Intracameral phenylephrine for surgical mydriasis and intraoperative floppy-iris syndrome: systemic adverse effects and optimal dose.

Phenylephrine, a potent sympathomimetic, induces mydriasis via iris dilator muscle contraction. Intracameral (IC) phenylephrine has been successfully used in cataract surgery for initial mydriasis, maintaining mydriasis, and management of intraoperative floppy-iris syndrome. Serious systemic adverse events (mainly cardiovascular) have been described with topical phenylephrine drops, but we found very little evidence of such adverse events associated with IC phenylephrine use. However, we suspect under-reporting of such adverse events, as they may instead be ascribed to anxiety, positioning, anesthesia, etc. Optimal dosage/concentrations for IC phenylephrine use in different purposes have not been fully studied. In the absence of robust evidence, we suggest that lower but effective IC phenylephrine concentrations are used: a lower concentration (0.31%), in conjunction with an anticholinergic and lidocaine, may be used for initial mydriasis. For management of intraoperative floppy-iris syndrome, 0.31% may be effective, though a higher concentration (1% to 1.25%) may be required.

A Routine over the Counter Phenylephrine Causing Rarer Drug Eruption as Adverse Drug Reaction - A Case Report.

BACKGROUND: Phenylephrine is a sympathomimetic, which means it acts analogous to adrenaline. Phenylephrine can be taken orally to treat nasal congestion symptoms. It is also frequently mixed with other medicines in products meant to relieve cough and cold symptoms. Given the widespread usage of phenylephrine, related drug eruptions appear to be uncommon. CASE PRESENTATION: Here we discuss a case of a 19-year-old female patient who reported to our hospital with blebs on the skin throughout her legs and torso. The drug eruption or adverse drug response was linked with itching, had a slow beginning, and progressed. Her medical history indicated that she had been taking phenylephrine 10 mg orally twice a day. On the sixth day, she experienced an adverse medication response caused by the medicine phenylephrine. Phenylephrine was stopped immediately and the other medications, such as levocetirizine, montelukast, and nasal spray, were continued. The patient was told not to use phenylephrine, either alone or in combination with FDCs. There are no other complaints. As a result, the patient was diagnosed with phenylephrine- induced eruption. CONCLUSION: We present this case to highlight the importance of inspiring a pharmacovigilance mindset among all clinicians providing care as a routine alert drug, phenylephrine-induced drug eruption.

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.

Tripartite motif­containing 14 may aggravate cardiac hypertrophy via the AKT signalling pathway in neonatal rat cardiomyocytes and transgenic mice.

Tripartite motif­containing 14 (TRIM14) is an E3 ubiquitin ligase that primarily participates in the natural immune response and in tumour development via ubiquitination. However, the role of TRIM14 in cardiac hypertrophy is not currently clear. The present study examined the role of TRIM14 in cardiac hypertrophy and its potential molecular mechanism. TRIM14 was overexpressed in neonatal rat cardiomyocytes using adenovirus and cardiomyocyte hypertrophy was induced using phenylephrine (PE). Cardiomyocyte hypertrophy was assessed by measuring cardiomyocyte surface area and markers of hypertrophy. In addition, TRIM14­transgenic (TRIM14­TG) mice were created and cardiac hypertrophy was induced using transverse aortic constriction (TAC). Cardiac function, heart weight­to­body weight ratio (HW/BW), cardiomyocyte cross­sectional area, cardiac fibrosis and hypertrophic markers were further examined. The expression of AKT signalling pathway­related proteins was detected. TRIM14 overexpression in cardiomyocytes promoted PE­induced increases in cardiomyocyte surface area and hypertrophic markers. TRIM14­TG mice developed worse cardiac function, greater HW/BW, cross­sectional area and cardiac fibrosis, and higher levels of hypertrophic markers in response to TAC. TRIM14 overexpression also increased the phosphorylation levels of AKT, GSK­3ß, mTOR and p70S6K in vivo and in vitro. To the best our knowledge, the present study was the first to reveal that overexpression of TRIM14 aggravated cardiac hypertrophy in vivo and in vitro, which may be related to activation of the AKT signalling pathway.

