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The risk of stroke was progressively lower in progressively higher quintiles of calcium intake. Similar to the Japanese study, the typical calcium intake was relatively low by Western standards (the average dietary calcium intake was approximately 520 mg/day). Those in the lower two tertiles had about a 50 percent increased risk of ischemic stroke than those in the highest tertile (>591 mg/day). The third study of combined men and women, of older Finns (described above under Cardiac events, total), found no significant association with stroke among 755 people followed for 10 years (stroke incidence 9. The study was of methodological quality C because there was large misclassification of stroke outcomes in a sample of subjects (5-21 percent). However, the trend of associations across quintiles was not statistically significant. One longitudinal cohort study (with subanalyses in men and women separately) and one nested case-control study (in men) evaluated fatal strokes. Both studies of men found no significant association between calcium intake and risk of stroke death. In a prospective cohort of about 18,000 men aged 45 to 64 years, regardless of cardiovascular history, 245 died of stroke (1. The study also found no consistent association between calcium intake and stroke death. Among the outcomes for which studies had either statistically significant associations or suggestions of associations between calcium intake and cardiovascular events, the following findings of calcium intake level were reported. The association can be seen for quintiles 2 to 4, where women in the lowest quintile had a median calcium intake of 266 mg/day and those in the second quintile had a median calcium intake of 379 mg/day. Those in the second quintile had a median calcium intake of 344 mg/day and those in the lowest quintile 233 mg/day. The median calcium intakes in the first and second quintiles were 876 and 1178 mg/day, respectively. The median calcium intakes in the first and second quintiles were 395 and 645 mg/day, respectively. The majority of studies (and the large majority of individuals) included mostly people between the ages of about 40 and 70 years. Only a small Finnish study (Marniemi 200548) restricted the study cohort to only older adults (65 years and older). This study found no significant associations between calcium intake and cardiovascular events. The findings that could be interpreted as an association between calcium intake and cardiovascular risk were mostly found in women (low calcium intake being associated with increased risk of cardiac death (in one of three studies) and stroke (in a single study), but with lowered risk of overall cardiovascular death (in one of two studies). The only potential associations between calcium intake and cardiovascular events in men were found for stroke; however, the two studies had opposite findings about the direction of the association. However, the one study of stroke in women was conducted in women who were mostly in this life stage. Overall, the majority of analyses found no significant association between calcium intake and most cardiovascular events. Only for stroke did at least two studies find significant associations between calcium intake and the outcome. For studies of people within this life stage, other significant associations were found in one of three studies of cardiac death in women (calcium intake below 696 mg/day was associated with increased risk) and in one of two studies of cardiovascular death in women (calcium intake above about 300 mg/day may be associated with increased risk). The one study of people in this life stage found no association between calcium intake and cardiac events or stroke in a relatively small, quality C study. In their analysis, calcium intake below 696 mg/day was associated with increased risk of ischemic heart disease death. Stroke risk stratified by calcium intake 152 Calcium and Body Weight We searched for systematic reviews and primary studies that evaluated associations between calcium intake or body stores and incidence of overweight or obesity; no such studies were found. No studies evaluated the association of calcium intake and incidence of overweight or obesity.

