Pharmacological pupil dilatation after sinus surgery.

Orbital complications after endoscopic sinus surgery are serious problems. Inadvertent contamination of the eye by pharmacological solution can lead to early postoperative anxiety to patients and high concern to surgeons. This is a rare case report of retrograde epinephrine flow through lacrimal duct in sinus surgery with learning tips during postoperative assessment for reassurance in temporary pharmacological effect rather than serious complication.

Distribution of Adrenergic Receptor Subtypes and Responses to Topical 0.5% Apraclonidine in Patients With Blepharoptosis.

PURPOSE: To determine the relationship between the distribution of adrenergic receptors in the human eyelid and the eyelid elevation after topically instilling 0.5% apraclonidine in blepharoptosis patients. METHODS: A total of 26 blepharoptotic patients (30 eyelids) were included in the experimental study. Marginal reflex distance 1 was measured before and after topical instillation of 0.5% apraclonidine. Eyelids were divided into 2 groups according to the responses to topical 0.5% apraclonidine. Patients who positively responded to apraclonidine were classified as group A and those that negatively responded to it were classified as group B. Müller's muscle was obtained during the blepharoptotic surgery, followed by immunohistochemical staining and scoring. This study was approved by the Institutional Review Board of Kim's Eye Hospital and the study protocol adhered to the tenets of the Declaration of Helsinki. RESULTS: α-1D staining intensity was significantly higher in group A than in B (p < 0.001) and α-2C and ß-1 staining intensities were significantly higher in group B than in A (p < 0.001 and p < 0.05, respectively). The difference in ß-2 staining intensity between groups A and B was not statistically significant. CONCLUSIONS: α-1D adrenoceptor was predominant in patients showing a positive response to topical 0.5% apraclonidine. Because apraclonidine has an α-1 agonistic effect, α-1D adrenoceptor may contribute to apraclonidine's elevating effect in patients with blepharoptosis.

Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery.

BACKGROUND: The surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may help prevent postoperative cardiac complications. OBJECTIVES: To determine the efficacy and safety of α-2 adrenergic agonists for reducing mortality and cardiac complications in adults undergoing cardiac surgery and non-cardiac surgery. SEARCH METHODS: We searched CENTRAL (2017, Issue 4), MEDLINE (1950 to April Week 4, 2017), Embase (1980 to May 2017), the Science Citation Index, clinical trial registries, and reference lists of included articles. SELECTION CRITERIA: We included randomized controlled trials that compared α-2 adrenergic agonists (i.e. clonidine, dexmedetomidine or mivazerol) against placebo or non-α-2 adrenergic agonists. Included trials had to evaluate the efficacy and safety of α-2 adrenergic agonists for preventing perioperative mortality or cardiac complications (or both), or measure one or more relevant outcomes (i.e. death, myocardial infarction, heart failure, acute stroke, supraventricular tachyarrhythmia and myocardial ischaemia). DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality, extracted data and independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials. We evaluated included studies using the Cochrane 'Risk of bias' tool, and the quality of the evidence underlying pooled treatment effects using GRADE methodology. Given the clinical heterogeneity between cardiac and non-cardiac surgery, we analysed these subgroups separately. We expressed treatment effects as pooled risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: We included 47 trials with 17,039 participants. Of these studies, 24 trials only included participants undergoing cardiac surgery, 23 only included participants undergoing non-cardiac surgery and eight only included participants undergoing vascular surgery. The α-2 adrenergic agonist studied was clonidine in 21 trials, dexmedetomidine in 24 trials and mivazerol in two trials.In non-cardiac surgery, there was high quality evidence that α-2 adrenergic agonists led to a similar risk of all-cause mortality compared with control groups (1.3% with α-2 adrenergic agonists versus 1.7% with control; RR 0.80, 95% CI 0.61 to 1.04; participants = 14,081; studies = 16). Additionally, the risk of cardiac mortality was similar between treatment groups (0.8% with α-2 adrenergic agonists versus 1.0% with control; RR 0.86, 95% CI 0.60 to 1.23; participants = 12,525; studies = 5, high quality evidence). The risk of myocardial infarction was probably similar between treatment groups (RR 0.94, 95% CI 0.69 to 1.27; participants = 13,907; studies = 12, moderate quality evidence). There was no associated effect on the risk of stroke (RR 0.93, 95% CI 0.55 to 1.56; participants = 11,542; studies = 7; high quality evidence). Conversely, α-2 adrenergic agonists probably increase the risks of clinically significant bradycardia (RR 1.59, 95% CI 1.18 to 2.13; participants = 14,035; studies = 16) and hypotension (RR 1.24, 95% CI 1.03 to 1.48; participants = 13,738; studies = 15), based on moderate quality evidence.There was insufficient evidence to determine the effect of α-2 adrenergic agonists on all-cause mortality in cardiac surgery (RR 0.52, 95% CI 0.26 to 1.04; participants = 1947; studies = 16) and myocardial infarction (RR 1.01, 95% CI 0.43 to 2.40; participants = 782; studies = 8), based on moderate quality evidence. There was one cardiac death in the clonidine arm of a study of 22 participants. Based on very limited data, α-2 adrenergic agonists may have reduced the risk of stroke (RR 0.37, 95% CI 0.15 to 0.93; participants = 1175; studies = 7; outcome events = 18; low quality evidence). Conversely, α-2 adrenergic agonists increased the risk of bradycardia from 6.4% to 12.0% (RR 1.88, 95% CI 1.35 to 2.62; participants = 1477; studies = 10; moderate quality evidence), but their effect on hypotension was uncertain (RR 1.19, 95% CI 0.87 to 1.64; participants = 1413; studies = 9; low quality evidence).These results were qualitatively unchanged in subgroup analyses and sensitivity analyses. AUTHORS' CONCLUSIONS: Our review concludes that prophylactic α-2 adrenergic agonists generally do not prevent perioperative death or major cardiac complications. For non-cardiac surgery, there is moderate-to-high quality evidence that these agents do not prevent death, myocardial infarction or stroke. Conversely, there is moderate quality evidence that these agents have important adverse effects, namely increased risks of hypotension and bradycardia. For cardiac surgery, there is moderate quality evidence that α-2 adrenergic agonists have no effect on the risk of mortality or myocardial infarction, and that they increase the risk of bradycardia. The quality of evidence was inadequate to draw conclusions regarding the effects of alpha-2 agonists on stroke or hypotension during cardiac surgery.

Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the First REVEAL Trial.

An unmet need exists for a safe, tolerable, effective treatment for moderate to severe persistent facial erythema in patients with rosacea. This pivotal phase 3, multicenter, double-blind study evaluated the efficacy and safety of topical oxymetazoline in patients with facial erythema associated with moderate to severe rosacea. Patients were randomly assigned to treatment with oxymetazoline hydrochloride cream 1.0% or vehicle applied once daily for 29 days, and were followed for 28 days posttreatment. The primary efficacy outcome was having at least a 2-grade decrease from baseline on both the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment for rosacea facial redness (SSA) scales (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Safety assessments included treatment-emergent adverse events (TEAEs) and posttreatment worsening of erythema (composite CEA/SSA increase of 1-grade severity from baseline; rebound effect). A total of 440 patients (mean age, 49.5 years; 78.9% females) were randomized (oxymetazoline, n=222; vehicle, n=218); most had moderate erythema. On day 29, significantly greater proportions of oxymetazoline recipients achieved the primary efficacy outcome at each time point (P less than 0.02) and overall (P less than 0.001) compared with vehicle recipients. The incidence of discontinuation due to TEAEs was low in both groups (oxymetazoline group, 1.8%; vehicle group, 0.5%). The most common TEAEs reported during the entire study period were application-site dermatitis, application-site erythema, and headache in the oxymetazoline group (1.4% each), and headache (0.9%) in the vehicle group. Following cessation of treatment, low proportions of patients experienced rebound effect (oxymetazoline group, 2.2%; vehicle group, 1.1%). Oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in patients with moderate to severe persistent facial erythema of rosacea.

J Drugs Dermatol. 2018;17(1):97-105.

Role of Topical Oxymetazoline for Management of Erythematotelangiectatic Rosacea.

