Dav y C.H. Cheng, MD, MSc, FRCPC, FCAHS

• Distinguished University Professor and Chair
• Department of Anesthesia and Perioperative Medicine
• University of Western Ontario
• Chief of Anesthesia and Perioperative Medicine
• London Health Sciences Center and St. Joseph's Health Care
• London, Ontario, Canada

Even with appropriate precautions virus nyc generic fosfomycin 3 gr without prescription, acute attacks of gout often follow surgical procedures in patients with a history of gout antibiotics for sinus infection and alcohol cheap generic fosfomycin uk. Extraarticular manifestations of gout and side effects of drugs used to control the disease deserve consideration when formulating the plan for anesthesia management infection questions on nclex generic 3 gr fosfomycin otc. Renal function is evaluated antibiotic overview proven 3 gr fosfomycin, since clinical manifestations of gout usually increase with deteriorating renal function antimicrobial underwear for women buy fosfomycin paypal. Abnormalities detected on the electrocardiogram could reflect urate deposits in the myocardium uti antibiotics have me yeast infection order fosfomycin 3 gr free shipping. The increased incidence of systemic hypertension, ischemic heart disease, and diabetes mellitus in patients with gout must be considered. Although rare, adverse renal and hepatic effects may be associated with the use of probenecid and colchicine. Limited temporomandibular joint motion from gouty arthritis, if present, can make direct laryngoscopy difficult. Primary gout is due to an inherited Lesch-Nyhan Syndrome Lesch-Nyhan syndrome is a genetically determined disorder of purine metabolism that occurs exclusively in males. Clinically, patients are often mentally retarded and exhibit characteristic spasticity and self-mutilation. Self-mutilation usually involves trauma to perioral tissues, and subsequent scarification may caused difficulties with direct laryngoscopy for tracheal intubation. Seizure disorders associated with this syndrome are often treated with benzodiazepines. Hyperuricemia is associated with nephropathy, urinary tract calculi, and arthritis. Management of anesthesia is influenced by co-existing renal dysfunction and possible impaired metabolism of drugs administered during anesthesia. The presence of a spastic skeletal muscle disorder suggests caution in using succinylcholine. The sympathetic nervous system response to stress is enhanced, which requires caution in the administration of exogenous catecholamines to these patients. Lactate-containing solutions for intravenous infusion are also avoided to minimize the theoretical possibility of metabolic acidosis because of lactate administration during the perioperative period. Glycogen Storage Disease Type 1b Glycogen storage disease type 1b is a rare autosomal recessive disease in which glucose-6-phosphate, a product of metabolic cleavage of glycogen, cannot be transported to the inner surface of microsomes because of a deficiency in its transport system. In glycogen storage disease type 1b, glycogen accumulates in the liver, kidneys, and intestinal mucosa, and glucose availability to tissues is impaired. Clinical signs and symptoms resemble those described for glycogen storage disease type 1a. In addition, patients with type 1b experience recurrent infections resulting from impaired neutrophil activity. If surgery is planned, preoperative fasting is minimized, and glucose-containing infusions are administered intravenously throughout the perioperative period. Preoperative normalization of the blood glucose concentration may improve platelet function and decrease the likelihood of intraoperative bleeding. Intraoperative monitoring of blood glucose concentration is recommended, since hypoglycemia may be profound and difficult to recognize during general anesthesia. Iatrogenic hyperventilation and its associated respiratory alkalosis may stimulate the release of lactate from skeletal muscles and aggravate metabolic acidosis. Treatment of significant metabolic acidosis might include administration of sodium bicarbonate. The defect can result in a deficiency or an excess of a precursor or end product of metabolism that is normally involved in the production of glycogen from glucose. Ultimately, the signs and symptoms of a specific disorder of carbohydrate metabolism are a reflection of the effects produced by alterations in the amount of precursors or end products of metabolism that result from the enzyme defects. As a result, glycogen cannot be hydrolyzed in hepatocytes, neutrophils, and possibly other cells, which leads to its intracellular accumulation. Hypoglycemia can be severe, and oral feedings are required every 2 to 3 hours to maintain acceptable blood glucose concentrations. Mental retardation, growth retardation, and seizures resulting from hypoglycemia are likely. Renal enlargement, also caused by accumulation of glycogen, can manifest as chronic pyelonephritis. A hemorrhagic diathesis may be due to platelet dysfunction, and recurrent epistaxis and bleeding after minor trauma and surgery may occur. Survival beyond 2 years of age is unusual, although surgical creation of a portocaval shunt may benefit some patients. Management of anesthesia must include provision of exogenous glucose to prevent intraoperative hypoglycemia. Classic manifestations include mental retardation, seizures, and aminoaciduria (Table 15-5). Management of anesthesia in patients with disorders of amino acid metabolism is directed toward maintenance of intravascular fluid volume and acid-base homeostasis. Use of anesthetics that could evoke seizure activity should be avoided, since these patients are likely to have seizure disorders. Phenylketonuria Phenylketonuria is the prototype of disorders attributable to abnormal amino acid metabolism. Phenylalanine accumulates as a result of an enzymatic deficiency of phenylalanine hydroxylase. The skin may be friable and vulnerable to damage from pressure or friction created by adhesive materials. Also, these patients are likely to have associated vitamin B12 deficiency, especially with their strict die. If this is the case and the patient has B12 deficiency resulting from a lack of supplementary vitamin treatment, nitrous oxide should probably be avoided. Complications arising from this vascular disease are the most common causes of morbidity and mortality early in life. The diagnosis of homocystinuria is confirmed by demonstrating homocystine in the urine. Thromboembolism can be life threatening and is presumed to reflect activation of Hageman factor by homocystine, which results in increased platelet adhesiveness. Measures to minimize the risk of thromboembolism during the perioperative period should include administration of pyridoxine or betaine, both of which decrease homocystine concentrations and thus platelet adhesiveness. Preoperative hydration, infusion of dextran, and early ambulation may also help prevent deep vein thrombosis. Maple Syrup Urine Disease Maple syrup urine disease is a rare inborn error of metabolism that results from defective carboxylation of branchedchain amino acids. In the absence of adequate enzyme activity, consumption of foods containing branched-chain amino acids results in the accumulation of these amino acids as well as ketoacids in tissues and blood. Excess concentrations of Homocystinuria Homocystinuria is due to failure of transsulfuration of precursors of cystine, an important constituent of cross-linkages in collagen. Growth retardation and delayed psychomotor development are often a consequence of this chronic metabolic imbalance. Infection or fasting commonly results in acute metabolic decompensation, with increased plasma levels of branched-chain amino acids and ketoacids resulting from the breakdown of endogenous proteins. Increased plasma levels of ketoacids contributes to the production of metabolic acidosis. Hypoglycemia is a possibility and presumably reflects the ability of increased plasma leucine concentrations to stimulate release of insulin. Treatment is directed at decreasing the plasma levels of branched-chain amino acids and ketoacids with peritoneal dialysis or hemodialysis. Parenteral nutrition using preparations devoid of branched-chain amino acids may also be effective. Surgery and anesthesia introduce a number of hazards in the perioperative management of patients with maple syrup urine disease. For example, catabolism of body proteins produced by surgery or infection can result in increased blood concentrations of branched-chain amino acids. Even blood in the gastrointestinal tract, as can occur following tonsillectomy, produces an added metabolic load in patients with maple syrup urine disease. Accumulation of branched-chain amino acids in the circulation can produce neurologic deterioration during the perioperative period. The danger of hypoglycemia in affected patients is exacerbated by the period of fasting that precedes elective surgery. Therefore, it is useful to initiate an intravenous infusion of glucose-containing solution intraoperatively. Measurement of arterial pH is helpful for detecting metabolic acidosis caused by accumulation of ketoacids. Experience with anesthesia in patients with this disorder is limited, and recommendations are based more on theory than on clinical experience. The impact of preoperative fasting on amino acid metabolism and intravascular fluid