Cardiovascular Adverse Reactions Research Articles

English

The aim of the present survey was to evaluate different aspects of cardiovascular drug adverse reactions in a cardiac care unit (CCU). All patients admitted to CCU during a 16 months period were recruited into this study. Detection of adverse drug reactions (ADRs) was based on daily chart review and face to face interview with patients. Causality assessment was performed by the World Health Organization (WHO) probability criteria. Seriousness of ADRs was determined by WHO definition. Schumock and Thornton scale was applied to assess preventability of ADRs. Statistical analysis was performed. Among 740 cardiovascular patients admitted to CCU, 70 ADRs were recorded from 44 patients. Headache (15.71%) was the most frequent ADR. The highest ADR rates were attributed to digoxin (44.29%) and atenolol (12.86%). Fifty five (78.57%) of ADRs were serious. The rate of preventable ADRs was 62.86%. Regarding outcome, one (1.43%) ADR led to death. Multivariate logistic regression showed that length of CCU stay (OR = 1.09, 95%CI = 1.02-1.17) and non-ischemic heart diseases (OR = 3.26, 95% CI = 1.57-6.78) were risk factors for ADR occurrence. Cardiovascular drugs could develop fatal adverse reactions in CCU patients. Primary admission diagnosis and duration of CCU stay were risk factors for ADR development.

A Case of Atrial Fibrillation Induced by Inhaled Fluticasone Propionate

Atrial fibrillation (AF) is the most common rhythm disorder observed in clinical practice. Several case reports and case-control studies have associated this condition with the use of systemic corticosteroids. However, to our knowledge, no case of AF induced by inhaled corticosteroids has been reported in the literature. We describe here the case of a 15-year-old boy who reported a paroxysmal AF with fast ventricular response after the administration of fluticasone propionate, which resolved after discontinuation of the drug. Use of the Naranjo adverse-drug-reaction probability scale indicated a possible relationship between the patient's development of AF and fluticasone propionate therapy. More studies are needed to confirm the association between this arrhythmia and the use of high doses of inhaled corticosteroids. Data from this report already suggest that clinicians should be aware of the possibility of adverse cardiovascular reactions when corticosteroids are prescribed also as inhaled preparations.

Safety of Herbal Supplements: A Guide for Cardiologists

Many patients use herbal supplements to treat chronic cardiovascular conditions and often combine herbal ingredients with cardiovascular medications. However, physicians do not reliably elicit a history of herbal use from their patients and may overlook herbal supplements' adverse effects. Although often considered harmless by patients, herbal supplements may cause adverse cardiovascular effects from an herbal ingredient, a contaminant, or an herb-drug interaction. Herbal stimulants, including bitter orange, ephedra, caffeine, guarana, maté, kola, areca, lobelia, khat, and others are the most common category of herbal therapies to cause cardiovascular effects. However, dozens of other herbal ingredients have also been linked to adverse cardiovascular events. In addition to listed ingredients, herbal supplements may become contaminated at a number of stages during production. Pesticides, heavy metals, bacteria, and pharmaceutical agents have been detected in herbal supplements. Supposedly "herbal" products that are adulterated with prescription anorectics, antidepressants, diuretics, phosphodiesterase-5 inhibitors along with other medications have been identified throughout Europe, North America, and Asia. All of these adulterants have potential cardiovascular effects. Herbal interactions with a variety of cardiovascular medications may also lead to adverse events. Herbal ingredients may cause pharmacokinetic as well as pharmacodynamic herb-drug interactions. We review clinically relevant patterns of adverse cardiovascular reactions to herbal supplements, and we provide resources and recommendations for practicing cardiologists evaluating patients with suspected herbal adverse effects.