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Two metaanalyses of small randomized controlled trials suggest that blood-pressure­lowering therapies (including volume control) are associated with a nearly 30% risk reduction for cardiovascular events and 25% risk reduction for cardiovascular death compared with control treatment. Further studies are needed to evaluate the long-term effects of lipid-lowering therapies on kidney function. Survival with any kidney replacement modality is generally worse for patients with diabetes compared with nondiabetic patients, and cardiovascular complications markedly contribute to premature deaths. Accordingly, we recommend not initiating a statin in patients treated with hemodialysis but often do continue statin treatment in those that are already receiving these agents at dialysis initiation. An overview of novel agents that target wellestablished or novel pathophysiologic pathways is provided in the next section. Many of these novel agents not only affect the target for which they are developed (on-target risk factor) but impact multiple other risk markers as well (off-target risk factors) (Table 25. Optimizing drug regimens to impact multiple parameters may lead to better drug use in the future. However, the pharmacokinetic properties vary among the different agents, which could render a specific agent particularly useful for a certain subpopulation. Plasma glucose is filtered in the glomerulus and reclaimed by tubular reabsorption along with two positively charged sodium ions per glucose molecule. Another approach is to use mineralocorticoid synthase inhibitors, which are effective in reducing serum aldosterone and have blood-pressure­lowering capacity. Whether this approach will effectively decrease the incidence of hyperkalemia in patients with diabetes and nephropathy is still unknown. Whether the benefits of this approach will outweigh possible risks of hyperkalemia as well as safety concerns associated with potassium-binding resins remains unknown, although novel potassium-binding resins are in development. Endothelin Antagonists Endothelin receptor blockers are promising given potent effects on both blood-pressure and proteinuria reduction; however, the hard outcome study on one of the first agents in this class (avosentan) demonstrated an increased incidence of edema and hospitalization for heart failure with avosentan, leading to the premature discontinuation of the trial. Unfortunately, there was no benefit with darbepoetin, and perhaps a suggestion of increased stroke risk. Accordingly, current erythropoiesis-stimulating agents cannot be recommended for cardiovascular or kidney risk reduction in patients with diabetic nephropathy. Inflammation In the past years, increasing evidence has indicated an important role for underlying, low-grade inflammatory processes in the pathogenesis of diabetic nephropathy. Consequently, research in antiinflammatory strategies may open a therapeutic window to halt the progression of disease. Pyridoxamine dihydrochloride (Pyridorin, NephroGenex) inhibits formation of advanced glycation end products and scavenges reactive oxygen species and toxic carbonyls. Whether these effects translate into kidney protection is unknown, although a year-long study of the effects of pyridoxamine dihydrochloride in patients with type 2 diabetes and proteinuria failed to show a difference in kidney function decline with pyridoxamine dihydrochloride in daily doses of 300 or 600 mg versus placebo treatment. Pentoxifylline is a methylxanthine phosphodiesterase inhibitor with favorable antiinflammatory effects and immunoregulatory properties. Despite this theoretical benefit, pentoxifylline offers at best a small beneficial effect on kidney function and reduction in albuminuria and proteinuria with no apparent serious adverse effects. Importantly, most studies of this agent were poorly reported, small, and methodologically flawed. Until then, current evidence does not support the use of pentoxifylline in this patient population. Bardoxolone methyl is an antiinflammatory drug that activates the Nrf2-Keap1 pathway, resulting in inhibition of the proinflammatory cytokine Nf-B. Emerging data suggest an important role for the vitamin-D axis in kidney and cardiovascular health. Fioretto P, Mauer M: Histopathology of diabetic nephropathy, Semin Nephrol 27:195-207, 2007. Kunz R, Friedrich C, Wolbers M, et al: Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease, Ann Intern Med 148:30-48, 2008. Patel A, MacMahon S, Chalmers J, et al: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes, N Engl J Med 358:2560-2572, 2008. Shurraw S, Hemmelgarn B, Lin M, et al: Association between glycemic control and adverse outcomes in people with diabetes mellitus and chronic kidney disease: a population-based cohort study. The diabetes control and complications trial research group: the effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, N Engl J Med 329:977-986, 1993. As outlined in this section, various novel treatment options are in development that may offer additional renoprotection and have the potential to reduce the high morbidity and mortality rates typically seen in patients with diabetes. Sanders 26 Paraproteinemic kidney diseases are typically the result of deposition of immunoglobulin fragments (heavy chains and light chains).

