Grainne Nicholson

Brief review: Angiotensin converting enzyme inhibitors and angioedema: anesthetic implications

PurposeAngiotensin converting enzyme inhibitors (ACEIs) are a group of drugs used to treat hypertension and heart failure, with additional benefits, such as cardiovascular and renal protection, in patients with diabetes. However, angioedema as a complication of ACEI therapy is under-recognized. As there are important implications for anesthesiologists and emergency medicine physicians, a review was undertaken to document the scope of the problem of ACEI-induced angioedema.MethodsA review of the published literature (identified by searching Medline, EMBASE and CINAHL) was undertaken, addressing the clinical uses of ACEIs and the incidence, risk factors, pathophysiology, clinical presentation and management of angioedema associated with the use of these drugs.Principal findingsThe incidence of ACEI related angioedema has increased from 0.1-0.2% to 1% over the last decade. Patients who are receiving ACEIs are predisposed to developing angioedema which may be triggered by trauma, airway instrumentation, infection, and irritant fumes, particularly in those who are at increased risk. Cases of acute facial and airway oedema, due to ACEI drug administration, may be misdiagnosed as an anaphylactic reaction, and the association with ACEIs may be ignored. Some cases of intraoperative and postoperative airway edema may be precipitated by airway instrumentation in patients receiving ACEI drugs. The severity of airway compromise ranges from mild facial edema to severe laryngeal or subglottic edema which may prove life-threatening.ConclusionIn view of the widespread clinical indications and ever-increasing use of ACEI drugs, the potentially life-threatening adverse reaction of ACEI-associated angioedema, and its treatment, must be recognized by anesthesiologists and all clinicians involved in airway management.RésuméObjectifLes inhibiteurs de l’enzyme de conversion de l’angiotensine (IECA) sont utilisés contre l’hypertension et l’insuffisance cardiaque et aussi pour la protection cardiovasculaire et rénale, chez les patients diabétiques. L’œdème de Quincke est toutefois peu connu comme complication de l’usage des IECA. Cette situation ayant des répercussions sur le travail des anesthésiologistes et des urgentistes, une revue a été réalisée pour montrer l’étendue du problème de l’œdème de Quincke induit par l’IECA.MéthodeUne revue des articles publiés (découverts dans Medline, EMBASE et CINAHL) a été faite en abordant les usages cliniques des IECA, l’incidence, les facteurs de risque, la physiopathologie, la présentation et le traitement cliniques de l’œdème de Quincke associés à ces médicaments.Constatations principalesL’incidence d’œdème de Quincke relié aux IECA est passée 0,1–0,2% à 1 % pendant la dernière décennie. Les patients qui prennent des IECA sont prédisposés à l’œdème de Quincke qui peut être déclenché par un traumatisme, une exploration instrumentale, une infection et des émanations irritantes, surtout chez ceux qui sont à haut risque. L’œdème aigu du visage et des voies aériennes peut être diagnostiqué à tort comme une réaction anaphylactique et l’association avec les IECA restée inconnue. L’œdème peropératoire et postopératoire des voies aériennes peut dépendre de l’utilisation d’instruments dans les voies aériennes. La sévérité de l’atteinte peut être un léger œdème facial jusqu’à un œdème laryngé ou sous-glottique important et même très grave.ConclusionDans l’optique des indications cliniques largement répandues, et en augmentation constante, de l’usage des IECA, la réaction indésirable et possiblement grave qu’est l’œdème de Quincke, et son traitement, doivent être connus des anesthésiologistes et de tous les cliniciens concernés par le contrôle des voies aériennes.

Ropivacaine for peribulbar anesthesia

BACKGROUND AND OBJECTIVES We compared the efficacy of a mixture of ropivacaine and lidocaine with a mixture of bupivacaine and lidocaine for providing peribulbar anesthesia for cataract surgery. We used the time to adequate block for surgery and ocular and eyelid movement scores as clinical end points. METHODS Ninety patients were allocated randomly to receive 7-10 mL of an anesthetic mixture of equal parts 0.75% bupivacaine and 2% lidocaine or a mixture in which ropivacaine 1% was substituted for bupivacaine. Hyaluronidase 15 IU x mL(-1) was added to both solutions. RESULTS The median time at which the block was adequate to start surgery was 8 minutes for each group. Median ocular movement scores were similar in both groups at all times. Ropivacaine produced decreased eyelid movement scores at 2 (P = .047), 6 (P = .038), and 8 minutes (P = .016). No differences were observed between the groups in the incidence of minor complications or of pain during insertion of the block. Seven patients in the ropivacaine group and 12 patients in the bupivacaine group required supplementary anesthesia. CONCLUSIONS Ropivacaine 1% is an effective alternative to 0.75% bupivacaine for peribulbar anesthesia, when combined with lidocaine and hyaluronidase.

