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.

An outcome study of adult in-hospital cardiac arrests in non-monitored areas with resuscitation attempted using AED.

OBJECTIVES: To investigate the outcomes of patients with in-hospital cardiac arrest (IHCA) who underwent cardiopulmonary resuscitation (CPR) using an automated external defibrillator (AED) in non-monitored areas. Additionally, to detect correlated factors associated with rate of return of spontaneous circulation (ROSC) and survival rate, among collected data. METHODS: This study included 109 patients. After investigating patient characteristics and resuscitation-related factors, the correlated factors associated with ROSC rates and survival rate were analyzed using univariate and multivariate analyses. RESULTS: The rate of survival to hospital discharge was 21.1%. CPR with AED performed since 2013 was associated with a higher ROSC rate (adjusted odds ratio [AOR] 3.24, 95% confidence interval [CI]: 1.21 to 9.52, p < 0.05), but not with the survival rate after ROSC. Tracheal intubation was significantly associated with a higher ROSC rate (AOR 3.62, 95% CI: 1.27 to 11.7, p < 0.05) and a lower survival rate after ROSC (hazard ratio 6.6, 95% CI: 1.2 to 43.3, p < 0.05). Dysrhythmia as the cause of cardiac arrest and intensive care unit (ICU) admission after ROSC were associated with higher survival rates (hazard ratio 0.056, 95% CI: 0.004 to 0.759, p < 0.05, and hazard ratio 0.072, 95% CI: 0.017 to 0.264, p < 0.0001, respectively). CONCLUSIONS: The factors associated with ROSC rate and those associated with the survival rate after ROSC were different. Although initial shockable rhythms on AED were not associated with the survival rate, dysrhythmia as the etiology of cardiac arrest, and ICU admission were significantly associated with higher survival rates after ROSC.

Pharmacological Strategies for Presbyopia Correction.

PURPOSE: To summarize the pharmacological strategies that are being explored for presbyopia correction. METHODS: The review concentrates on pharmacologically induced pupillary miosis to increase depth-of-focus and lens softening or other measures to restore active accommodation. RESULTS: Several studies suggest that near vision improves and distance vision is unaffected for many hours after either monocular or binocular instillation of any one of several drug combinations that cause miosis. Unfortunately, in most studies, measurements were limited to photopic visual acuity for near and distance vision, whereas it is anticipated that pupil constriction may have adverse effects on mesopic and scotopic vision. It is not clear whether improved near vision was due entirely to increased depth-of-focus, or whether, for example, a drug-induced myopic shift in refraction was also involved. Currently, no study has provided direct evidence for drug-induced restoration/enhancement of true accommodation involving an ocular power change. CONCLUSIONS: Although it is possible that, in the future, pharmacological drops may offer a safe and reliable solution for presbyopia correction, more evidence of their effectiveness and limitations is required. [J Refract Surg. 2019;35(12):803-814.].

Comparative evaluation of a local anesthetic effect between lignocaine and lignocaine administered with epinephrine in healthy children.

Lignocaine a first amino amide-type local anesthetic, when combined or co-administered with epinephrine, a sympathomimetic amine, allows to administer larger doses for numbing, to decrease bleeding, and to make the numbing effect last longer. The study presented here focuses on measures to prove this activity in patients with abdominal surgery. Liposomal formulations of lignocaine and lignocaine plus epinephrine were prepared by a thin film evaporation method. This formulation was injected successfully as liposomal infusion. Thus prepared liposomes were found to be fit for drug delivery when evaluated as per physicochemical parameters. The smooth, even surfaced liposomes with PDI of 0.298 (p<0.05) were found to be efficient in delivering the drug when tested in-vitro (lignocaine as a single drug was at 93.78%, and from combined dosage lignocaine was at 96.29% with 94.62% of release of epinephrine). The randomized, controlled trial was conducted with a population of children that had undergone abdominal surgery and who were grouped into three groups depending upon the type of formulation they received. The three groups of subjects were first one receiving lignocaine liposomal infusion only; second one with lignocaine plus epinephrine liposomal infusion; the third group served as control and received a saline solution only. The serum Cortisol concentration was found to be the least in Group II when compared to Group I. Similarly, end point measurements such as the cool sensation, warm sensation, hot pain, and the sensory blockade test had indicated the superiority of combination of lignocaine with epinephrine in lowering the pain threshold. The result obtained from the above study has shown that epinephrine markedly enhances the local anesthetic activity of lignocaine.

Anaphylaxis to patent blue dye in a 17-year-old boy.