volume is lessened by permitting ingestion of clear fluid up to 2 hours before surgery. Generous administration of intravenous fluids and glucose is also helpful in minimizing hypovolemia and protein catabolism. Methylmalonyl-Coenzyme A Mutase Deficiency Methylmalonyl-coenzyme A mutase deficiency is an inborn error of metabolism that can result in methylmalonicacidemia. Acute treatment includes intravenous administration of crystalloid solution containing bicarbonate. Events during the perioperative period that increase protein catabolism (fasting, bleeding into the gastrointestinal tract, stress, tissue destruction) may predispose to acidosis. Because of its detrimental impact on overall health and functional status, obesity is now considered one of the leading preventable causes of medical illness in the world. Surgeon General considers obesity a "national epidemic" and "a serious public health threat. Controlling the obesity epidemic will depend on a better understanding of its causes as well as a systems-based team approach to its medical management. It should be noted that the weight category term morbid obesity has been replaced with the term clinically severe obesity. Epidemiology Over the past 20 years, obesity has increased dramatically, and it is now recognized as a national public health threat. In the United States in 2007 and 2008, it was estimated that approximately two thirds of adults (73 million people) were overweight or obese. Obesity prevalence has steadily increased, and in 2007 and 2008, it affected approximately 32% of men and 35% of women. Over the last few years, the prevalence of childhood obesity has nearly tripled and is currently estimated at about 25%. On average, the annual health care costs for an obese patient are approximately 42% more than for a normal-weight patient. This reduction in basal metabolic rate leads to slow weight loss during the dieting phase but rapid weight gain when normal caloric intake is resumed. The risk of premature death is doubled in the obese population and the risk of death resulting from cardiovascular disease is increased fivefold in the obese compared with the nonobese. Pathophysiology Weight gain results when caloric intake exceeds energy expenditure. Energy expenditure is primarily determined by basal metabolic rate, which is responsible for maintaining homeostasis of bodily functions. Most metabolic activity occurs within lean tissue and involves small sources of energy expenditure, including the thermal effect of physical activity and the heat produced by food digestion, absorption, and storage. Exercise can increase energy consumption not only during exercise but for up to 18 hours afterward. It does so by increasing the A positive caloric balance is stored by the body as fat in adipocytes. Triglycerides serve as an efficient form of energy storage because of their high caloric density and hydrophobic nature. The increase in metabolic activity of abdominal fat may contribute to the higher incidence of metabolic disturbances associated with central obesity. Abdominal obesity is more common in men and is therefore known as android fat distribution. Peripheral fat around the hips and buttocks is more common in women and is known as gynecoid fat distribution. Environmental factors such as stress and cigarette smoking stimulate cortisol production, which may facilitate deposition of extra calories as abdominal fat. These cytokines worsen glucose intolerance by decreasing the secretion of adiponectin, a powerful insulin sensitizer. Leptin, another hormone secreted by adipose tissue, travels centrally to the ventromedial hypothalamus and modulates the secretion of neuropeptides that regulate energy expenditure and food intake. Leptin secretion accelerates inflammatory changes by activating monocytes and decreasing the capacity of neutrophils to migrate and activate. Ghrelin appears to modulate appetite both peripherally and centrally by affecting the mechanosensitivity of gastric vagal afferents, making them less sensitive to distention and thus facilitating overeating. An antiobesity vaccine directed against the hormone ghrelin is currently under development. The developers are hoping to produce a vaccine that induces an autoimmune response against ghrelin, preventing it from reaching the central nervous system so that its effects on appetite are suppressed. With abdominal obesity, the high level of fatty infiltration of omental adipocytes (usually devoid of fat) leads to an increased influx of fatty acids, hormones, and cytokines. All of these substances eventually stimulate the liver to produce increased levels of very low-density lipoproteins and apolipoprotein B. As a result the pancreas is stimulated to secrete more insulin and more pancreatic polypeptides. However, it is clear that the metabolic consequences from inheritance of maladaptive genes are not entirely responsible for the current obesity epidemic. However, in affluent societies where food is very calorie dense and serving sizes are abnormally large, this ability to conserve and store energy may actually prove deleterious to survival.

It is important to understand the anatomy of each joint in order to appreciate how mechanical disturbances can cause a clinical problem antimicrobial nanotechnology buy generic fosfomycin on line. The rotator cuff comprises the supraspinatus antibiotics for uti duration buy 3 gr fosfomycin with amex, infraspinatus infection jaw bone purchase discount fosfomycin, teres minor and subscapularis tendons virus x book discount 3 gr fosfomycin amex, which insert into the greater and lesser tuberosities of the humerus antibiotic blue pill cheap fosfomycin amex. This forms a musculotendinous cover to the front antibiotic vantin purchase fosfomycin on line, top and back of the head of the humerus the impingement syndrome (often also called supraspinatus tendonitis or subacromial bursitis) Rotator cuff tears, which may be partial or complete. The impingement can occur between the rotator cuff, the subacromial bursa, the anterior third of the acromion, the coracoacromial ligament and the acromioclavicular joint. Impingement tests may be performed in which local anaesthetic is injected into the subacromial space. Physiotherapy and a short course of antiinflammatory medication are the first-line management. Injection of local anaesthetic and cortisone into the subacromial space is performed if this fails. Subacromial decompression can be performed if the patient fails to improve with non-operative measures, either as an arthroscopic or now less commonly as an open procedure. The undersurface of the anterolateral acromion is cleared and smoothed, the coracoacromial ligament is released and the subacromial bursa excised. The scan can be used as a dynamic test to show the impingement as the patient moves their arm. Management Non-operative treatment Approximately 65 per cent of patients can expect significant relief of symptoms with non-operative treatment. Corticosteroid injection into the subacromial space may also be tried, but repeat injections should be limited to avoid further weakening of the rotator cuff structures. Surgical repair the following questions must be considered before surgical intervention: Is the patient symptomatic, i. If these investigations show no evidence of ectopic calcium, blood investigations, including measuring inflammatory markers, should be considered as the differential diagnosis of acute calcific tendonitis includes septic arthritis of the glenohumeral joint. The pain, which is caused by swelling and pressure within the tendon, is sometimes so intense that the patient will present themselves to the Accident and Emergency Department as an emergency. In chronic calcific tendonitis, the patient will present with signs and symptoms more consistent with impingement. An ultrasound scan can also be used to assess the rotator cuff and sometimes shows evidence of residual calcium deposits not seen on a plain X-ray. Operative intervention is often contraindicated in the first phase as it is likely to leave the patient with significant postoperative pain, which will reduce their ability in the second and third stages to mobilize the shoulder. In the second (frozen) phase, when the pain is less severe yet the shoulder remains stiff, a physiotherapy exercise programme should be undertaken. Investigation Clinical diagnostic indicators Characteristically, there are three clinical phases as the process progresses: freezing: characterized by severe pain especially at night, with a restricted range of movement. Auto antibodies should be measured to exclude an inflammatory arthritis or other rheumatological conditions, including polymyalgia rheumatica. An ultrasound-guided injection of steroids around the biceps tendon can be employed if symptoms persist. Alternatively, in elderly patients, a biceps tenotomy can be performed, in which the long head of biceps is simply cut. Occasionally, a patient presents with a rupture of the long head of biceps, often preceded by chronic symptoms of bicipital tendonitis commonly found in association with other rotator cuff pathology. An ultrasound scan can be used to assess inflammation and swelling, particularly in the bicipital groove. Management Initially, non-operative treatment consists of rest and the use of anti-inflammatory medication. Arthroscopy and a washout of the joint can give