[Possibilities of differential diagnosis of chronic diseases of the nasal cavity after surgical treatment and topical antibiotic therapy]. / Vozmozhnosti differentsial'noi diagnostiki khronicheskikh zabolevanii polosti nosa posle khirurgicheskogo lecheniya i topicheskoi antibakterial'noi terapii.

OBJECTIVE: The study was performed to assess the endoscopic state of the nasal mucosa after the use of local anti-inflammatory and antibacterial therapy, in particular, Polydexa nasal spray with phenylephrine containing Dexamethasone sodium metasulfobenzoate + Neomycin + Polymyxin B + Phenylephrine, and for the treatment of granulomatosis with polyangiitis. MATERIAL AND METHODS: The study included 940 patients who underwent examination and treatment for chronic rhinosinusitis in the clinic of otorhinolaryngology of I.P. Pavlov SPbSMU surgical treatment of the paranasal sinuses underwent 907 patients. In the postoperative period, the first group (211 patients) underwent toileting of the nasal cavity. The second group (307 patients) received irrigation therapy. The third group (389 patients) received a topical treatment combined of Polydexa with phenylephrine. The dynamics of the condition was assessed on the 1st, 3rd and 7th days of treatment, the evaluation of the effectiveness of the treatment was carried out on the 3rd and 7th days. Differential diagnosis with granulomatosis with polyangiitis was carried out in 33 patients. All patients with granulomatosis with polyangiitis showed signs of chronic rhinosinusitis. Patients were prescribed local anti-inflammatory and antibacterial therapy with Polydexa with phenylephrine for 7 days with endoscopic control of the nasal cavity. CONCLUSION: The use of the combined topical drug Polydexa with phenylephrine in patients with chronic rhinosinusitis and in patients with granulomatosis with polyangiitis has a positive effect, which reduces the clinical manifestations of chronic rhinosinusitis.

Fluid management and vasopressor use during colorectal surgery: the search for the optimal balance.

BACKGROUND: Although it is known that excessive intraoperative fluid and vasopressor agents are detrimental for anastomotic healing, optimal anesthesiology protocols for colorectal surgery are currently lacking. OBJECTIVE: To scrutinize the current hemodynamic practice and vasopressor use and their relation to colorectal anastomotic leakage. DESIGN: A secondary analysis of a previously published prospective observational study: the LekCheck study. STUDY SETTING: Adult patients undergoing a colorectal resection with the creation of a primary anastomosis. OUTCOME MEASURES: Colorectal anastomotic leakage (CAL) within 30 days postoperatively, hospital length of stay and 30-day mortality. RESULTS: Of the 1548 patients, 579 (37%) received vasopressor agents during surgery. Of these, 201 were treated with solely noradrenaline, 349 were treated with phenylephrine, and 29 received ephedrine. CAL rate significantly differed between the patients receiving vasopressor agents during surgery compared to patients without (11.8% vs 6.3%, p < 0.001). CAL was significantly higher in the group receiving phenylephrine compared to noradrenaline (14.3% vs 6%, p < 0.001). Vasopressor agents were used more often in patients treated with Goal Directed Therapy (47% vs 34.6%, p < 0.001). There was a higher mortality rate in patients with vasopressors compared to the group without (2.8% vs 0.4%, p = 0.01, OR 3.8). Mortality was higher in the noradrenaline group compared to the phenylephrine and those without vasopressors (5% vs. 0.4% and 1.7%, respectively, p < 0.001). In multivariable analysis, patients with intraoperative vasopressor agents had an increased risk to develop CAL (OR 2.1, CI 1.3-3.2, p = 0.001). CONCLUSION: The present study contributes to the evidence that intraoperative use of vasopressor agents is associated with a higher rate of CAL. This study helps to create awareness on the (necessity to) use of vasopressor agents in colorectal surgery patients in striving for successful anastomotic wound healing. Future research will be required to balance vasopressor agent dosage in view of colorectal anastomotic leakage.