OBJECTIVE: To review and summarize topical oxymetazoline's pharmacology, pharmacokinetics, efficacy, safety, cost, and place in therapy for persistent redness associated with erythematotelangiectatic rosacea. DATA SOURCES: Literature searches of MEDLINE (1975 to September 2017), International Pharmaceutical Abstracts (1975 to September 2017), and Cochrane Database (publications through September 2017) using the terms rosacea, persistent redness, α -agonist, and oxymetazoline. STUDY SELECTION AND DATA EXTRACTION: Results were limited to studies of human subjects, English-language publications, and topical use of oxymetazoline. Relevant materials from government sources, industry, and reviews were also included. DATA SYNTHESIS: Data support the efficacy of oxymetazoline for persistent facial redness. Little study beyond clinical trials cited in the drug approval process has been conducted. Current data suggest that oxymetazoline is similar in safety and efficacy to brimonidine. Head-to-head comparisons of topical α-agonists for erythema caused by rosacea are needed. CONCLUSION: The topical α-agonist, oxymetazoline, is safe and effective for reducing persistent facial redness associated with erythematotelangiectatic subtype of rosacea. Health care practitioners selecting among treatments should consider not only the subtype of rosacea but also individual patient response, preference, and cost.

Oxymetazoline hydrochloride cream for facial erythema associated with rosacea.

INTRODUCTION: Rosacea is a chronic skin condition characterized by transient and persistent erythema of the central face. The symptom of persistent erythema can be particularly frustrating for both patients and physicians as it is difficult to treat. Areas covered: Current treatment options for the treatment of rosacea include metronidazole, azelaic acid, sodium sulfacetamide-sulfur, and brimonidine. Until recently, brimonidine gel was the only option approved specifically for the treatment of facial erythema. However, oxymetazoline hydrochloride 1% cream is a newly FDA approved topical medication for adult rosacea patients. A primarily alpha-1a agonist, oxymetazoline hydrochloride (HCl) is thought to diminish erythema through vasoconstriction. Our paper seeks to evaluate evidence for topical oxymetazoline HCl with respect to its efficacy and safety for its approved indication of treating the persistent erythema associated with rosacea. Expert commentary: While assessment of available clinical trial data indicates that the medication is as effective as other available treatment for controlling rosacea-associated erythema with minimal risk of adverse effects, studies of long-term duration and direct comparison will be necessary to establish its place in treatment guidelines and clinical practice. As further evidence becomes available, the real-world clinical potential of topical oxymetazoline cream will become clearer.

Preoperative clonidine use in trans-sphenoidal pituitary adenoma surgeries - a randomized controlled trial.

BACKGROUND: Pituitary masses are common lesions accounting for about 15-20% of all brain tumours. Oozing blood is an annoyance in microscopic sublabial trans-sphenoidal approach for these masses. There have been many ways of reducing the ooze, having their own pros and cons. OBJECTIVE: To find out the efficacy and safety of clonidine in reducing blood loss in pituitary adenoma surgery through a randomized masked trial. METHODS: It was a prospective randomized controlled trial done. Total 50 patients of pituitary adenomas were randomized into two groups. Group A (25 patients) was given 200 µg clonidine orally, while Group B (25 patients) was given placebo. Surgeon, anaesthesiologist and patient were blinded for the trial. Sublabial trans-septal trans-sphenoidal approach to sella and excision of mass was performed in each patient. Patients were studied for pre-, intra- and post-operative blood pressure and heart rate, pre- and post-operative imaging findings, intra-operative blood loss, bleeding grading by surgeon, surgeon's satisfaction about condition of specific part and quality of surgical field, operative time and extent of resection. RESULTS: Blood loss during the surgery, operative time and bleeding grading by the surgeon were found significantly less in the clonidine group, while quality of surgical field, condition of the specific part and extent of resection were found significantly better in the clonidine group (p value <.05). There was no untoward adverse effect of the drug in the test group. CONCLUSION: Clonidine is a safe and effective drug to reduce bleeding in trans-sphenoidal microscopic pituitary adenoma surgeries.

Pharmacological Treatment of Post-Prostatectomy Incontinence: What is the Evidence?