Effect of psychological care on changes in auditory evoked potential and hemodynamics during anesthetic induction with remifentanil

Objective To explore psychological care on changes in auditory evoked potential (AEP) and hemodynamics during anesthetic induction with remifentanil. Methods 30 ASA Ⅰ-Ⅱ patients were divided into study group and conrol group. The study group received psychological care one day before surgery, a intravenous injection of remifentanil of 1μg/kg 4 min before anaesthestic induction, and then a continuous infusion of remifentanil 0.1 μg/kg/min, which was decreased to 0.05μg/kg/min during anesthetic induction; while the control group received esmolol of 300μg/kg/min, which was reduced to 200 μg/kg/min during induction. The medications were terminated 10 min after intubation. AEP, ECC, HR, SBP, and RPP were compared between the two groups and then analyzed statistically. Results AEP did not differ significantly between the two groups at different time points (P>0.05). SBP, HR, and RPP changed slightly in the study group after intubation. Conclusions Psychological care is helpful in making remifentanil more effectively suppress the adverse cardiovascular reactions during intubation. Key words: Remifentanil; Tracheal intubation; Vecuronium bromide; Fentanil; Haemodynamics; Psychological care

Effects of patient's tolerance to laryngeal mask airway and tracheal tube on the appropriate level of sevoflurane anesthesia

Objective To compare the effects of patient's tolerance to laryngeal mask airway (LMA) and tracheal tube (TT) on the appropriate level of sevoflurane anesthesia.Methods Eighty ASA Ⅰ or Ⅱ patients aged 30-60 yr weighing 50-70 kg undergoing elective thyroid or breast surgery were randomly divided into 2 groups (n=40 each):LMA group and TT group.Anesthesia wag induced with propofol 1.6mg/kg,fentanyl 3μg/kg and recuronium 0.6mg/kg.LMA or tracheal tube was inserted,and the patients were mechanically ventilated.Anesthesia was maintained with inhalation of 1.5%-3.0% sevoflurane and 50% N2O in O2 in group LMA,and with 2.5%-5.0% sevoflurane and 50% N2O in O2 in group TT.The flow of O2 and N2O was 0.7-1.0L/min,and the concentration of sevofluranee was adjusted to maintain AAI at 15-25.ECG,HR,MAP,SpO2,PETCO2,AEP and end-tidal sevoflurane concentration were continuonsly monitored.The end-tidal sevoflurane concentration was recorded at 1,5 and 10 min after LMA/TT was placed (T1-3),at 1h after skin incision (T4) and at the end of operation before removal of LMA or extubation (T5).The recovery time of consciousness,adverse cardiovascular events and adverse reactions were recorded.Results The end-tidal sevoflurane concentration was significantly lower,the recovery time of consciousness and removal of LMA or extubation time were shorter,and the incidence of adverse cardiovascular events and adverse reactions was lower in LMA group than in TT group.Conclusion At the same depth of anesthesia (AAI 15-25),sevoflurane concentration is significantly lower in LMA group than in TT group,with fewer complications and smaller cardiovascular reaction. Key words: Laryngeal masks; Intubation,intratracheal; Sevoflurane

Cardiovascular adverse reactions from NSAIDs are more than COX-2 inhibition alone

This editorial refers to ‘Association of myocardial infarctions with COX-2 inhibition may be related to immunomodulation towards a Th1 response resulting in atheromatous plaque instability: an evidence-based interpretation’, by Ireneusz T. Padol et al.

Neurological and Cardiovascular Adverse Events Associated with Antimanic Treatment in Children and Adolescents

To identify the factors associated with incident neurological and cardiovascular adverse events in children and adolescents treated with antimanic agents, a retrospective, longitudinal study was conducted. Medicaid medical and pharmacy claims between January 1996 and December 2005 were used to identify 3657 children and adolescents prescribed antimanic medications, and a random sample of 4500 children not treated with psychotropic medications. All adverse events examined (sedation/drowsiness, headaches, involuntary movements/extrapyramidal symptoms (EPS), cardiovascular events, hypertension, and orthostatic hypotension) were more prevalent in the antimanic-treated cohort. The odds of developing incident sedation/drowsiness and headaches were significantly higher for those prescribed carbamazepine, and co-prescribed selective serotonin reuptake inhibitors or antipsychotics. The odds of incident involuntary movements/EPS were significantly higher for those co-prescribed antimanic and antipsychotic agents, and those with comorbid central nervous system (CNS), organic brain disorders/mental retardation, or epilepsy. Incident cardiovascular events, hypertension, and orthostatic hypotension odds were significantly higher for those co-prescribed antimanic agents and antipsychotics, or those with comorbid epilepsy or metabolic conditions. Co-prescription of antimanic and antipsychotic agents is more likely associated with neurological and cardiovascular adverse reactions, especially in young patients with preexisting CNS/neurological disorders.