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Refer neonates with meningitis not responding to adequate treatment to paediatrician. If there are no signs of generalized infection (no danger signs), start Cloxacillin 25mg/kg/dose 2 times a day orally for 5 days. If there are danger signs or if the pustules are extensive, hospitalize the newborn and treat with antibiotics against staphylococcus aureus. Apply nystatin/clotrimazole cream 2 times a day or after every nappy change for 14 days minimum. Thrush (oral candidiasis) · · · Apply nystatin oral solution in the mouth 4 times a day. Neonatal conjunctivitis · · · · Characterized by redness of conjunctivas or purulent eye secretions in the newborn. The eyes must be washed with physiologic serum or boiled water (boiled, then let to cool down) with a sterile gauze. Apply antibiotic ointment (for example tetracycline 1% eye ointment) 4 times a day until resolved. The umbilical cord is an intact structure at the level of the abdominal skin, just to the left of the defect. The opening on the abdominal wall is 2-4cm in diameter, and the solid organs (liver and spleen) reside in the peritoneal cavity. These are usually covered by a peritoneal sac which may rupture prior to or during birth. There is a high association with other congenital anomalies which need to be ruled out prior to surgical intervention. Protective covering: put a warm, moist abdominal swab (soaked with saline) over the intestines to prevent evaporative heat loss. Prompt diagnosis with appropriate clinical management and expeditious referral to a tertiary care centre improves survival of these infants. Classically, the neonate with oesophageal atresia presents with: » Copious, fine, white, frothy bubbles of mucus in the mouth and the nose. In patients with atresia, the tube typically stops at 10 to 12cm (normal distance 17cm). Chest radiographs (posteroanterior and lateral views) should be obtained to confirm the position of the tube. Such studies increase the risk of aspiration pneumonitis and reactive pulmonary oedema, and usually add little to plain film radiographs. Outcome Most neonates who undergo repair of oesophageal tracheoesophageal fistula have some degree of: · · Oesophageal dysmotility. Clinical presentation · · · Delayed passing of meconium (most healthy babies pass meconium within 24 hrs of birth). All babies with imperforate anus should have X-ray studies of the lumbosacral spine and urinary tract, because there is a high incidence of dysmorphism in these areas. Contributing factors of neural tube defects · · · · · · · Chromosomal abnormalities. Management · A multidisciplinary approach is required which includes the physician, geneticist, genetic counsellor, neonatologist, urologist, neurosurgeon, orthopaedic surgeon and social worker. Closure of the back lesion within 24 or 48 hours to prevent infection and further loss of function is essential. Prophylactic antibiotics to prevent infection for open or ruptured neural tube defect. Dressings should be changed daily or at any moment if they are wet or soaked with stools. Many genitourinary anomalies are diagnosed in utero via routine prenatal ultrasonography. Overview of congenital genitourinary anomalies · · · · · · · · · Bladder anomalies. Most infants with congenital hypothyroidism appear unaffected at birth, probably because of placental transfer of thyroid hormone. However, screening before discharge or transfusion is still preferable to missing the diagnosis. The aim of treatment is to keep the serum T4 or free T4 concentration in the upper half of the normal range.

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Interfering factors · A radioactive scan performed within 1 week before the test may alter the test results. However, it is not present in patients with most other rheumatoid-collagen diseases. The antihistidyl transfer synthase (anti­Jo-1) antibodies occur in patients with autoimmune interstitial pulmonary fibrosis and in a minority of patients with aggressive autoimmune myositis. Goodpasture syndrome is an autoimmune disease characterized by the presence of antibodies circulating against antigens in the basement membrane of the renal glomerular and the pulmonary alveoli. These immune complexes activate the complement system and thereby cause tissue injury. Patients with this problem usually display a triad of glomerulonephritis (hematuria), pulmonary hemorrhage (hemoptysis), and antibodies to basement membrane antigens. About 60% to 75% of patients with immune-induced glomerular nephritis have these pulmonary complications. Lung or renal biopsies are required to obtain tissue on which to demonstrate these antibodies with immunohistochemical techniques. Serum assays are faster and more reliable methods for diagnosing Goodpasture syndrome, especially in patients in whom a renal or lung biopsy may be difficult or contraindicated. Furthermore, serum levels can be used in monitoring response to therapy (plasmapheresis or immunosuppression). Antibodies to glycans can be instigated by bacterial, fungal, and parasite infections. Utilizing enzyme-linked immunosorbent assays, these antibodies can be identified and quantified. The presence of antimitochondrial antibodies is consistent with primary biliary cirrhosis. These antibodies react with a short linear sequence of the recombinant antigen cytochrome monooxygenase P450 2D6. The diagnosis of autoimmune liver disease cannot be made on antibody testing alone. In many instances, autoimmune liver disease panel testing, including the antibodies discussed in the preceding paragraph, is performed. Testing is performed by semi-quantitative enzymelinked immunosorbent assay/semi-quantitative indirect fluorescent antibody. It has a slow, progressive course marked by elevated liver enzymes, especially alkaline phosphatase and gamma-glutamyl transpeptidase (see pp. This test is used both in the detection of an autoimmune cause for these conditions and for monitoring their response to