Müller Muscle-Conjunctival Resection for Treatment of Contralateral Ptosis following Unilateral External Levator Advancement.

BACKGROUND: One of the main causes of unsatisfactory outcomes after unilateral blepharoptosis surgery is asymmetry of the upper eyelid height, which occurs as a result of a contralateral eyelid droop. Therefore, the authors evaluated the efficacy of Müller muscle-conjunctival resection (MMCR) for the treatment of contralateral ptosis following unilateral external levator advancement (ELA). METHODS: This study analyzed 26 eyelids of 26 patients with upper eyelid height asymmetry following unilateral ELA who underwent contralateral MMCR retrospectively. The phenylephrine test was performed before ELA and before MMCR. The main outcome measures were symmetry outcomes and clinical outcomes. RESULTS: The mean patient age was 55.81 ± 7.98 years (range, 44 to 70 years); 15 were female (57.7%). The Hering dependency was observed in 13 of the patients (50%) before ELA. An adequate response to phenylephrine was observed before MMCR but not before ELA. Symmetry outcomes after MMCR were perfect (<0.5 mm), good (≥0.5 mm and <1 mm), and fair (≥1 mm) in seven, 17, and two patients, respectively. An optimal upper eyelid height was noted in 47 of the 52 eyelids after the MMCR, whereas three of the 52 eyelids had minimal overcorrection, and two eyelids had undercorrection. The mean change in marginal reflex distance 1 of the contralateral eyelid droop was greater for patients with than without the Hering dependency ( P < 0.0001) after ELA but not after MMCR. Two patients (7.6%) underwent revision ELA surgery. CONCLUSION: MMCR and use of the phenylephrine test to predict the eyelid position may represent an alternative approach in patients who require management of contralateral ptosis following unilateral ELA. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Correlation Between Cerebral Tissue Oxygen Saturation and Oxygen Extraction Fraction During Anesthesia: Monitoring Cerebral Metabolic Demand-supply Balance During Vasopressor Administration.

BACKGROUND: The speculation that cerebral tissue oxygen saturation (SctO 2 ) measured using tissue near-infrared spectroscopy reflects the balance between cerebral metabolic rate of oxygen and cerebral oxygen delivery has not been validated. Our objective was to correlate SctO 2 with cerebral oxygen extraction fraction (OEF) measured using positron emission tomography; OEF is the ratio between cerebral metabolic rate of oxygen and cerebral oxygen delivery and reflects the balance between these 2 variables. MATERIALS AND METHODS: This cohort study was based on data collected in a previously published trial assessing phenylephrine versus ephedrine treatment in anesthetized patients undergoing brain tumor surgery. The variables of interest were measured twice over the healthy hemisphere before surgery: the first measurement performed after anesthesia induction and the second measurement performed after induction of a ∼20% increase in blood pressure using either phenylephrine or ephedrine. RESULTS: Data from 24 patients were analyzed. The overall vasopressor-induced relative changes in SctO 2 (ΔSctO 2 ) and OEF (ΔOEF) were 3.16% [interquartile range, -0.73% to 6.04%] and -12.5% [interquartile range, -24.0% to -6.19%], respectively. ΔSctO 2 negatively correlated with ΔOEF after phenylephrine treatment (Spearman rank correlation coefficient [ rs ]=-0.76; P =0.007), ephedrine treatment ( rs =-0.76; P =0.006), and any treatment ( rs =-0.79; P <0.001). ΔSctO 2 significantly associated with ΔOEF based on multivariable analysis with ΔOEF, relative changes in mean arterial pressure, arterial blood oxygen tension, and the bispectral index as covariates ( P =0.036). CONCLUSIONS: The negative correlation between changes in SctO 2 and OEF suggests that SctO 2 may reflect the cerebral metabolic demand-supply balance during vasopressor treatment. The generalizability of our findings in other clinical scenarios remains to be determined.

