

OBJECTIVES: Nasal anaesthetic-decongestant sprays are commonly used prior to nasal instrumentation, such as flexible and rigid nasal endoscopy. Co-phenylcaine (lignocaine 5%, phenylephrine 0.5%, ENT Technologies Pty Ltd., Melbourne, VIC, Australia) is a combination spray commonly used for this purpose. However, lignocaine is less potent than other local anaesthetics, and both active constituents of Co-phenylcaine have a bitter taste. It was hypothesised that a combination spray containing tetracaine and oxymetazoline would both offer more potent topical anaesthesia and have a better taste. METHODS: Four anaesthetic-decongestant nasal sprays were tested in 10 healthy participants (Co-phenylcaine, and tetracaine 0.5%, 1% and 2% with oxymetazoline 0.05%). Sensory thresholds were sequentially measured at the head of the inferior turbinate using Semmes-Weinstein monofilaments over the following hour. Participants also rated taste on a Likert-style scale, and reported whether they experienced subjective numbness of the maxillary teeth. RESULTS: A median peak sensory threshold of 60 g (the maximum tested) was observed with Co-phenylcaine, but this threshold was exceeded by all the tetracaine-based sprays. Tetracaine 2% with oxymetazoline 0.05% had a significantly more rapid onset than Co-phenylcaine (4 min vs. 6 min, p < 0.05) and a longer duration of action. Eight participants reported dental numbness after administration of tetracaine 2% with oxymetazoline 0.05%, but only one participant after Co-phenylcaine. Tetracaine-based sprays were generally perceived to taste less unpleasant than Co-phenylcaine. CONCLUSION: Tetracaine 2% with oxymetazoline 0.05% is a more potent and rapidly acting anaesthetic-decongestant spray than Co-phenylcaine, with a longer duration of action.

Prophylactic phenylephrine infusion versus treatment with vasopressor bolus as needed during non-urgent cesarean delivery and neonatal acidemia: a retrospective cohort study (2016-2021).

INTRODUCTION: Prophylactic vasopressor administration reduces spinal hypotension during cesarean delivery, however the effects of vasopressor administration on neonatal acidemia remain uncertain. We examined the occurrence of neonatal acidemia in the setting of non-urgent cesarean delivery and compared outcomes between cases receiving prophylactic phenylephrine infusion versus cases treated with boluses of phenylephrine. METHODS: Retrospective cohort study with ethical approval, comparing non-urgent cesarean delivery cases performed under spinal anesthesia (2016 to 2021), receiving either prophylactic phenylephrine infusion or boluses as needed. Data were collected from anesthesia and labor ward electronic medical records. Records with missing pH or missing blood pressure data were excluded. The independent variable was prophylactic phenylephrine administration, a strategy implemented following international recommendations in 2018. The main outcome was neonatal acidemia, defined as umbilical artery pH < 7.1. The secondary outcome was maternal hypotension, defined as at least one systolic blood pressure (SBP) measurement below 100 mmHg or below 80% baseline. RESULTS: A total of 4392 patients were included in the final analysis; 1318 (30.0%) received prophylactic phenylephrine infusion. Neonatal acidemia (umbilical artery pH < 7.1) occurred in 28 (2.1%) cases receiving prophylactic phenylephrine versus 50 (1.6%) treated with boluses as needed (p = 0.188). Prophylactic phenylephrine infusion was not associated with occurrence of neonatal acidemia (aOR 0.83; 95% CI 0.52 to 1.33, p = 0.435). Prophylactic phenylephrine infusion was associated with a reduced spinal hypotension rate when defined as SBP < 100 mmHg (OR 0.47; 95% CI 0.37 to 0.57; p < 0.001), with similar results when hypotension was defined as a drop below 80% or 90% of baseline SBP. CONCLUSION: In this pragmatic study, prophylactic phenylephrine infusion was associated with a reduction in maternal spinal hypotension, but not reduced neonatal acidemia.

The common cold: The need for an effective treatment amid the FDA discussion on oral phenylephrine.

