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Journal Meeting

What's new in adult and pediatric emergency medicine ( Up to

20110617 )

• 急診討論室Reported by Stanley. Wang. Date: 2011-11-29

Originated from Up To Date

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Adult cardiology - IV loop diuretic dosing for acute heart failure 

• The DOSE trial found that no single intravenous dosing regimen for a loop diuretic is superior in treating acute heart failure [1].

• Patients were randomly assigned to receive furosemide via bolus versus continuous infusion and at either a low dose (equivalent to the patient’s previous oral dose) or high dose (2.5 times the previous oral dose).

• There was no significant difference in efficacy or safety for bolus versus continuous infusion.

• There was an almost significant trend toward greater improvement in patients’ global assessment of symptoms with high-dose therapy, and the mean change in serum creatinine was similar for both groups.

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ADULT PROCEDURESPropofol for procedural sedation 

Propofol is a widely used and highly effective medication for procedural sedation, but it provides no analgesia. A systematic review of 177 randomized controlled trials involving 25,260 adult patients found that the following measures were most effective at reducing pain caused by propofol injection [2]:

• Injecting into an antecubital vein rather than a hand vein.

• Lodocaine pretreatment while occluding the vein. • Pretreatment with lidocaine-propofol admixture. • Lidocaine pretreatment without vein occlusion. • Opioid pretreatment. • Ketamine pretreatment.

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ADULT TRAUMAAntifibrinolytic therapy 

• The CRASH-2 trial, which spanned 274 hospitals in 40 countries and included over 20,000 trauma patients with

or at risk of significant hemorrhage, concluded that treatment with the antifibrinolytic agent tranexamic acid significantly reduced overall mortality [3].

• A follow-up analysis of the CRASH-2 trial confirmed the benefit of tranexamic acid in reducing mortality from bleeding when the drug was given within one hour, but noted that mortality increased when the drug was administered after three hours from the time of injury [

4].

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ADULT TRAUMAAntifibrinolytic therapy

• Trauma-associated hemorrhage (unlabeled use): I.V.: Loading dose: 1000 mg over 10 minutes,

followed by 1000 mg over the next 8 hours.

• Note: Clinical trial included patients with significant hemorrhage (SBP <90 mm Hg, heart rate >110 bpm, or both) or those at risk of significant hemorrhage.

• Treatment began within 3 hours of injury (CRASH-2 Trial Collaborators, 2011).

• Transamin 250 mg /amp.

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ADULT TRAUMA Delayed fluid resuscitation 

• Delayed fluid resuscitation remains controversial, but may be beneficial in patients with hemorrhagic shock

from penetrating torso injuries.• In a preliminary analysis of a trial conducted at a major trauma center,

90 young adults with penetrating (n=84) or blunt (n=6) trauma resulting in at least one systolic blood pressure reading below 90 mmHg, and hemorrhage requiring immediate laparotomy or thoracotomy, were randomly assigned upon arrival to the operating theater to fluid resuscitation using a low goal mean arterial pressure of 50 mmHg (LMAP group) or a high goal mean arterial pressure of 65 mmHg (HMAP) [5].

• Patients in the LMAP group had lower postoperative mortality, received fewer blood products, and did not develop coagulopathy or multiple organ failure. However, there was no significant difference between the groups in overall mortality at 30 days.

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Mean Arterial Pressure

• MAP = ( CO x SVR ) + CVP.

• MAP ( 2 x DP + SP )/3≒• MAP DP + 1/3 ( SP - DP ) ≒• MAP 2/3 DP + 1/3 SP≒

• MAP DP + 1/3 PP ( PP = SP - DP ) ≒

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Delayed fluid resuscitation/controlled hypotension (1)

• Questions remain whether reversal of hypovolemia or control of hemorrhage should take priority in trauma resuscitation.

• Some researchers describe aggressive fluid administration as ineffective and potentially harmful [26-28], and suggest that limited volume

replacement that maintains minimally adequate organ perfusion may improve outcomes [29].

• This strategy is often referred to as delayed fluid resuscitation or controlled hypotension, an approach which targets early fluid resuscitation only to a systolic blood pressure of 70 mmHg.