Nonsteroidal Anti-Inflammatory Drugs: A Critical Review on Current Concepts Applied to Reduce Gastrointestinal Toxicity

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs worldwide. Nevertheless, their intake is frequently associated with gastrointestinal side effects, representing still an important medical and socio-economic problem. In recent years efforts focused on the development of highly selective COX-2 inhibitors with an improved gastric tolerability profile. However, severe cardiovascular adverse reactions challenged the initial enthusiasm in this new class of anti-inflammatory drugs. In addition, the market withdrawals of some coxibs led to a relative reluctance in prescribing COX-2 inhibitors in clinical practice. As a consequence, the interest for alternative approaches to reduce gastrointestinal side effects associated with NSAIDs has re-emerged. There are two main components of gastric damaging properties of NSAIDs: (1) the acute toxicity associated with the short-term intake of NSAIDs, which is principally caused by local irritation of the gastric mucosa (2) the chronic toxicity resulting mainly from systemic effects associated with prolonged administration of NSAIDs. Based on that background two different approaches were pursued in the search for GI sparing NSAIDs: a) modification of classical NSAIDs by associating them with phospholipids, cyclodextrins, or chemical moieties that release gastroprotective mediators and b) defining novel targets as well as developing new compounds like dual COX/5-LO or mPGES-1 inhibitors. This review provides the first comprehensive overview of all currently applied approaches taken to improve the risk-benefit ratio of NSAIDs focusing on the structure activity relationships and the respective mechanism of action underlying the individual approaches. The insight gained in this review is useful for further research activity in this field.

Efficacy and safety of carvedilol for heart failure in children and patients with congenital heart disease

There have been few reports describing the use of carvedilol in children or patients with congenital heart disease. Therefore, its optimal regimen, efficacy, and safety in these patients have not been adequately investigated. Subjects were 27 patients with two functioning ventricles, for whom carvedilol was initiated (from December 2001 to December 2005) to treat heart failure. All patients had failed to respond to conventional cardiac medication. They consisted of 12 males and 15 females, aged 23 days to 47 years (median age: 2 years). Heart failure due to ischemia (myocardial infarction, intraoperative ischemic event) or due to myocardial disease (cardiomyopathy, myocarditis), and heart failure with atrial or ventricular tachyarrhythmia represented 70% of all cases. Carvedilol was initiated at a dose of 0.02-0.05 mg/kg/day, which was increased by 0.05-0.1 mg/kg/day after 2 days, 0.1 mg/kg/day after 5 days, and 0.05-0.1 mg/kg/day every month thereafter with a target dose of 0.8 mg/kg/day. This study retrospectively assessed the efficacy and adverse reactions based on changes of symptoms, cardiothoracic ratio (CTR), left ventricular ejection fraction (LVEF), and human atrial natriuretic peptide (hANP)/b-type natriuretic peptide (BNP) blood levels. The mean follow-up period was 10.2 months (range: 1-46 months). Twenty-six (96.3%) patients showed improvement in symptoms and were discharged from the hospital. However, the remaining one patient failed to respond and died. Significant cardiovascular adverse reaction was seen in none of the patients. The mean CTR decreased from 61.8% +/- 5.3% before treatment to 57.6% +/- 7.4% after treatment (P < 0.05, n = 25), and the mean LVEF improved from 41.4% +/- 23.1% to 61.1% +/- 10.1% (P < 0.05, n = 10), respectively. Mean hANP and BNP levels showed a decrease from 239.1 pg/ml to 118.3 pg/ml and a significant decrease from 437.9 pg/ml to 120.5 pg/ml, respectively (P < 0.05, n = 10). Improvements in these data were also demonstrated when analyzed individually among the pediatric group (aged younger than 18) and the congenital heart disease group. Initiation of carvedilol at a lower dose with more gradual dose escalation, compared with previously reported regimens, might have efficacy with low incidence of adverse effects in pediatric patients and patients with congenital heart disease. Carvedilol may be effective in treating heart failure in children due to ischemia, myocardial disease, and complicated by tachyarrhythmia.