An episode of the common cold can have a significant negative impact on quality of life, mood, and daily activities. In line with this fact, there is a growing demand for health care and treatments associated with the common cold. Current treatments aim to (1) inhibit symptom severity and (2) shorten the duration of an episode of the common cold. These products include analgesics, antihistamines, and decongestants. In addition, various supplements, including vitamins, minerals, and herbs, are marketed to treat the common cold. The current products marketed for treating the common cold may reduce the severity of some (but not all) common cold symptoms, but they usually do not shorten the common cold episode. The recent indication that phenylephrine is not effective means that it will ultimately need to be removed from the over-the-counter monograph. Manufacturers will consequently need to reformulate their products and withdraw oral phenylephrine-containing products. Several newly developed common cold products are currently under investigation. These clinical trials should evaluate their efficacy and safety, as there remains a clear need for common cold products that significantly reduce both the symptom severity and the duration of episodes of the common cold.

Transpulmonary cardiac output with room temperature saline is accurate and tracks directional changes in anesthetized dogs.

OBJECTIVE: To assess the performance of transpulmonary thermodilution (TPTD) using room-temperature saline (CORT) and waveform-derived continuous CO (CCO) compared with TPTD using iced saline (COICED) as the indicator for measurements of CO in isoflurane-anesthetized dogs. METHODS: 8 Beagles aged 1 to 2 years (7.4 to 11.2 kg) were enrolled in this experimental study from March 21 to 31, 2023. Dogs were anesthetized with 0.01 mg/kg acepromazine, 5 to 6 mg/kg propofol, and isoflurane and were mechanically ventilated. Dogs were instrumented with a central venous catheter and a femoral arterial catheter equipped with a thermistor. The COICED, CORT, and pulse wave-derived CCO values were obtained at baseline, during infusions of phenylephrine and norepinephrine, and during blood withdrawal and replacement. Data were analyzed with a mixed effect model, Bland-Altman plots, and concordance. Percent error was calculated. P < .05 was used for significance. RESULTS: Data were collected from 8 dogs. Significant effects of time and the interaction of time and method were found. Bland-Altman plots showed negligible bias with limits of agreement between -0.35 and 0.25 L/min for CORT versus COICED and -1.23 and 1.15 L/min for CCO versus COICED. Percent errors were 17.7% and 66.6%, respectively. In the 4-quadrant plots, the concordance rate was 95% and 68% for measurements obtained with CORT and for CCO, respectively. CONCLUSIONS: Transpulmonary thermodilution using room temperature saline was accurate and able to track changes in CO. Continuous CO had a large percent error and low tracking ability. CLINICAL RELEVANCE: Transpulmonary thermodilution using room temperature saline is reliable for monitoring CO and obviates the need for iced preparations in clinical scenarios.

Increased packed cell volume alters point of care viscoelastic clotting parameters in horses.

BACKGROUND: Polycythaemia and coagulopathy are identified risk factors for non-survival in critically ill horses. Assessment of coagulation is recommended for critical care monitoring but may be affected by concurrent polycythaemia. OBJECTIVE: To evaluate the effects of induced polycythaemia on coagulation parameters as measured by a point-of-care viscoelastic coagulation device (VCM Vet™). STUDY DESIGN: Prospective interventional study. METHODS: Healthy adult horses (n = 7) were given 6 mcg/kg of phenylephrine IV over 15 min to induce transient polycythaemia. Samples for packed cell volume (PCV), total solids (TS), complete blood count (CBC), activated partial thromboplastin time (PTT), prothrombin (PT) and VCM Vet™ viscoelastic testing were collected at baseline (T0), 5 min (T1) and 2 h (T2) post-phenylephrine infusion. Splenic volume was measured by transabdominal ultrasonography. VCM Vet™ and plasma-based coagulation parameters, splenic volume and haematologic values were compared within and between time points. RESULTS: Splenic volume decreased from T0 (11.5 ± 4.8 L) to T1 (6.1 ± 2 L, p = 0.04) and returned to baseline volume by T2 (12.1 ± 3.9 L, p = 0.8), consistent with phenylephrine-induced splenic contraction. PCV increased from T0 (37% ± 4%) to T1 (56.3% ± 5.3%; p < 0.001) and returned to baseline at T2 (41.6% ± 3.6%; p = 0.1). A10 and A20 (amplitude at 10 and 20 min, VCM units) were decreased from T0 (12.6 ± 1.6, 18.9 ± 5) to T1 (5.4 ± 1.9, 7.6 ± 2.4; both p < 0.001) and remained lower than baseline at T2 (9.3 ± 2.1, 12.7 ± 3; both p = 0.01). PT and PTT remained within reference ranges with no significant difference over time (p = 0.5 and 0.09, respectively). PCV was negatively correlated with CFT (R = -0.61, p = 0.003), A10 (R = -0.9, p < 0.001) and A20 (R = -0.87, p < 0.001). MAIN LIMITATIONS: Small sample size, limited to healthy mares. CONCLUSIONS: Phenylephrine-induced polycythaemia was associated with hypocoagulable viscoelastic traces using the VCM Vet™ device without effect on plasma-based coagulation assessments or platelet number. Further investigation of viscoelastic testing is needed in horses with increased PCV due to clinical illness.

