Transcript 新光醫院感染科敗血症標準作業流程 新光醫院 感染科 黃建賢

新光醫院感染科敗血症標準作業流程
severe sepsis and septic shock
新光醫院
感染科
黃建賢
SEPSIS
DEFINITIONS
– microbes involves a
rapidly amplifying
polyphony of signals
and responses that
may spread beyond
the invaded tissue.
1. 敗血症的定義
1.
敗血症的定義
1.1宿主因微生物感染大量繁殖並造而造成全身性症狀，
臨床上可表現出發燒，低體溫，寒顫，呼吸加速，心
搏加速，宿主因為微生物的侵犯而表現出”系統性發
炎反應症候群”(systemic inflammatory response
syndrome，SIRS)
1.2 ”系統性發炎反應症候群”定義為包函下列或兩者以
上
1.2.1 體溫38度C以上或36度C以下
1.2.2 心跳速度超越每分鐘90下
1.2.3 呼吸速率超越每分鐘20下
1.2.4 血液中白血球大於每毫升12000或小於每毫升4000
或含百分之10以上之不成熟白血球(bands)
ETIOLOGY
gram-negative and grampositive bacteria
–
–
–
–
–
fungi,
mycobacteria,
rickettsiae,
viruses,
or protozoans…
Positive blood cultures :
– 30 to 60 % of patients with sepsis
– 60 to 80 % of patients with septic
shock
Sepsis
Definitions Used to Describe
the Condition of Septic Patients
Bacteremia
Presence of bacteria in blood
Systemic inflammatory
response syndrome (SIRS)
Fever, tachypnea, tachycardia,
leukocytosis/leukopenia
Sepsis
SIRS has a proven or suspected
microbial etiology
Severe sepsis
Sepsis with ≥1 signs of organ
dysfunction
Septic shock
Sepsis with hypotension or need
for vasopressor
Multiple-organ dysfunction
syndrome (MODS)
Dysfunction of ≥1 organ
Epidemiology of Sepsis in the
United States from 1979-2000
N Engl J Med 2003; 348: 1546-54.
EPIDEMIOLOGY
2/3: in hospitalized patients.
Risk Factors to GNB bacteremia
–
–
–
–
–
–
diabetes mellitus
lymphoproliferative diseases
cirrhosis of the liver
burns
invasive procedures or devices
drugs that cause neutropenia
EPIDEMIOLOGY
Risk factors for GPC bacteremia
–
–
–
–
vascular catheters,
indwelling mechanical devices,
burns,
intravenous drug injection.
Fungemia :
–
–
–
–
–
immunosuppressed patients
neutropenia
broad-spectrum antimicrobial therapy
TPN
Intestinal perforation
PATHOPHYSIOLOGY
Endotoxin
Gram negative bacilli
Lipopolysaccharide (LPS, also called
endotoxin)
PATHOPHYSIOLOGY
Microbial signals
Gram positive cocci
peptidoglycan and lipoteichoic acids
extracellular enzymes
敗血症的症狀
Fever or hypothermia (low body temperature)
Hyperventilation
Chills
Shaking
Warm skin
Skin rash
Rapid heart beat
Confusion or delirium
Decreased urine output
CLINICAL MANIFESTATIONS
S/S:
– fever, chills, tachycardia, tachypnea, altered mental
status, and hypotension.
afebrile
– common in neonates, in elderly patients
– and in persons with uremia or alcoholism.
CLINICAL MANIFESTATIONS
Llaboratory finding:
–
–
–
–
–
–
C-reactive protein
fibrinogen
complement components
transferrin
inhibits albumin synthesis
Leukocytosis, left shift
LABORATORY FINDINGS
Early sepsis
–
–
–
–
–
–
leukocytosis with a left shift
Respiratory alkalosis
Thrombocytopenia
Hyperbilirubinemia
proteinuria.
neutrophils may contain toxic granulations, Dohle
bodies, or cytoplasmic vacuoles
LABORATORY FINDINGS
Progressing of sepsis:
–
–
–
–
–
–
thrombocytopenia worsens
prolongation of the thrombin time
decreased fibrinogen
presence of D-dimers, suggesting DIC)
Azotemia, hyperbilirubinemia become prominent
Elevated GOT GPT
LABORATORY FINDINGS
Progressing sepsis:
–
–
–
–
hyperventilation induces respiratory alkalosis.
accumulation of lactate,
metabolic acidosis (with increased anion gap)
hyperglycemia, severe infection may precipitate
diabetic ketoacidosis(DKA)
Multiple organ dysfunction
syndrome
MOF:
– Dysfunction or failure of multiple organs
– reflecting widespread vascular endothelial
injury
– associated with high fatality rates.
– Mortality and morbidity correlate with the
number of organs affected.
DIAGNOSIS
S/S --Progressing sepsis
– tachypnea,
– tachycardia,
– altered mental status,
– The septic response can be quite variable
– systemic inflammatory response syndrome
SIRS
DIAGNOSIS
Definitive diagnosis
– isolation of the microorganism from blood or a local
infected site
– Gram's stain
– culture of the primary site of infection.
TREATMENT
Sepsis may be fatal quickly.