symptomatic relief but does not alter the underlying arthritic process. If there is a disturbance of this balance the shoulder becomes unstable and may dislocate or subluxate. Investigation Clinical diagnostic indicators the patient may present with pain and reduced range of movement in the shoulder, secondary to apprehension and loss of confidence. Management When a patient under the age of 20 years dislocates their glenohumeral joint for the first time, they have at least a 60 per cent chance of a further dislocation in the next 2 years, which is independent of physiotherapy provision. Operative intervention may be undertaken as either an arthroscopic or open procedure. There are two main types of operative intervention: Investigation Clinical diagnostic indicators the patient presents with pain on the lateral aspect of the elbow, often aggravated by lifting objects, shaking hands and exercise, particularly when wielding a tennis racket. Following surgery the arm is generally immobilized for a period of 2 weeks to allow the capsulolabral complex to heal before physiotherapy is commenced. Imaging A plain X-ray may show sclerosis of the lateral epicondyle in the region of the insertion of the common extensor tendons. Injection of a corticosteroid may prove beneficial initially but, in the long term, seldom conveys any advantage over physiotherapy alone. The injection of autologous blood at the site of the pain and tenderness has been described. The extensor tendon origin is released from the lateral epicondyle of the humerus and any damaged tissue and bone is also removed. Elbow pain is a common complaint and can arise from any of the bones, tendons, muscles and ligaments that support the joint. Less commonly pain can be referred to the elbow from the neck, the shoulder or distal structures. It is usually caused by the accumulation of inflammatory fluid in the olecranon bursa in response to repeated minor trauma. Aspiration and injection of the bursa with a corticosteroid can be considered if rest and oral medication fail to produce any improvement; but the patient should be told that injection carries the risk of introducing infection, which can lead to skin breakdown and the development of a sinus. The whole bursa can be excised if the swelling is a cosmetic and physical inconvenience. If this fails to resolve the situation, the bursa can be drained and excised, but this may leave a problem with wound closure. The results of replacement surgery are not as good as hip and shoulder replacement, as there is a greater risk of the prosthesis becoming loose. For the chronically painful elbow, with failed non-operative measures, open or arthroscopic excision of the radial head and synovectomy may improve symptoms. Investigation Clinical diagnostic indicators the patient will present with pain extending down to the hand with a variety of clinically detectable sensory, motor, reflex, autonomic and trophic changes in its region of innervation. Operative repair of the distal biceps can be performed using either a single- or two-incision approach. The tendon is repaired either by inserting anchors into the radial tuberosity or by tunnelling it within the bone. In addition to the median nerve, the tendons to the finger flexors (flexor digitorum superficialis, flexor digitorum profundus and flexor pollicus longus) pass through the carpal tunnel. There is very little space within the tunnel and any change in the volume of adjacent structures causes pressure on the median nerve which affects its function. Investigation Clinical diagnostic indicators the pain is generally centred over the anterolateral proximal forearm in the region of the neck of the radius. Maximum tenderness is usually found four finger breadths distal to the lateral epicondyle. Management Non-operative treatment includes the provision of a splint to prevent movement, particularly at night. It most commonly affects the first dorsal compartment (abductor pollicis longus and extensor pollicis brevis) and the second dorsal compartment (extensor carpi radialis, longus and brevis). Management Conservative treatment comprises rest, splintage and anti-inflammatory medication. For chronic symptoms, the injection of a corticosteroid into the tendon sheath can be undertaken. If this fails, then operative release of the tendon sheath under local anaesthesia can be performed. Investigation Clinical diagnostic indicators the patient will have had troublesome wrist pain following a fracture of the scaphoid or following an injury when a fracture was not detected. Imaging Plain X-rays show joint space narrowing, subchondral sclerosis, osteophyte formation and cystic change. If symptoms continue to progress, then excision of the trapezium and ligament reconstruction and tendon interposition may help. Imaging Plain X-rays usually show an intact lunate but, depending on the stage of disease, subsequent X-rays may show sclerosis followed by collapse and fragmentation and, ultimately, superimposed arthritic change. In some cases, where there is an abnormally large difference in length between the radius and ulna, which potentially could cause pressure on the lunate contributing to the avascularity, a radial shortening may be performed. Revascularization techniques involving a bone graft taken from elsewhere in the body can be undertaken. Prosthetic replacement has been described but there is an incidence of instability and dislocation of the prosthesis. Other alternatives include excision arthroplasty, interposition arthroplasty and silastic replacement arthroplasty. Management Non-operative management with splintage, antiinflammatory drugs and disease-modifying medication can be effective. It mostly affects the distal interphalangeal joints, causing pain and swelling spreading to involve all the fingers of the hands. Investigation Clinical diagnostic indicators As the radioulnar joint and the extensor tendons become involved in the disease process they become painful, swollen and tender. Surgical intervention includes repair of ruptured tendons, transfer of tendons, joint replacement, synovectomy, arthroplasty and arthrodesis. It is associated with: Management Rest may allow the swelling to resolve and the condition improve. If the patient is unable to place their hand flat on a table, a test implying a fixed flexion contracture, surgical treatment is worthwhile although many elderly people are content to live with quite a severe deformity. Aspiration and/or corticosteroid injection of the ganglion is associated with a high rate of recurrence. They are small, hard swellings, usually in the mid-line of the flexor tendon sheaths. No specific investigation is required if the triggering can be demonstrated and there is the expected palpable swelling on the volar aspect of the hand overlying the heads of the metacarpals. The hand should then be splinted in a neutral position of function to avoid a contracture. This very stable configuration allows flexion, extension, abduction, adduction, internal and external rotation. The main problems caused by diseases of the hip are pain and restriction of movement. Pain in the hip joint is classically felt in the groin, but may also be referred down to the knee. Restriction of movement as well as activityrelated symptoms, night pain and stiffness in the morning are common, especially in the degenerate hip. The patient may walk with a limp, use a walking stick and complain of functional inabilities, such as being unable to put on their socks and shoes. Do not forget that pain felt in the hip may be a referred pain from the lower lumbar spine and sacroiliac joints because of their shared nerve supply from the L2, 3 and 4 nerve roots. Clinical diagnostic indicators Patients with trochanteric bursitis are often athletes or older overweight women. It causes pain in the groin and along the medial aspect of the thigh which can be reproduced by resisted adduction of the hip. The two muscles merge to form a large tendon which inserts into the lesser trochanter. The pain of iliopsoas tendonitis is experienced over the lesser trochanter, where there may be palpable 192 the bones, joints and soft tissues of the lower limb tenderness, although the overlying structures may mask this sign. The pain is exacerbated by flexion of the hip, as iliopsoas is the primary flexor of the hip. Investigation All of the above soft tissue causes of pain can be investigated in the same way. Rarely, a surgical exploration and excision of the bursae or division of the iliopsoas tendon may be required. Clinical diagnostic indicators All children should be clinically screened at a routine postnatal examination. Management Treatment should be designed to achieve and maintain a concentric reduction of the joint, and varies with age. In children where the hip joint is not satisfactorily reduced, further surgery may be necessary to obtain coverage of the femoral head within the acetabulum. The femoral head undergoes osteonecrosis, becomes softer and deformed and then remodels. Clinical examination reveals decreased abduction and internal rotation of the hip joint. Surgery involving osteotomies about the hip joint can be considered if the above methods fail. It is not uncommon for these patients to develop secondary osteoarthritis later in life and require a hip replacement. It may follow a recent viral infection, particularly of the upper respiratory tract.