Urinary incontinence is a common and debilitating problem, and post-prostatectomy incontinence (PPI) is becoming an increasing problem, with a higher risk among elderly men. Current treatment options for PPI include pelvic floor muscle exercises and surgery. Conservative treatment has disputable effects, and surgical treatment is expensive, is not always effective, and may have complications. This article describes the prevalence and causes of PPI and the current treatment methods. We conducted a search of the PUBMED database and reviewed the current literature on novel medical treatments of PPI, with special focus on the aging man. Antimuscarinic drugs, phosphodiesterase inhibitors, duloxetine, and α-adrenergic drugs have been proposed as medical treatments for PPI. Most studies were small and used different criteria for quantifying incontinence and assessing treatment results. Thus, there is not enough evidence to recommend the use of these medications as standard treatment of PPI. To determine whether medical therapy is a viable option in the treatment of PPI, randomized, placebo-controlled studies are needed that also assess side effects in the elderly population.

Age and clear eyes are associated with an increased risk of cutaneous squamous cell carcinomas in vemurafenib-treated melanoma patients.

Cutaneous squamous cell carcinoma (cSCC) is a frequent side-effect of vemurafenib treatment. The main aim of this study was to identify the clinical risk factors associated with the development of cSCC in melanoma patients treated with vemurafenib. We carried out a retrospective study, including 63 consecutive melanoma patients treated with vemurafenib for BRAF-mutant metastatic melanoma in an oncodermatological department. Clinical and follow-up data were collected and analysed, and a comparison of the subgroups who did and did not develop cSCC was performed. A total of 42.9% of patients (n=27) treated with vemurafenib developed one or more cSCC. Patients with cSCC were significantly older (P=0.01). Clear eyes were also associated with a higher risk of developing cSCC (odds ratio=3.50; 95% confidence interval: 1.08-12.43). Three patients developed cSCC more than 1 year after the initiation of treatment (12, 16 and 18 months, respectively). Clinicians should be vigilant in older patients undergoing vemurafenib therapy as well as patients with clear eyes as they seem to be at increased risk of developing cSCC, even late after the initiation of treatment.

Alpha-2 adrenergic agonists for the prevention of shivering following general anaesthesia.

BACKGROUND: Shivering after general anaesthesia is common. It is unpleasant but can also have adverse physiological effects. Alpha-2 (α-2) adrenergic agonist receptors, which can lead to reduced sympathetic activity and central regulation of vasoconstrictor tone, are a group of drugs that have been used to try to prevent postoperative shivering. OBJECTIVES: To assess the following: the effects of α-2 agonists on the prevention of shivering and subsequent complications after general anaesthesia in people undergoing surgery; the effects of α-2 agonists on the risk of inadvertent perioperative hypothermia; and whether any adverse effects are associated with these interventions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE on 13 June 2014. Our search terms were relevant to the review question and limited to studies that assessed shivering or hypothermia. We also carried out searches of clinical trials registers, and forward and backward citation tracking. SELECTION CRITERIA: We considered all randomized controlled trials, quasi-randomized studies, and cluster-randomized studies with adult participants undergoing surgery with general anaesthesia in which an α-2 agonist was compared with another α-2 agonist or a placebo for the prevention of shivering. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data, consulting a third review author in the case of disagreements. We used standard Cochrane methodological procedures, including an assessment of risk of bias and use of GRADEpro software to interpret findings. MAIN RESULTS: We included 20 studies with 1401 surgical participants comparing an α-2 agonist against a control. Thirteen studies compared clonidine with a control, whilst seven compared dexmedetomidine with a control. The doses, methods, and time of administration varied between studies: three studies gave the drug orally or as an intravenous bolus preoperatively and nine intraoperatively; one study gave the drug as an infusion starting preoperatively and seven started at varying points from anaesthetic induction to the end of surgery. Whilst all the studies were described as randomized, many provided insufficient detail on methods used. We had anticipated that attempts would be made to reduce performance bias by blinding of personnel and participants, however this was detailed in only six of the papers. Similarly, in some studies detail was lacking on methods to reduce the risk of detection bias. We therefore downgraded the quality of evidence in our 'Summary of findings' table by one level for risk of bias using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.All 20 included studies presented outcome data for postoperative shivering, and in meta-analysis α-2 agonists were shown to significantly reduce the risk of shivering (Mantel-Haenszel risk ratio 0.28, 95% confidence interval 0.18 to 0.43, P value < 0.0001). We found significant evidence of heterogeneity (I(2) = 80%) for this result that was not explained by sensitivity or subgroup analysis; we therefore downgraded the inconsistency of the evidence by one level. Although we did not feel that there were concerns with imprecision or indirectness of the data, we downgraded the quality of the evidence for the risk of publication bias following visual analysis of a funnel plot. Using GRADEpro, we rated the overall quality of the data for shivering as very low. Only one study reported the incidence of core hypothermia, whilst 12 studies measured core temperature. However, as the results for core temperature were reported in different styles, pooling the results was inappropriate. We found no studies with participant-reported outcomes such as experience of shivering or participant satisfaction. We found limited data for the outcomes of length of stay in the postanaesthetic care unit (three studies, 200 participants) and the following adverse effects: sedation (nine studies, 875 participants), bradycardia (eight studies, 716 participants), and hypotension (seven studies, 688 participants). Unpooled analysis suggested that sedation and bradycardia were significantly more common with dexmedetomidine than placebo, with all seven dexmedetomidine studies and none of the clonidine studies reporting statistically significantly higher levels of sedation as an adverse effect. AUTHORS' CONCLUSIONS: There is evidence that clonidine and dexmedetomidine can reduce postoperative shivering, but patients given dexmedetomidine may be more sedated. However, our assessment of the quality of this evidence is very low.

