Intraoperative Use of Phenylephrine versus Ephedrine and Postoperative Delirium: A Multicenter Retrospective Cohort Study.

BACKGROUND: The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. The hypothesis was that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium. METHODS: A total of 103,094 hospitalized adults undergoing general anesthesia for noncardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within 7 days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied. RESULTS: Between the two healthcare networks, 78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery; 770 patients (0.8%) developed delirium within 7 days. The median (interquartile range) total intraoperative dose of phenylephrine was 1.0 (0.2 to 3.3) mg and 10.0 (10.0 to 20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within 7 days (adjusted odds ratio, 1.35; 95% CI, 1.06 to 1.71; and adjusted absolute risk difference, 0.2%; 95% CI, 0.1 to 0.3%; P = 0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence, 3.2%; adjusted odds ratio, 1.88; 95% CI, 1.49 to 2.37; P < 0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient, 0.08; 95% CI, 0.02 to 0.14; P = 0.013, per each µg/kg increase in the cumulative phenylephrine dose). CONCLUSIONS: The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on these data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.

The effects of mydriatic eye drops on cerebral blood flow and oxygenation in retinopathy of prematurity examinations.

Mydriatic eye drops used during retinopathy examination have been associated with cardiovascular, respiratory, and gastrointestinal side effects. The aim of our study was to investigate the effects of the drops used for pupil dilatation on cerebral blood flow and cerebral oxygenation. The study included 62 infants who underwent retinopathy screening exams. Vital signs, heart rate (HR), arterial oxygen saturation (SpO2), and mean arterial pressure (MAP) were recorded. Cerebral oxygenation and middle cerebral artery blood flow velocity were evaluated using near-infrared spectroscopy (NIRS) and Doppler ultrasonography, respectively, and the cerebral metabolic rate of oxygen (CMRO2) was also calculated. The mean gestational age of the infants included was 31.29 ± 1.42 weeks, and the mean birth weight was 1620 ± 265 g. Heart rate was found to be significantly decreased after mydriatic eye drop instillation; however, there were no significant differences regarding blood pressure and oxygen saturation levels (HR: p < 0.001; MAP: p = 0.851; SpO2: p = 0.986, respectively). After instillation while cerebral regional oxygen saturation (rScO2) measurements were significantly decreased at the 60th minute (p = 0.01), no significant difference was found in Vmax and Vmean of MCA before and after mydriatic eye drop instillation (p = 0.755, p = 0.515, respectively). Regarding CMRO2 measurements, we also did not find any statistical difference (p = 0.442).    Conclusion: Our study has shown that although eye drops may affect heart rate and regional cerebral oxygen saturation, they do not alter cerebral blood flow velocities and metabolic rate of oxygen consumption. Current recommendations for mydriatic eye drop use in retinopathy exam appear to be safe. What is Known: • Mydriatic eye drop installation is recommended for pupil dilatation during ROP screening exams. • It's known that mydriatics used in ROP examination have affects on the vital signs, cerebral oxygenation and blood flow. What is New: • This is the first study evaluating the changes in cerebral oxygenation and blood flow velocity after mydriatic drop instillation using NIRS and Doppler US concomitantly. • While the eye drops may affect heart rate and regional cerebral oxygen saturation, they do not alter cerebral blood flow velocities and metabolic rate of oxygen consumption.

Incidence of bradycardia during noradrenaline or phenylephrine bolus treatment of postspinal hypotension in cesarean delivery: A randomized double-blinded controlled trial.