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.

Association of the exclusive use of intraoperative phenylephrine for treatment of hypotension with the risk of acute kidney injury after noncardiac surgery.

STUDY OBJECTIVE: The hypothesis that the exclusive use of the commonly used vasopressor phenylephrine during the intraoperative period in noncardiac surgery is associated with postoperative acute kidney injury (AKI) was tested. DESIGN: A retrospective cohort analysis of 16,306 adults undergoing major noncardiac surgery who either did or did not receive phenylephrine was conducted. The primary outcome was the association of the use of phenylephrine with the risk of postoperative AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Logistic regression models with all independently associated potential confounders, and an exploratory model considering only patients with no untreated minutes of hypotension (post-phenylephrine in the exposed cohort, or entire case in the unexposed cohort) were used in the analysis. SETTING: The study was conducted in a tertiary care university hospital where a total of 8,221 patients were exposed to phenylephrine, and 8,085 were not. RESULTS: In unadjusted analysis, phenylephrine exposure was associated with an increased risk of AKI (OR 1.615, 95% CI [1.522-1.725], p < 0.001). In an adjusted model including several variables associated with AKI, phenylephrine remained associated with AKI (OR 1.325 [1.153-1.524]), as did post-phenylephrine exposure lengths of hypotension. Exclusion of patients with >1 min of post-phenylephrine exposure hypotension, also demonstrated that phenylephrine use was associated with AKI (OR 1.478, [1.245-1.753]). CONCLUSIONS: The exclusive use of intraoperative phenylephrine is associated with an increased risk of postoperative renal injury. Anesthesiologists must consider a balanced approach to correct hypotension under anesthesia, including judicious choices for fluids, inotropic support when indicated, and an appropriate adjustment of the plane of anesthesia.

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.

A Review of Push-Dose Vasopressors in the Peri-operative and Critical Care Setting.

During hospitalization, the risk of hypotension and associated sequelae remain important considerations for patient outcomes. The use of push-dose vasopressors (PDP) outside of the operating room has increased in recent years to combat the negative effects of hypotension. This narrative review evaluates the utility of PDP in its traditional perioperative setting as well as in areas of increasing use such as the emergency department and intensive care unit. Articles evaluating PDP highlight successful increases in blood pressure with all agents but differ in rates of adverse events and most lack direct comparison of PDP agents in regard to safety and efficacy. Agents utilized as PDP, including epinephrine, phenylephrine, norepinephrine, vasopressin, and ephedrine vary in mechanism of action, onset of action, and duration of action. These variations in pharmacology along with published literature may lead to differences in the preferred PDP for various clinical scenarios. Many adverse events associated with PDP have been due to dosing errors highlighting the importance of education surrounding the use of these agents. Additional research is necessary to further elucidate the risks and benefits of PDP in clinical practice, and to determine which PDP is truly preferred. Careful consideration should be given when determining the appropriateness of this administration method of vasopressors in various clinical scenarios.

Phenylephrine versus cafedrine/theodrenaline (Akrinor) for the treatment of spinal anaesthesia-induced maternal hypotension during caesarean section: a retrospective single-centre cohort study.