The Regional Cerebral Oxygen Saturation Effect of Inotropes/Vasopressors Administered to Treat Intraoperative Hypotension: A Bayesian Network Meta-analysis.

One of the main concerns of intraoperative hypotension is adequacy of cerebral perfusion, as cerebral blood flow decreases passively when mean arterial pressure falls below the lower limit of cerebral autoregulation. Treatment of intraoperative hypotension includes administration of drugs, such as inotropes and vasopressors, which have different pharmacological effects on cerebral hemodynamics; there is no consensus on the preferred drug to use. We performed a network meta-analysis (NMA) to pool and analyze data comparing the effect on cerebral oxygen saturation (ScO 2 ) measured by cerebral oximetry of various inotropes/vasopressors used to treat intraoperative hypotension. We searched randomized control trials in Embase, Ovid Medline, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science. We included studies that enrolled adult patients undergoing surgery under general/spinal anesthesia that compared at least 2 inotropes/vasopressors to treat hypotension. We reviewed 51 full-text manuscripts and included 9 randomized controlled trials in our study. The primary outcome was change in ScO 2 . Our results showed the likelihood that dopamine, ephedrine, and norepinephrine had the lowest probability of decreasing ScO 2 . The suggested rank order to maintain ScO 2 , from higher to lower, was dopamine

Comparison of Preoperative Alpha-blockade for Resection of Paraganglioma and Pheochromocytoma.

OBJECTIVE: Phenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine. METHODS: We conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs. RESULTS: Twenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin. CONCLUSION: Phenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.

Application of Phenylephrine Combined with Goal-Directed Fluid Therapy in Elderly Patients Undergoing Hip Arthroplasty: A Randomized Controlled Trial.

Objective: To investigate the therapeutic effect of phenylephrine combined with goal-directed fluid therapy (GDFT) in elderly patients undergoing total hip arthroplasty. Methods: From June 2018 to May 2019, a total of 80 patients, age > 70 years, scheduled for total hip arthroplasty at Guangzhou Red Cross Hospital in China were consecutively included in this prospective randomized controlled trial. The patients were divided into 2 groups of 40 patients each by the random number table method. Patients in the control group were given GDFT alone, and patients in the experimental group were given phenylephrine combined with GDFT. The duration of surgery, blood loss, intraoperative urine output, and fluid input were analyzed. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI) and stroke volume variation (SVV) were compared in the 2 groups at different times: before surgery (T0), after induction (T1), before bone cement placement (T2), after bone cement placement (T3) and after surgery (T4). Lactate, oxygenation index and cerebral oxygen uptake rate were compared perioperatively. Meanwhile, the incidence of abdominal distension, nausea and vomiting, pulmonary infection and cognitive dysfunction within 7 days after surgery were compared. Results: The intraoperative fluid input in the experimental group was significantly lower than in the control group (P < .05). In T1 and T3, heart rate (HR) and stroke volume variability (SVV) in the control group were significantly higher than in the experimental group (P < .05), but mean arterial pressure (MAP) and cardiac index (CI) were significantly lower than in the experimental group (P < .05). The intraoperative lactic acid in the control group was significantly higher than in the experimental group (P < .05). In addition, we found that the intraoperative oxygenation index and the postsurgical oxygenation index in the control group decreased by 86.86% and 87.49%, respectively, compared with the preoperative values (P < .05). In addition, at T1 and T3, HR and SVV in the control group were significantly higher than T0 (P < .05), while MAP and CI were significantly lower than T0 (P < .05). In the experimental group, there was no significant difference in HR, SVV, MAP or CI at any time points compared with those of T0 (P < .05). The oxygenation index in the control group was lower than before surgery (P < .05). There was no significant difference in urine volume or brain oxygen uptake between the 2 groups (P < .05). Conclusion: Phenylephrine combined with GDFT can be used in elderly patients undergoing hip arthroplasty to reduce fluid input and improve intraoperative hemodynamic stability, to reduce the occurrence of postoperative related complications.