The treatment of choice for spinal anesthesia-induced hypotension during cesarean section is phenylephrine. As this vasopressor can cause reflex bradycardia, noradrenaline is a suggested alternative. This randomized double-blinded controlled trial included 76 parturients undergoing elective cesarean delivery under spinal anesthesia. Women received noradrenaline in bolus doses of 5 mcg or phenylephrine in bolus doses of 100 mcg. These drugs were used intermittently and therapeutically to maintain systolic blood pressure ≥ 90% of its baseline value. The primary study outcome was bradycardia incidence (<60 bpm) with intermittent bolus administration of these drugs. Secondary outcomes included extreme bradycardia (<40 bpm), number of bradycardia episodes, hypertension (systolic blood pressure > 120% of baseline value), and hypotension (systolic blood pressure < 90% of baseline value and requiring vasopressor use). Neonatal outcomes per the Apgar scale and umbilical cord blood gas analysis were also compared. The incidence of bradycardia in both groups (51.4% and 70.3%, respectively; p = 0.16) were not significantly different. No neonates had umbilical vein or artery pH values below 7.20. The noradrenaline group required more boluses than phenylephrine group (8 vs. 5; p = 0.01). There was no significant intergroup difference in any of the other secondary outcomes. When administered in intermittent bolus doses for the treatment of postspinal hypotension in elective cesarean delivery, noradrenaline, and phenylephrine have a similar incidence of bradycardia. When treating hypotension related to spinal anesthesia in obstetric cases, strong vasopressors are commonly administered, thought these can also have side effects. This trial assessed bradycardia after bolus administration of noradrenaline or phenylephrine, and found no difference in risk for clinically meaningful bradycardia.

Prevention of spinal hypotension during cesarean section: A systematic review and Bayesian network meta-analysis based on ephedrine, phenylephrine, and norepinephrine.

AIM: The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine, phenylephrine, and norepinephrine for the prevention of spinal hypotension during cesarean section. METHODS: The Web of Science, PubMed, EMBASE, Cochrane Library were searched until to May 20, 2022. The indicators included incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, umbilical artery pH, and Apgar scores. RESULTS: About 3125 related records were obtained and 17 RCTs met our eligibility criteria. Based on the results, prophylactic bolus injection of 21-30 mg ephedrine (82%) was the best efficacious option for preventing hypotension, followed by 13-16 µg norepinephrine and 81-120 mg phenylephrine; 121-150 µg phenylephrine had the highest probability (62%) caused reactive hypertension, followed by 11-30 mg ephedrine; phenylephrine was most likely to cause bradycardia in a dose-dependent manner; 81-120 µg phenylephrine had the highest probability (37%) which associated with IONV; 6-12 µg norepinephrine (31%) had the lowest influence on IONV and had highest probability (34%) associated with improving umbilical arterial pH; 13-16 µg norepinephrine had highest probability (67% at 1 min, 49% at 5 min) which associated with improving Apgar scores. CONCLUSIONS: Based on this study, 5-10 mg ephedrine and 13-16 µg norepinephrine prophylactic bolus injection may be the optimum dosage of three drugs prevent spinal-induced hypotension, which has the least impact on maternal and neonatal outcomes.

The safety and efficacy of push dose vasopressors in critically ill adults.

PURPOSE: To evaluate practice patterns, efficacy, and safety of push dose pressors (PDP) in critically ill patients outside of the operating room (OR) at a large academic medical center. MATERIALS AND METHODS: This was a single-center, retrospective cohort study (June 2018 to July 2020) conducted at a 1273-bed academic medical center. The primary outcome was efficacy, defined as a 25% increase in systolic blood pressure, and the cohort was analyzed according to PDP response (i.e. responders versus non-responders). A logistic regression model was used to assess predictors of response to PDPs. Safety outcomes included the incidence of hypertension, bradycardia, and tachycardia. RESULTS: 1727 patients were included in the final analysis. The median doses of phenylephrine and epinephrine administered were 400 µg (IQR 200-888 µg) and 50 µg (IQR 20-100 µg). The primary outcome was achieved in 102 (71.8%) patients in the epinephrine group and 1140 (55.9%) of patients in the phenylephrine group. Adverse effects after PDP receipt were minimal, with the most common being hypertension in 6.6% and 13.4% of the phenylephrine and epinephrine groups respectively. CONCLUSIONS: This study demonstrates that PDP phenylephrine and epinephrine are safe and efficacious in treating the acute hypotensive period.

Comparison of push-dose phenylephrine and epinephrine in the emergency department.