Reversal of Pharmacologically Induced Mydriasis with Phentolamine Ophthalmic Solution.

PURPOSE: Evaluate safety and efficacy of 0.75% phentolamine ophthalmic solution (POS), an alpha-1 antagonist, in reversal of pharmacologically induced mydriasis. DESIGN: Two Phase 3, multicenter, placebo-controlled, randomized, double-masked clinical trials in healthy subjects. SUBJECTS: 553 healthy 12 to 80 year old subjects were randomized 1:1 (MIRA-2) and 2:1 (MIRA-3) to receive either POS or placebo eye drops OU. METHODS: Subjects received POS or placebo administered 1 hour after mydriasis, induced by instillation of either 2.5% phenylephrine, 1% tropicamide, or Paremyd (1% hydroxyamphetamine / 0.25% tropicamide). MAIN OUTCOME MEASURES: Primary endpoint was percent of subjects returning to ≤0.2 mm greater than baseline pupil diameter in study eye at 90 minutes after POS administration. Safety measures included treatment-emergent adverse events (TEAEs) and tolerability measures, including conjunctival hyperemia. RESULTS: In MIRA-2, 185 subjects were randomized to treatment with placebo (94) or POS (91). In MIRA-3, 368 subjects were randomized to treatment with placebo (124) or POS (244). A statistically significant greater percentage of subjects treated with POS had study eyes that showed reversal of mydriasis at 90 minutes (primary endpoint) compared with the placebo treatment (48.9% vs 6.6% for MIRA-2; p<0.0001 and 58% VS 6% for MIRA-3; p<0.0001) and as early as 60 minutes (24.5% vs 5.5% for MIRA-2; p<0.0003 and 42% VS 2% for MIRA-3; p<0.0001). Between 28 to 34% of placebo-treated subjects had not returned to baseline PD at 24 hours following pharmacological dilation compared to 8 to 11% treated with POS (p<0.0001). CONCLUSION: POS treatment had a rapid onset in reducing PD within 60- to 90-minutes, with a statistically significant time savings of 3 to 4 hours to return to baseline PD compared to placebo. One or 2 drops of POS rapidly reversed mydriasis in all subjects regardless of mydriatic agent or iris color. More subjects receiving POS reported a perceived benefit in the resolution of visual symptoms caused by pharmacologically induced mydriasis compared to placebo, with statistically significant differences noted as early as 1 hour. The safety profile was favorable, with the most common adverse effects being mild transient conjunctival hyperemia (11.2%), instillation site discomfort (10.9%), and dysgeusia (3.6%).

Pharmacological characterization of alpha adrenoceptor-mediated motor responses in the rat colon.