OBJECTIVE: The main objective of this study was to assess the impact of phenylephrine and cafedrine/theodrenaline on the mother and newborn after spinal anaesthesia for caesarean section. SETTING: University teaching hospital. DESIGN: A single-centre retrospective data cohort study. PATIENTS: All obstetric patients who were scheduled for caesarean section in a 2-year period. INTERVENTIONS: Administration of either intravenous phenylephrine prophylactically or cafedrine/theodrenaline (Akrinor) reactively to maintain blood pressure after spinal anaesthesia. MAIN OUTCOME MEASURE: Maternal hypotension, heart rate during caesarean section and after admission to IMC, fetal arterial cord pH and base excess levels, maternal volume resuscitation and the use of rescue medication. RESULTS: 852 data sets could be included: n=440 Akrinor, n=412 in the phenylephrine cohort. During caesarean section blood pressure was slightly higher in the phenylephrine group compared with the Akrinor group, while hypotension <100 mm Hg systolic blood pressure (SBP) occurred significantly more often during arrival at the IMC after surgery when phenylephrine was used. Heart rate was lower and rescue medication was significantly more frequently given in the phenylephrine cohort. Irrespective of the medication used, women with baseline levels of <120 mm Hg SBP had a high risk to develop hypotension <100 mm Hg after spinal anaesthesia for caesarean section. While there was no statistical difference in mean umbilical arterial pH levels, the incidence of acidosis, defined as pH <7.2, was significantly higher with phenylephrine. CONCLUSION: Phenylephrine was not superior to Akrinor to treat spinal anaesthesia-induced maternal hypotension during caesarean section. TRIAL REGISTRATION NUMBER: DRKS00025795.

Evaluation of efficacy of intracameral lidocaine and tropicamide injection in manual small-incision cataract surgery: A prospective clinical study.

Purpose: The study was conducted to evaluate efficacy of intracameral lidocaine hydrochloride 1% and tropicamide injection 0.02% for anaesthesia and mydriasis in manual small-incision cataract surgery (MSICS) and to report any adverse drug reaction. Methods: This was a randomized, prospective, observational study on 32 participants that took place from October 2021 to March 2022 (6 months). Patients between age group 40-75 year with nuclear sclerosis cataract and pupil diameter >6 mm in preoperative evaluation were included in the study. Patients with pseudoexfoliation, rigid pupil, senile miosis, history of uveitis, ocular trauma, recent ocular infections, with known allergy to tropicamide, all types of glaucoma were excluded from the study. Results: Thirty-two eyes with nuclear sclerosis cataract who underwent MSICS were studied. Fixed dose combination of 2 ml phenyl epinephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) intracamerally was used for mydriasis and analgesia. More than 7 mm pupillary dilatation was achieved within 20 seconds of injection in 29 cases (90.6%). Mild pain and discomfort was noted in 12 cases (37.5%). Postoperative day 1 unaided visual acuity was in the range of 6/18-6/12 for all patients and grade 1 iritis was seen in 7 cases (21.8%) which was self-limiting. No adverse event like corneal decompensation or TASS were noted. Conclusion: Thus, Intracameral injection of mydriatic provides rapid and sustainable mydriasis and analgesia for manual SICS.

The Safety and Efficacy of Peripherally Administered Norepinephrine during the Perioperative Period.

Intraoperative hypotension (IOH) is a highly prevalent adverse event associated with the induction and maintenance of general anesthesia. While the etiology of IOH is complex and multifactorial, hypotension most often occurs because anesthetic agents decrease vascular smooth muscle tone, impair myocardial contractility, and decrease levels of circulating catecholamines. The vasopressor drugs phenylephrine, norepinephrine (NE), and ephedrine have been traditionally used to counteract anesthesia-induced hypotension, with the sympathomimetic agent phenylephrine historically viewed as the first-line agent. However, NE may have a more advantageous clinical profile for treating hypotension by maintaining or increasing cardiac output and restoring decreased concentrations of circulating catecholamines. Yet despite these advantages, concerns of the safety of peripherally administered NE have limited its use to specific clinical settings such as central line in situ. Recent bench and clinical research examining the efficacy and safety profile of peripherally administered NE indicates that this stigma bears reexamination. Data from human and animal studies suggest that the peripheral administration of NE for the treatment of IOH may not only be acceptable, but in many cases, may be the best option.

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.