Patent blue V dye (PBV) is frequently used as a perioperative drug for lymphangiography, as well as a food additive. Hypersensitivity to PBV is poorly documented in adults and had not been previously described in children. The diagnosis of PBV allergy depends on corroboration of history consistent with an IgE-mediated reaction and confirmatory skin tests. We present in this paper a paediatric case of PBV anaphylaxis and of biphasic reaction that exemplifies the challenges involved in diagnosing and managing this rare but potentially life-threatening allergic reaction.

Reconocimiento y manejo de la anafilaxia en pediatría / Detection and management of anaphylaxis in children

INTRODUCCIÓN: La anafilaxia es una emergencia. De acuerdo con las últimas recomendaciones internacionales el reconocimiento de los criterios clínicos y el tratamiento temprano con adrenalina intramuscular se asocian a mayor sobrevida. OBJETIVO: Determinar el conocimiento de los médicos pediatras de un Hospital Pediátrico de tercer nivel sobre los criterios diagnósticos y el tratamiento de la anafilaxia. MATERIAL Y MÉTODO: Estudio descriptivo transversal que considera diseño, aplicación y validación de una encuesta anónima a médicos con residencia completa en pediatría que realizan guardias en un hospital de tercer nivel. Los ítems de la Encuesta comprendieron tres dimensiones, experiencia del operador (2 ítems), manejo farmacológico (3 ítems) e identificación del cuadro (4 ítems). El análisis estadístico utilizó el programa SPSS v.21, presentando medidas de tendencia central (mediana, rango y tabla de frecuencias) y para su comparación prueba de Chi cuadrado. Se consideró significativo un valor de p < 0,05. RESULTADOS: Se encuestaron 71 médicos con una mediana de 3 años transcurridos desde el fin de la residencia. 35% identificó todos los criterios clínicos; 99% (70) indicó adrenalina, 73% por vía intramuscular y 55% a dosis correcta (solo el 48% contestó la dosis y vía correctamente). En forma global la adecuación para identificación más manejo correcto fue del 21%. Los médicos con menos de 5 años de experiencia tuvieron mejor desempeño en la administración de adrenalina intramuscular (83% vs 52% p = 0,005) y en la detección de síntomas gastrointestinales (60%vs35% p = 0,043). CONCLUSIONES: Existen dificultades para la identificación y el manejo apropiado de la anafilaxia por pediatras de un Hospital de tercer nivel en un escenario teórico. Aunque la mayoría eligió la adrenalina como droga de primera línea, la mitad no la indicó de forma correcta y solo un tercio reconoció el cuadro en todos sus escenarios.

INTRODUCTION: Anaphylaxis is an emergency condition. According to the latest international guide lines, early recognition and treatment with intramuscular epinephrine are associated with increased survival. OBJECTIVE: To determine the level of knowledge of pediatricians in a tertiary Pediatric Hos pital about the diagnostic criteria and treatment of anaphylaxis. MATERIAL AND METHOD: A cross-sec tional descriptive study was conducted, designing, applying, and validating an anonymous survey to physicians with complete residency in pediatrics who are on call at a third level hospital. The statisti cal analysis was made using the SPSS v.21 software, presenting measures of central tendency (median, range, and frequency table) and Chi-square test for comparison. A value of p < 0.05 was considered significant. RESULTS: 71 physicians completed the survey with a median of three years after the end of residency.35% of them identified all clinical criteria, 99% (70) indicated epinephrine, 73% chose the intramuscular route, and 55% indicated the correct dose. Only 48% of responders chose the dose and administration route correctly. In general, 21% recognized anaphylaxis and used epinephrine correctly. Physicians with less than five years of experience performed better in the intramuscular administration of epinephrine (83% vs 52% p = 0.005) and in the detection of gastrointestinal symp toms (60% vs 35% p = 0.043). CONCLUSIONS: There are difficulties in the identification and proper management of anaphylaxis by pediatricians of a tertiary Pediatric Hospital in a theoretical clinical setting. Although most of pediatricians chose epinephrine as a first-line drug, half of them did not indicate it correctly, and only one-third recognized anaphylaxis in all scenarios.