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.

Effect of low dose phenylephrine infusion on shivering and hypothermia in patients undergoing cesarean section under spinal anesthesia: a randomized clinical trial.

BACKGROUND: Shivering is a common complication of spinal anesthesia. Phenylephrine, due to its peripheral vasoconstrictive effect, may limit the core to periphery redistribution of body temperature following spinal anesthesia, and reduce hypothermia and shivering. We hypothesized that prophylactic phenylephrine infusion would reduce shivering and hypothermia in women undergoing cesarean section under spinal anesthesia. METHODS: A two-arm randomized, double-blind, placebo-controlled trial in term pregnant patients undergoing cesarean section. In the phenylephrine group (n=75) prophylactic phenylephrine infusion was administered at 25 µg/min immediately after initiation of spinal anesthesia and continued until the end of the operative period. In the placebo group (n=75) a normal saline infusion was administered during the same period. The primary outcome was the incidence of shivering; secondary outcomes were severity of shivering, changes in nasopharyngeal (core) temperature, and incidence of hypotension and bradycardia. RESULTS: The incidence of shivering in the phenylephrine and control groups was 24.0% (95% CI 14.3% to 33.7%) and 53.3% (95% CI 42.0% to 64.6%), respectively. The severity of shivering was greater in the control group (P=0.002) and the mean (±SD) end of surgery core temperature was significantly higher in the phenylephrine group (35.84°C ±â€¯0.60) compared with controls (35.61°C ±â€¯0.48) (P=0.009). The incidence of hypotension was higher in controls (53.4% vs. 2.7%; P <0.001) but bradycardia more frequent in group P (P=0.023). CONCLUSION: The incidence of shivering and degree of hypothermia were significantly reduced by a prophylactic phenylephrine infusion during cesarean section under spinal anesthesia.

Pain control and reduction of opioid use associated with intracameral phenylephrine1.0%-ketorolac 0.3% administered during cataract surgery.

PURPOSE: To compare pain and the need for the opioid fentanyl use associated with the administration of phenylephrine 1.0%-ketorolac 0.3% (P/K) with those of epinephrine administration during cataract surgery. SETTING: Ambulatory surgery center. DESIGN: Single-center, prospective, randomized, double-masked, self-controlled trial. METHODS: Patients undergoing bilateral, topical anesthetic cataract surgery were randomized to receive either intracameral P/K or epinephrine in their balanced salt solution for the first eye and the other for the second eye, 2 weeks later. Fentanyl was used to manage intraoperative pain. The primary end point was the need for fentanyl administration intraoperatively. Secondary outcomes included pain measurements; surgery duration; effective phacoemulsification time; pupil size; and complications. RESULTS: 112 eyes of 56 patients were enrolled. Significantly fewer eyes in the P/K group (7 [12.5%]) than in the epinephrine group (19 [33.9%]; P = .013) required intraoperative fentanyl administration. Mean pain scores were lower in the P/K group than those in the control group at all timepoints. For patients with no pain to mild pain (pain scores ≤ 3), 85.7% (n = 48) of the P/K group and 58.9% (n = 33) of the epinephrine group met this benchmark ( P = .003) intraoperatively. The combined outcome, the number of patients not receiving intravenous fentanyl and experiencing no pain to mild pain, was significantly higher in the study (82.1%, n = 46) than in the control group (58.9%, n = 33; P = .013). CONCLUSIONS: P/K administration significantly reduced pain and the need for fentanyl use. Using P/K is a practical way for cataract surgeons to provide better patient care and reduce the need for intraoperative opioids.