The rate of recovery depends on both the clearance rate of the drug and the ability of marrow megakaryocytes to proliferate and increase platelet production 0157 infection purchase discount fosfomycin line. Even if the platelet count is very low bacteria lqp-79 cheap fosfomycin 3 gr online, bleeding is unlikely and patients can be allowed to recover without platelet transfusion virus neck pain buy 3 gr fosfomycin. About 60% of these patients will show a response antimicrobial ointment making buy fosfomycin cheap online, and up to 50% will have long-lasting improvement in platelet count antimicrobial 7287 buy fosfomycin 3 gr without prescription. Among patients who do not respond to zidovudine antibiotics and diabetes 3 gr fosfomycin with amex, splenectomy can be helpful in more than 85% of cases if done early in the course of the thrombocytopenia. Substitution of low-molecular-weight heparin for unfractionated heparin is not an option, because there is significant antibody cross-reactivity. Oral anticoagulants should never be started until there is continuous and successful coverage with a direct thrombin inhibitor. The immediate reduction in protein C levels that occurs with the initiation of warfarin therapy can lead to worsening thrombosis, including massive skin necrosis and limb gangrene. If this occurs, warfarin should be discontinued and vitamin K given to reverse its effect. This diagnosis can be made only by excluding all other causes of nonimmune and immune platelet destruction. Platelet survival in severely affected patients can be measured in hours rather than days, with destruction occurring mainly in the spleen. Some patients demonstrate only modest shortening of platelet survival, which suggests a subnormal rate of platelet production. If there is a need for emergency surgery or clinical evidence of intracranial hemorrhage, the patient should also be given intravenous immunoglobulin and platelet transfusions at least every 8 to 12 hours, regardless of the effect on the platelet count. Some patients who receive platelet transfusions will show a relatively normal posttransfusion platelet count and reasonable platelet survival. Even when there is no posttransfusion improvement in the platelet count, however, sufficient numbers of the transfused platelets may survive to improve hemostasis. In this case, splenectomy should be considered if the platelet count is less than 10,000 to 20,000/mm3. Approximately 50% of patients will achieve a permanent remission after splenectomy. If the thrombocytopenia becomes severe, a higher daily dose of steroids together with weekly intravenous immunoglobulin, especially during the last 2 to 3 weeks of pregnancy, may be needed to prevent maternal bleeding. Therefore, in children at risk, platelet counts should be checked every 2 to 3 days until the platelet count begins to increase. Consequently, this is not a time when an accurate diagnosis is easily made, so treatment should address as many potential contributing factors as possible. It is inherited as either an autosomal dominant or autosomal recessive trait with an estimated prevalence ranging from 1 in 100 to 3 in 100,000 individuals. In those with more severe disease, the bleeding time is markedly prolonged but the platelet count is normal. These individuals should be treated for any bleeding episode and given prophylactic treatment for even minor surgical procedures. Qualitative Platelet Disorders Abnormalities in platelet function are often first noted as a complication of an acute illness or surgery. These patients experience severe bleeding with mucosal hemorrhage, hemarthroses, and muscle hematomas reminiscent of that in hemophilia A or B. However, unlike patients with hemophilia, these patients have a very prolonged bleeding time. The value of treatment with desmopressin in patients with type 2 disease is less certain. This formulation can also be effective in controlling bleeding associated with tooth extraction or minor surgery. Desmopressin therapy is most effective in treating mild bleeding episodes or in preventing bleeding during minor surgery. However, even if the response is suboptimal, bleeding may be partially contained, or, in the case of surgical prophylaxis, blood loss and the need for transfusion can be reduced. The response can decrease with repeated doses because of the development of tachyphylaxis. Patients with myeloproliferative disorders, such as polycythemia vera, myeloid metaplasia, idiopathic myelofibrosis, essential thrombocythemia, and chronic myelogenous leukemia, frequently exhibit abnormal platelet function. Some patients have very high platelet counts and demonstrate either abnormal bleeding or a tendency for arterial or venous thrombosis. In patients with polycythemia vera, expansion of the total blood volume and an increase in blood viscosity may contribute to the thrombotic risk. The most consistent laboratory abnormalities in patients with bleeding are defects in epinephrine-induced aggregation and in dense granule and -granule function. Abnormal platelet function, including defects in adhesion, aggregation, and procoagulant activity, are observed in patients with dysproteinemia. The concentration of the monoclonal protein spike appears to correlate with the abnormalities in platelet function. It appears that the uncleared metabolic product guanidinosuccinic acid acts as an inhibitor of platelet function by inducing endothelial cell nitric oxide release. Platelet adhesion, activation, and aggregation are abnormal and thromboxane A2 generation is decreased. Most patients with uremia have a prolonged bleeding time that is corrected by hemodialysis. For acute bleeding episodes, desmopressin therapy can improve platelet function transiently. In general, the most likely cause of hemorrhage in severe liver disease is a discrete defect, such as bleeding varices or a gastric or duodenal ulcer. However, if a cirrhotic patient has widespread bleeding, including ecchymoses and oozing from puncture sites, a coagulopathy should be considered. Platelet dysfunction resulting from high levels of circulating fibrin degradation products increases the bleeding tendency. Aspirin and other nonsteroidal antiinflammatory drugs have a well-recognized impact on platelet function. Nonsteroidal antiinflammatory drugs such as indomethacin, ibuprofen, and sulfinpyrazone also inhibit platelet cyclooxygenase, but their effect is reversible and lasts only as long as the particular drug is in the circulation. Such agents are weak inhibitors of platelet function and are not usually associated with severe clinical bleeding. However, they can contribute to bleeding when other aggravating factors, such as treatment with other anticoagulants, a gastrointestinal disorder, or surgery, are present. Certain foods, food additives, vitamins, and herbal products-such as vitamins C and E, -3 fatty acids, and Chinese black tree fungus-can also reversibly inhibit platelet function through the cyclooxygenase pathway. The impact of antibiotics on platelet function can be a major contributor to hemorrhage in critically ill patients. The penicillins, including carbenicillin, penicillin G, ticarcillin, ampicillin, nafcillin, and mezlocillin, can interfere with both platelet adhesion and platelet activation and aggregation. Significant clinical bleeding can occur if these antibiotics are administered in very high dosages. The presence of aggravating factors related to the critical illness must be important, since abnormal bleeding is rarely seen when these antibiotics are used in generally healthy patients. Volume expanders, such as dextran, can interfere with platelet aggregation and procoagulant activity when infused in large amounts. This can be a significant disadvantage in the trauma setting but can be useful in the vascular surgery setting to prevent platelet thrombosis. Hydroxyethyl starch is less likely to interfere with platelet function but can cause a detectable defect if given in amounts in excess of 2 L. Because the platelets are dysfunctional, the absolute platelet number does not predict bleeding risk. Treatment with desmopressin may improve a mild to moderate platelet defect, especially if the risk of bleeding is relatively minor. The bleeding time, results of platelet function analysis, or the thromboelastogram may be used to measure end points of coagulation but will not guarantee adequacy of platelet function for the challenge of surgery. As a general rule, sufficient platelet transfusions to increase the percentage of normal/functional