2008年7月30日 星期三

Brain tumors

Brain Tumors and Anticoagulation
Patients with malignant gliomas are at increased risk for venous thromboembolism originating from leg and pelvic veins, with a cumulative incidence of 20 to 30%. The risk of intratumoral hemorrhage associated with anticoagulation therapy in patients with gliomas who have venous thromboembolism is low, whereas inferior vena cava filters are associated with high complication rates. Unless a patient with malignant glioma and venous thromboembolism has an intracerebral hemorrhage or other contraindications, it is generally safe to provide anticoagulation therapy for the venous thromboembolism. Low-molecular-weight heparin may be more effective and safer than warfarin.

Brain Tumors and Antiepileptics
The use of prophylactic antiepileptic drugs in patients with malignant gliomas who have never had a seizure is controversial. The American Academy of Neurology issued a practice guideline indicating that there is no evidence that prophylactic antiepileptic drugs are beneficial and advises against the routine use of antiepileptic drugs in patients with brain tumors who have not had seizures. Patients who present with seizures and a brain tumor should be treated with antiepileptic drugs. Since antiepileptic drugs that induce hepatic P-450 enzymes, such as phenytoin and carbamazepine, increase the metabolism of many chemotherapeutic agents, antiepileptic drugs that do not induce these enzymes, such a levetiracetam, are generally preferred.

New England Journal of Medicine - Vol. 359, No. 5, July 31, 2008

2008年7月23日 星期三

FQ Tendinitis

Fluoroquinolone-Related Tendinitis and Tendon Rupture
A boxed warning must be added to the prescribing information for systemic fluoroquinolones.

On July 8, 2008, the FDA announced that the prescribing information for systemic fluoroquinolones must now include a boxed warning regarding the risk for tendinitis and tendon rupture. The prescribing information for these drugs has long listed tendon-related problems as potential adverse events, but the incidence of these events has not declined, prompting the FDA to require the stronger warning. The manufacturers must also develop and distribute a medication guide for patients.

The risk for tendinitis and tendon rupture is especially increased in patients who are aged >60, those who are concomitantly taking steroids, and those who have received kidney, heart, or lung transplants.

Patients should be warned of this risk and should be advised, at the first sign of tendon pain, swelling, or inflammation, to stop taking the fluoroquinolone, to avoid exercise or use of the affected area, and to seek medical advice about switching to a nonfluoroquinolone antimicrobial.

Lynn L. Estes, PharmD
Published in Journal Watch Infectious Diseases July 16, 2008

Citation(s): U.S. Food and Drug Administration. Information for healthcare professionals: Fluoroquinolone antimicrobial drugs

2008年7月17日 星期四

葉克膜 是天使還是魔鬼






急救存活率 葉克膜打敗CPR

當病人停止心跳,傳統心肺復甦術(CPR)施行卅分鐘後無反應,即被宣告死亡。台大醫院研究發現,若及時採用葉克膜(ECMO,體外心肺循環系統),即使心跳停止一小時,病人仍有百分之十七的存活機會。 台大昨天發表相關研究,並將主題訂為「不與死神妥協」。
台大醫學院長楊泮池指出,葉克膜已改變醫學對於生與死的界定;負責撰寫論文的台大外科教授陳益祥說,台大近年累積上千例裝置葉克膜經驗,裝置時間由一個多小時縮短到十五分鐘,最重要的是,印證了接受葉克膜急救的病人比傳統CPR存活率要高出一倍以上。這篇研究預計下周刊登在國際頂尖醫學期刊「刺胳針雜誌(The Lancet)」,美國心臟學會負責撰寫CPR指引的賓州大學急救醫學科主任貝克(Lance B.Becker),特地到台大觀摩實際操作程序,他預言,葉克膜將可望改寫CPR的觀念。
陳益祥表示,台大收集一百七十二名在院內突發心因性休克的病患,其中一百一十三人接受傳統CPR,五十九人則接受葉克膜急救,兩組年齡、性別及心臟狀況類似,經回溯研究發現,依賴葉克膜急救者,即使心跳停止超過一小時,但仍有百分之十七可以救活,而CPR組則無人存活。 不過,台大外科加護病房主任柯文哲強調:「葉克膜讓醫界掌握打開生死之門的鑰匙,卻也嚴重衝擊傳統醫學倫理。」臨床上已有更多家屬要求用葉克膜,央求醫師「再試試看」,讓醫師陷入天人交戰。
柯文哲說,因為「醫師沒有辦法預測救回來是不是植物人」,「未來也可能衍生明明已急救無效,但家屬還要求醫師裝葉克膜急救的糾紛」,所以醫師會陷入天人交戰。 陳益祥則說,如果病人還年輕,且各器官功能皆好,只是心跳停止,或許還有拚搏的機會。

