The impact of neuraxial clonidine on postoperative analgesia and perioperative adverse effects in women having elective Caesarean section-a systematic review and meta-analysis.

Neuraxial clonidine improves postoperative analgesia in the general surgical population. The efficacy and safety of neuraxial clonidine as a postoperative analgesic adjunct in the Caesarean section population still remains unclear. This systematic review and meta-analysis aims to evaluate the effect of perioperative neuraxial clonidine on postoperative analgesia in women having Caesarean section under neuraxial anaesthesia. We included randomized controlled trials comparing the analgesic efficacy of the perioperative administration of neuraxial clonidine alone or in combination with a local anaesthetic and/or opioids in women having elective Caesarean section under neuraxial anaesthesia when compared with placebo. PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE were searched until February 2017. Eighteen studies were included in the meta-analysis. Neuraxial clonidine reduced 24 h morphine consumption [mean difference (MD): -7.2 mg; 95% confidence interval (CI): -11.4, -3.0 mg; seven studies] and prolonged time to first analgesic request (MD: 135 min; 95% CI: 102, 168 min; 16 studies) when compared with the control group. Neuraxial clonidine increased intraoperative hypotension [odds ratio (OR): 2.849; 95% CI: 1.363, 5.957], intraoperative sedation (OR: 2.355; 95% CI: 1.016, 5.459), but reduced the need for intraoperative analgesic supplementation (OR: 0.224; 95% CI: 0.076, 0.663). The effect of clonidine on intraoperative bradycardia, intraoperative and postoperative nausea and vomiting, postoperative sedation, and pruritus were inconclusive. Neuraxial clonidine did not negatively impact neonatal umbilical artery pH or Apgar scores. This review demonstrates that neuraxial clonidine enhances postoperative analgesia in women having Caesarean section with neuraxial anaesthesia, but this has to be balanced against increased maternal adverse effects.

Dexmedetomidine: the new all-in-one drug in paediatric anaesthesia?

PURPOSE OF REVIEW: Dexmedetomidine is a drug with sedative, anxiolytic, sympatholytic and analgesic properties, which is finding widespread practice in paediatric anaesthesia and related practices. The present review summarizes its pharmacology and current experience with the drug. RECENT FINDINGS: Dexmedetomidine is proving useful in many diverse areas in paediatric anaesthesia where its sedative properties are useful for premedication, fibreoptic intubation and radiologic procedures. Its use as an adjunct for balanced anaesthesia where it can decrease the use of other drugs, reduce emergence delirium, postoperative shivering and vomiting. Muted apoptotic neuroprotective effects may realize benefits in neonates. Cardiac conduction delay, an adverse effect, may prove beneficial for arrhythmias after congenital cardiac surgery. SUMMARY: Most of the paediatric published studies concerning dexmedetomidine are observational in nature, with limited control groups or comparators. Adverse effects (e.g. bradycardia) still require greater scrutiny in the paediatric population and particularly with respect to different age groups. Dexmedetomidine currently has a firm position in the armamentarium of anaesthesia pharmacology. It is not the new all-in-one drug, but it is shaping up as a valuable adjunct for diverse indications within paediatric anaesthesia. VIDEO ABSTRACT: http://links.lww.com/COAN/A44.

A Novel Compound Analgesic Cream (Ketamine, Pentoxifylline, Clonidine, DMSO) for Complex Regional Pain Syndrome Patients.

BACKGROUND: Evidence suggests that complex regional pain syndrome (CRPS) is a manifestation of microvascular dysfunction. Topical combinations of α2-adrenergic receptor agonists or nitric oxide donors with phosphodiesterase or phosphatidic acid inhibitors formulated to treat microvascular dysfunction have been shown to reduce allodynia in a rat model of CRPS-I. Driven by these findings, we assessed the outcomes of CRPS patients treated with a compound analgesic cream (CAC) consisting of ketamine 10%, pentoxifylline 6%, clonidine 0.2%, and dimethyl sulfoxide 6% to 10%. METHODS: An audit was conducted on 13 CRPS patients who trialed the CAC. A detailed report was compiled for each patient which comprised baseline characteristics, including CRPS description, previous treatments, and pain scores (numerical pain rating scale; 0 to 10). Recorded outcomes consisted of pain scores, descriptive outcomes, and concurrent medications/treatments, for which basic analysis was performed to determine the effectiveness of the CAC. Case reports are presented for 3 patients with varying outcomes. RESULTS: Nine patients (69%) reported pain/symptom reduction (4.4 ± 2.1 vs. 6.3 ± 1.9) with use of the CAC. Six patients reported sustained benefits after 2 months of CAC use, and 2 patients reported complete resolution of pain/symptoms: one had early CRPS-I and the other received a partial CRPS diagnosis. An otherwise medication refractory and intolerant patient found partial benefit with the CAC. CONCLUSIONS: These results demonstrate promise for this topical combination as a useful treatment in multimodal therapy for patients with CRPS, with the potential to resolve pain/symptoms in early CRPS patients.