BACKGROUND: There is limited evidence to support the efficacy and safety of push-dose vasopressor (PDP) use outside of the operating room (OR). Specifically, there are few head-to-head comparisons of different PDP in these settings. The purpose of this study was to compare the efficacy and safety of push-dose phenylephrine (PDP-PE) and epinephrine (PDP-E) in the Emergency Department (ED). METHODS: This retrospective, single-center study evaluated adults given PDP-PE or PDP-E in the ED from May 2017 to November 2020. The primary outcome was a change in heart rate (HR). Secondary outcomes included changes in blood pressure, adverse effects, dosing errors, fluid and vasopressor requirements, ICU and hospital lengths of stay (LOS), and in-hospital mortality. RESULTS: Ninety-six patients were included in the PDP-PE group and 39 patients in the PDP-E group. Median changes in HR were 0 [-7, 6] and - 2 [-15, 5] beats per minute (BPM) for PDP-PE and PDP-E, respectively (p = 0.138). PDP-E patients had a greater median increase in systolic blood pressure (SBP) (33 [24, 53] vs. 26 [8, 51] mmHg; p = 0.049). Dosing errors occurred more frequently in patients that received PDP-E (5/39 [12.8%] vs. 2/96 [2.1%]; p = 0.021). PDP-E patients more frequently received continuous epinephrine infusions before and after receiving PDP-E. There were no differences in adverse effects, fluid requirements, LOS, or mortality. CONCLUSION: PDP-E provided a greater increase in SBP compared to PDP-PE. However, dosing errors occurred more frequently in those receiving PDP-E. Larger head-to-head studies are necessary to further evaluate the efficacy and safety of PDP-E and PDP-PE.

Acute drug reaction to phenylephrine and tropicamide collyrium in a late-preterm newborn: a case report.

BACKGROUND: Collyrium administration is a common procedure in the neonatal ward, both in preterm and at term babies. Various molecules are used to induce mydriasis and cycloplegia: among them, phenylephrine and tropicamide are the most popular, and their administration is generally considered safe. CASE PRESENTATION: A 35 + 2 weeks-old, 2510 g, well-appearing male newborn required an ophthalmologic evaluation after a doubtful red reflex test. A collyrium with 1% phenylephrine and 0.95% tropicamide was administered prior to the consult, one drop per eye. Two minutes after the administration, the baby developed a severe apnea that required tactile stimulation. Moreover, the area around his eyes became visibly pale. Three minutes later, the baby became severely bradycardic (59 bpm), but remained in good general condition, so that resuscitation maneuvers were not required. Bradycardia lasted for almost three hours and then gradually resolved. CONCLUSIONS: Cardiopulmonary manifestations, such as bradycardia and even cardiopulmonary arrest, are severe complications that can happen after phenylephrine collyrium administration in preterm newborns. However, they have been described in babies below 1500 g or with concurrent respiratory manifestations. Our patient, on the other hand, was late preterm, and never required a ventilatory support prior to the collyrium administration. Practitioners who deal with premature babies, even if late preterm, must be aware of these possible complications and administer phenylephrine collyrium carefully, where cardiopulmonary resuscitation equipment and personnel are available.

A randomized comparison of hemodynamic changes in response to a heart rate-dependent phenylephrine/ephedrine protocol versus ephedrine-only for spinal hypotension during elective cesarean section.

AIM: To compare incidences of abnormal heart rate (HR) between the phenylephrine/ephedrine protocol (P/E protocol) against the ephedrine-only (C) protocol, conventionally used for treating predelivery hypotension following spinal anesthesia for cesarean section. METHODS: Two hundred and sixty-eight parturients with pre-delivery hypotension after spinal anesthesia were equally randomized to (1) Group P/E (n = 134), phenylephrine 100 mcg in 10 mL intravenously if HR ≥ 60 beats/min (bpm), or ephedrine 6 mg intravenously if HR < 60 bpm, and 2) Group C (n = 134). The primary outcome was the incidence of the parturients with abnormal HR after vasopressor administration. The secondary outcome was the mean differences of HR and hypotensive periods during the pre-delivery period. RESULTS: There was no significant difference of between-group incidences of bradycardia (12.0% in Group P/E vs 6.7% in Group C, p = 0.136) and tachycardia (26.9% vs 35.8%, p = 0.114). Mean HR was 81.9 bpm (95% confidence interval [CI] 79.9, 84.3) in Group P/E, and 88.8 bpm (86.8, 90.6) in Group C (p < 0.001). The duration of hypotension in relation to the time interval from spinal anesthesia to delivery was 20.9% (95% CI 18.4-23.2) in Group P/E, and 26.5% (23.9-29.3) in Group C (p < 0.01). The calculated area under the curve (AUC) of abnormal HR in relation to time was significantly reduced only in Group P/E (p < 0.010). CONCLUSIONS: The incidences of out-of-range HR were comparable, but the P/E protocol resulted in a lower mean HR and better control of systolic blood pressure than the ephedrine-only protocol.