platelets to the 10% to 20% range will be sufficient to correct drug-related platelet dysfunction. The thrombotic event usually occurs in association with some triggering event that further increases hypercoagulability. Synthesis of both protein C and protein S is vitamin K dependent, so individuals who are protein C deficient are at particular risk of thrombosis if warfarin therapy is initiated in the absence of protective anticoagulation with heparin. In patients with protein C deficiency, purified protein C concentrate and activated protein C can be used. Therefore, factor Va Leiden stays active in the circulation longer than normal, which promotes increased thrombin generation. The prevalence of factor V Leiden varies considerably in different ethnic populations. It is present in 5% of people of northern European descent but only rarely in those of African or Asian descent. Another thrombophilia that operates via an increase in prothrombotic proteins is known as the prothrombin gene mutation (prothrombin 20210A), which causes levels of prothrombin to be considerably higher in affected individuals than in the general population. The importance of this thrombophilia is similar to that of factor V Leiden and lies in the frequency of the gene rather than its potency. Also as with factor V Leiden, ethnicity plays a significant role in the prevalence of this gene. It occurs in about 4% of individuals of European descent but rarely in patients of African or Asian descent. Patients with these conditions are also at risk of thrombosis of splenic, hepatic, portal, and mesenteric blood vessels. The pathogenesis of these thromboses is not clear, but increased activation and aggregation of platelets may be important for this hypercoagulable state. Adenocarcinoma of the pancreas, colon, stomach, and ovaries are the tumors most often associated with thromboembolic events. Indeed, these malignancies often present with an episode of deep vein thrombosis or migratory superficial thrombophlebitis. Of all patients who develop primary thrombophlebitis, 25% to 30% will have a recurrence, and 20% of these will turn out to have cancer. The pathogenesis of the thrombotic tendency appears to relate to a combination of release of one or more procoagulant factors by the tumor that can directly activate factor X, endothelial damage by tumor invasion, and blood stasis. The overall incidence of thrombosis is approximately 1 in 1500 pregnancies but is higher in women who have an inherited hypercoagulable state, a history of deep vein thrombosis or pulmonary embolism, or a family history of thromboembolic disease; who are obese; who are kept at bed rest for a prolonged period; or who require cesarean section. The risk of pulmonary embolism is highest during the third trimester and immediately postpartum and is a significant cause of maternal death. The association of oral contraceptive use with thrombosis and thromboembolism appears to be multifactorial. Women who also smoke, have a history of migraine headaches, or have an inherited hypercoagulable defect are at increased risk (30-fold higher) of venous thrombosis, pulmonary embolism, and cerebrovascular thrombosis. There appears to be a weaker relationship between estrogen use at the time of menopause and the occurrence of thrombosis. The term antiphospholipid antibody syndrome is used when patients experience thromboses or pregnancy complications and have laboratory evidence of antiphospholipid antibodies in their blood. Antiphospholipid antibody syndrome can be primary, as the sole manifestation of autoimmune disease, or secondary in association with systemic lupus erythematosus (secondary antiphospholipid antibody syndrome). The risk of thrombosis appears to be greater with lupus anticoagulants or antibodies with activity specifically directed at 2-glycoprotein I. The exact mechanism of the thrombotic action of these antibodies has yet to be defined. The antibodies might activate endothelial cells to increase the expression of vascular adhesion molecule 1 and E-selectin. This would increase the binding of white blood cells and platelets to the endothelial surface and lead to thrombus formation. Patients with lupus anticoagulants have an increased propensity for thrombosis, with 30% to 60% of patients experiencing one or more thrombotic events during their lifetime. Isolated venous thrombosis or thromboembolism make up two thirds of the events and cerebral thrombosis accounts for the other third. Along with factor V Leiden and the prothrombin gene mutation, the presence of an antiphospholipid antibody must be considered as a likely cause of thromboembolic disease in younger individuals. Hyperlipidemia and hypoalbuminemia have also been proposed as possible etiologic factors. Management of Anesthesia in Venous Hypercoagulable Disorders Current antithrombotic strategies range from simple management approaches such as early ambulation to a combination of elastic stockings and subcutaneous heparin therapy followed by conversion to outpatient warfarin therapy. Recent meta-analyses have found that regional and general anesthesia for hip surgery appear to produce comparable results in terms of most outcomes. Food and Drug Administration advisory prohibiting neuraxial anesthesia in patients receiving low-molecular-weight heparin resulting from an increased risk of epidural hematomas may further limit the use of regional anesthesia or its extension into the postoperative period. Patients with an absolute contraindication to anticoagulant therapy or those with a major bleeding complication may benefit from placement of a vena caval filter to prevent recurrent pulmonary emboli.

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Whether or not harmful cardiac effects from sulfonylureas have been demonstrated is controversial antibiotics meningitis generic 3 gr fosfomycin mastercard. Sulfonylureas may inhibit this protective response and potentially delay contractile recovery bacteria or virus discount fosfomycin 3 gr visa, which results in larger myocardial infarction areas virus scan software fosfomycin 3 gr free shipping. In addition to lowering glucose levels antibiotic for pneumonia order discount fosfomycin on-line, they decrease plasma levels of triglycerides and low-density lipoprotein cholesterol and reduce postprandial hyperlipidemia and plasma-free fatty acids antibiotics for sinus infection necessary fosfomycin 3 gr without prescription. Lactic acidosis is a rare but serious side effect of the biguanides; the risk is particularly high in patients with renal insufficiency antibiotic weight loss discount fosfomycin 3 gr overnight delivery. These drugs influence the expression of genes encoding proteins for glucose and lipid metabolism, endothelial function, and atherogenesis and, as a result, may influence diabetic dyslipidemia in addition to hyperglycemia. The -glucosidase inhibitors inhibit -glucosidase enzymes in the brush border of enterocytes in the proximal small intestine, which results in a delay in the intraluminal production and subsequent absorption of glucose. They are administered before a main meal to ensure their presence at the site of action. Combination therapy with oral agents directed at more than one mechanism is often effective. If combination oral therapy is unsuccessful, a bedtime dose of intermediate-acting insulin is added, since hepatic glucose overproduction is typically highest at night. If oral agents plus single-dose insulin therapy is ineffective, type 2 diabetic patients are switched to insulin therapy alone. Not only must hyperglycemia be treated but all abnormalities of insulin resistance (metabolic syndrome) must be managed, with the goals of therapy including an Hb A1c level of less than 7%, a low-density lipoprotein level of less than 100 mg/dL, a high-density lipoprotein level of more than 40 mg/dL in men and more than 50 mg/dL in women, a triglycerides level of less than 200 mg/dL, and a blood pressure of less than 130/80 mm Hg. In the United States, 30% of patients with type 2 diabetes are treated with insulin. Conventional insulin therapy usually requires twice-daily injections of combinations of intermediate-acting and short- or rapid-acting insulins. Defective counterregulatory responses by glucagon and epinephrine to reduced plasma glucose levels contribute to this complication. Repetitive episodes of hypoglycemia, especially at night, can result in hypoglycemia unawareness, a condition in which the patient does not respond with the appropriate autonomic