Management of autism in the adult intensive care unit.

Autism comprises a growing segment of the population and can be a management challenge in the intensive care unit (ICU). We present the case of a 22-year-old male with severe autism and intellectual disorder who developed respiratory failure and required a prolonged ICU course. This patient exhibited severe distress, aggression, and self-injurious behavior. Management challenges included sedation, weaning from sedation, and liberation from mechanical ventilation. Success was achieved with a multispecialty team and by tailoring the environment and interactions to the patient's known preferences. The use of dexmedetomidine to wean high-dose benzodiazepines and opiates also permitted successful liberation from mechanical ventilation.

Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study.

Once-daily topical brimonidine tartrate (BT) gel 0.5% was shown to be efficacious and safe for the treatment of erythema of rosacea in previous studies including a 4-week treatment phase. In the present 1-year study, we aimed to assess the long-term safety and efficacy of the treatment. Subjects with moderate to severe erythema of rosacea were instructed to apply topical BT gel 0.5% once daily for 12 months. Severity of erythema and adverse events (AEs) were evaluated. Approximately 345 subject years of exposure to BT gel 0.5% was achieved in the study. The incidence of AEs and AEs judged to be related to the study drug was higher at the beginning and decreased over the course of the study. Similar safety profiles were observed between the subjects who had received or not received concomitant therapies for the inflammatory lesions of rosacea. Effect of topical BT gel 0.5% on erythema severity was observed after the first application and the durability of the effect was maintained until the end of the study at month 12, with no tachyphylaxis observed. In conclusion, once-daily topical BT gel 0.5% is safe and consistently effective for the long-term treatment of moderate to severe erythema of rosacea, even in the presence of concomitant therapies for the inflammatory lesions of rosacea.

Successful treatment of the face post acne erythema using a topically applied selective alpha 1-Adrenergic receptor agonist, oxymetazoline 1.5%, a controlled left to right face comparative trial.

BACKGROUND: Post-inflammatory erythema (PIE) is a common sequalae of acne inflammation, persistent post acne erythema (PAE) is cosmetically unacceptable and sometimes its complete clearance could not be achieved. Oxymetazoline (OXZ) is a synthetic, direct-acting, sympathomimetic agonist that is highly selective for the 1α-adrenoceptor. It is a potent vasoconstrictor and well known for its ability to clinically 'get the red out'. AIM: The aim of this study was to evaluate the efficacy and safety of topical oxymetazoline (OXZ) 1.5% in treatment of post acne erythema (PAE) in a left to right face comparative study. METHODS: This study was conducted on 40 patients diagnosed with post acne erythema for at least 3 months, the left side of the face was treated with topical OXZ 1.5% in liposomal base and was compared to the right side to which topical lipogel was applied as a control. RESULTS: According to the investigator's global assessment of photographs and the analysis of erythema with image analysis software, topical OXZ was significantly effective in diminishing PAE when compared to topical placebo lipogel. CONCLUSION: Topical OXZ is a safe and effective treatment for post-acne erythema.

Review article: the role of the perioperative period in recurrence after cancer surgery.

A wealth of basic science data supports the hypothesis that the surgical stress response increases the likelihood of cancer dissemination and metastasis during and after cancer surgery. Anesthetic management of the cancer patient, therefore, could potentially influence long-term outcome. Preclinical data suggest that beneficial approaches might include selection of induction drugs such as propofol, minimizing the use of volatile anesthetics, and coadministration of cyclooxygenase antagonists with systemic opioids. Retrospective clinical trials suggest that the addition of regional anesthesia might decrease recurrence after cancer surgery. Other factors such as blood transfusion, temperature regulation, and statin administration may also affect long-term outcome.

Managing Food Allergy in Schools During the COVID-19 Pandemic.