A Survey of Neonatal Nurses on Mydriatic Regimens Used in Neonatal Retinopathy of Prematurity Eye Examinations.

OBJECTIVE: This study was aimed to determine mydriatic regimen(s) used in neonatal units in Aotearoa, New Zealand (NZ), and Australia and to estimate the frequency of adverse drug events following mydriatic administration in preterm neonates. STUDY DESIGN: A cross-sectional survey was sent to neonatal nursing staff listed in the Australian and New Zealand Neonatal Network contact list. Participants were asked to state what mydriatic regimen they use, and to estimate the frequency of adverse drug events when eye drops were administered for retinopathy of prematurity eye examinations (ROPEE). RESULTS: Thirteen different mydriatic regimens were identified; phenylephrine 2.5% and cyclopentolate 0.5% (1 standard drop of each) was the most commonly used regimen. Two of the regimens exceeded adult doses and five regimens included a mydriatic that is equivalent to an adult dose. Following mydriatic instillation, the three most common adverse effects were apnea, tachycardia, and periorbital pallor. CONCLUSION: Low-concentration single-microdrop regimens are currently in use and resulting in successful ROPEE, yet doses exceeding adult doses are in use throughout Aotearoa, NZ, and Australian units. We know from this dataset that neonates are experiencing unwanted and potentially preventable, adverse effects associated with mydriatics, and every effort should be made to minimize this risk. KEY POINTS: · Thirteen different regimens are in use in Aotearoa, NZ, and Australia.. · Three regimens use doses in excess of adult doses.. · Phenylephrine 2.5% and cyclopentolate 0.5% (one standard drop of each) is the most common regimen.

Neonatal outcomes following prophylactic administration of phenylephrine or noradrenaline in women undergoing scheduled caesarean delivery: A randomised clinical trial.

BACKGROUND: There is limited evidence to support the use of noradrenaline over phenylephrine during elective caesarean section with regards to its impact on foetal acidosis. Concerns regarding a deleterious effect of noradrenaline on foetal blood gas analysis because of its ß-mimetic activity cannot currently be ruled out by data from randomised controlled trials. OBJECTIVE: We hypothesised that noradrenaline would be associated with higher umbilical artery base excess values and less foetal acidosis compared with phenylephrine. This study aimed to observe the effect of prophylactic infusions of phenylephrine or noradrenaline in low-risk elective caesarean delivery on umbilical artery blood gas analysis. DESIGN: A prospective, randomised, double-blind trial. SETTING: Labour room operating theatre of tertiary care hospital in Northern India from April 2020 to November 2020. PATIENTS: Full-term, nonlabouring pregnant women, scheduled for elective caesarean delivery under spinal anaesthesia. INTERVENTION: Equipotent prophylactic infusions of either phenylephrine 100 µg min-1 or noradrenaline 5 µg min-1 were administered to maintain maternal SBP between 90 and 110% of baseline using a predefined algorithm. MAIN OUTCOME MEASURE: The primary outcome was umbilical artery base excess in noradrenaline versus the phenylephrine group. The incidence of foetal acidosis defined as umbilical artery base excess less than -6 mmol l-1 was also assessed for noradrenaline versus phenylephrine. RESULTS: Median [IQR] umbilical artery base excess was significantly higher in the noradrenaline group: -5.4 [-6.6 to -4.03] versus -6.95 [-9.02 to -4.53] in the phenylephrine group (P = 0.014). No significant difference in the incidence of foetal acidosis was observed between noradrenaline and phenylephrine groups: 36 versus 54% (P 0.07); difference 18% (95% CI, -1.4 to 35.6%). CONCLUSION: Prophylactic noradrenaline 5 µg min-1 infusion resulted in higher base excess values compared with phenylephrine 100 µg min-1 infusion. A comparable incidence of foetal acidosis was observed in women receiving either noradrenaline or phenylephrine. Maternal bradycardia was more pronounced with phenylephrine while targeting blood pressure goals. CTRI: CTRI/2020/03/023986.