Coronary Vasospasm and Atrial Fibrillation Associated with Ondansetron Therapy

To provide further evidence of cardiovascular adverse effects of ondansetron, including new-onset atrial fibrillation, ST segment elevation, and chest pain subsequent to ondansetron administration, and to review cardiovascular adverse events related to several 5-hydroxytryptamine type 3 (5-HT(3)) receptor antagonists. A 51-year-old male with an uncomplicated past medical history was admitted for an elective inguinal hernia repair and septoplasty. His maintenance medications were discontinued prior to surgery. After a second 4-mg dose of intravenous ondansetron was administered, he developed nausea and diaphoresis. His electrocardiograph revealed new-onset atrial fibrillation and inferolateral ST segment elevation with ST segment alternans. During emergent cardiac catheterization, no obstructive coronary artery disease was evident. The patient's heart rhythm was electrically converted to normal sinus rhythm. During 3 years of follow-up, he has had no return of chest pain or hypotension. Although considered a safe class of medications by many clinicians, several of the 5-HT(3) receptor antagonists have been associated with serious cardiovascular effects. Three case reports described cardiac dysrhythmias and 9 documented coronary vasospasm and chest pain, possibly resulting from ondansetron. This is the first reported case of a combination of hypotension, atrial fibrillation, ST segment elevation, and chest pain following ondansetron administration after elective surgery in a healthy adult male with a nonconfounding medication profile. The Naranjo probability scale indicated that ondansetron was the probable cause of these cardiovascular events. This case report supports the concern regarding cardiovascular adverse effects of ondansetron. Clinicians should be aware of cardiovascular adverse reactions that may be associated with intravenous ondansetron and monitor for electrocardiographic changes as indicated. Further investigation is needed to delineate the actual incidence of cardiovascular effects associated with ondansetron and whether the intravenous rate of administration is a contributing factor.

A pharmacovigilance study of antihypertensive medicines at a South delhi hospital.

The aim of the present study was to monitor adverse drug reactions associated with antihypertensive drugs. The study was conducted in medicine out patient department of 150-bed Majeedia Hospital at Hamdard University Campus in New Delhi. The study was conducted by way of one to one patient interview by a registered pharmacist using a questionnaire-based Adverse Drug Reaction Monitoring Form drafted according to the World Health Organisation Monitoring Guidelines. A total of 34 adverse drug reactions were observed in 250 hypertensive patients during the four month study. A high percentage of adverse drug reactions occurred in middle aged and female patients. Of the 34 adverse drug reactions, 18 (52.9%) were mild, 14 (41.2%) moderate and only 2 (5.8%) were classified as severe. Combination therapy was associated with significantly high occurrence (P < 0.05) of adverse drug reactions, with a total of 21 (61.8%) as compared to monotherapy (n=13, 38.2%). Cardiovascular adverse drug reactions constituted a major component, followed by gastrointestinal and respiratory complaints. Beta-blockers were the drug category associated with majority of adverse drug reactions, followed by angiotensin-converting enzyme inhibitors and calcium channel blockers. The above pharmacovigilance study presents the adverse drug reaction profile of antihypertensive medicines prescribed in our University Teaching Hospital. It was concluded that calcium channel blockers were the most frequently prescribed drug category but beta blockers were associated with higher frequency of adverse drug reactions.

Does memantine induce bradycardia? A study in the French PharmacoVigilance Database

To review the cardiovascular adverse drug reactions (ADRs) with memantine reported to the French PharmacoVigilance Database. We reviewed all the observations of cardiovascular ADRs with memantine reported to the French PharmacoVigilance Database up to May 2007. We recorded the characteristics of patients (age, sex and underlying disease) and of ADRs (nature, seriousness, delay in occurrence, evolution, imputability). After exclusion of 16 cases, the cardiac origin of which was not clearly assessed, 36 cardiac ADRs with memantine were recorded between its commercialisation in France (July 2003) and May 2007. These ADRs consisted of 18 reports of bradycardia and 18 reports of various cardiovascular ADRs (orthostatic hypotension with fall[6] electrocardiogram perturbations[4] fainting[2] malaise with arterial hypotension[2] arterial hypotension and acute renal failure[1] fatal heart failure[1] sudden death[2]). Among the 18 reports of bradycardia, 7 cases occurred with memantine as the sole suspected drug and all but one resolved after memantine's discontinuation. Cardiovascular properties of memantine seem to be complex and remain quite unclear. Despite its drawbacks and its descriptive design, our study suggests that memantine could determine some cardiac ADRs, especially bradycardia; the mechanism of which remains unexplained.