2008年7月16日 星期三

NAC for Acetaminophen Poisoning

N-Acetylcysteine and Acetaminophen Poisoning
N-acetylcysteine prevents hepatic injury primarily by restoring hepatic glutathione. The primary pathways for acetaminophen metabolism are glucuronidation and sulfation to nontoxic metabolites. Approximately 5% of a therapeutic dose is metabolized by cytochrome P450 2E1 to the electrophile N-acetyl-p-benzoquinone imine (NAPQI). NAPQI is extremely toxic to the liver. Ordinarily, NAPQI is rapidly detoxified by interaction with glutathione to form cysteine and mercapturic acid conjugates. If glutathione is depleted, NAPQI interacts with various macromolecules, leading to hepatocyte injury and death. As long as sufficient glutathione is present, the liver is protected from injury.

Dosing of N-Acetylcysteine
The choice of oral or intravenous administration of N-acetylcysteine depends on the clinical scenario. For the treatment of acute acetaminophen ingestion, oral N-acetylcysteine is given as a loading dose of 140 mg per kilogram of body weight, with maintenance doses of 70 mg per kilogram that are repeated every 4 hours for a total of 17 doses. The intravenous loading dose is 150 mg per kilogram over a period of 15 to 60 minutes, followed by an infusion of 12.5 mg per kilogram per hour over a 4-hour period, and finally an infusion of 6.25 mg per kilogram per hour over a 16-hour period.

Q: What is the maximum recommended dose of acetaminophen for an adult in one day?
A: The maximum recommended dose of acetaminophen is 4 g per day.

Q: What are the side effects of N-acetylcysteine?
A: N-acetylcysteine has an unpleasant smell and taste, and vomiting is common with oral administration. The most commonly reported adverse effects of intravenous N-acetylcysteine are anaphylactoid reactions, including rash, pruritus, angioedema, bronchospasm, tachycardia, and hypotension. Kerr et al. reported that approximately 15% of patients who were treated with intravenous N-acetylcysteine had an anaphylactoid reaction within 2 hours after the initial infusion and that increasing the infusion time from 15 to 60 minutes did not alter the rate of adverse events.

The Rumack–Matthew Nomogram


New England Journal of Medicine - Vol. 359, No. 3, July 17, 2008

2008年7月15日 星期二

Acute Pyelonephritis

KALYANAKRISHNAN RAMAKRISHNAN, M.D., and DEWEY C. SCHEID, M.D., M.P.H.University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma

2008年7月11日 星期五

DKA associated with high amylase and lipase

Elevated serum amylase and lipase in pediatric diabetic ketoacidosis

Pediatric Critical Care Medicine. 9(4):418-422, July 2008.

Objectives: Pancreatic enzyme concentrations are frequently elevated in children with diabetic ketoacidosis (DKA). We sought to determine the clinical and biochemical characteristics associated with patients with these elevations. Our hypothesis was that pancreatic enzyme elevations would be associated with biochemical markers of hypoperfusion.

Design: Prospective cohort study.
Setting: Three university-affiliated children's hospitals.
Patients: We collected data on consecutive children <18 yrs of age hospitalized with the diagnosis of DKA.
Interventions: Serum electrolyte and lactate concentrations and venous pH and Pco2 were measured every 3 hrs from hours 0 to 12 and then every 6 hrs until hour 24. Serum calcium, phosphate, and magnesium concentrations were measured every 6 hrs from hours 0 to 24. Serum amylase, lipase, and triglyceride concentrations were measured at hour 0 and then 12, 24, and 48 hrs after the initiation of therapy.