Metformin suppresses phenylephrine-induced hypertrophic responses by inhibiting p300-HAT activity in cardiomyocytes.

INTRODUCTION: Heart failure is the final pathway for a wide spectrum of myocardial stress, including hypertension and myocardial infarction. However, the potential effects of metformin on cardiac hypertrophy are still unclear. PURPOSE: The purpose of this study was to investigate whether metformin leads to suppression of hypertrophic responses in cardiomyocytes. METHODS AND RESULTS: To investigate whether metformin inhibited p300-histone acetyltransferase (HAT), we performed an in vitro HAT assay. Metformin directly inhibited p300-mediated acetylation of histone-H3K9. To examine the effects of metformin on hypertrophic responses, cardiomyocytes prepared from neonatal rats were treated with metformin and stimulated with saline or phenylephrine (PE), a α1-adrenergic agonist for 48 h. PE stimulus showed an increase in cell size, myofibrillar organization, expression of the endogenous atrial natriuretic factor and brain natriuretic peptide genes, and acetylation of histone-H3K9 compared with saline-treated cells. These PE-induced changes were inhibited by metformin. Next, to examine the effect of metformin on p300-mediated hypertrophy, cardiomyocytes were transfected with expression vector of p300. Metformin significantly suppressed p300-induced hypertrophic responses and acetylation of histone-H3K9. CONCLUSIONS: The study demonstrates that metformin can suppress PE-induced and p300-mediated hypertrophic responses. Metformin may be useful for the treatment of patients with diabetes and heart failure.

Unilateral mydriasis following septoplasty with inferior turbinate reduction.

Nasal septoplasty and inferior turbinate reduction are common procedures performed in the treatment of nasal obstruction. These procedures are generally considered to be safe with minimal reported complications. Herein, we describe a case of a 43-year-old female who developed transient unilateral mydriasis following septoplasty with inferior turbinate reduction, likely due to the sympathomimetic agents used for vasoconstriction and mucosal decongestion.

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

BACKGROUND: Phenylephrine 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. OBJECTIVE: To evaluate the safety of bronchoscopic instillation of phenylephrine during bronchoscopy. METHODS: We 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. RESULTS: We 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. CONCLUSION: In 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.

Dose-Response Study of 4 Weight-Based Phenylephrine Infusion Regimens for Preventing Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia.

BACKGROUND: Prophylactic IV infusion of phenylephrine has been recommended to prevent hypotension during spinal anesthesia for cesarean delivery. However, the optimal infusion dose is unknown. This study aimed to determine the infusion dose of phenylephrine that would be effective in preventing hypotension in 50% (ED50) and 90% (ED90) of patients when administered as a prophylactic infusion at a fixed rate based on the individual body weight. METHODS: Eighty parturients scheduled for elective cesarean delivery were randomly allocated to receive IV infusion of prophylactic phenylephrine at 0.25, 0.375, 0.5, or 0.625 µg/kg/min (n = 20 per group) started immediately after intrathecal injection of 10 mg hyperbaric bupivacaine and 5 µg sufentanil using a combined spinal-epidural technique. An effective dose was defined by the occurrence of no hypotension (defined as a decrease in systolic blood pressure by ≥20% below baseline and to <90 mm Hg) during the interval from the initiation of spinal anesthesia to delivery of the infant. Values for ED50 and ED90 of prophylactic phenylephrine were calculated using probit analysis. RESULTS: Hypotension occurred in 13/20, 8/20, 2/20, and 1/20 patients in the groups that received phenylephrine infusion at 0.25, 0.375, 0.5, or 0.625 µg/kg/min, respectively. The calculated values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively. No difference was found in the incidence of adverse effects and neonatal outcomes among groups. CONCLUSIONS: Under the conditions of this study, when phenylephrine was given as a fixed-rate prophylactic infusion during spinal anesthesia for cesarean delivery to prevent hypotension, the values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively.

Push dose pressors: Experience in critically ill patients outside of the operating room.