In the wake of the COVID-19 pandemic and massive disruptions to daily life in the spring of 2020, in May 2020, the Centers for Disease Control (CDC) released guidance recommendations for schools regarding how to have students attend while adhering to principles of how to reduce the risk of contracting SARS-CoV-2. As part of physical distancing measures, the CDC is recommending that schools who traditionally have had students eat in a cafeteria or common large space instead have children eat their lunch or other meals in the classroom at already physically distanced desks. This has sparked concern for the safety of food-allergic children attending school, and some question of how the new CDC recommendations can coexist with recommendations in the 2013 CDC Voluntary Guidelines on Managing Food Allergy in Schools as well as accommodations that students may be afforded through disability law that may have previously prohibited eating in the classroom. This expert consensus explores the issues related to evidence-based management of food allergy at school, the issues of managing the health of children attending school that are acutely posed by the constraints of an infectious pandemic, and how to harmonize these needs so that all children can attend school with minimal risk from both an infectious and allergic standpoint.

A study on Fu-Yuan Pellet, a traditional chinese medicine formula for detoxification of heroin addictions.

BACKGROUND: Efforts toward researching effective and safe therapies for the treatment of drug addiction and acute heroin withdrawal syndrome remain important objectives in the field of drug addiction. Traditional Chinese medicine (TCM) is viewed as a potential approach to the treatment of drug addiction, and especially to opiate addiction. OBJECTIVES: The objective is to investigate the efficacy and safety of Fu-Yuan Pellet (FYP), a Chinese traditional medicine formula, for the treatment of acute heroin withdrawal syndrome. METHODS: A multicenter, randomized, double-blind, double-dummy, and positive-controlled trial was conducted at 3 drug abuse treatment centers in China. Patients (n = 225) who met a diagnosis of opiate dependence based on DSM IV classification were recruited for this study, ranging in age from 18 to 55 years. Inclusion criteria included a heroin-positive urinalysis, as measured between 8 to 36 hours from last use of heroin, and total withdrawal syndrome scores above 50 before treatment (actual range 65-140). These patients were treated with either FYP or lofexidine in a fixed schedule of doses for 10 days. The total withdrawal syndrome scores and the daily reduction rate were used to measure the effect of FYP vs. lofexidine. RESULTS: Both treatments significantly reduced withdrawal symptoms by day 3, but there was no significant difference overall between lofexidine and FYP in efficacy or safety. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This clinical trial has shown that FYP is effective in the treatment of moderate-to-severe acute heroin withdrawal and has few adverse effects compared to lofexidine. Further study is warranted to determine whether FYP is similar to lofexidine in its potential for reducing stress induced opiate relapse.

The safety and efficacy of glaucoma medication in the pediatric population.

Topical glaucoma medications are widely used for childhood glaucoma, although little is known concerning the use of the newer glaucoma medications in this population. The majority of the references cited were extracted from PubMed. A literature review of all English language reports related to glaucoma medication in the pediatric population since 1980 was performed. Medical therapy of pediatric glaucoma contains four groups of drugs: beta-blockers (timolol and betaxolol), carbonic anhydrase inhibitors (dorzolamide), alpha2-agonists (brimonidine), and prostaglandin analogs (latanoprost). Timolol is the first choice in pediatric glaucoma. In cases with insufficient reduction of the intraocular pressure (IOP), the combination of timolol once a day and dorzolamide twice a day brings about a good control of the IOP. Both medications are effective and well tolerated. The alpha2-agonists have more and potentially serious adverse effects in children and are contraindicated for children younger than 2 years of age. Latanoprost tends to be less effective in lowering IOP in children than in adults. However, no studies are reported where latanoprost is used in monotherapy. Additional study may further delineate this drug's role in treating pediatric glaucoma. The safety profile of latanoprost in children appears excellent.

Multimodal analgesia for controlling acute postoperative pain.

PURPOSE OF REVIEW: Multimodal analgesia is needed for acute postoperative pain management due to adverse effects of opioid analgesics, which can impede recovery; a problem that is of increasing concern with the rapid increase in the number of ambulatory surgeries. Yet, the literature on multimodal analgesia often shows variable degrees of success, even with studies utilizing the same adjuvant medication. RECENT FINDINGS: Nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors consistently reduce postoperative opioid consumption. The N-methyl-D-aspartate antagonists have produced variable results in studies, which may be due to the dose and timing of drug administration. Alpha-2 adrenergic agonists have been useful as adjuvant for regional analgesia but not when administered orally. The alpha-2-delta receptor modulators such as gabapentin have shown early promising results in multimodal analgesia. Local anesthetic injection at the surgical site, though not as a preemptive analgesic, has recently been demonstrated to be beneficial in multimodal analgesia. No new adjuvants have appeared in the last year, which robustly reduce opioid consumption and opioid-related adverse effects. SUMMARY: There is a continuing need to explore new drug combinations to achieve all of the purported goals of multimodal anesthesia.

Alpha2-adrenergic agonists and their role in the prevention of perioperative adverse cardiac events.