Measurements and Main Results: We performed multivariable analyses to test for associations between clinical variables and pancreatic enzyme elevation in 67 children with DKA. Lipase was elevated in 21 (31%) and amylase in 16 (24%) of the children. Pancreatic enzyme values peaked 12-24 hrs after admission. There was no significant correlation between pancreatic enzyme elevation and abdominal pain. In multivariable analyses, an elevated blood urea nitrogen (BUN) concentration was associated with elevated serum amylase (odds ratio 1.04 per unit increase; 95% confidence interval, 1.01-1.09; p = .02), and elevated BUN concentrations and hypophosphatemia were associated with elevated serum lipase (odds ratio 1.04 per unit increase; 95% confidence interval, 1.00-1.08; p = .04; and odds ratio 0.35 per unit increase; 95% confidence interval, 0.15-0.81; p = .01, respectively).

Conclusions: Elevation of pancreatic enzymes is common in children with DKA, but clinical pancreatitis is rare. Pancreatic enzyme levels reach a peak 12-24 hrs after initiation of treatment for DKA. Pancreatic enzyme elevation is associated with increased BUN concentrations at presentation but is not associated with abdominal pain.

Septic shock & steroid

Should we abandon corticosteroids during septic shock?

Current Opinion in Critical Care. 14(4):384-389, August 2008.
Groeneveld, Arie Bastiaan Johan; Molenaar, Nienke; Beishuizen, Bert

Purpose of review: With the publication of the results of the recent CORTICUS trial, stress ('low') doses of corticosteroids for the treatment of vasopressor-dependent septic shock in adults can still be considered controversial. The purpose of this narrative review is to elaborate the pros and cons of this treatment in clinical practice and to formulate clinical and research directions.

Recent findings: The recent CORTICUS study only shows a beneficial effect of stress doses of corticosteroids in the time interval to shock reversal and not on mortality, potentially explained by an increased risk for superinfection. The mortality in the placebo arm was relatively low and lower than in earlier randomized studies in which stress doses of corticosteroids had a favorable hemodynamic effect and conferred a survival benefit in septic shock.

Summary: Treatment by stress doses of corticosteroids should not be abandoned during septic shock. Additional studies are needed, however, to better delineate the patient group with the highest likelihood to benefit from this therapy, as a function of severity of illness, response to adrenocorticotrophic hormone testing or both. For now, results of the CORTICUS study should not change current clinical practice of administering 200-300 mg of hydrocortisone daily (in divided doses) in case of fluid and vasopressor-insensitive septic shock and rapid tapering of this treatment on the basis of a hemodynamic response.

2008年7月9日 星期三

NIPPV in pulmonary edema

Noninvasive Ventilation in Pulmonary Edema
CPAP and NIPPV improve symptoms but do not alter death rates compared with standard oxygen therapy.

The widely held belief that noninvasive ventilation is beneficial in patients with acute pulmonary edema is based on studies that were either not randomized or too small to show unequivocal outcome effects, particularly with respect to mortality. In a multicenter study from the U.K., investigators randomized 1156 emergency department patients with acute pulmonary edema to one of three treatments: standard oxygen therapy, continuous positive airway pressure (CPAP), or noninvasive intermittent positive pressure ventilation (NIPPV, also called bilevel positive airway pressure; JW Emerg Med Mar 3 2004).

In all groups, oxygen was delivered to maintain peripheral oxyhemoglobin saturation above 92%. CPAP was started at 5 cm water and was increased to a maximum of 15 cm water. NIPPV was started at an inspiratory pressure of 8 cm water and an expiratory pressure of 4 cm water and was increased to maximum pressures of 20 cm and 10 cm, respectively. The assigned treatment was administered for a minimum of 2 hours. Blood gas analyses were performed at 1 hour and 2 hours. Patients rated their degree of dyspnea on a visual analog scale at enrollment and at 1 hour. Overall, 19% of patients did not complete treatment for reasons such as discomfort, worsening arterial blood gas values, and respiratory distress. Discomfort was significantly more common with noninvasive ventilation.