Effects of anaesthesia on the inflammatory response to injury.

Purpose of review The systemic inflammatory response to injury is essential for wound healing and recovery in concert with other endocrinological, metabolic and immunological changes. However, recent studies suggest that a hyperinflammatory state is associated with adverse perioperative outcomes. Therefore interventions that modulate the inflammatory response, surgical, anaesthetic and pharmacological, may enhance recovery with fewer complications. Recent findings Basic research on wound biology has shown the importance of genetic variability in determining the initial inflammatory response. Clinically, studies of cardiac surgery predominate in which genetic polymorphisms have been shown to result in a hyperinflammatory state. Summary The use of an interleukin-1 receptor antagonist to control wound pain and limit local inflammation is under consideration. The role of glucocorticoids in obtunding the inflammatory response to injury with improved outcome requires confirmation with better-quality trials. Systemic lidocaine is anti-inflammatory but is effective only in abdominal surgery. NSAIDs are neglected, despite their widespread clinical use and merit detailed investigation.

Current therapeutic drugs for type 2 diabetes, still useful after 50 years?

Grainne Nicholson, MD, FFARCSI In 2008 it was estimated by the International Diabetes Federation that 246 million adults worldwide have diabetes mellitus (DM) and the prevalence is expected to reach 380 million by 2025. However, this projection is likely to be an underestimate. A recent study using a validated diabetes registry in Ontario found a steady increase in prevalence of 6.2% per year over a decade. This increase in DM has been attributed to a rise in new cases of Type 2 diabetes which is a consequence of obesity, lack of exercise, increased migration of susceptible patients, and an aging population. DM is a costly chronic disease and patients develop microand macrovascular complications that often need surgery. Improved glycemic control has been shown to delay the onset of microvascular complications (nephropathy, retinopathy, and neuropathy), whereas the beneficial effects on macrovascular complications are less clear. Increased knowledge of the pathophysiology of Type 2 diabetes, particularly insulin signaling and insulin resistance, has contributed to the development of novel treatments. In this issue of the journal Chen et al. have highlighted two new groups of drugs: those acting on the incretin pathway, exenatide, and sitagliptin and the synthetic amylin analog, pramlintide. In this article, we briefly review the principal treatments available for Type 2 diabetes to enable the new drugs to be placed in perspective. The primary aim of managing Type 2 diabetes is to delay, or even prevent, the complications of the disease by achieving good glycemic control. In addition to drug therapy, this often involves changes in lifestyle, such as diet and exercise. The main groups of oral drugs available are the sulfonylureas, biguanides, and thiazoldinediones (TZDs), with less common usage of the meglitinides and -glucosidase inhibitors. Insulin is increasingly considered part of a treatment regimen in Type 2 diabetics, particularly the use of long-acting preparations to provide a constant basal insulin release. Sulfonylureas have been used since the 1950s and their efficacy is well established. They have been shown to decrease glycosylated hemoglobin concentrations by 1%–2% and fasting blood glucose concentrations by 3.3–3.9 mmol/L (59–70 mg/dL). Sulfonylureas act primarily by stimulating insulin secretion from the cells of the pancreas. This is achieved by binding to a specific receptor, which closes an ATP-dependent potassium channel resulting in depolarization of the cell membrane, an influx of calcium ions, and the release of preformed insulin granules. All sulfonylureas can cause hypoglycemia, although this is uncommon and usually results from excessive dosage. Other important side effects include an increase in appetite and weight gain so that these drugs may not be the first choice in obese patients. Treatment failure may also occur. Primary failure occurs in 20%–25% of patients started on a sulfonylurea and is shown by an inadequate decrease in fasting blood glucose of 1.1 mmol/L ( 20 mg/dL). In secondary failure, which occurs in 5%–10% patients per year, an initial favorable response of a decrease in fasting blood glucose 1.7 mmol/L ( 30 mg/dL) is not sustained. There has been considerable controversy about the possible enhanced cardiovascular risks to patients taking these drugs. The earlier results of From the Department of Anesthesia, St. George’s, University of London, London, UK. Accepted for publication February 25, 2009. Address correspondence and reprint requests to George M. Hall, MBBS, PhD, DSc (Med), FIBiol, FRCA, Department of Anaesthesia, St. George’s, University of London, Cranmer Terrace, London SW17 0RE. Address e-mail to ghall@sgul.ac.uk. Copyright