Physiopathology of the Priapism Secondary to Tamsulosin: Clinical Cases of Our Hospital and Literature Review.

OBJECTIVE: To describe two cases of man with the diagnosis of ischemic priapism after the intake of tamsulosin and to revise the scientific literature. METHODS: We present two cases of men that developed an ischemic priapism after the intake of tamsulosin prescribed for STUI and were treated in our hospital. We described the two cases, from the diagnosis until the surgery that was performed. Also, we review the scientific literature about this topic. RESULTS: In one hand, a 67 years old man with the previous diagnosis of diabetes mellitus, hypertension and dyslipidemia that take a one single dosis of tamsulosin and developed a priapism of 9 hours of duration. He was diagnosticated of low-flow priapism that was reverted after the use of intracavernosal phenylephrine. On the other hand, a 61 years old man without any medical condition. He developed a priapism after the intake of also one single dosis of tamsulosin and came to the hospital after 48 hours of the beginning of the erection. In this case, the use of intracavernosal phenylephrine wasn´t effective so we decided to performed a distal shunt between cavernosal and spongy body according to the techniques of Winter, Ebbehoj and Al-Ghorab. All of them without results. At the end, we tried a proximal shunt according Quackles technique, also ineffective. The patient declined another surgery for implantation of a pennis prothesis and went home after four days of hospitalization with the disappearance of the pain. CONCLUSIONS: The tamsulosin is a drug well known by urologist that have a safety profile probed with the years. Nevertheless, it's association with a disease like the priapism forced us to explain to our patients this rare adverse effect.

Comparative Dose-Response Study of Phenylephrine Bolus for the Treatment of the First Episode of Spinal Anesthesia-Induced Hypotension for Cesarean Delivery in Severe Preeclamptic versus Normotensive Parturients.

Background: It is well-known that severe preeclamptic parturients have less vasopressor requirements than normotensive parturients; however, the exact dose difference is poorly documented. This study aimed to determine and compare the ED50 and ED90 of a single bolus phenylephrine for the treatment of spinal anesthesia-induced hypotension in parturients with severe preeclampsia and parturients with normotension. Methods: Seventy-five parturients with severe preeclampsia scheduled for cesarean delivery under combined spinal-epidural anesthesia were enrolled and randomly allocated to receive a single bolus of phenylephrine at five different doses (40, 50, 60, 70, and 80 µg), whereas 75 parturients with normotension were randomized to receive a single bolus of phenylephrine at five different doses (70, 80, 90, 100, and 110 µg) for the treatment of the first episode of hypotension. Phenylephrine dose values were log-transformed, the proportions of the successful interventions at each dose were converted to probits, and regression analysis was performed. Results: The ED50 and ED90 (95% CI) of bolus phenylephrine were 72.1 (61.7 to 79.9) µg and 107 (95.9-128.6) µg in parturients with normotension. The ED50 and ED90 values in parturients with severe preeclampsia were 47.6 (41.3-52.7) µg and 70.7 (62.9-86.7) µg. The relative median potency was 1.51 (1.16-2.61). Conclusion: Under this study conditions, severe preeclamptic parturients required a 34% reduction of ED50 of phenylephrine dose compared with normotensive parturients.

Norepinephrine versus phenylephrine for postspinal hypotension in parturients undergoing cesarean section: a systematic review and meta-analysis.