treatment. Antibodies against heart muscle are also found in 20% to 40% of postcardiac surgery patients and in a smaller number of postmyocardial infarction patients. These antibodies are usually associated with a pericarditis that follows the myocardial injury associated with cardiac surgery or myocardial infarction (Dressler syndrome). It also is useful in following the course of the disease, monitoring the response to therapy, and providing early detection of relapse. Low-level titers are considered negative, while increased titers are positive and indicate an elevated concentration of antinuclear antibodies. An example of a positive result might be: "Positive at 1:320 dilution with a homogeneous pattern. It is thought that these antibodies contribute to the destruction of the gastric mucosa in these patients. As the disease becomes less active because of therapy, the Scl-70 antibody titers can be expected to fall. This autoantibody is strongly associated with diffuse cutaneous scleroderma and with an increased risk of acute renal crisis. Interfering factors Drugs that may cause increased levels include aminosalicylic acid, isoniazid, methyldopa, penicillin, propylthiouracil, streptomycin, and tetracycline. The titers are not helpful in prognosis, nor do they indicate disease response to therapy. This test is used in the evaluation of an infertile couple usually after a postcoital test is positive. For fertilization to occur, the sperm head must first attach to the zona pellucida of the egg. Although there is consensus that these antibodies play a role in infertility, the percentage of sperm that must be bound by antibodies before fertility is adversely affected is less clear.

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The use of antiplatelet agents such as aspirin and clopidogrel to preserve vascular access may be associated with an unacceptably high rate of bleeding and is not recommended. This may be responsible for the transient hypoxia that is sometimes observed during hemodialysis, and it is completely reversed by the end of the dialysis treatment. The function of granulocytes, including chemotaxis, adherence, phagocytosis, and production of reactive oxygen species, is altered in uremia; these changes may also be exacerbated by exposure to unmodified cellulosic membranes. Impaired granulocyte function is associated with increased susceptibility to infection with encapsulated bacteria, such as Staphylococcus, contributing to the high incidence of these infections in dialysis patients. Monocyte and lymphocyte function are also impaired in uremia, leading to a decrease in cellular-type immunity. This may manifest as an increased susceptibility to viral infections such as influenza, decreased response to vaccinations, and anergy to immunologic skin testing. The activity of autoimmune diseases such as systemic lupus erythematosus may be attenuated after uremia supervenes. An impairment of cytokine release decreases the febrile response to pathogens in uremic patients, so that infections may go unnoticed and may become more serious before diagnosis. The clinical implication is that symptoms suggestive of infection must trigger an aggressive diagnostic and therapeutic response in this vulnerable population. Besarab A, Coyne D: Iron supplementation to treat anemia in patients with chronic kidney disease, Nat Rev Nephrol 6:699-710, 2010. Coyne D: From anemia trials to clinical practice: understanding the risks and benefits when setting goals of therapy, Semin Dialysis 21: 212-216, 2008. Pfeffer M, Burdmann E, Chen C, et al: A trial of darbepoetinalfa in type 2 diabetes and chronic kidney disease, N Engl J Med 361:2019-2032, 2009. It is important to note that the distribution of pore sizes for high-flux membranes is such that it does not allow for the passage of albumin. The two major components of the hemodialysis procedure that will be discussed are the dialyzer and the dialysate. These hollow fibers are made of thin, semipermeable membranes and are encased in a plastic tubing device that allows blood to be pumped from the patient into the inside of these hollow fibers while an aqueous solution, the dialysate, is pumped outside these hollow fibers, typically in the opposite direction of the blood flow, to maximize the diffusion gradients across the membranes. The manufacturing process of these membranes is such that, regardless of whether it is a low-flux or a high-flux membrane, the pore sizes are not uniform, and there is a distribution of pore sizes that allows the diffusion or removal Diffusion describes the movement of solutes from a milieu with high concentrations across a semipermeable membrane into a milieu where it is in lower concentration. The rate and amount of solute that diffuses across the membrane in either direction depends on the difference in concentration between the blood and dialysate compartments, the molecular size of the solute, the characteristics of the membrane including its surface area, thickness, and porosity, and the conditions of flow. These membrane characteristics are generally labeled "mass transfer characteristic" or "coefficient of diffusion," and are specific for the membrane used and the solute under consideration. Using urea as the prototype solute, hemodialysis allows the movement of urea from the blood compartment, where it is in high concentration, to the dialysate compartment across the hollow fiber membranes. Thus, as blood is pumped and traverses through the dialyzer inside hollow fibers, urea concentration of the blood is reduced; concurrently, the urea concentration of the dialysate increases as it traverses outside the hollow fibers in the opposite direction. If the blood and dialysate were to flow in the same direction, then the urea concentration gradient between the blood and dialysate compartments would be considerably reduced at the exit site of the dialyzer, whereas a countercurrent flow ensures maximum difference in concentration and therefore higher