Alpha2-adrenergic agonists have been shown to reduce the incidence of perioperative myocardial morbidity and mortality. The purpose of this review article is to summarize the current data pertaining to alpha2-adrenergic agonists and their role in the prevention of perioperative adverse cardiac events. The MEDLINE and Cochrane databases were searched for randomized trials from 1980 to 2006 that assessed perioperative alpha2-agonists and myocardial ischemia, myocardial infarction, and mortality. All recently published studies were reviewed and the data summarized. The currently published randomized controlled trials indicate that alpha2-agonists reduce the incidence of myocardial ischemic episodes in patients with known or suspected coronary artery disease undergoing noncardiac surgery, and clonidine was shown to reduce mortality in noncardiac surgical patients. The authors of the studies concluded that while alpha2-agonists exert beneficial effects on hemodynamics and myocardial protection, large-scale, prospective, controlled trials are still needed.

Brimonidine tartrate for the treatment of glaucoma.

INTRODUCTION: Brimonidine tartrate is a commonly used eyedrop for short- and long-term lowering of intraocular pressure. Its use has been popularized due to its effects on aqueous suppression and uveoscleral outflow, as well as the suggestion of neuroprotection. Although available with alternative preservative vehicles, brimonidine is associated with high rates of local allergy and is contraindicated in breastfeeding women, neonates, young children, and the elderly due to risk of central nervous system depression. Other topical agents with differing advantages have challenged brimonidine's role in the treatment algorithm of ocular hypertension and glaucoma. Areas covered: The authors review the development of topical alpha-adrenergic agonists, with particular attention to the currently available formulations of brimonidine tartrate. Its mechanism of action, pharmacodynamics and safety, and clinical efficacy are analyzed. Expert opinion: Despite clinical familiarity with brimonidine after two decades of use, agents that offer daily dosing, nocturnal effect, and more favorable ocular and systemic side effect profiles have ultimately led to brimonidine's adjunctive use in patients with elevated intraocular pressure or high- or low-tension glaucomas. Still, brimonidine may be advantageous in patients undergoing laser trabeculoplasty or iridotomy, in certain forms of glaucoma, or in pregnant individuals prior to the last trimester, underscoring its clinical importance.

Long-term, open-label extension study of guanfacine extended release in children and adolescents with ADHD.

INTRODUCTION: Guanfacine is a noradrenergic agonist that is believed to improve symptoms of attention-deficit/hyperactivity disorder (ADHD) through selective actions at alpha2A-adrenoceptors in the prefrontal cortex. A recent double-blind, multicenter trial supports the efficacy and safety of guanfacine extended release (GXR) for pediatric ADHD. This long-term, open-label extension was conducted to study the safety profile and effectiveness of GXR for up to 2 years. METHODS: Subjects were 240 children 6-17 years of age with a diagnosis of ADHD who participated in the preceding randomized trial. GXR was initiated at 2 mg/day and titrated as needed in 1-mg increments to a maximum of 4 mg/day to achieve optimal clinical response. RESULTS: The most common adverse events were somnolence (30.4%), headache (26.3%), fatigue (14.2%), and sedation (13.3%). Somnolence, sedation, and fatigue were usually transient. Cardiovascular-related adverse events were uncommon, although small reductions in mean blood pressure and pulse rate were evident at monthly visits. ADHD Rating Scale, Version IV, total and subscale scores improved significantly from baseline to endpoint for all dose groups (P<.001 for all comparisons, intent-to-treat population). CONCLUSION: Long-term treatment with GXR was generally safe for up to 24 months of treatment, and effectiveness was maintained over this treatment period.

Feasibility of dexmedetomidine in facilitating extubation in the intensive care unit.