warning symptoms before neuroglycopenia. Symptoms are adrenergic (sweating, tachycardia, palpitations, restlessness, pallor) and neuroglycopenic (fatigue, confusion, headache, somnolence, convulsions, coma). Treatment includes the administration of sugar in the form of sugar cubes, glucose tablets, or soft drinks if the patient is conscious, and glucose 0. The infrequent but devastating development of cerebral edema can result from correction of hyperglycemia without simultaneous correction of serum sodium level. High glucose levels exceed the threshold for renal tubular absorption, which creates a significant osmotic diuresis with marked hypovolemia. A tight metabolic coupling between hepatic gluconeogenesis and ketogenesis leads to an overproduction of ketoacids by the liver. An increase in production of ketoacids (-hydroxybutyrate, acetoacetate, acetone) creates an anion gap metabolic acidosis (Table 19-4). Substantial deficits of water, potassium, and phosphorus exist, although laboratory values of these electrolytes may be normal or increased. Hyponatremia results from the effect of hyperglycemia and hyperosmolarity on water distribution. The deficit of potassium is usually substantial (3 to 5 mEq/kg), and the deficit of phosphorus can lead to diaphragmatic and skeletal muscle dysfunction and impaired myocardial contractility. Insulin administration must be continued until a normal acid-base status is achieved. The insulin rate is reduced when hyperglycemia is controlled, the blood pH is higher than 7. Sodium Hyperglycemic hyperosmolar syndrome is characterized by severe hyperglycemia, hyperosmolarity, and dehydration. It usually occurs in patients with type 2 diabetes who are older than 60 years of age in the context of an acute illness. When the glucose load exceeds the renal tubular maximum for glucose reabsorption, a massive solute diuresis occurs with total body water depletion. The patient experiences polyuria, polydipsia, hypovolemia, hypotension, tachycardia, and organ hypoperfusion. Hyperosmolarity (>340 mOsm/L) is responsible for mental obtundation or coma (Table 19-5). Patients may have some degree of metabolic acidosis but do not demonstrate ketoacidosis. Vascular occlusions secondary to low-flow states and diffuse intravascular coagulation are important complications of hyperglycemic hyperosmolar syndrome. Treatment includes significant fluid resuscitation, insulin administration, and electrolyte supplementation. If the plasma osmolarity is greater than 320 mOsm/L, large volumes of hypotonic saline (1000 to 1500 mL/hr) should be administered until the osmolarity is less than 320 mOsm/L, at which time large volumes of isotonic saline (1000 to 1500 mL/hr) can be given. Insulin therapy is initiated with an intravenous bolus of 15 units of regular insulin followed by a 0. The insulin infusion is decreased to 2 to 3 units/hr when the glucose level decreases to approximately 250 to 300 mg/dL. Hyperglycemia is essential for the development of these changes, and intensive glycemic control delays the onset and slows the progression of microvascular effects. The kidneys demonstrate glomerulosclerosis with glomerular basement membrane thickening, arteriosclerosis, and tubulointerstitial disease. The clinical course is characterized by hypertension, albuminuria, peripheral edema, and a progressive decrease in glomerular filtration rate. When the glomerular filtration rate decreases to less than 15 to 20 mL/min, the ability of the kidneys to excrete potassium and acids is impaired and patients develop hyperkalemia and metabolic acidosis. Hypertension, hyperglycemia, hypercholesterolemia, and microalbuminuria accelerate the decrease in the glomerular filtration rate. If end-stage renal disease develops, there are four options: hemodialysis, peritoneal dialysis, continuous ambulatory peritoneal dialysis, and transplantation. Combined kidney-pancreas transplantation results in lower mortality than dialysis or renal transplantation alone and may prevent recurrence of diabetic nephropathy in the transplanted kidney. More than 50% of patients who have had diabetes for longer than 25 years develop a peripheral neuropathy. Sensory deficits usually overshadow motor abnormalities and appear in the toes or feet and progress proximally toward the chest in a "stocking and glove" distribution. Loss of large sensory and motor fibers produces loss of light touch and proprioception as well as muscle weakness. Loss of small fibers decreases the perception of pain and temperature and produces dysesthesia, paresthesia, and neuropathic pain. Foot ulcers develop from mechanical and traumatic injury as a result of loss of cutaneous sensitivity to pain and temperature and impaired perfusion. The treatment of peripheral neuropathy includes optimal glucose control, as well as the use of nonsteroidal antiinflammatory drugs, antidepressants, and anticonvulsants for pain control. Diabetic retinopathy results from a variety of microvascular changes, including blood vessel occlusion, dilation, increased permeability, and microaneurysm formation resulting in hemorrhage, exudation, and growth of abnormal blood vessels and fibrous tissue. Visual impairment can range from minor changes in color vision to total blindness. Strict glycemic control and blood pressure control can reduce the risk of development and progression of retinopathy. Retinopathy Peripheral Neuropathy Nephropathy Diabetic autonomic neuropathy can affect any part of the autonomic nervous system and is the result of damaged vasoconstrictor fibers, impaired baroreceptor function, and ineffective cardiovascular reactivity. Symptomatic autonomic neuropathy is rare and is present in fewer than 5% of diabetics. The pathogenesis is not completely understood, but may involve metabolic, microvascular, and/or autonomic abnormalities. Cardiovascular signs of autonomic neuropathy include abnormalities in heart rate control as well as central and peripheral vascular dynamics. Resting tachycardia and loss of heart rate variability during deep breathing are early signs. A heart rate that fails to respond to exercise is indicative of significant cardiac denervation and is likely to result in substantially reduced exercise tolerance. The heart may demonstrate systolic and diastolic dysfunction with a reduced ejection fraction. The presence of cardiovascular autonomic neuropathy can be demonstrated by measuring orthostatic changes in heart rate and blood pressure and the hemodynamic response to exercise. Diabetic autonomic neuropathy may also impair gastric secretion and gastric motility, eventually causing gastroparesis diabeticorum in approximately 25% of diabetic patients. Although it is often clinically silent, symptomatic patients will have nausea, vomiting, early satiety, bloating, and epigastric pain. Treatment of gastroparesis includes strict blood glucose control, consumption of multiple small meals, reduction of the fat content of meals, and use of prokinetic agents such as metoclopramide. Diarrhea and constipation are also common among diabetic patients and may be related to diabetic autonomic neuropathy. In addition, patients with diabetic autonomic neuropathy may demonstrate altered respiratory reflexes and impaired ventilatory responses to hypoxia and hypercapnia. Between 20% and 30% of patients coming to the hospital with a myocardial infarction have diabetes. Patients with poorly controlled diabetes demonstrate elevated triglyceride levels, low levels of high-density lipoprotein cholesterol, and an abnormally small, dense, more atherogenic low-density lipoprotein cholesterol. This dyslipidemia is caused by lack of appropriate insulin signaling and is exacerbated by poor glucose control. Measures to prevent coronary artery disease include maintaining lipid levels, glucose level, and blood pressure within normal limits. Silent ischemia is possible if autonomic neuropathy is present, and stress testing should be considered in patients with multiple cardiac risk factors and poor or indeterminate exercise tolerance. Meticulous attention to hydration status, avoidance of nephrotoxins, and preservation of renal blood flow are also essential. The presence of autonomic neuropathy predisposes the patient to perioperative dysrhythmias and intraoperative hypotension. In addition, loss of compensatory sympathetic responses interferes with the detection and treatment of hemodynamic insults. Preoperative evaluation of the musculoskeletal system should look for limited joint mobility caused by nonenzymatic glycosylation