flux of solute from the blood compartment; accordingly, most dialysis procedures use countercurrent flow of blood and dialysate. The principles of diffusion apply not only to urea and other solutes that have a higher concentration in the blood than dialysate, but also to the diffusion of substances that have a higher concentration in the dialysate than blood. An example of the latter is the diffusion of bicarbonate from the dialysate into the blood compartment. A useful way to express the diffusion of a substance across the dialysis membrane is termed "clearance," analogous to the clearance of solutes in the native kidney. The curves are constructed based partially on data and partially on theoretical projection. The actual values may vary depending on the surface area of the membrane and operating conditions. The curve for native glomeruli represents the summation of all the glomeruli in two normal kidneys. Clearance of solutes by diffusion (via either conventional or high-efficiency/high-flux dialysis) deteriorates rapidly with increase in molecular mass of the solute.

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The differential diagnosis includes urethritis due to sexually transmitted diseases such as Neisseria gonorrheae or Chlamydia trachomatis, yeast vulvovaginitis, or genital herpes. Antimicrobial therapy is selected based on consideration of patient tolerance, documented efficacy for treating urinary infection, and local prevalence of resistance in community-acquired E. Recommended alternates are nitrofurantoin for 5 days, single-dose fosfomycin trometamol, or 5 days of pivmecillinam; all of these have indications virtually limited to treatment of this syndrome. Fluoroquinolones and -lactam antimicrobials are not considered first-line therapy because of the propensity to induce resistance in gut flora and, for -lactams, a lower efficacy. A longer course of 7 days is recommended when the duration of symptoms is more than 7 days, for women with an early recurrence of symptomatic infection (less than 30 days) following prior antimicrobial therapy, and when treatment is with a -lactam antimicrobial. Frequent recurrent acute cystitis is a disruptive and distressing problem for many women. Antimicrobial prophylaxis, given either as a long-term low-dose regimen or after intercourse, will prevent 95% or more of recurrent episodes (Table 48. Continuous low-dose prophylaxis taken at bedtime is recommended, with an initial course of 6 to 12 months. When prophylactic therapy is discontinued, the frequency of urinary infection is similar to that observed before prophylaxis. Postcoital prophylaxis is, obviously, most appropriate for women who identify sexual intercourse as a precipitating factor for recurrent symptomatic episodes. An alternate approach preferred by some women, especially with less frequent recurrences, is self-treatment. It is appropriate for women who are compliant with management and reliable in identifying their symptomatic episodes. The most important nonantimicrobial intervention for prevention of recurrent urinary infection is avoidance of spermicide use. The daily intake of cranberry or lingonberry juice or cranberry tablets was previously reported to decrease the frequency of recurrent infection by 30%, but recent blinded placebo controlled trials have not reported a benefit. Vaccines to prevent recurrent uncomplicated urinary infection and use of probiotics to reestablish normal gut or vaginal flora are being investigated, but studies to date have not shown consistent benefit with either of these approaches. Women who experience acute uncomplicated urinary infection are also at risk for nonobstructive pyelonephritis, with the frequency of episodes of cystitis relative to pyelonephritis reported to be 18-29 to 1. Risk factors for developing acute pyelonephritis are similar to those for acute cystitis for premenopausal women; frequency of sexual intercourse is the most important. The P fimbria, an adhesin that attaches to uroepithelial cells and induces an inflammatory response, is the most important. Additional organism virulence factors include production of hemolysin, which may lyse host cells, and aerobactin, an iron scavenger, which may promote bacterial growth. Acute pyelonephritis presents classically with fever and costovertebral angle pain and tenderness. A urine specimen for culture and susceptibility testing should be obtained before the initiation of antimicrobial therapy from every woman with a suspected diagnosis of pyelonephritis. Growth of 104 cfu/ mL of a uropathogen with pyuria together with consistent clinical findings is sufficient for diagnosis, but 105 cfu/ mL of organisms is isolated from 95% of cases. Bacteremia occurs in about 10% of episodes, and is more frequent in older adult women and women with diabetes. When women with pyelonephritis present with sepsis or shock, urgent imaging should be obtained to exclude obstruction or other lesions requiring immediate intervention for source control, as severe presentations are unusual with acute nonobstructive pyelonephritis. The majority of women can be treated as outpatients with oral antimicrobial therapy (see Table 48. Hospitalization and initial parenteral antimicrobial therapy are recommended for women with hemodynamic instability, for whom oral medication may not be tolerated because of severe gastrointestinal symptoms, or when there are significant systemic signs of illness and concern about compliance with outpatient therapy. The parenteral antimicrobial can usually be replaced by oral therapy once clinical improvement has occurred, usually by 48 to 72 hours. The urine culture results are also available by this time and will direct selection of a specific oral antimicrobial for continuing therapy. By 48 to 72 hours following initiation of effective antimicrobial therapy, there should be evidence of clinical improvement, including decreased costovertebral angle discomfort and a decrease in or resolution of fever.