Topical Oxymetazoline Cream 1.0% for Persistent Facial Erythema Associated With Rosacea: Pooled Analysis of the Two Phase 3, 29-Day, Randomized, Controlled REVEAL Trials

Background: Rosacea is a chronic dermatologic condition with limited treatment options. Methods: Data were pooled from two identically designed phase 3 trials. Patients with moderate to severe persistent erythema of rosacea were randomized to receive oxymetazoline cream 1.0% or vehicle once daily for 29 days and were followed for 28 days posttreatment. The primary efficacy outcome was the proportion of patients with ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) at 3, 6, 9, and 12 hours postdose, day 29. Results: The pooled population included 885 patients (78.8% female); 85.8% and 91.2% had moderate erythema based on CEA and SSA, respectively. The primary outcome was achieved by significantly more patients in the oxymetazoline than vehicle group (P<0.001). Individual CEA and SSA scores and reduction in facial erythema (digital image analysis) favored oxymetazoline over vehicle (P<0.001). The incidence of treatment-emergent adverse events was low (oxymetazoline, 16.4%; vehicle, 11.8%). No clinically relevant erythema worsening (based on CEA and SSA) was observed during the 28-day posttreatment follow-up period (oxymetazoline, 1.7%; vehicle, 0.6%). Conclusion: Oxymetazoline effectively reduced moderate to severe persistent facial erythema of rosacea and was well tolerated. J Drugs Dermatol. 2018;17(11):1201-1208.

Sinus arrest with prolonged asystole due to the trigeminocardiac reflex during application of local anaesthetic in the nasal mucosa.

The trigeminocardiac reflex (TCR) is defined as a sudden onset of parasympathetic dysrhythmias during stimulation of the trigeminal nerve. We describe a peripheral variation of TCR during manipulation of the nasal mucosa. A 42-year-old patient suffering from severe obstructive sleep apnoea was scheduled for surgical treatment. After inducted anaesthesia, the surgeon infiltrated the nasal mucosa with a local anaesthetic. The patient immediately showed an asystole and was treated with ephedrine and five chest compressions, despite spontaneous sinus rhythm return after ceasing of manipulation. Treatment with atropine established this TCR episode and ensured an event-free surgery.The authors present here, for the first time, a prolonged asystole caused by the TCR, triggered by minimal manipulation of the nasal mucosa. This severe manifestation of peripheral TCR demonstrates its importance in daily clinical business. This case was treated according to a modified treatment algorithm for all subtypes of TCR which is presented here.

Analgesic Effect of Local Infiltration of the Surgical Wound Containing Levobupivacaine, Ibuprofen, and Epinephrine in Rats Undergoing Laparotomy.

BACKGROUND: Inappropriate use of drugs and their combinations for analgesics has made it difficult to determine the optimal drug combinations for pain mangement. AIM: To reduce postoperative pain effectively and safely. MATERIALS AND METHODS: Laparotomy was performed in an adult rat under isoflurane anesthesia. During surgery, the surgical wounds were infiltrated with 50 µL solution containing 0.3% w/v levobupivacaine, 2 mg/mL ibuprofen, and 8 mg/mL epinephrine (treatment group) over the sutured muscle wound before skin closing, and compared to infiltration of that of the normal saline (vehicle group). The 10-fold higher dose of the same combination of medications was injected systemically as a control. Postoperative pain assessed by rodent grimace scales scoring. One-way ANOVA following Dunnett multiple comparisons test was used at 95% of confidence level. RESULTS: There was decreased pain for the treatment group (p = 0.025, q = 4.527) and the control group (p = 0.031, q = 4.178) only 24 h after the end of the successful infiltration. The rodent GS scale scoring showed the fall in pain was started within three hours post-surgery in the treatment group. There was decreased pain in the treatment group (p = 0.048, q = 3.527) and the control group (p = 0.043, q = 3.891) only as compared to vehicle group 24 h after the end of the successful infiltration. CONCLUSION: The infiltration of the surgical wound with levobupivacaine, ibuprofen, and epinephrine combination was effective in the healing of wounds after laparotomy.

Tocolysis with the ß2-sympathomimetic fenoterol does not increase the occurrence of infantile hemangioma in preterm and term infants.

PURPOSE: ß2-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the ß2-sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other ß2-mimetic tocolytic agents like fenoterol. METHODS: Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups. RESULTS: N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a subgroup of neonates < 32 weeks of gestation or with a birth weight < 1500 g (OR 1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p < 0.005). CONCLUSIONS: Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different ß2-sympathomimetic tocolytic drugs.

Epinephrine versus dopamine in neonatal septic shock: a double-blind randomized controlled trial.