A clinical trial of using antiplatelet therapy to prevent restenosis following peripheral artery angioplasty and stenting

To evaluate the clinical effect and restenosis rate of antiplatelet therapy following peripheral artery angioplasty and stenting. After successful placement of peripheral artery stents to 103 patients with peripheral arterial occlusive disease (PAOD) in were randomized assigned to 2 groups: antiplatelet therapy group receiving clopidogrel 75 mg plus aspirin 100 mg (n = 56) and control group (n = 47) receiving anticoagulation therapy low molecular weight heparin (LWMH) for 7 d plus long-term warfarin. The patients were followed up 1 day, and 1, 6, 12, and 18 months after the operation to undergo color Doppler ultrasonography, and examinations of blood routine, bleeding time, coagulation time, and ankle-brachial Index. The primary endpoint events included major bleeding rate, and composite rate of restenosis and reocclusion. The secondary endpoint events included cardiovascular events, death, and adverse drug reaction. There were no significant differences in the baseline data between these two groups. The thrombotic occlusion rate was 1.8% in the antiplatelet group and 0% in control group, and the restenosis rate was 14.3% in the antiplatelet group and 25.5% in control group (both P > 0.05). The bleeding complication rate of the antiplatelet group was 1.8%, significantly lower than that of the anticoagulation group (19.1%, P < 0.01). There were not significant differences in cardiovascular event rate and mortality 18 months after operation between these two groups. Antiplatelet therapy combined with clopidogrel plus aspirin is effective and safe in preventing restenosis following peripheral artery angioplasty and stenting.

Carbonic Anhydrase Inhibition: Insight into Non-COX-2 Pharmacological Effect of some Coxibs

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent the most commonly used medications for the treatment of pain and inflammation, but numerous well-described adverse drug reactions (ADRs) limit their use. These drugs act via the inhibition of cyclooxygenase (COX) enzyme of which at least two isoforms were described: COX-1 which plays important roles in homeostatic processes such as thrombogenesis and homeostasis of the gastrointestinal tract and kidneys and COX-2 expressed in pathological conditions such as inflammation or cancer proliferation. Selective COX-2 inhibitors or "coxibs" were initially developed as a therapeutic strategy to avoid not only the gastrointestinal but also the renal and cardiovascular side effects of non specific NSAIDs. However, this class of drug did not fulfill all their promises. Indeed, numerous unexpected side effects have limited their use and some of them have been withdrawn or suspended from the market for different safety reasons including cardiovascular, hepatic and skin adverse reactions. For instance, cardiovascular warnings have been applied to the whole class of coxibs and more recently for all classical NSAIDs as well. However, differences in the chemical structures should be taken into consideration in order to discriminate between coxibs and the development of some ADRs of which renal events and hypertension. The aim of this paper is to focus on the differences in chemical structures of all marketed COX-2 inhibitors and their unexpected effects on carbonic anhydrase in order to provide non-COX-2 mechanistic insights into some of the differences observed between coxibs.

Effets cardio-vasculaires des inhibiteurs de la cholinestérase dans la maladie d’Alzheimer

In the treatment of mild to moderate Alzheimer's disease, cholinesterase inhibitors (ChEIs) have shown modest clinical benefits. Use of donepezil, galantamine and rivastigmine is widespread in clinical practice. Although relatively safe, ChEIs are prescribed for a frail population and may have clinically significant adverse drug effects on the cardiovascular system. Arrhythmia and syncope have been reported. Most of the cardiovascular adverse drug reactions to ChEIs might be related to stimulation of the parasympatic nervous system. Early and accurate recognition of past and present arrhythmia or syncope appears to be essential. Monitoring for pharmacokinetic (cytochromes P450 CYP2D6 or CYP3A4) and pharmacodynamic interactions and a more systematic clinical follow-up are mandatory. In patients with relevant risk factors or with cardiovascular adverse drug reactions a multidisciplinary approach with a cardiologist is required. Prevention of cardiac adverse events requires a careful clinical evaluation before the introduction of the ChEIs and an early recognition of cardiac disturbances under treatment.