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After volume expansion is achieved, calcium reabsorption can be further reduced with intravenous loop diuretics, such as furosemide, that block the Na+-K+-2Cl- cotransporter in the thick ascending limb, thereby disrupting the favorable electrochemical gradient for passive (paracellular) calcium reabsorption. As patients must be adequately hydrated before the diuretic is administered to avoid worsening hypovolemia and hypercalcemia, accurate assessment of intake and output is critical to optimize this treatment approach. If these conservative treatments fail to restore normocalcemia, other pharmacologic options should be used (Table 11. Because the response to these agents is not immediate, their use in patients with severe symptoms of hypercalcemia may be appropriate early in the course of management. In the United States, the bisphosphonates pamidronate and zoledronic acid are approved for the treatment of malignancy-associated hypercalcemia. These agents block osteoclast-mediated bone resorption by inducing osteoclast apoptosis. Typically, a clinical response is seen within 2 to 4 days, with a nadir in serum calcium within 4 to 7 days. Caution is required, because acute kidney injury has been reported with rapid administration of bisphosphonates or in settings of volume depletion. Calcitonin has the advantage of rapid reduction of serum calcium, but its use is limited by a short duration of action and tachyphylaxis. Glucocorticoids are effective first-line agents, along with saline diuresis, when the hypercalcemia is mediated by elevated circulating levels of calcitriol due to granulomatous disorders or lymphoma. Mild hypercalcemia is usually not symptomatic and may not require aggressive therapy. In primary hyperparathyroidism, intervention may be indicated only if symptoms (nephrolithiasis, lethargy, fatigue) are present. A National Institutes of Health consensus conference recommended that patients undergo surgical removal of the enlarged parathyroid gland if any of the following conditions are satisfied: (1) serum calcium 1. An alternative to surgical parathyroidectomy is the use of cinacalcet, a calcimimetic. For primary hyperparathyroidism, the dose is usually 30 mg twice daily, titrating up to 90 mg twice daily. In patients with excess citrate (from blood transfusions) or acute administration of bicarbonate, the percentage of calcium that is bound to these negatively charged ions increases; this reduces the free ionized calcium, usually with only a minimal change in total calcium. A decrease in the hydrogen ion concentration leads to protons dissociating from binding sites on other proteins. This increases protein binding of ionized calcium, thereby decreasing ionized calcium. Because the actual magnitude of any change in these circumstances may be hard to predict, the ionized calcium concentration is best measured directly. Large or abrupt changes in ionized calcium may lead to symptoms including perioral numbness and spasms of the hands and feet. This increased neuromuscular reactivity can be demonstrated by eliciting Chvostek sign or Trousseau sign. Chvostek sign is tested by tapping on the facial nerve near the temporal mandibular joint and watching for grimacing caused by spasm of the facial muscles. If these clinical signs are positive, hypocalcemia should be confirmed by measurement of ionized calcium. Vitamin D Deficiency Similarly, the infusion of citrate, a preservative in blood and plasma transfusions, can reduce ionized calcium as discussed earlier. Last, sepsis is also associated with hypocalcemia, although the mechanism is not clear. Intravenous calcium comes in two forms: calcium gluconate (10 mL vial = 94 mg elemental calcium) and calcium chloride (10 mL vial = 273 mg elemental calcium). Calcium chloride is typically used only during cardiopulmonary resuscitation because its infusion is painful and can cause vein sclerosis. Importantly, patients who are not symptomatic should be repleted with oral, not intravenous, calcium. The most common oral supplement is calcium carbonate, starting with 1 to 2 g of elemental calcium three times daily (1250 mg calcium carbonate = 500 mg elemental calcium), given apart from meals. Any hypomagnesemia should be treated concomitantly, and, if appropriate, patients may be changed from loop to thiazide diuretics to decrease urinary calcium excretion.