Seguridad del uso combinado de lidocaína y fenilefrina como midriáticos intracamerales en la cirugía de catarata / Safety of the combined use of lidocaine and phenylephrine as intracameral mydriatics in cataract surgery

Objetivo: Evaluar la seguridad ocular y sistémica de una combinación de lidocaína 2 por ciento y fenilefrina 1 por ciento administrada por vía intracameral para provocar midriasis intraoperatoria en la cirugía de catarata. Métodos: Se realizó un estudio prospectivo de serie de casos en 70 ojos de igual número de pacientes sometidos a facoemulsificación con implante de lente intraocular. El grupo midriasis intraoperatoria en la cirugía lo conformaron 35 pacientes dilatados con una inyección intracameral de lidocaína y fenilefrina antes de la cirugía, mientras otros 35 ojos se dilataron de manera tradicional, con un colirio midriático previo. Para la seguridad ocular se evaluaron múltiples parámetros del examen oftalmológico pre- y posoperatorio. Resultados: La presión intraocular, el espesor corneal central, la densidad celular del endotelio corneal y el edema corneal posoperatorio como hallazgo del segmento anterior se comportaron de manera similar en ambos grupos de estudio. Se reportó una complicación transoperatoria en el grupo de manera tradicional y un caso con edema quístico macular posoperatorio en el grupo midriasis intraoperatoria en la cirugía que no representaron diferencias significativas. Conclusión: La inyección de lidocaína más fenilefrina intracameral es una opción segura tanto ocular como sistémica para provocar midriasis durante la facoemulsificación(AU)

Objective: Evaluate the ocular and systemic safety of a combination of 2 percent lidocaine and 1 percent phenylephrine administered intracamerally to achieve intraoperative mydriasis in cataract surgery. Methods: A prospective study was conducted of a case series of 70 patients (70 eyes) who underwent phacoemulsification with intraocular lens implantation. The intraoperative mydriasis group was composed of 35 patients dilated with an intracameral injection of lidocaine and phenylephrine before surgery, whereas another 35 eyes were dilated by the conventional method, with mydriatic eye drops. Ocular safety evaluation was based on the analysis of a wide variety of pre- and postoperative ophthalmological examination parameters. Results: Intraocular pressure, central corneal thickness, corneal endothelial cell density and postoperative corneal edema as an anterior segment finding, behaved in a similar manner in both study groups. An intraoperative complication was reported in the conventional method group and a case with postoperative cystoid macular edema in the intraoperative mydriasis group group, neither of them exhibiting significant differences. Conclusion: Intracameral lidocaine plus phenylephrine injection is a safe ocular and systemic option to achieve mydriasis during phacoemulsification(AU)

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

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

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

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

Real-world opioid prescribing after cataract surgery among patients who received intracameral phenylephrine and ketorolac 1.0%/0.3.

OBJECTIVE: To examine opioid prescribing following cataract surgery among patients who did or did not receive Omidria (phenylephrine and ketorolac intraocular solution 1.0%/0.3%) referred to as "P/K". METHODS: The retrospective study compared adults over 65 without recent opioid use in the MarketScan databases who had a cataract-related surgical procedure between 1 January 2015 and 31 July 2019. Opioid prescription fills in the initial 2 and 7 days following surgery were compared between patients who did or did not receive P/K during surgery. RESULTS: We identified 218,672 older adults with cataract-related surgical procedures, of whom 5145 received P/K during surgery. Within 2 days of surgery, 0.50% of P/K patients and 0.68% of non-P/K patients received at least one opioid prescription. Pill counts in the first prescription post-surgery were lower for patients who received P/K than those who did not receive P/K (20 vs 45 respectively, p = .015). Findings were similar when a 7 day window was used. The reduction in opioids prescribed to patients who received P/K occurred despite the P/K-treated patients having a significantly higher incidence of preoperative comorbidities or risk factors for surgical complexity than patients who did not receive P/K (46.6% vs 31.3%, p < .001). CONCLUSIONS: Patients without recent opioid use who received P/K during cataract surgery, despite greater incidence of preoperative comorbidities and higher risk for surgical complexity, were prescribed fewer opioid pills following surgery than patients who did not receive P/K.