Update on guidelines for the treatment of chronic musculoskeletal pain

Chronic musculoskeletal pain is a major - and growing - burden on today's ageing populations. Professional organisations including the American College of Rheumatology (ACR), American Pain Society (APS) and European League Against Rheumatism (EULAR) have published treatment guidelines within the past 5 years to assist clinicians achieve effective pain management. Safety is a core concern in all these guidelines, especially for chronic conditions such as osteoarthritis that require long-term treatment. Hence, there is a consensus among recommendations that paracetamol should be the first-line analgesic agent due to its favourable side effect and safety profile, despite being somewhat less effective in pain relief than anti-inflammatory drugs. Cyclooxygenase-2 (COX-2)-selective anti-inflammatory drugs were developed with the goal of delivering effective pain relief without the serious gastrointestinal (GI) side effects linked with traditional non-selective non-steroidal anti-inflammatory drugs (NSAIDs). Clinical trial evidence supported these benefits, and COX-2 inhibitors were widely adopted, both in clinical practice and in official guidelines. Recently, accumulating data have linked COX-2 inhibitors with serious cardiovascular and/or cardiorenal effects and/or serious cutaneous adverse reactions (SCARs), particularly at anti-inflammatory doses or when used long term. Regulatory authorities in both Europe and the USA have responded to these data with the withdrawal of rofecoxib and valdecoxib, and the strengthening of prescribing advice on all anti-inflammatory drugs. COX-2 inhibitors and non-selective NSAIDs should now be used with increased caution in patients at increased cardiovascular and/or cardiorenal risk, e.g., patients with congestive heart failure, hypertension, etc. Regulatory advice and good clinical practice are to use anti-inflammatory drugs at the lowest effective dose and for the shortest possible time. There are as yet no updated official guidelines that incorporate these new data and regulatory advice. An international multidisciplinary panel, the Working Group on Pain Management, has generated new recommendations for the treatment of moderate-to-severe musculoskeletal pain. These guidelines, formulated in response to recent developments concerning COX-2 inhibitors and other NSAIDs, focus on paracetamol as the baseline drug for chronic pain management; when greater analgesia is desired, the addition of weak opioids is recommended based on a preferable GI and cardiovascular profile, compared with non-steroidal anti-inflammatory drugs.

The use of COX-2 inhibitors for acute dental pain: A second look

On the basis of their perceived better safety profile compared with other analgesic agents, cyclo-oxygenase-2 (COX-2) inhibitors have been prescribed frequently as first-line agents to treat acute dental pain. However, recently identified cardiovascular adverse reactions associated with these drugs mandate a reappraisal of their use in dental practice. TYPES OF STUDIES REVIEWED. The authors reviewed 18 clinical studies that evaluated the efficacy of a COX-2 inhibitor for the treatment of acute dental pain. All of the studies used the widely established third-molar surgical extraction model to induce postsurgical inflammatory based pain, and all were randomized, double-blinded and placebo-controlled. However, numerous vagaries in overall study design made direct comparisons difficult. None of the studies established any of the COX-2 inhibitors as clearly better than ibuprofen, the current gold standard for the treatment of surgically induced dental pain. However, in single-dosing scenarios, the COX-2 inhibitor often demonstrated a longer duration of action compared with ibuprofen. The evidence to date fails to demonstrate any therapeutic advantage to using a COX-2 inhibitor to treat acute dental pain compared with ibuprofen. In the rare event that a COX-2 inhibitor may be appropriate, the clinician must inform the patient of the potential risks, and the drug should be used for the shortest possible time.

Introduction — The coxib controversies

Much concern has arisen in the past year concerning the occurrence of serious cardiovascular adverse reactions from rofecoxib, celecoxib and some other members of the coxib group of NSAIDs. Factors underlying the sudden appearance of these events have been proposed to include the use of high doses of the drugs, undue reliance on their safety profile from controlled clinical trails and potent marketing leading to exposure of a large population who would inevitably present risks of cardiovascular adverse events. Suggestions are presented for future uses of the coxibs and approaches for their more cautious use and marketing. The use of the term "COX-2 inhibitor" to describe the coxibs is unhelpful and should be avoided since all NSAIDs have some degree of COX-2 inhibitory effect, though they may vary in their selectivity. Coxibs should be set aside in a group of their own within the broader category of the NSAIDs in view of both their cardiovascular risk and unique pharmacology.