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Administration of crystalloid or colloid solutions can continue simultaneously, but the advantages of rapid volume expansion must be weighed against the risk of dilutional anemia and coagulopathy. Fibrinogen replacement is also frequently indicated in these circumstances, and either evaluation for or empiric treatment of hypofibrinogenemia should be considered. Further risks related to massive transfusion include citrate toxicity and associated hypocalcemia, hyperkalemia, and hypothermia. It cannot be overemphasized that administration of any blood product should be individualized to the patient and circumstance at hand, and be given the same consideration as any other risk-bearing therapy. Summary Allogeneic blood product transfusion is a very common procedure in critically ill patients. Classically thought to be a relatively simple decision, contemporary practice regarding when to transfuse reflects increasing awareness of potential drawbacks, including transfusion reactions, infectious risks, and potential longer term sequelae such as immune modulation and adverse long-term outcomes. This coupled with limited blood product supplies has led to a growing culture of blood 344 conservation. The above discussion aims to provide a basic outline of the considerations regarding this complex clinical decision. Franchini M, Lippi G: Fibrinogen replacement therapy: a critical review of the literature. A 56-year old man with atrial fibrillation on warfarin therapy is admitted with melena. After transfusion of 4 total units of appropriately selected blood components, the patient develops dyspnea, hypoxemia, and bilateral pulmonary infiltrates. Transfusion-associated lung injury 346 Chapter 9 Infectious Disease Topics Section 1 Sepsis and Septic Shock Key Points: · Sepsis is common in the intensive care unit setting. It can present with a variety of signs and symptoms and providers must always have a high index of suspicion. Cultures should be obtained prior to administration when possible, but should not delay administration. A family member at the bedside states that his only medical history is insulin dependent diabetes for which he rarely checks his blood sugars and frequently forgets to take his insulin as directed. In addition to hypotension and tachycardia, you note a small wound on the plantar surface of his foot with erythema spreading up the leg. Blood and urine cultures are sent prior to administration of broad-spectrum antibiotics. After administration of 30ml/kg of lactated ringers, he remains hypotensive and has minimal urine output. The decision is made to place an arterial catheter and central line for infusion of norepinephrine. These terms have recently been redefined based on current understanding of sepsis-induced changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation. Sepsis and septic shock remain one of the leading causes of mortality and critical illness worldwide. The European Society of Intensive Care Medicine and the Society of Critical Care Medicine have helped redefine sepsis and clarify guidelines for treatment that are also endorsed by the Surviving Sepsis Campaign. They provided and rated statements on management and resuscitation of patients in sepsis or septic shock as "strong", "weak", or "best-practice". They are nonspecific criteria that may help aid in the general diagnosis of infections but more is needed to assess severity. It is recommended that patients suspected of having sepsis have blood cultures drawn before initiation of antibiotics if clinically appropriate and possible, along with imaging studies to help confirm a potential source of infection. This score takes into account abnormality by organ system along with specific lab values: PaO2, platelet count, bilirubin level and creatinine level. The Surviving Sepsis Campaign recently released 2016 guidelines for the management of sepsis and septic shock. Additional fluids should be guided by frequent reassessment of hemodynamic status with dynamic variables (versus static measurements) used to predict fluid responsiveness c. Once the diagnosis of sepsis has been made or is strongly suspected, a search for the source must be further pursued.

References:

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  • http://www.thelancet.com/pdfs/journals/lanpsy/PIIS2215-0366%2815%2900505-2.pdf
  • http://medreviews.com/sites/default/files/2016-11/RIND_21_30_0.pdf
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