of proteins and abnormal cross-linking of collagen. Firm, woody, nonpitting edema of the posterior neck and upper back (scleredema of diabetes) coupled with impaired joint mobility may limit range of motion of the neck and render endotracheal intubation difficult. Gastroparesis may increase the risk of aspiration, regardless of nothing-by-mouth status. Management of insulin in the preoperative period depends on the type of insulin that the patient takes and the timing of dosing. If the patient uses an insulin pump, the overnight rate should be decreased by 30%. On the morning of surgery, the pump can be kept infusing at the basal rate or discontinued and replaced with a continuous insulin infusion at the same rate; alternatively, the patient can be given subcutaneous glargine and the pump discontinued 60 to 90 minutes after administration. If the patient uses glargine and lispro or aspart for daily glycemic control, the patient should take two thirds of the glargine dose and the entire lispro or aspart dose the night before surgery and hold all morning dosing. Serum glucose level should be monitored at least every hour and even every 30 minutes in patients undergoing coronary artery bypass surgery or patients with high insulin requirements. Glucose determination is preferentially made using venous plasma or serum samples; arterial and capillary blood yields glucose values approximately 7% higher than those for venous blood, and whole-blood determinations are usually 15% lower than plasma or serum values. Avoidance of hypoglycemia is especially critical, since recognition of hypoglycemia may be delayed in patients receiving anesthetics, sedatives, analgesics, -blockers, or sympatholytics and in those with autonomic neuropathy. If hypoglycemia does occur, treatment consists of administration of 50 mL of 50% dextrose in water, which typically increases the glucose level 100 mg/dL or 2 mg/dL/mL. Hyperglycemia has been associated with poor outcomes in postoperative and critically ill patients. However, the optimal target for blood glucose level in the perioperative period has not yet been defined. In addition, this target may be different for patients with newly diagnosed hyperglycemia than for those with preexisting diabetes. Currently, the American Diabetes Association recommends that glucose levels be maintained between 140 and 180 mg/dL in critically ill patients and that insulin treatment be initiated if serum glucose levels exceed 180 mg/dL. They usually occur as an isolated finding but may present as part of multiple endocrine neoplasia syndrome type I (insulinoma, hyperparathyroidism, and a pituitary tumor). They occur in women twice as often as in men and usually in the fifth or sixth decade of life. An inappropriately high insulin level (>5 to 10 microunits/mL) during a 48- to 72-hour fast confirms the diagnosis. Ideally, a continuous infusion of insulin should be initiated at least 2 hours before surgery. Intraoperative serum glucose levels should be maintained between 120 and 180 mg/dL. Levels above 200 mg/dL are likely to cause glycosuria and dehydration and to inhibit phagocyte function and wound healing. The initial hourly rate for a continuous insulin infusion is determined by dividing the total daily insulin requirement by 24. An insulin infusion can be prepared by mixing 100 units of regular insulin in 100 mL of normal saline (1 unit/mL).

The pathophysiology of this disease is unknown but may be related to dopamine hyperactivity or dysfunction of the basal ganglia infection from earring buy 3 gr fosfomycin otc. Drug therapy (antidopaminergics antibiotic resistant bacteria documentary generic fosfomycin 3 gr with amex, anticholinergics antibiotic 3 days for respiratory infection order fosfomycin 3 gr overnight delivery, acetylcholine agonists infection bladder order fosfomycin visa, -aminobutyric acid agonists) may have some effect bacteria ua rare effective 3 gr fosfomycin, and facial nerve block has been reported to provide sustained relief infection klebsiella purchase 3 gr fosfomycin with amex. Multicore Myopathy Multicore myopathy is a heterogeneous group of diseases characterized by proximal skeletal muscle weakness, a decrease in muscle mass, and musculoskeletal abnormalities such as scoliosis and high-arched palate. Recurrent pulmonary infection is common and may be related to the severity of the associated kyphoscoliosis. Unlike in other myopathies, serum creatine kinase concentration is usually normal in these individuals. This syndrome typically manifests as abnormal phonation but on rare occasions is associated with respiratory distress. Stress can exacerbate it, and associated neurologic symptoms (tremors, weakness, dystonia of other skeletal muscle groups) are present in most patients. Botulinum toxin, which blocks neuromuscular transmission, may be effective for treating the spasms of torticollis, blepharospasm, and spasmodic dysphonia. Difficulty swallowing and an inability to clear secretions may reflect pharyngeal and laryngeal muscle involvement. Postoperative aspiration may be associated with impaired upper airway reflexes and the lingering effects of drugs administered during anesthesia. It is important to recognize the potential relationship between multicore myopathy and malignant hyperthermia. Centronuclear Myopathy Centronuclear myopathy is a rare congenital myopathy characterized by progressive muscle weakness of extraocular, facial, neck, and limb muscles. The defect is a mutation in a gene important for muscle cell growth and differentiation. There are severe neonatal forms of this disease as well as slowly progressive forms that can begin anytime from birth to adulthood. Development of scoliosis with restrictive lung disease is an important manifestation of disease severity. The association of ptosis and strabismus with this myopathy Preoperative fiberoptic or direct laryngoscopy may be necessary to define anatomic abnormalities and to estimate airway dimensions. The presence of laryngeal stenosis may necessitate the use of smaller than usual tracheal tubes. The risk of pulmonary aspiration may be increased by vocal cord dysfunction caused by therapeutic interventions such as botulinum toxin injection or recurrent laryngeal nerve interruption. Continued monitoring during the postoperative period is important, because these patients may experience respiratory difficulties. Juvenile Hyaline Fibromatosis Juvenile hyaline fibromatosis is a rare syndrome characterized by the presence of numerous dermal and subcutaneous nodules. Patients may have hypertrophic gingivae, osteolytic bone lesions, and stunted growth with normal mental development. Resistance to the effects of succinylcholine has been described in patients with juvenile hyaline fibromatosis. It manifests as erratic cartilage calcification resulting in bone and skin lesions, cataracts, and cardiac malformations. In surviving children, abnormal growth leads to dwarfism, kyphoscoliosis, and subluxation of the hips. Orthopedic procedures are often necessary to offset functional limitations of the disease and to stabilize spine and limb malformations. Tracheal cartilage may be involved by the disease process; this results in tracheal stenosis, which may complicate perioperative airway management. Perioperative steroid supplementation may be a consideration when adrenal hyperactivity is present, because these patients may exhibit an altered cortisol response to stress. These patients may have fragile bones, and particular care is needed during intraoperative positioning. Tracheal intubation may be difficult because of airway distortion associated with acromegaly or hypertrophy of soft tissue in the upper airway. The feet, especially the soles, are most often involved, and males are affected twice as often as females. Primary erythromelalgia occurs more frequently than secondary erythromelalgia, which is associated with myeloproliferative disorders such as polycythemia vera. Aspirin is the most effective treatment for secondary erythromelalgia resulting from myeloproliferative diseases. Patients may seek relief by exposing the affected extremity to a cooler environment, such as immersing the extremity in cold water. Klippel-Feil Syndrome Klippel-Feil syndrome is characterized by a short neck resulting from a reduced number of cervical vertebrae or fusion of several vertebrae. Management of anesthesia must consider the risk of neurologic damage during direct laryngoscopy resulting from cervical spine instability. Preoperative lateral neck