BACKGROUND: Spontaneous breathing trials (SBT) and intermittent mandatory ventilation (IMV) are common techniques utilized to expedite the ventilator weaning process. These techniques often require the reduction and/or discontinuation of sedatives and analgesics. Reducing these medications can lead to agitation and the inability to conduct SBTs or weaning by IMV. Adding dexmedetomidine (dex), a potent alpha-2-adrenergic receptor agonist that possesses sedative, anxiolytic and analgesic effects without causing significant respiratory depression, may facilitate extubation in these patients. OBJECTIVE: To assess the feasibility of adding dex to facilitate extubation in a group of difficult-to-extubate patients secondary to agitation. METHODS: Mechanically ventilated patients who were deemed difficult to wean and extubate secondary to agitation were evaluated for dex therapy. Inclusion criteria were location in an intensive care unit, intubated and mechanically ventilated, required IV sedation, deemed suitable by unit criteria for weaning and extubation within 24 h of dex initiation, previous attempts at weaning sedation and/or analgesia resulted in agitation causing either severe patient ventilator dyssynchrony, prolong need for intubation, or an inability to conduct a successful SBT. Additional inclusion criteria were unsuccessful use of traditional intravenous agents to control agitation. Recommended dex dosing was a bolus of 1 microg/kg followed by an infusion of 0.2-0.7 microg/kg/h. RESULTS: Twenty-five patients were evaluated for dex therapy with 20 meeting the criteria to treat. All had failed prior attempts at weaning. Fourteen of the 20 patients were successfully weaned and extubated and one patient was reintubated within 48 h, giving a 65% success rate. Heart rate trended down after dex initiation in most patients but did not result in the discontinuation of dex in any patient. The addition of dex was associated with minimal changes in mean arterial pressure. CONCLUSIONS: Dexmedetomidine was initiated in a group of mechanically ventilated patients who failed previous attempts at weaning and extubation secondary to agitation. After dex initiation, 65% of the patients was successfully extubated. Dexmedetomidine was associated with a reduction in concomitant sedative and analgesic use with minimal adverse effect.

Costs and persistence of brimonidine versus brinzolamide in everyday glaucoma care: an analysis conducted on the UK General Practitioner Research Database.

OBJECTIVE: To compare the persistence and costs of brimonidine versus brinzolamide therapy according to data collected by the UK General Practitioner Research Database (GPRD). METHODS: Patients with diagnoses of ocular hypertension or glaucoma, or treated for glaucoma by surgery or laser therapy were identified. Selected patients were prescribed either brimonidine or brinzolamide as monotherapy. Treatment failure was defined as a glaucoma prescription change (adding, removing or replacing a drug, or initiating surgery or laser therapy). Times to treatment failure were compared with an adjusted Cox model using a propensity score method. RESULTS: A total of 2,172 patients received brimonidine and 485 brinzolamide. Mean age was 69.5 years and 46.4% were male. Age and gender did not differ significantly whereas disease duration was longer with brinzolamide. Treatment failure at 1 year was experienced by 47.7% of patients given brinzolamide and by 55.9% given brimonidine (p<0.001). The hazard ratio for failure was less with brinzolamide (0.79: p<0.001) compared to brimonidine, after adjusting for age, gender, comorbidities and duration of follow-up. Adjusted annual costs of glaucoma management (in pound2005) were significantly (p<0.0042) lower with brinzolamide (pound196) than brimonidine (pound230). CONCLUSIONS: According to data from everyday practice collected by the UK GPRD, brinzolamide was found to be more persistent than brimonidine when given as glaucoma monotherapy. Patients continued longer with brinzolamide treatment at a lower cost.

Treatment of children and adolescents with tics and Tourette syndrome.

Tics, patterned movements distinct from stereotypies, myoclonus, and other hyperkinetic movements, are quite common in children, particularly among those with developmental and psychiatric disorders. Thus, tics can indicate the presence of atypical neurodevelopment or broader difficulties with cognition or mood. Tics are also the cardinal feature of Tourette syndrome, a childhood-onset neurobehavioral disorder characterized by a chronic inability to suppress or an urge to perform patterned, repetitive movements. Patients with Tourette syndrome most commonly have, in addition to tics, symptoms of inattention, hyperactivity, obsessiveness, or anxiety. Achieving the most effective treatment of a child with tics is contingent on proper diagnosis of the movement disorder and thorough assessment for other problems, followed by consideration of both nonpharmacologic and pharmacologic interventions for any and all symptoms interfering with the child's function and quality of life. This review focuses primarily on the diagnosis and medical treatment of tics in children and adolescents with Tourette syndrome.

A Nonhormonal Treatment for Moderate to Severe Vasomotor Symptoms of Menopause.

It is estimated that up to 80% of women experience symptoms related to declining estrogen levels that occur with menopause. The most common bothersome symptoms reported by women during and after this transition are vasomotor symptoms, which can include hot flashes, flushing, night sweats, and sleep disturbances. These symptoms are the most common reason women seek care during menopause. Until recently, the mainstay of treatment and symptom relief has been estrogen supplementation. In 2013, the U.S. Food and Drug Administration approved paroxetine, a low-dose selective serotonin reuptake inhibitor, as the first nonhormonal treatment for moderate to severe vasomotor symptoms of menopause. This article provides an overview of the use of paroxetine to treat vasomotor symptoms of menopause, including potential adverse reactions, special considerations for use, and implications for nursing practice.