PURPOSE: Evaluate push dose vasopressor (PDP) practice patterns, efficacy, and safety in critically ill patients. METHODS: Critically ill patients receiving phenylephrine or ephedrine PDP from November 2015-March 2017 were included. Patient demographics, medication administration details, vital signs pre- and post-administration, adverse effects, and medications errors were collected. Descriptive data are presented and comparisons were made with paired samples t-test, Wilcoxon Rank Sum and Chi-squared analysis or Fisher's Exact Test as appropriate. RESULTS: A total of 146 patients (155 PDP events) were included; mean age 64.5 ±â€¯13.3 years and 66.4% males, respiratory failure (39.8%) or sepsis (24.9%) admission diagnosis. The surgical intensive care unit (ICU) (44.5%) and medical ICU (33.6%) used PDPs most often, and during the peri-intubation period (57.3%) or for other transient hypotension (38.2%). Following PDP, mean systolic blood pressure (BP), diastolic BP, and heart rate (HR) increased 32.5% (80 to 106 mmHg), 27.2% (48 to 61 mmHg), and 6.4% (93 to 99 bpm), respectively. There were 17 (11.6%) adverse events; most often related to excessive increases in BP or HR and one incidence of dysrhythmia. Thirteen patients (11.2%) had a dose related medication error (phenylephrine dose >200 µg or ephedrine dose >25 mg), nine (6.2%) received PDP with normal/elevated hemodynamics (systolic BP > 100 mmHg or HR > 160 bpm) and 15% while on a continuous infusion vasopressor. CONCLUSION: PDPs were used in a variety of patient diagnoses and for select indications. Overall, they were efficacious but associated with adverse drug events and medication errors.

Efficiency and safety of phenylephrine and tropicamide used in premature retinopathy: a prospective observational study.

BACKGROUND: To determine effects and side effects of topical application of phenylephrine 2.5% and tropicamide 0.5% combination in preterm infants. METHODS: In this prospective observational study, 60 infants undergoing retinopathy of prematurity (ROP) screening were prospectively observed. Pupillary diameter, blood pressure, heart rate, and oxygen saturation were monitored before and after up to 24 h during ROP screening examinations. RESULTS: The mean pupillary diameter 1 h after the instillation of drops was 5.58 ± 0.75 mm for both eyes. The mean systolic and diastolic pressure and oxygen saturation of infants did not change statistically until the end of the study. The average heart rate decreased by a mean of 4.96 beats/minute from the baseline following eye drops instillation. General condition deterioration, fall in oxygen saturation and bradycardia were observed in 4 infants that already had respiratory distress syndrome. CONCLUSION: The phenylephrine 2.5% plus tropicamide 0.5% drop is effective and safe as mydriatic combination for retinopathy of prematurity screening. In infants with an additional systemic disease such as respiratory distress syndrome, the side effects of mydriatic drops may be more common. Such babies should be kept under close observation. TRIAL REGISTRATION: The trial was retrospectively registered on 28 February 2018. The ClinicalTrials.gov Identifier is NCT03448640.

Allergic contact dermatitis to phenylephrine eye drops in an infant.

Ophthalmic medications used for diagnostic or therapeutic purposes are common causes of allergic contact dermatitis around the eyes. We report a case of periocular allergic contact dermatitis due to tropicamide and phenylephrine eye drops in a 1-year-old infant.

Morphological Stages of Mitochondrial Vacuolar Degeneration in Phenylephrine-Stressed Cardiac Myocytes and in Animal Models and Human Heart Failure.

Background and objectives: Derangements in mitochondrial integrity and function constitute an important pathophysiological feature in the pathogenesis of heart failure (HF) and play an important role in myocardial remodeling and systolic dysfunction. In systolic HF, we and others have shown an imbalance in mitochondrial dynamics toward mitochondrial fission and fragmentation with evidence of mitophagy, mitochondrial vacuolar degeneration, and impairment in mitochondrial oxidative capacity. The morphological stages of mitochondrial vacuolar degeneration have not been defined. We sought to elucidate the progressive stages of mitochondrial vacuolar degeneration, which would serve as a measure to define, morphologically, the severity of mitochondrial damage. Materials and Methods: Transmission electron microscopy was used to study mitochondrial morphology and pathology in phenylephrine-stressed cardiac myocytes in vitro and in left ventricular myocardium from a rat model of pressure overload induced systolic dysfunction and from patients with systolic HF. Results: In phenylephrine-stressed cardiomyocytes for two hours, alterations in mitochondrial cristae morphology (Stage A) and loss and dissolution of mitochondrial cristae in one (Stage B) or multiple (early Stage B→C) mitochondrion area(s) were evident in the earliest stages of mitochondrial vacuolar degeneration. Mitochondrial swelling and progressive dissolution of mitochondrial cristae (advanced Stage B→C), followed by complete loss and dissolution of mitochondrial cristae and permeabilization and destruction of inner mitochondrial membrane (Stage C) then outer mitochondrial membrane rupture (Stage D) constituted advanced stages of mitochondrial vacuolar degeneration. Similar morphological changes in mitochondrial vacuolar degeneration were seen in vivo in animal models and in patients with systolic HF; where about 60-70% of the mitochondria are mainly observed in stages B→C and fewer in stages C and D. Conclusion: Mitochondrial vacuolar degeneration is a prominent mitochondrial morphological feature seen in HF. Defining the progressive stages of mitochondrial vacuolar degeneration would serve as a measure to assess morphologically the severity of mitochondrial damage.