We compared epinephrine and dopamine as a first-line vasoactive drug in 40 neonates (enrolled in two gestational age strata ≤ 306/7 and ≥ 310/7 weeks) with fluid-refractory septic shock. Epinephrine or dopamine was initiated at 0.2 or 10 µg/kg/min, respectively. If shock persisted after 15 min, epinephrine or dopamine was increased to 0.3 or 15 µg/kg/min, respectively (16-30 min), and thereafter to 0.4 or 20 µg/kg/min (31-45 min). Proportion of neonates achieving 'reversal of shock' (defined as systolic and diastolic BP > fifth centile and capillary filling time < 3 s and left ventricular output ≥ 150 mL/kg/min) by 45 min [5 (25%) vs 6 (30%), RR 0.83 (95% CI 0.30, 2.29)]; haemodynamic stability (shock reversal for ≥ 120 min without escalation of vasoactive drugs) anytime during therapy [10 (50%) vs 6 (30%), RR 1.67 (95% CI 0.75, 3.71)]; and all-cause mortality by 28 days [14 (70%) vs 16 (80%), RR 0.87 (95% CI 0.61, 1.26)] were comparable in the epinephrine and dopamine groups, respectively. On stratified analysis, we observed an interaction of gestational age strata with the group of allocation favouring epinephrine in neonates ≤ 306/7 weeks.Conclusion: Epinephrine (0.2-0.4 µg/kg/min) and dopamine (10-20 µg/kg/min) had comparable efficacy and safety in neonatal septic shock.Clinical Trial registry name and registration number: The study was registered with Clinical Trial Registry of India CTRI/2015/10/006285. What is Known: • The choice of vasoactive drugs in neonatal septic shock is empirical and dopamine is the conventional first-line vasoactive drug. • There are no randomized controlled trials comparing dopamine and epinephrine in neonatal septic shock. What is New: • In this study, epinephrine and dopamine had comparable efficacy and safety as a first-line vasoactive drug in management of neonatal septic shock. • On stratified analysis in a limited sample, epinephrine was associated with better outcomes in neonates ≤ 306/7 weeks.

Successful Management of Chylothorax With Etilefrine: Case Report in 2 Pediatric Patients.

Chylothorax is defined as the accumulation of chyle within the pleural space. Originally described in 1917 by Pisek, it is the most common cause of pleural effusion in the neonatal period. The leading cause of chylothorax is laceration of the thoracic duct during surgery, which occurs in 0.85% to 6.6% of children undergoing cardiothoracic surgery. Few authors of reports in the literature have looked at etilefrine, a relatively unknown sympathomimetic, as an option for the medical treatment of chylothorax. In this case report, we review the clinical course of 2 infants with type III esophageal atresia who developed chylothorax after thoracic surgery and were successfully treated with intravenous etilefrine after failing initial dietary and pharmacological management.

Facial nerve palsy and laryngospasm as a complication of local anaesthesia during adenotonsillectomy.

Tonsil surgeries are the most frequently performed surgical procedures in ENT departments. We would like to present the case of a 5-year-old patient who suffered from unilateral peripheral facial nerve palsy and laryngeal spasm following adenotonsillectomy. Paresis was observed immediately after the transfer of the patient to the postoperative room. The activity of facial muscles was restored within 2 hours from the beginning of the surgery. We assume that this was the direct effect of an anaesthetic on the extracranial processes of the facial nerve.

Falsely elevated plasma metanephrine in patients taking midodrine.

Plasma metanephrines have become the biochemical test of choice for suspected phaeochromocytomas and paragangliomas in many institutions. We encountered two separate cases of significantly elevated plasma metanephrines in patients taking midodrine, a sympathomimetic drug used in the treatment of severe postural hypotension, in the absence of a diagnosis of phaeochromocytomas and paragangliomas. Upon stopping midodrine treatment, plasma metanephrine concentrations returned to normal in both patients. To explore the hypothesis that midodrine or its metabolite desglymidodrine might interfere with the metanephrines assay, we tested the interaction of midodrine with metanephrine assays from two different centres. High-performance liquid chromatography tandem mass spectrometry on plasma samples and on methanolic extract of midodrine demonstrated co-elution of the metabolite desglymidodrine with metanephrine. We conclude that patients taking midodrine may have falsely elevated plasma metanephrine as a result of analytical interference, and clinicians need to be aware of this problem.

Priapism due to essential thrombocythaemia: a rare causation.

Priapism is rarely caused by essential thrombocytosis, a disorder characterised by increased number of megakaryocytes. We report a case of a 21-year-old man who presented with priapism and on investigation was found to have essential thrombocytosis as the cause.

A confirmed case of sugammadex-induced anaphylaxis in a UK hospital.