Effect of intracameral phenylephrine 1.0%-ketorolac 0.3% on postoperative cystoid macular edema, iritis, pain, and photophobia after cataract surgery.

PURPOSE: To assess the effectiveness of intracameral phenylephrine-ketorolac during cataract surgery compared with postoperative topical steroids in reducing the incidence of postoperative clinical cystoid macular edema (CME) confirmed via optical coherence tomography (OCT), breakthrough iritis, pain, and photophobia. SETTING: Ambulatory surgical center/clinical practice. DESIGN: Retrospective 2-cohort study. METHODS: This study of cataract surgery patients compared the incidence of postoperative CME, breakthrough iritis, pain, and photophobia between patients receiving either intracameral phenylephrine 1.0%-ketorolac 0.3% during surgery or topical loteprednol 0.5% 2 days preoperatively, tapered postoperatively. Patients with prior CME or at high risk for postoperative CME, combined cataract/glaucoma surgery, and medication protocols different from those studied here were excluded. All eyes received bromfenac 2 days preoperatively and 10 weeks postoperatively. RESULTS: The study enrolled 2218 eyes (n = 1402). The phenylephrine/ketorolac treatment group included 1334 eyes (n = 830) and the topical loteprednol control group included 884 eyes (n = 572). The groups were comparable in age, race, gender, and perioperative characteristics. Clinical CME incidence was significantly lower in the phenylephrine-ketorolac group (0.52% vs 1.47%, P = .021). The phenylephrine-ketorolac group also had significantly lower breakthrough iritis (1.72% vs 4.86%, P < .001) and pain (1.27% vs 4.19%, P < .001) than the topical loteprednol group. The incidence of photophobia trended lower for the phenylephrine/ketorolac group relative to the topical loteprednol group (0.90% vs 1.13%, respectively, P = .590) but was not statistically significant. CONCLUSIONS: Intracameral phenylephrine/ketorolac and topical nonsteroidal antiinflammatory drugs (NSAIDs) without postoperative topical steroids significantly reduced postoperative clinical CME, breakthrough iritis, and pain after cataract surgery when compared with conventional perioperative topical steroids and NSAIDs.

Ephedrine versus Phenylephrine Effect on Cerebral Blood Flow and Oxygen Consumption in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial.

BACKGROUND: Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine. METHODS: In this double-blinded, randomized clinical trial, 24 anesthetized patients with brain tumors were randomly assigned to ephedrine or phenylephrine treatment. Positron emission tomography measurements of cerebral blood flow and cerebral metabolic rate of oxygen in peritumoral and normal contralateral regions were performed before and during vasopressor infusion. The primary endpoint was between-group difference in cerebral metabolic rate of oxygen. Secondary endpoints included changes in cerebral blood flow, oxygen extraction fraction, and regional cerebral oxygen saturation. RESULTS: Peritumoral mean ± SD cerebral metabolic rate of oxygen values before and after vasopressor (ephedrine, 67.0 ± 11.3 and 67.8 ± 25.7 µmol · 100 g · min; phenylephrine, 68.2 ± 15.2 and 67.6 ± 18.0 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 1.5 [-13.3 to 16.3] µmol · 100 g · min [P = 0.839]). Corresponding contralateral hemisphere cerebral metabolic rate of oxygen values (ephedrine, 90.8 ± 15.9 and 94.6 ± 16.9 µmol · 100 g · min; phenylephrine, 100.8 ± 20.7 and 96.4 ± 17.7 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 8.2 [-2.0 to 18.5] µmol · 100 g · min [P = 0.118]). Ephedrine significantly increased cerebral blood flow (difference [95% CI], 3.9 [0.7 to 7.0] ml · 100 g · min [P = 0.019]) and regional cerebral oxygen saturation (difference [95% CI], 4 [1 to 8]% [P = 0.024]) in the contralateral hemisphere compared to phenylephrine. The change in oxygen extraction fraction in both regions (peritumoral difference [95% CI], -0.6 [-14.7 to 13.6]% [P = 0.934]; contralateral hemisphere difference [95% CI], -0.1 [- 12.1 to 12.0]% [P = 0.989]) were comparable between groups. CONCLUSIONS: The cerebral metabolic rate of oxygen changes in peritumoral and normal contralateral regions were similar between ephedrine- and phenylephrine-treated patients. In the normal contralateral region, ephedrine was associated with an increase in cerebral blood flow and regional cerebral oxygen saturation compared with phenylephrine.