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Delayed fluid resuscitation/controlled hypotension (2) 

• Controlled hypotension may be beneficial in patients with hemorrhagic shock due to torso injuries

from gunshot or stab wounds. However, it may be detrimental to blunt trauma patients with brain injury, as hypotension reduces cerebral

perfusion and increases mortality [30]. • The rationale for improved outcomes with delayed

fluid resuscitation is that aggressive fluid administration might, via augmentation of blood

pressure, dilution of clotting factors, and production of hypothermia, disrupt thrombus formation and enhance bleeding [31,32].

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Delayed fluid resuscitation/controlled hypotension (3) 

• Factors that should be considered when determining whether this strategy is appropriate include the patient’s mental status and likelihood of

intracranial injury, type of injury (penetrating versus blunt), severity of injury (eg, ongoing hemorrhage), and proximity to a trauma center.

• Delayed fluid administration and controlled hypotension should probably not be implemented

unless emergent surgical exploration with rapid control of the bleeding source can be performed.

• Further research is needed in this area [43,44].

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INFECTIOUS DISEASEHUS and E coli 0104:H4 

• In May 2011, a rare Shiga toxin-producing Escherichia coli (E. coli) strain, O104:H4, was identified as the cause of an outbreak of shiga- like toxin associated hemolytic uremic syndrome (Stx HUS) in Germany. This strain is particularly virulent, as 30 percent of infected patients developed HUS.

• Unlike cases due to E. coli O157:H7 that primarily affect children, more than 80 percent of HUS cases due to E. coli O104:H4 occurred in adults.

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Hemolytic-uremic syndrome

• Hemolytic-uremic syndrome ( HUS ), is a disease characterized by microangiopathic hemolytic anemia, acute renal

failure ( uremia ), and a low platelet count ( thrombocytopenia ).

• It predominantly but not exclusively affects children. Most cases are preceded by an episode of diarrhea caused by E. coli O157: H7, which is acquired as a foodborne illness.

• It is a medical emergency and carries a 5–10% mortality; Of the remainder, the majority recover without major consequences (self-limited illness) but a small proportion develop CKD & become reliant on renal replacement therapy.

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INFECTIOUS DISEASETreatment of skin and soft tissue infections 

• Drainage is the cornerstone of treatment of skin & soft tissue infections (SSTI), but adjunctive antimicrobial therapy is often provided.

• In a randomized trial comparing agents with & without activity (clindamycin and cephalexin, respectively) against methicillin-resistant Staphylococcus aureus (MRSA) in children (6 months to 18 years) with uncomplicated SSTI, drainage (surgical or spontaneous) occurred in virtually all patients [9]. MRSA was isolated from approximately two-thirds of wound cultures.

• Improvement & complete resolution occurred in ≥94 percent of children, whether or not they were treated with an agent with activity against MRSA, suggesting that drainage is more important than the choice of antimicrobial therapy in the successful treatment of uncomplicated SSTI. However, we still suggest adjunctive oral antimicrobial therapy when MRSA is a consideration.

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PEDIATRIC RESUSCITATIONFluid therapy in resource limited settings 

• In settings with a high prevalence of malaria or severe anemia (hemoglobin <5 grams/dL) that cannot provide advanced airway & circulatory support, bolus administration of albumin or normal saline may be harmful for some children with severe febrile illness and circulatory impairment that has not progressed to severe decompensated shock.

• A multicenter trial of 3141 children between 60 days and 12 years of age in Sub-Saharan Africa with severe febrile illness and impaired perfusion (eg, delayed capillary refill time ≥3 seconds, weak pulses, severe tachycardia) found that 48 hour mortality was significantly higher among those who received boluses of albumin or normal saline when compared to controls who did not receive fluid boluses (10.6, 10.5, and 7.3 percent, respectively).

• These children had a high frequency of malaria parasitemia (57 percent) and severe anemia (hemoglobin <5 grams/dL, 32 percent). Thus, these findings may not be generalizable either to resource limited settings where malaria is not prevalent or to medical systems with more resources.

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PEDIATRIC TRAUMARadiologic cervical spine clearance in children 

• A systematic review has led to consensus cervical spine clearance guidelines for children with reliable and unreliable physical examinations [12].

• Based upon this review, plain radiographs should be the initial radiologic study to evaluate for cervical spine injury in children who cannot be cleared clinically. Computed tomography of the cervical spine should be used as a follow-up study for suspected bony injury on plain radiographs or when more diagnostic certainty is required based upon clinical factors, such as

mechanism of injury, associated injuries, or altered mental status.