In a comparison between standard oxygen therapy and the two modes of noninvasive ventilation (CPAP or NIPPV), the primary outcome of death within 7 days did not differ significantly. In a comparison between CPAP and NIPPV, the composite primary endpoint of death or tracheal intubation within 7 days did not differ significantly. Fewer than 5 patients in any group were intubated, but 56 of 367 patients in the standard oxygen-therapy group were changed to CPAP or NIPPV to maintain target oxygen saturation. Mortality rates at 30 days did not differ between groups in either comparison. However, compared with standard oxygen therapy, noninvasive ventilation yielded greater reductions in some secondary outcome measures, including dyspnea, heart rate, acidosis, and hypercapnia.

Comment(1): The finding that noninvasive ventilation did not decrease mortality compared with standard oxygen therapy is not surprising because oxygen therapy was titrated to maintain adequate levels in all groups. Nonetheless, trying noninvasive ventilation in ED patients with acute heart failure is reasonable. If tolerated, treatment will improve symptoms and patient comfort, even if the state of the heart, not the therapy, is what ultimately dictates mortality.
J. Stephen Bohan, MD, MS, FACP, FACEP
Published in Journal Watch Emergency Medicine July 9, 2008

Comment(2): The results of this open randomized trial of noninvasive ventilation failed to show a reduction in the risk for death or intubation. The finding that fewer noninvasive-ventilation recipients than oxygen-therapy recipients experienced respiratory distress or metabolic abnormalities did not translate into any clinically meaningful change in outcome. The authors conclude with a "glass-is-half-full" assessment of their findings; nonetheless, this trial provides little support for noninvasive ventilation as an initial approach to patients with acute heart failure.
Harlan M. Krumholz, MD, SM
Published in Journal Watch Cardiology July 9, 2008

Citation(s): Gray A et al. Noninvasive ventilation in acute cardiogenic pulmonary edema. N Engl J Med 2008 Jul 10; 359:142.

Aortic dissection

http://www.thelancet.com/ Vol 372 July 5, 2008

2008年7月2日 星期三

Stool exam for parasitic infection

Does a negative stool examination for ova and parasites rule out an intestinal parasitic infection?

A single negative stool examination does not exclude a parasitic infection, since the sample may have been collected during the prepatent period (i.e., the time between infection and the production of detectable ova or larvae) or because the target organism may have been shed inconsistently or in low numbers, as is frequently the case with strongyloides larvae.

New England Journal of Medicine - Vol. 359, No. 1, July 3, 2008

DDx of Diarrhea

Diarrhea can be due to a number of infectious and noninfectious causes, including persistent intestinal infections, inflammatory enteropathies, and neoplastic disorders.

Travel-associated infections can include giardiasis, cryptosporidiosis, amebiasis, isoporiasis, strongyloidiasis, and schistosomiasis. Other infectious causes of diarrhea include tuberculosis, tropical sprue, human immunodeficiency virus (HIV), and Tropheryma whippelii.

Noninfectious causes include inflammatory bowel disease, adult-onset celiac disease, and neoplastic disorders such as intestinal lymphoma, villous adenoma, and functional neuroendocrine tumors including gastrinoma, carcinoid, and pancreatic endocrine tumors.

New England Journal of Medicine - Vol. 359, No. 1, July 3, 2008

Epinephrine and Vasopressin in CPR

Although epinephrine is the vasopressor of choice for cardiopulmonary resuscitation (CPR), the prognosis of patients with cardiac arrest who require epinephrine remains extremely poor, regardless of the cumulative epinephrine dose given. Studies of CPR in animals have demonstrated that vasopressin increases blood flow in vital organs, cerebral oxygen delivery, short-term survival, and neurologic outcome, as compared with epinephrine. However, clinical studies of CPR in patients with in-hospital and out-of-hospital cardiac arrest show that the effects of vasopressin and epinephrine are similar, and that there is no benefit of adding vasopressin to epinephrine.

New England Journal of Medicine - Vol. 359, No. 1, July 3, 2008