radiographs help in evaluating the stability of the cervical spine. Osteogenesis Imperfecta Osteogenesis imperfecta is a rare, autosomal dominant, inherited disease of connective tissue that affects bones, the sclera, and the inner ear. Osteogenesis imperfecta can manifest in two forms: osteogenesis imperfecta congenita and osteogenesis imperfecta tarda. With the congenital form, fractures occur in utero and death often occurs during the perinatal period. The tarda form typically manifests during childhood or early adolescence with blue sclerae fractures after minor trauma, kyphoscoliosis, bowing of the femur and tibia, and gradual onset of otosclerosis and deafness. Hyperthermia with hyperhidrosis can occur in patients with osteogenesis imperfecta. An increased serum thyroxine concentration associated with an increase in oxygen consumption occurs in at least 50% of patients with this disease. Progressive arthropathy, psychomotor retardation, and nutritional failure are present, and most affected individuals die by 2 years of age as a result of airway and respiratory problems. Acute renal and hepatic failure may reflect accumulation of ceramide in these organs. Difficulty in airway management is a common problem because of granuloma formation in the pharynx or larynx. Tracheal intubation is best avoided in patients with upper airway involvement, because laryngeal edema or bleeding from laryngeal granulomas is possible. Conductive and neural deafness occur when osseous lesions involve the temporal bone and impinge on the cochlea. Some patients show other endocrine Management of anesthesia is influenced by the co-existing orthopedic deformities and the potential for additional fractures during the perioperative period. Patients with osteogenesis imperfecta often have a decreased range of motion of the cervical spine resulting from remodeling of bone. Awake fiberoptic intubation or videolaryngoscopy may be prudent if orthopedic deformities suggest that it will be difficult to visualize the glottic opening with direct laryngoscopy. Dentition is often defective, and teeth are vulnerable to damage during direct laryngoscopy. Kyphoscoliosis and pectus excavatum decrease vital capacity and chest wall compliance and can result in arterial hypoxemia caused by ventilation/perfusion mismatching. Use of automated blood pressure cuffs may be hazardous, since inflation can result in fractures. Regional anesthesia is acceptable in selected patients because it avoids the need for endotracheal intubation, but it may be technically difficult because of kyphoscoliosis. The coagulation status should be evaluated before a regional anesthetic technique is selected, because osteogenesis imperfecta may be associated with a prolonged bleeding time despite a normal platelet count. These patients may have mild hyperthermia intraoperatively, but it is not a forerunner of malignant hyperthermia. Considerable narrowing of the distance between the posterior sternum and the anterior border of the vertebral bodies can be tolerated with little effect on cardiopulmonary function. Rarely is pectus excavatum associated with increased cardiac filling pressures or dysrhythmias. Obstructive sleep apnea may be more common in young children with pectus excavatum, perhaps because of greater inward movement of the sternum and the pliable costochondral apparatus. Macroglossia Macroglossia is an infrequent but potentially lethal postoperative complication that is most often associated with posterior fossa craniotomy performed in the sitting position. Possible causes of macroglossia include arterial compression, venous compression resulting from excessive neck flexion or a headdown position, and mechanical compression of the tongue by the teeth, an oral airway, or an endotracheal tube. When the onset of macroglossia is immediate, it is easily recognized and airway obstruction does not occur because tracheal extubation is delayed. In some patients, however, obstruction to venous outflow from the tongue leads to development of regional ischemia from compression of the lingual arteries. This is followed by a reperfusion injury that does not occur until the outflow obstruction is relieved. As a result, the development of macroglossia may be delayed for 30 minutes or longer. There is then the risk of complete airway obstruction occurring at an unexpected time during the postoperative period. Fibrodysplasia Ossificans Fibrodysplasia ossificans is a rare inherited autosomal dominant disease that usually presents before 6 years of age and is characterized by myositis and proliferation of connective tissue. The term myositis ossificans is also applied to this disease, but fibrodysplasia ossificans may be a more correct term because this is principally a disease of connective tissue rather than of skeletal muscle. Connective tissue undergoes cartilaginous and osteoid transformation, which eventually leads to displacement of skeletal muscles by ectopic bone. Ectopic bone formation typically affects the muscles of the elbows, hips, and knees, leading to serious limitations of joint movement. There may be varying degrees of cervical fusion, and atlantoaxial subluxation is possible. Muscles of the face, larynx, eyes, anterior abdominal wall, diaphragm, and heart usually escape involvement. During the early stages of the disease, fever may occur at the same time that localized lumps appear in affected skeletal muscles. A restrictive breathing pattern can result from limitation of rib movement, but progression to respiratory failure is rare. Decreased mandibular motion and narrowing of the oral aperture caused by taut skin may make endotracheal intubation difficult. Hypotonia of the lower esophageal sphincter puts patients at risk of regurgitation and aspiration. Increased permeability of skeletal muscle membranes precedes clinical evidence of muscular dystrophy. This inability of skeletal muscle to relax after voluntary contraction or stimulation results from abnormal calcium metabolism. The clinical course of myasthenia gravis is marked by periods of exacerbation and remission. Ptosis and diplopia resulting from extraocular muscle weakness are the most common initial signs. Weakness of pharyngeal and laryngeal muscles results in dysphagia, dysarthria, and difficulty handling saliva. However, patients with myasthenia gravis demonstrate resistance to the effects of succinylcholine. Myasthenic syndrome (Eaton-Lambert syndrome) is a disorder of neuromuscular transmission that resembles myasthenia gravis. Myasthenic syndrome is an acquired autoimmune disease characterized by the presence of immunoglobulin G antibodies to voltage-sensitive calcium channels that causes a deficiency of these channels at the motor nerve terminal. Cervical spine involvement is frequent in patients with rheumatoid arthritis and may result in pain and neurologic complications. The most significant abnormality of the cervical spine is atlantoaxial subluxation and consequent separation of the atlantoodontoid articulation. When this separation is severe, the odontoid process may protrude into the foramen magnum and exert pressure on the spinal cord or impair blood flow through the vertebral arteries. Involvement of the cricoarytenoid joints by rheumatoid arthritis is suggested by the presence of hoarseness or stridor or by the observation of erythema or edema of the vocal cords during direct laryngoscopy. Diminished movement of these joints can result in narrowing of the glottic opening and interference with passage of the endotracheal tube or an increased risk of cricoarytenoid joint dislocation. These diseases have a shared predilection for new bone formation at sites of chronic inflammation, and joint ankylosis often results. This process is different from rheumatoid arthritis because there is minimal inflammatory reaction in the joints with osteoarthritis. Spinal curvature of more than 40 degrees is considered severe and is likely to be associated with physiologic derangements in cardiac and pulmonary function. Restrictive lung disease and pulmonary hypertension progressing to cor pulmonale are the principal causes of death in patients with kyphoscoliosis. During corrective surgery for scoliosis or kyphosis, spinal cord monitoring now utilizes measurement of evoked potentials (sensory and motor) much more frequently than the wake-up test. Labor analgesia for the parturient with an uncommon disorder: a common dilemma in the delivery suite. Epidemic diseases such as smallpox and bubonic plague were declared things of the past.