Phenylephrine infusion impact on surgical site infections after lower extremity bypass surgery.

OBJECTIVE: Lower extremity bypass (LEB) operations have high rates of surgical site infections (SSI). Phenylephrine is a commonly used vasoconstrictor which may reduce skin blood flow and increase the likelihood of SSI in these patients. We studied the potential effect of phenylephrine infusion during LEB surgery on SSI. METHODS: LEB cases and their demographic data were identified through the Vascular Quality Initiative registry. SSI in this population was identified using the hospital epidemiology surveillance database. Phenylephrine use in this population was identified through chart review. RESULTS: We identified 699 patients who underwent LEB; 82 (11.7%) developed an SSI, and 244 of 698 (35.0%) were treated with phenylephrine infusion. In bivariate analysis, higher body mass index (28.8 kg/m2 vs 27.3 kg/m2; P = .034), diabetes (14.6% vs 9.4%; P = .035), hypertension (12.6% vs 4.7%; P = .038), groin incision (13.2 vs 5.4%; P = .013) and longer procedure times (17.1% for >220 minutes and 8.9% for ≤220 minutes; P = .003) were associated with higher rates of SSI. Whereas phenylephrine infusion exhibited a trend toward a higher rate (14.8% vs 9.9%; P = .057). In the logistic regression model, diabetes (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0-3.2; P = .032), total procedure time (OR, 1.85; 95% CI, 1.1-3.1; P = .026) and vertical groin incision (OR, 2.6; 95% CI, 1.1-6.5; P = .035) were independent predictors of increased SSI rates, whereas body mass index (OR, 1.04; 95% CI, 0.99-1.08; P = .09), hypertension (OR, 2.5; 95% CI, 0.6-10.9; P = .22), and phenylephrine infusion (OR, 1.08; 95% CI, 0.63-1.85; P = .78) were not independent predictors of increased SSI rates. CONCLUSIONS: Phenylephrine infusion did not increase the risk of SSI in patients who underwent LEB.

SOX2-mediated inhibition of miR-223 contributes to STIM1 activation in phenylephrine-induced hypertrophic cardiomyocytes.

Stromal interaction molecule 1 (STIM1) is the key molecule responsible for store-operated Ca2+ entry (SOCE). Numerous studies have demonstrated that STIM1 levels appeared to be enhanced during cardiac hypertrophy. However, the mechanism underlining this process remains to be clarified. In this study, phenylephrine (PE) was employed to establish a model of hypertrophic neonatal rat cardiomyocytes (HNRCs) in vitro, and low expression of primary and mature miR-223 was detected in PE-induced HNRCs. Our results have revealed that downregulation of miR-223 by PE contributed to the increase of STIM1, which in turn induced cardiac hypertrophy. As expected, overexpression of miR-223 could prevent the increase in cell surface and reduce the mRNA levels of ANF and BNP in cardiomyocytes. To address the mechanism triggering downregulation of miR-223 under PE, we demonstrated that PE-induced inhibition of GSK-3ß activity led to the activation of ß-catenin, which initiates the transcription of SOX2. Increased expression of SOX2 occupied the promoter region of primary miR-223 and suppressed its transcription. Therefore, miR-223 appears to be a promising candidate for inhibiting cardiomyocyte hypertrophy, and miR-223/STIM1 axis might be one of interesting targets for the clinical treatment of hypertrophy.