A model of prediction system for adverse cardiovascular reactions by calcineurin inhibitors among patients with renal transplants using gene-based single-nucleotide polymorphisms

The application of pharmacogenomic information to diagnostic assays is expected to improve the prediction of drug efficacy and toxicity, leading to appropriate therapeutic regimens for individual patients. Cardiovascular events are common and severe adverse drug reactions (ADRs) among transplant patients treated with calcineurin inhibitors (CNIs). We conducted case-control association studies using 50,947 gene-based single-nucleotide polymorphisms (SNPs) to identify genetic variations that might be associated with cardiovascular risk factors in 72 renal transplant recipients with CNI therapy. The overall incidence of cardiovascular events was 13.9% (10/72) among patients receiving cyclosporine or tacrolimus; arrhythmias in six patients (8.3%), ischemic heart diseases in two patients (2.8%), and heart failure in two patients (2.8%). On the basis of results of the genome-wide association studies, we attempted to establish a scoring system to predict individual risks for cardiovascular toxicity of cyclosporine and tacrolimus. Estimation of the predictive performance was carried out by the use of internal leave-one-out cross-validation test. When we combined arrhythmia, ischemic heart disease and heart failure cases as subjects with a cardiotoxicity phenotype, nine of ten ADR patients and 50 of 62 non-ADR patients were correctly classified into the respective categories using the top eight SNPs. In addition, the proportion of individuals in the control population (n=246) with scores over the cut-off (11.0%) was close to the cardiovascular ADR frequency (8.3%) among renal transplant patients in the previous clinical study. Our results open the possibility that prediction of CNI-induced cardiovascular complications can lead to better prognosis and quality of life among kidney-transplant patients, and to improved immunosuppressive regimens.

Current Trends in Local Anesthesia in Cosmetic Plastic Surgery of the Head and Neck: Results of a German National Survey and Observations on the Use of Ropivacaine

The goal of this study was to evaluate at the national level the current practice in the use of local anesthetics in cosmetic head and neck surgery and to compare the results with the novel local anesthesia technique used in the authors' department over the past 2 years. A questionnaire was posted to all 211 board-certified members of the Association of German Plastic Surgeons. The questions related to the daily practice in rhinoplasty, blepharoplasty, otoplasty, face lift, and forehead lift. The focus was laid on anesthesia techniques, local anesthetics, vasoconstricting agents, dosages, activity onset, observed side effects, mean duration of each procedure type, and surgeon satisfaction with the anesthetic used. A total of 86 questionnaires (40.8 percent) were returned. The overall analysis revealed that local anesthetics were used in 88.9 percent of all cosmetic procedures of the head and neck. Prilocaine 1% (Xylonest; AstraZeneca, Wedel, Germany) was the most frequently used local anesthetic (32.0 percent), followed by lidocaine 1% (Xylocaine; AstraZeneca) and mepivacaine 1% (Scandicaine; AstraZeneca). Ropivacaine 0.2% (Naropin; AstraZeneca) was used only by 1.1 percent and ropivacaine 0.75% only by 0.9 percent (including two of the authors). Approximately half of the respondents (47.2 percent) used epinephrine 1:100,000 for vasoconstriction. In face lifts, the necessity of repeated "top-up" infiltration was reported in more than half (54.7 percent) of the procedures. Ten percent of surgeons surpassed the maximum recommended dosages when working without ropivacaine. Overall adverse cardiovascular effects were reported in 5.9 percent of rhinoplasties and 8.1 percent of face lifts performed mostly with prilocaine and lidocaine. No adverse cardiovascular reactions or overdoses were noticed with the use of ropivacaine. The survey showed a clear trend toward the increasing use of local anesthetics in cosmetic surgery of the head and neck. Although the use of prilocaine and lidocaine prevailed, adverse cardiovascular reactions in up to 8.1 percent seem high for cosmetic procedures. Furthermore, the need of additional intraoperative top-up infiltration adds to an uncontrolled cumulative effect and patient discomfort. On the basis of their positive 2 years of experience with ropivacaine, the authors strongly believe that ropivacaine offers significant advantages, both in efficacy and prolonged duration of analgesia, while reducing the risk for adverse side effects due to lesser toxicity. This observation deserves further investigation in an established comparative study.