BACKGROUND: Inhibitory neuromuscular transmission in the gastrointestinal tract is mediated by intrinsic nitrergic and purinergic neurons. Purines activate G protein-coupled receptor P2Y1 receptors, increasing intracellular Ca2+ that activates small conductance calcium-activated potassium (SKCa) channels. Little is known about the effect of adrenergic receptor activation on intestinal smooth muscle. In vascular tissue, stimulation of α-adrenoceptors causes smooth muscle contraction, while their effect on intestinal tissue is poorly understood. This study aimed to pharmacologically characterize the effect of α-adrenoceptor activation in the rat colon, which shares similar inhibitory pathways to the human colon. METHODS: Muscle bath experiments were performed with the rat proximal, mid, and distal colon oriented both circularly and longitudinally. RESULTS: The α1-adrenoceptor agonist phenylephrine (PE) (10-8-10-5 M) evoked concentration-dependent relaxations of the intestinal smooth muscle from all regions and orientations. However, in the mid-circular colon at low PE concentrations, a contraction sensitive to 10-5 M phentolamine (non-selective α-adrenoceptor blocker), the neural blocker tetrodotoxin (TTX; 10-6 M), and atropine (10-6 M) was recorded. PE-induced relaxations were insensitive to TTX (10-6 M) and the nonselective ß-adrenoceptor blocker propranolol (10-6 M). In contrast, PE-induced relaxations were blocked by phentolamine (10-5 M), prazosin (10-6 M) (α1-adrenoceptor blocker), and RS17053 (10-6 M) (α1A-blocker), but not by yohimbine (10-6 M) (α2-adrenoceptor blocker). Apamin (10-6 M), a SKCa channel blocker, abolished PE-induced relaxations. CONCLUSIONS: Contractile responses in the circular muscle of the mid colon could be attributed to α-adrenoceptors located on enteric cholinergic neurons. Stimulation of α1A-adrenoreceptors activates SKCa channels to cause smooth muscle relaxation, which constitutes a signaling pathway that shares similarities with P2Y1 receptors.

Endothelial α1-adrenergic receptor activation improves cardiac function in septic mice via PKC-ERK/p38MAPK signaling pathway.

Cardiomyopathy is particularly common in septic patients. Our previous studies have shown that activation of the alpha 1 adrenergic receptor (α1-AR) on cardiomyocytes inhibits sepsis-induced myocardial dysfunction. However, the role of cardiac endothelial α1-AR in septic cardiomyopathy has not been determined. Here, we identified α1-AR expression in mouse and human endothelial cells and showed that activation of α1-AR with phenylephrine (PE) improved cardiac function and survival by preventing cardiac endothelial injury in septic mice. Mechanistically, activating α1-AR with PE decreased the expression of ICAM-1, VCAM-1, iNOS, E-selectin, and p-p38MAPK, while promoting PKC and ERK1/2 phosphorylation in LPS-treated endothelial cells. These effects were abolished by a PKC inhibitor or α1-AR antagonist. PE also reduced p65 nuclear translocation, but this suppression is not blocked by PKC inhibition. Treatment with U0126 (a specific ERK1/2 inhibitor) reversed the effects of PE on p38MAPK phosphorylation. Our results demonstrate that cardiac endothelial α1-AR activation prevents sepsis-induced myocardial dysfunction in mice by inhibiting the endothelial injury via PKC-ERK/p38MAPK signaling pathway and a PKC-independent inhibition of p65 nuclear translocation. These findings offer a new perspective for septic patients with cardiac dysfunction by inhibiting cardiac endothelial cell injury through α1-AR activation.

Interaction of simultaneous hypoxia and baroreflex loading on control of sympathetic action potential subpopulations.