Eficacia del uso combinado de lidocaína y fenilefrina como midriáticos intracamerales en la cirugía de catarata / Efficacy of the combined use of lidocaine and phenylephrine as intracameral mydriatics in cataract surgery

RESUMEN Objetivo: Evaluar la eficacia de una combinación de lidocaína 2 por ciento y fenilefrina 1 por ciento administrada intracameralmente para provocar midriasis intraoperatoria en la cirugía de catarata. Métodos: Realizamos un estudio prospectivo, comparativo, de serie de casos en 70 ojos de igual número de pacientes quienes fueron sometidos a cirugía de catarata mediante facoemulsificación con implante de lente intraocular, en el Instituto Cubano de Oftalmología "Ramón Pando Ferrer" entre septiembre del año 2017 y febrero de 2018. 35 pacientes fueron dilatados con una combinación de fenilefrina y lidocaína inyectada en la cámara anterior justo antes de la cirugía (grupo midriáticos intracamerales) y otros 35 ojos se dilataron con un colirio midriático como se realiza cotidianamente y de manera tradicional (grupo midriáticos tópicos). La eficacia se evaluó mediante la medición del diámetro pupilar (pupilometría) realizada con un compás quirúrgico en diferentes momentos de la cirugía en ambos grupos de estudio. Los resultados de ambos grupos se compararon entre sí. Resultados: En ambos grupos de pacientes se lograron diámetros pupilares superiores a los 7 mm justo antes de la capsulorrexis, aunque fueron ligeramente mayor en el grupo midriáticos tópicos (8,17 vs. 7,55 mm). En las mediciones posteriores todas las pupilometrías del grupo midriáticos intracamerales fueron superiores y se mantuvieron por encima de los 7 mm, mientras las del grupo midriáticos tópicos sufrieron una reducción paulatina hasta el final de la cirugía (5,68 mm). Conclusiones: La combinación de lidocaína más fenilefrina aplicada de manera intracameral es efectiva para provocar una midriasis adecuada y mantenida durante la cirugía de catarata(AU)

ABSTRACT Objective: Evaluate the efficacy of the combination 2 percent lidocaine / 1 percent phenylephrine administered intracamerally to achieve intraoperative mydriasis in cataract surgery. Methods: A prospective comparative study was conducted of a case series of 70 patients (70 eyes) who underwent cataract surgery by phacoemulsification with intraocular lens implantation at Ramón Pando Ferrer Cuban Institute of Ophthalmology from September 2017 to February 2018. Of the total eyes, 35 were dilated with a combination of phenylephrine and lidocaine injected into the anterior chamber just before surgery (MIC group), whereas the remaining 35 were dilated with mydriatic eye drops in the habitual traditional manner (MT group). Efficacy was evaluated in the two study groups measuring the pupil diameter (pupilometry) with a surgical compass at several moments during the surgery. The results for each group were compared. Results: In both groups patients achieved pupil diameters above 7 mm just before capsulorhexis, though values were slightly higher in the MT group (8.17 vs. 7.55 mm). Later measurement showed that in the MIC group all pupilometries were higher, remaining above 7 mm, whereas in the MT group they underwent gradual reduction until the end of surgery (5.68 mm). Conclusions: The combination of lidocaine and phenylephrine administered intracamerally is effective to achieve appropriate, sustained mydriasis during cataract surgery(AU)

Phenylephrine alleviates 131I damage in submandibular gland through promoting endogenous stem cell regeneration via lissencephaly-1 upregulation.