The Successful Treatment of Opioid Withdrawal-Induced Refractory Muscle Spasms with 5-HTP in a Patient Intolerant to Clonidine.

Instituting drug holidays for chronic opioid using patients is becoming commonplace for pain practitioners initiating procedures such as intrathecal pump or spinal cord stimulator trials. As such, pain practitioners need to be adept in their management of acute opioid withdrawal. Successfully weaning an opioid dependent patient off of chronic opioids requires a thorough knowledge of the available adjuvants to assist in this process. However, that selection can become exhausted by adjuvant side effects or by ineffective attenuation of opioid withdrawal symptoms. In that case, novel drugs, or novel application of currently available medications must be sought after to assist in the drug holiday. We present a case in which refractory muscle spasms secondary to opioid withdrawal were successfully treated with an over-the-counter supplement that is not typically used for the attenuation of opioid withdrawal symptoms. In a patient intolerant to the side effects of clonidine, we were able to successfully wean chronic opiates by treating refractory muscle spasms with the serotonin precursor, 5-hydroxytryptophan (5-HTP). We hypothesize that our success with this medication gives further credence to the role of serotonin in opioid withdrawal somatic symptomatology, and supports the need for future research to clarify the role of serotonin precursors or serotonin modulating drugs as potential alternatives in those unable to follow standard treatment protocols.

Naphazoline as a confounder in the diagnosis of carotid artery dissection.

Diagnosing Horner Syndrome can be difficult in the setting of an incomplete triad. A 27-year-old man presented with unilateral eyelid droop and intermittent ipsilateral headaches, having already seen 7 physicians. Physical examination revealed unilateral ptosis but no pupillary miosis or facial anhidrosis. Inspection of his clinical photographs revealed elevation of the ipsilateral lower eyelid, suggesting sympathetic dysfunction. On further questioning, he admitted to naphazoline dependence. Reexamination after ceasing the naphazoline unveiled the anisocoria. Vascular imaging subsequently revealed carotid dissection, and the patient was started on anticoagulant and antiplatelet therapy. The ptosis persisted after conjunctival Müllerectomy. External levator resection was recommended, but patient declined. This case underscores the importance of clinical photography, meticulous medical record review, and complete medication history including over-the-counter preparations. Clinicians should meticulously inspect the lower eyelid in cases of atypical blepharoptosis and consider the effects of eye drops when inspecting pupils for miosis.

The effect of fentanyl and clonidine on early postoperative negative behavior in children: a double-blind placebo controlled trial.