Efferent muscle sympathetic nerve activity (MSNA) is under tonic baroreflex control. The arterial baroreflex exerts the strongest influence over medium-sized sympathetic action potential (AP) subpopulations in efferent MSNA recordings. Prior work from multiunit MSNA recordings has shown baroreflex loading selectively abolishes the sympathetic response to hypoxia. The purpose of the study was to examine baroreflex control over different-sized AP clusters and characterize the neural recruitment strategies of sympathetic AP subpopulations with baroreflex and combined baroreflex/chemoreflex (i.e., hypoxia) activation. We loaded the arterial baroreceptors [intravenous phenylephrine (PE)] alone and in combination with systemic hypoxia ([Formula: see text] 80%) in nine healthy young men. We extracted sympathetic APs using the wavelet-based methodology and quantified baroreflex gain for individual AP clusters. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability versus diastolic blood pressure for 10 normalized clusters. Baroreflex loading with phenylephrine decreased MSNA and AP firing compared with baseline (all P < 0.05). However, the phenylephrine-mediated decrease in AP firing was lost with concurrent hypoxia (P = 0.384). Compared with baseline, baroreflex loading reduced medium-sized AP cluster baroreflex threshold slope (condition P = 0.005) and discharge probability (condition P < 0.0001); these reductions from baseline were maintained during simultaneous hypoxia (both P < 0.05). Present findings indicate a key modulatory role of the baroreceptors on medium-sized APs in blood pressure regulation that withstands competing signals from peripheral chemoreflex activation.NEW & NOTEWORTHY This study provides a novel understanding on baroreflex control of efferent sympathetic nervous system activity during competing stressors: baroreflex loading and peripheral chemoreflex activation. We show chemoreflex activation buffers baroreflex-mediated reductions in sympathetic nervous system activity. More importantly, baroreflex loading reduced baroreflex threshold gain of sympathetic action potential clusters and this reduction withstood chemoreflex activation. These data suggest the arterial baroreflex holds a primary regulatory role over medium-sized sympathetic neurons despite competing chemoreflex signals.

Efficacy and Safety of Perioperative Angiotensin II Versus Phenylephrine as a First-Line Continuous Infusion Vasopressor in Kidney Transplant Recipients.

INTRODUCTION: Angiotensin II (ATII) maintains blood pressure via RAAS with a beneficial adverse effect profile versus catecholamines and phenylephrine. Head-to-head data comparing ATII to phenylephrine are lacking regarding renal allograft function, hemodynamic efficacy, and safety within the perioperative period of kidney transplantation. METHODS: This single-center, retrospective study included adult kidney transplant recipients who received continuous infusions of ATII or phenylephrine within a 24-h perioperative period as a first-line vasopressor according to an institutional algorithm. The primary endpoint was allograft function. Secondary endpoints were hemodynamic efficacy and adverse effects. RESULTS: Among 105 patients, there was no significant difference in IGF (p = 0.545), SGF (p = 0.557), or DGF (p = 0.878) between patient cohorts. In the 34 patients with cold ischemia time (CIT) > 14-h, IGF was higher (p = 0.013) and DGF (p = 0.045) was lower in the ATII cohort versus phenylephrine. In all patients, ATII was associated with a decreased need for additional vasopressor agents (p < 0.001). Adverse effect profiles were similar between cohorts (p > 0.05). CONCLUSION: Among kidney transplant recipients, ATII may be a suitable first-line alternative compared with phenylephrine in the perioperative period for hypotension management with a reduced need for additional vasopressor support. Allograft benefits were observed in patients with prolonged CIT.

A Comparison of Norepinephrine versus Phenylephrine to Prevent Hypotension after Spinal Anesthesia for Cesarean Section: Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis aimed to compare the effects of using phenylephrine or norepinephrine on the pH and base excess (BE) of the umbilical artery and vein in parturients undergoing cesarean section. METHODS: The study protocol was registered in INPLASY. Independent researchers searched Ovid-Medline, Ovid-EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases and Google Scholar for relevant randomized controlled trials (RCTs). The primary outcome of this study was the umbilical artery (UA) or umbilical vein (UV) pH as neonatal condition at birth, and the secondary outcome was the UA or UV BE as an additional prognostic value over the measurement of umbilical pH. RESULTS: There was no evidence of a difference between phenylephrine and norepinephrine for overall, UA, and UV pH (mean difference (MD) -0.001, 95% confidence interval (CI) -0.004 to 0.007; MD 0.000, 95%CI -0.004 to 0.004; and MD 0.002, 95%CI -0.013 to 0.017). There was also no evidence of a difference between phenylephrine and norepinephrine for overall, UA, and UV BE (MD 0.096, 95% CI -0.258 to 0.451; MD 0.076, 95%CI -0.141 to 0.294; and MD 0.121, 95%CI; -0.569 to 0.811). A meta-regression showed that factors such as umbilical artery or vein, infusion method, single or twin, and the number of parturients per study had no effect on the UA pH, UV pH, UA BE, or UV BE. No evidence of publication bias was detected. CONCLUSIONS: There was no evidence of a difference between phenylephrine and norepinephrine for umbilical pH and BE. A subgroup analysis and meta-regression also did not show evidence of differences.