• Lateral plain radiographs alone failed to detect 46% of all cervical spinal injuries

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NEXUS Lower-Risk Criteria ( NLC )

• No midline cervical spine tenderness.• No focal neurologic deficit. • Normal alertness. • No intoxication. • No painful distracting injury.

NLC + Head F/E and rotate 45 degrees to both sides induce no pain Cervical spine clearance

( for alert adult and comprehensive children )

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TOXICOLOGYTreatment of Crotalinae snake bite 

• A unified approach to the management of rattlesnake, water moccasin (cottonmouth), & copperhead snake bites has been developed based upon expert consensus and literature review .

• The guidance recommends that treatment of Crotalinae snake bites with polyvalent Crotalinae ovine immune Fab antivenom (Crofab®) should be based upon the patients’ clinical severity & not the presumed species of snake responsible for the bite.

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off-label use 原則 ( 910208)

1. 需基於治療疾病之需要( 正當理由 ) 。2.需符合醫學原理及臨床藥理( 合理使用 )

。3.應據實告知病人。4.不得違反藥品使用當時，已知的、具公信

力的醫學文獻。5.用藥應盡量以單方為主，如同時使用多種

藥品，應特別注意其綜合使用的療效、藥品交互作用或不良反應等問題。

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unlabeled use (off-label use)• 醫師常會以標示外使用（ off-label use）方式處方藥品。

關 於 off-label use 之法律性質與合理範圍、使用標準等 ，我國相關法律規範不明確，而醫界、學界、法界彼此間 存有歧異。

• 國內關於 off-label use之研究文獻已討論單一藥品、法律定性、責任、藥害救濟補償，或對於醫師進行問卷調查。

• 本論文以質性訪談瞭解臨床現象及醫師態度，發現與結論如下：一、 Off-label use在國內法律上應為有條件合法之

醫 療行為，並非人體試驗或使用新藥。二、受訪醫師認為off-label use有其存在之必要，但也有安全上的疑慮

。 三、受訪醫師對於 off-label use合法性認知不一，期望 能有明確規則可循。四、合理的 Off-label use類型，應 可有條件納入藥害救濟給付範圍。五、國內主管機關應改

進申請及統一適應症之機制。

仿單標示外使用（ Off-label Use）與用藥安全 溫珮君 2010-12-31

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藥害救濟統計 (88-99 年 )

• 藥害救濟總給付金額 : 2億 2288萬 9980元。• 平均獲得救濟比率 : 50.8 % 。• 藥害不良反應類別中有 66%為皮膚及皮下組織疾患

， 而前三名不良反應分別為 Stevens Johnson Syndrome、 toxic epidermal

necrolysis 、 anaphylactic shock 。• 申請藥害救濟的藥物前三名為 allopurinol 、carbamazepine、 phenytoin ，皆會造成 Stevens Johnson Syndrome 。

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判定不予藥害救濟給付原因前三名

1. 與藥品無相關。2. 未依藥物許可證所載之適應症或效能而

為藥物之使用 ( off-label use ) 。

3. 常見可預期之藥物不良反應 ( 發生率 > 1 % )。

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藥害救濟法 100 年 5 月 6 日修正 (1)

•第十三條第八款、未依藥物許可證所載之適應症或效能而為藥物之使用。但符合當時醫學原理及用藥適當性者，不在此限。

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立法院附帶三項決議 (2)

• 1. 『符合當時醫學原理』的認定，由衛生署藥害救濟審議委員會依用藥當時

具 公信力的醫學文獻個案為之。• 2. 未來藥害救濟委員會在審議案件時，如發現醫師不當開立仿單適應症外使用藥品處方時，應移送主管機關懲處。

• 3.藥廠行銷仿單標示外使用藥物，屬於非法行為，主管機關應加強管制。

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『符合當時醫學原理』的認定標準共識 (3)

• 1. 有「藥品查驗登記審查準則」所稱十大先進國家已經核准之用藥適應症，而台灣尚

未 核准之情形。• 2.已收載於國內、外專科醫學會或政府機關出 版之臨床診治指引。

• 3.屬於傳統治療方法，且已廣為臨床醫學教學 書籍收載列為治療可選用藥物 ( drug of choice ) ，並符合目前醫學常規等。

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Thanks for your attention