BACKGROUND: Early negative postoperative behavior (e-PONB) is common in children and manifests itself as emergence agitation (EA), emergence delirium (ED), and pain. The objective of this prospective double blind, randomized, placebo-controlled trial was to determine whether IV clonidine or IV fentanyl prior to surgery modifies e-PONB in children. METHODS: Ninety children scheduled for subumbilical surgery under sevoflurane anesthesia supplemented with regional anesthesia were randomized to either receive IV clonidine 2 mcg·kg(-1) , IV fentanyl 2 mcg·kg(-1) or placebo (IV saline) before surgery. Primary outcome measures were the incidence of EA, ED and pain during the first hour after awakening. Secondary outcome measures were side effects such as nausea and vomiting and delayed discharge from PACU. RESULTS: Eighty-seven children (n = 29 per group) completed the study. EA was present in 10 children (six clonidine, none fentanyl, and four placebo, P = 0.04) whereas ED was observed in 20 children (nine clonidine, three fentanyl, and eight placebo P = 0.13). Sixteen children who received placebo had a CHIPPS score of ≥4 compared with nine children in fentanyl group and 18 children receiving clonidine (P = 0.04). Ten children receiving fentanyl vomited during the first postoperative day, compared with six children in placebo group and none in clonidine group (P = 0.003). Discharge from PACU was not affected. CONCLUSIONS: IV fentanyl before surgery but not IV clonidine modifies e-PONB in children undergoing lower abdominal surgery under general anesthesia supplemented with regional anesthesia. The use of fentanyl in this population was also associated with reduced pain scores after awakening but with significantly greater incidence of PONV.

Growth differentiation factor (GDF)-15 blocks norepinephrine-induced myocardial hypertrophy via a novel pathway involving inhibition of epidermal growth factor receptor transactivation.

Accumulating evidence suggests that growth differentiation factor 15 (GDF-15) is associated with the severity and prognosis of various cardiovascular diseases. However, the effect of GDF-15 on the regulation of cardiac remodeling is still poorly understood. In this present study, we demonstrate that GDF-15 blocks norepinephrine (NE)-induced myocardial hypertrophy through a novel pathway involving inhibition of EGFR transactivation. Both in vivo and in vitro assay indicate that NE was able to stimulate the synthesis of GDF-15. The up-regulation of GDF-15 feedback inhibits NE-induced myocardial hypertrophy, including quantitation of [(3)H]leucine incorporation, protein/DNA ratio, cell surface area, and ANP mRNA level. Further research shows that GDF-15 could inhibit the phosphorylation of EGF receptor and downstream kinases (AKT and ERK1/2) induced by NE. Clinical research also shows that serum GDF-15 levels in hypertensive patients were significant higher than in healthy volunteers and were positively correlated with the thickness of the posterior wall of the left ventricle, interventricular septum, and left ventricular mass, as well as the serum level of norepinephrine. In conclusion, NE induces myocardial hypertrophy and up-regulates GDF-15, and this up-regulation of GDF-15 negatively regulates NE-induced myocardial hypertrophy by inhibiting EGF receptor transactivation following NE stimulation.

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.

[Dexmedetomidine]. / Dexmedetomidin.

Dexmedetomidine is a highly selective α2-receptor agonist with sedative, analgetic and anxiolytic effects. It is chemically related to clonidine and has been an authorized drug in Europe since September 2011. Dexmedetomidine enables a level of sedation in which mechanically ventilated patients may be woken by verbal stimulation (Richmond agitation sedation scale RASS 0--3). In this respect dexmedetomidine achieves the same desired effect as propofol and midazolam; however, in direct comparison to a sedation regime with benzodiazepines, dexmedetomidine reduces the prevalence, duration and severity of delirium in intensive care. Patients sedated by dexmedetomidine can statistically be extubated earlier and an influence on duration of stay in the intensive care unit (ICU) has not been shown. Daily therapy costs are approximately 5 times higher than those of propofol but an objective standpoint in relation to clinical cost efficiency is unattainable.

Reverse Takotsubo cardiomyopathy in the setting of anaphylaxis treated with high-dose intravenous epinephrine.

BACKGROUND: Takotsubo cardiomyopathy is seen, though rarely, in anaphylaxis treated with epinephrine. Stress cardiomyopathy is most likely to occur in middle-aged women. The underlying etiology is believed to be related to catecholamine release in periods of intense stress. Catecholamines administered exogenously, and those secreted by neuroendocrine tumors (e.g., pheochromocytoma) or during anaphylaxis have been reported to cause apical ballooning syndrome, or takotsubo syndrome. However, reverse takotsubo stress cardiomyopathy is rarely seen or reported in anaphylaxis treated with epinephrine. OBJECTIVES: To report a case illustrating that high-dose intravenous epinephrine can trigger stress cardiomyopathy, and that the risk is heightened with inappropriate dosing in the treatment of anaphylaxis. CASE REPORT: We report a rare case of iatrogenic reverse takotsubo syndrome in a young woman who was inappropriately treated with high-dose intravenous epinephrine for mild anaphylaxis. CONCLUSION: Inappropriately high doses of intravenous epinephrine can trigger stress cardiomyopathy. Emergency physicians should be familiar with the diagnosis, grading, and appropriate treatments of anaphylaxis to avoid this unnecessary complication.