Thyroid cancer is the most common endocrine malignancy. 131I ablation therapy is an effective treatment for patients with differentiated thyroid cancer (DTC) but frequently causes radiation damage in salivary glands (SGs). Stem cell-based regenerative therapy has been found to reduce radiation sialadenitis. We hypothesize that microtubule motor-regulating protein lissencephaly-1 (LIS1) may be a key stem cell regulator responsible for its efficacy and that upregulating LIS1 would decrease131I-induced radiation sialadenitis. Here, we report that LIS1 was reduced by 131I in submandibular glands (SMGs) of rats, using both proteomic analysis and Western blot approach. Moreover, the levels of LIS1-Sca-1 and LIS1-SOX2 were downregulated by 131I together with the decrease of LIS1. In contrast, phenylephrine pretreatment enhanced LIS1 and improved the co-expressions and co-localizations of LIS1-Sca-1 and LIS1-SOX2 in 131I-irradiated SMGs. Since Sca-1 and SOX2 are the established stem cell biomarkers in salivary gland, our findings demonstrate that LIS1 may be a potential target for regulating stem cell maintenance in irradiated SGs. Importantly, phenylephrine may have the ability to promote endogenous stem cell regeneration in SMGs via upregulating the LIS1/Sca-1 and LIS1/SOX2 signaling pathways, suggesting that phenylephrine application before 131I ablation therapy may provide a practical and effective way to prevent radiation sialadenitis for DTC patients.

Rate of pseudophakic cystoid macular edema using intraoperative and topical nonsteroidal antiinflammatory drugs alone without steroids.

PURPOSE: To determine the rate of postoperative cystoid macular edema (CME) in patients undergoing cataract surgery treated with intraoperative intracameral and postoperative topical nonsteroidal antiinflammatory drugs (NSAIDs) without steroids. SETTING: Academic outpatient surgery center Wake Forest Baptist Health in Bermuda Run, NC. DESIGN: Retrospective cohort study. METHODS: A retrospective chart review was performed. Patients were identified through a medical record search tool using criteria of the Current Procedural Terminology code (66984), a single surgeon, and a date range from January 1, 2016, through December 31, 2017. Medical records were reviewed to determine intraoperative and postoperative medication regimen, visual outcome, and development of postoperative CME. Patients with a history of uveitis, diabetic macular edema, retinal vein occlusions, epiretinal membranes, vitreomacular traction, or any prior macular edema were excluded. In addition, any patients with less than 6 weeks of postoperative follow-up were excluded. RESULTS: Overall, 824 patient records were reviewed, and the analysis included 504 eyes. Of these, 2 eyes developed postoperative CME (rate = 0.40%, 95% CI 0.0005 to 0.0143). CONCLUSIONS: The rate of CME in patients treated with intraoperative and postoperative NSAIDs without steroids was low and below the historical rates derived from a literature review of CME development with the use of steroids.

Vasoplegic syndrome following cardiothoracic surgery-review of pathophysiology and update of treatment options.

Vasoplegic syndrome is a common occurrence following cardiothoracic surgery and is characterized as a high-output shock state with poor systemic vascular resistance. The pathophysiology is complex and includes dysregulation of vasodilatory and vasoconstrictive properties of smooth vascular muscle cells. Specific bypass machine and patient factors play key roles in occurrence. Research into treatment of this syndrome is limited and extrapolated primarily from that pertaining to septic shock, but is evolving with the expanded use of catecholamine-sparing agents. Recent reports demonstrate potential benefit in novel treatment options, but large clinical trials are needed to confirm.