INTRODUCTION: Multiple studies have compared varying prophylactic and therapeutic doses of norepinephrine and phenylephrine given as either intermittent bolus or fixed-rate infusion to combat postspinal hypotension in patients undergoing cesarean section (CS). We conducted a systematic review to figure out the best alternative to treat postspinal hypotension. EVIDENCE ACQUISITION: PubMed and Cochrane databases were extensively searched for eligible RCTs. A total of 15 studies were found eligible and analyzed for the incidence of maternal bradycardia as the primary outcome and other maternal adverse effects, fetal acidosis and Apgar scores at 1 and 5 min as the secondary outcome. Data was analyzed using Review Manager Version 5.3. software. EVIDENCE SYNTHESIS: There was no significant difference in the efficacy of norepinephrine and phenylephrine for managing postspinal hypotension (OR=1.15 [95% CI: 0.91-1.45], P=0.24, I2=0%,moderate quality) in parturients undergoing CS. Odds of incidence of maternal bradycardia decrease significantly by 61% with norepinephrine versus phenylephrine (OR=0.39 [95% CI: 0.31-0.49], P<0.00001, I2=27%, high quality evidence). Significant higher umbilical artery mean pH values were observed with NE versus PE (MD=0.0 [95% CI: 0.00 to 0.01], P=0.03), although not clinical relevant. However, no significant difference was found in the incidence of other maternal adverse effects and fetal outcomes. CONCLUSIONS: Comparable efficacy for management of postspinal hypotension, though, norepinephrine was found to cause less incidence of maternal bradycardia as compared to phenylephrine.

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.

The safety of intracameral phenylephrine - A systematic review.

Intracameral phenylephrine is commonly used in ophthalmic surgery as an alternative or supplement to mydriatic eye drops; hence, the importance of an evidence-based understanding of its risk-benefit profile is vital. We performed a comprehensive search in the PubMed, Google Scholar, and Cochrane databases for published studies and case reports relating to the use of intracameral phenylephrine. Articles from 1958 to 2021 with the following keywords were used: "intracameral phenylephrine," "intracameral mydriatics," "phenylephrine," "pupil dilation," "complications." Intracameral phenylephrine was first used in 2003 as an alternative to topical mydriatics. Since then, it is being increasingly used with a variety of benefits, including rapid onset of mydriasis, and cost-effectiveness. There are various case reports, however, of ocular and systemic complications associated with intracameral phenylephrine such as generation of free radicals, toxic anterior segment syndrome, inconsistent pupillary dilation during surgery, and ventricular fibrillation. Alternatives to intracameral phenylephrine such as iris hooks, a Malyugin ring, intracameral epinephrine, and intracameral tropicamide were compared with intracameral phenylephrine. Intracameral phenylephrine appears to have a good safety profile.

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.

Trans-cinnamaldehyde protects against phenylephrine-induced cardiomyocyte hypertrophy through the CaMKII/ERK pathway.

BACKGROUND: Trans-cinnamaldehyde (TCA) is one of the main pharmaceutical ingredients of Cinnamomum cassia Presl, which has been shown to have therapeutic effects on a variety of cardiovascular diseases. This study was carried out to characterize and reveal the underlying mechanisms of the protective effects of TCA against cardiac hypertrophy. METHODS: We used phenylephrine (PE) to induce cardiac hypertrophy and treated with TCA in vivo and in vitro. In neonatal rat cardiomyocytes (NRCMs), RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out to identify potential pathways of TCA. Then, the phosphorylation and nuclear localization of calcium/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-related kinase (ERK) were detected. In adult mouse cardiomyocytes (AMCMs), calcium transients, calcium sparks, sarcomere shortening and the phosphorylation of several key proteins for calcium handling were evaluated. For mouse in vivo experiments, cardiac hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, and the expression of hypertrophic genes and proteins. RESULTS: TCA suppressed PE-induced cardiac hypertrophy and the phosphorylation and nuclear localization of CaMKII and ERK in NRCMs. Our data also demonstrate that TCA blocked the hyperphosphorylation of ryanodine receptor type 2 (RyR2) and phospholamban (PLN) and restored Ca2+ handling and sarcomere shortening in AMCMs. Moreover, our data revealed that TCA alleviated PE-induced cardiac hypertrophy in adult mice and downregulated the phosphorylation of CaMKII and ERK. CONCLUSION: TCA has a protective effect against PE-induced cardiac hypertrophy that may be associated with the inhibition of the CaMKII/ERK pathway.