Intrathecal granuloma formation as result of opioid delivery: systematic literature review of case reports and analysis against a control group.

OBJECTIVE: To investigate the existence of an association between formation of catheter tip intrathecal inflammatory masses with opioid dose and/or concentration. METHODS: A systematic review of catheter tip granulomas case reports and comparison with a control group was carried out. A boolean search was conducted in the electronic databases MEDLINE and EMBASE. The patients' data extracted from the case reports was tested for homogeneity with a control group. Subsequent analysis investigating the association of opioid dose, concentration and flow rate with the formation of catheter tip granulomas was performed. RESULTS: Seventeen articles resulting in 24 patients with granulomata were included in the review. One patient in our department with granuloma formation was added to this group. Control group comprised 31 patients with an average follow-up of 68.3±9.7 months. The groups were homogeneous considering the variables age, gender and duration of pain previous to implant. Morphine dose (r=0.821, p<0.001) and concentration (r=0.650, p<0.001) were significantly correlated with the development of catheter tip intrathecal masses. CONCLUSION: Opioid dose and concentration were significantly associated with the development of catheter tip granulomas. A correlation with opioid concentration was confirmed for the first time.

A prospective survey of patient-controlled epidural analgesia with bupivacaine and clonidine after total hip replacement: a pre- and postchange comparison with bupivacaine and hydromorphone in 1,000 patients.

BACKGROUND AND OBJECTIVES: Patient-controlled epidural analgesia (PCEA) with bupivacaine and hydromorphone provides high quality analgesia after orthopedic surgery but is associated with a frequent incidence of opioid-related side effects (15%-30%). Epidural clonidine has a different side effect profile, but there are no large surveys documenting its use. We performed this prospective survey to evaluate analgesia and the side effect profile in total hip replacement patients before and after a systematic change from PCEA with bupivacaine/hydromorphone to bupivacaine/clonidine. METHODS: Five hundred consecutive patients received PCEA with 0.06% bupivacaine and hydromorphone (10 mcg/mL) as a previously described prechange control group. The standard analgesic regimen was then systematically changed to 0.06% bupivacaine and clonidine (1 mcg/mL) without changing the PCEA settings or other aspects of perioperative care, and 500 consecutive patients were included as a postchange group. All data were prospectively entered and then abstracted from the electronic medical record. Data collection included daily verbal pain scores (VPS), pruritus, nausea, hypotension, need for IV fluid boluses, sedation, and respiratory depression. An online survey to measure staff satisfaction with the changeover was sent to all participating surgeons, anesthesiologists, physical therapists, and physician's assistants. RESULTS: Patient characteristics were similar between groups. Most patients received central neuraxial anesthesia (99%). The clonidine group had lower VPS at rest (2.3 vs 3.7, P<0.001 with 95% confidence interval [CI] of difference of 1.4 [1.1, 1.7]) on POD0. The incidence of nausea was 10%-11% for clonidine and 13%-15% for hydromorphone. The incidence of pruritus was less with clonidine (1 vs 10%, P<0.01 with 95% CI of difference of 9% [6, 12]). However, the incidence of hypotension (20 vs 11%, P<0.001 with 95% CI of differences 9% [5, 14]) and IV fluid boluses was more frequent with clonidine (36 vs 19%, P<0.001 with 95% CI of differences of 16 [11, 12]). Sixty-five percent of staff completed the online survey, and 70% considered clonidine worse than hydromorphone. CONCLUSION: The systematic changeover from epidural hydromorphone to clonidine produced mixed results without obvious superiority. The VPS at rest was reduced only on postoperative day 0; pruritus was reduced, but hypotension was increased. On the basis of medical staff preference, we discontinued the systematic change and returned to our previous standard solution of bupivacaine and hydromorphone for PCEA after total hip replacement.