We report the first published case of confirmed anaphylaxis to sugammadex in a UK hospital. The patient was given a bolus of sugammadex at the end of surgery. Four minutes later, he developed hypotension and a widespread erythematous rash. Multiple epinephrine boluses were administered and a continuous intravenous infusion of epinephrine commenced. The patient later reported auditory awareness, which occurred while the diagnosis of anaphylaxis was being made and initial treatment initiated. Serial serum tryptase levels were consistent with a type I hypersensitivity reaction. Skin prick and intradermal testing were performed 6 months later confirming allergy to sugammadex. This case restates the potential for hypersensitivity reactions to develop following the administration of sugammadex and makes clinicians aware that such reactions may require prolonged treatment with intravenous infusions of epinephrine. Finally, this case highlights the importance of maintaining or re-establishing anaesthesia while managing the emergent situation in order to avoid unintentional awareness.

Topical treatment of glaucoma: established and emerging pharmacology.

INTRODUCTION: Glaucoma is a collection of optic neuropathies consisting of retinal ganglion cell death and corresponding visual field loss. Glaucoma is the leading cause of irreversible vision loss worldwide and is forecasted to precipitously increase in prevalence in the coming decades. Current treatment options aim to lower intraocular pressure (IOP) via topical or oral therapy, laser treatment to the trabecular meshwork or ciliary body, and incisional surgery. Despite increasing use of trabecular laser therapy, topical therapy remains first-line in the treatment of most forms of glaucoma. Areas covered: Novel glaucoma therapies are a long-standing focus of investigational study. More than two decades have passed since the last United States Food and Drug Administration (FDA) approval of a topical glaucoma drug. Here, the authors review established topical glaucoma drops as well as those currently in FDA phase 2 and 3 clinical trial, nearing clinical use. Expert opinion: Current investigational glaucoma drugs lower IOP, mainly through enhanced trabecular meshwork outflow. Although few emerging therapies show evidence of retinal ganglion cell and optic nerve neuroprotection in animal models, emerging drugs are focused on lowering IOP, similar to established medicines.

Cerebral tissue oxygenation index and lactate at 24 hours postoperative predict survival and neurodevelopmental outcome after neonatal cardiac surgery.

IMPORTANCE: There are no well-established noninvasive biomarkers for identifying patients at risk for poor outcome after surgery for congenital heart disease. Few studies have assessed prognostic accuracy of cerebral tissue oxygenation index (cTOI) measured by near infrared spectroscopy (NIRS). OBJECTIVE: To assess the utility of noninvasive NIRS monitoring as a predictor of outcomes after neonatal cardiac surgery through measurement of cTOI. To examine the utility of noninvasive NIRS monitoring in combination with lactate concentration and inotropic score in prediction of outcomes after neonatal cardiac surgery. DESIGN: Prospective longitudinal cohort study. SETTING: Operating room and cardiac intensive care unit, Children's National Heart Institute. PARTICIPANTS: Seventy-five patients with complex congenital heart disease undergoing surgical repair within first month of life. EXPOSURE: Cerebral TOI, blood lactate, and inotropic scores were measured preoperative, intraoperative and up to 24 hours postoperative. MAIN OUTCOME MEASURES: Postoperative mortality and neurodevelopmental outcome assessed by the Bayley Scales of Infant Development (BSID II). Mental and motor scores were obtained at 6, 15, and 21 months. Good outcome was defined as survival and BSID mental and motor scores ≥70 points. Poor outcome was defined as death or BSID scores <70 at most recent follow-up. RESULTS: Cohort of 75 patients prospectively followed including 40 patients with single ventricle and 35 with two ventricles. Four patients died before discharge and ten died within 21 months. Seven patients were lost to follow-up. Among survivors with follow-up (n = 54), BSID was abnormal in 25 (46%). Patients with poor outcome (n = 39) had lower mean cTOI 60 minutes off-CPB (48% vs. 58%, P = .003) and 24 hours postoperative (49% vs. 59%, P < .001), higher lactate (8.2 vs. 5.0 mmol/L, P = .005) and higher inotropic scores (10 vs. 6, P = .02) at 24 hours postoperative. ROC analysis indicated that cTOI had moderate predictive accuracy of outcome (AUC = 0.751, P < .001). Multivariable regression analysis confirmed that predictive accuracy was improved using both cTOI and lactate at 24 hours postoperative (AUC = 0.813, 95% CI: 0.705-0.921, P < .001) with optimal cutoff values <58% and >7.4 mmol/L, respectively (sensitivity = 95%). CONCLUSION: Cerebral TOI combined with lactate at 24 hours postoperative are accurate non-invasive predictive biomarkers of patient survival and neurodevelopmental outcome in neonates with CHD undergoing cardiac surgery.