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

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

Dropless Cataract Surgery: The Effect of Intracameral Phenylephrine/Ketorolac Infusion as a Single Agent on Postoperative Outcomes.

Objective The objective of this study was to assess the feasibility of using an intracameral phenylephrine/ketorolac infusion during cataract surgery as a single agent to prevent postoperative pain, inflammation, and other complications. Methods A prospective, single-group feasibility study was conducted in which phenylephrine/ketorolac infusion was administered during cataract surgery and no perioperative topical drops were initially prescribed. Patients underwent optical coherence tomography, corrected distance visual acuity testing, and slit lamp biomicroscopy examination at perioperative visits, during which they also reported symptoms of pain, irritation, and/or photophobia. A goal adverse event (AE) rate was set at ≤5.0%. Results A total of 94 eyes (60 patients) were included in this study. The AE rate was 13.8% (13/94 eyes) with pain/irritation in eight eyes, cystoid macular edema (CME) in three eyes, and corneal edema in three eyes. Conclusions Based on an AE rate goal of ≤5.0%, using intraoperative, intracameral phenylephrine/ketorolac alone was not deemed a feasible alternative to current postoperative eye drop regimens in our clinical setting. However, a 13.8% AE rate is comparable to the rates of postoperative CME, corneal edema, pain, and irritation in the published literature. Thus, more research is needed to truly define this approach as inferior or non-inferior to the current standard of care.

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

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

A retrospective study of the effects of a vasopressor bolus on systolic slope (dP/dt) and dynamic arterial elastance (Eadyn).

BACKGROUND: To enhance the utility of functional hemodynamic monitoring, the variables systolic slope (dP/dt) and dynamic arterial elastance (Eadyn) are calculated by the Hypotension Prediction Index (HPI) Acumen® Software. This study was designed to characterize the effects of phenylephrine and ephedrine on dP/dt and Eadyn. METHODS: This was a retrospective, non-randomized analysis of data collected during two clinical studies. All patients required intra-operative controlled mechanical ventilation and had an indwelling radial artery catheter connected to an Acumen IQ sensor. Raw arterial pressure waveform data was downloaded from the patient monitor and all hemodynamic measurements were calculated off-line. The anesthetic record was reviewed for bolus administrations of either phenylephrine or ephedrine. Cardiovascular variables prior to drug administration were compared to those following vasopressor administrations. The primary outcome was the difference for dP/dt and Eadyn at baseline compared with the average after the bolus administration. All data sets demonstrated non-normal distributions so statistical analysis of paired and unpaired data followed the Wilcoxon matched pairs signed-rank test or Mann-Whitney U test, respectively. RESULTS: 201 doses of phenylephrine and 100 doses of ephedrine were analyzed. All data sets are reported as median [95% CI]. Mean arterial pressure (MAP) increased from 62 [54,68] to 78 [76,80] mmHg following phenylephrine and from 59 [55,62] to 80 [77,83] mmHg following ephedrine. Stroke volume and cardiac output both increased. Stroke volume variation and pulse pressure variation decreased. Both drugs produced significant increases in dP/dt, from 571 [531, 645] to 767 [733, 811] mmHg/sec for phenylephrine and from 537 [509, 596] to 848 [779, 930] mmHg/sec for ephedrine. No significant changes in Eadyn were observed. CONCLUSION: Bolus administration of phenylephrine or ephedrine increases dP/dt but does not change Eadyn. dP/dt demonstrates potential for predicting the inotropic response to phenylephrine or ephedrine, providing guidance for the most efficacious vasopressor when treating hypotension. TRIAL REGISTRATION: Data was collected from two protocols. The first was deemed to not require written, informed consent by the Institutional Review Board (IRB). The second was IRB-approved (Effect of Diastolic Dysfunction on Dynamic Cardiac Monitors) and registered on ClinicalTrials.gov (NCT04177225).

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

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

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

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

Vasoconstriction with phenylephrine increases cardiac output in preload dependent patients.

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

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

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