Successful management
–
–
–
–
urgent measures to treat the local site of infection,
hemodynamic and respiratory support
eliminate the offending microorganism
Therapy of acidosis and DIC, other complications
TREATMENT
Outcome
– influenced by the patient's underlying disease
– aggressively treated.
– Antimicrobial agents
PROGNOSIS
Mortality:
– More than 25 %
– 1/3 within the first 48 h
– mortality can occur 14 or more days later.
– Late deaths
poorly controlled infection
complications of intensive care
multiple organs failure
2.敗血症初期之緊急處理
2.1 敗血症最初七小時之緊急處理措施著眼於恢
復因敗血症所引起的低血流灌注，恢復組織
功能，應包含以下所有之緊急處理
2.1.1 中心靜脈壓維持8-12mmHg
2.1.2 平均動脈壓維持大於等於65 mmHg
2.1.3 小便量維持大於等於每小時每公斤體重0.5毫升
2.1.4 中心靜脈氧飽含量維持大於等於70﹪
2.敗血症初期之緊急處理
2.2 臨床檢驗
2.2.1由周邊靜脈至少抽取2至3套血液培養後盡快給予抗生素治療
2.2.2盡快找尋可能之感染部位並取得檢體，如導管相關之感染，呼
吸器相關之肺炎等
2.2.3在抗生素使用前須取得可能感染部位之培養檢體，如尿液，腦
脊髓液，傷口，呼吸道檢體或其他部位之組織液
2.2.4必要時可作血清學檢查、檢測抗體及抗原或檢測尿液中退伍軍
人菌抗體
2.敗血症初期之緊急處理
2.2 臨床檢驗
2.2.5如有液狀檢體，可作染色鏡檢如葛蘭氏染色，抗酸菌染色等
2.2.6軟組織感染時，除了做血液培養外，盡可能取得檢體做染色鏡檢
2.2.7必要時可在主治醫師同意下對病灶施行超音波檢查，電腦斷層或核
磁共振檢查以確立病灶及嚴重程度
2.2.8必要時可對病灶做抽吸或切片檢查以取得檢體
2.2.9如病灶有明顯積液、必要時可施以抽吸引流或外科治療
3.抗生素療法
3.1抗生素治療必須在取得適當檢體後盡快給予
3.2當病患有嚴重敗血症或敗血性休克時，要盡速給予體液補充，除非
有相當禁忌症(如急性肺水腫等)
3.3抗生素經驗療法必須依社區或院內感染，感染部位、菌種、抗生素
穿透能力及疾病人實際狀況來給予(參考本院每半年出版之菌種及抗
生素敏感試驗表)
3.3.1抗生素治療以一種抗生素為原則
3.3.2必要時可以合併抗生素使用以治療混合型感染或加強抗生素療效
3.3.3抗生素之選擇依病人過去病史，過敏史，合併疾病，合併症及臨床抗
生素敏感性做選擇
3.抗生素療法
3.4抗生素治療必須在使用48小時至72小時後重
新評估
3.4.1依細菌培養及抗生素敏感性試驗之結果做調整
3.4.2以窄效性抗生素為原則
3.4.3為避免抗藥性產生，抗生素之選擇以低毒性及同
類藥中價廉為原則
3.4.4治療以7-10天為原則，必要時可延長之
3.4.5抗生素之使用及停用以培養結果及臨床醫師判定
為原則
4 控制病源
4.1臨床上所有敗血症病患均盡量查出並除去感染源
4.1.1必要時以引流、清創或外科手術行之
4.1.2病患有外科手術需求時，必須在完成初步急救並
解釋病情之後、在家屬同意下、盡速施行之
5 輸液治療
5.1輸液治療包括自然血漿，人工血漿及一般輸液
5.1.1人工輸液較血漿易出現水份積蓄及水腫
5.1.2輸液速度以每30分鐘輸人工輸液300至1000毫升、或血漿
以每30分鐘300至500毫升為主
5.1.3輸液速度及輸液量以臨床反應、血壓及尿液量做調整
5.1.4密切監視病患以避免出現肺水腫及其他併發症
5.2 個人體液需求量依個體及疾病狀況不同依臨床狀況做
調整
6 血管收縮劑
6.1 當病患經輸液治療後仍無法維持適當的血壓及組織灌流時
得使用血管收縮劑治療
6.2 當低血壓足以危及生命時，血管收縮劑得以和輸液治療同
時給予
6.3 Nor-epinephrine或dopamine須以中心靜脈方式給予
6.4 使用血管收縮劑病患得施行動脈血壓監測
6.5 Nor-epinephrine起始劑量以0.01至0.04 units/分為原則
6.6 Cardiac index在2.5 L.min-1.m2以下者不宜使用血管收
縮劑
7 升壓劑(Dobutamine)
7.1 病患在經適當輸液治療後仍無法維持正常之
輸出量時得以使用升壓劑，必要時得合併血管
收縮劑使用
8 類固醇
8.1 休克病患在適當補充輸液，使用血管升壓劑後，仍無法
維持正常血壓時得以使用類固醇
8.2 劑量以每天hydrocortisone200至300毫克，分3至4次給
予，使用7天為原則、必要時得延長之
8.3 病患在檢測ATCH前得以使用dexamethasone取代
hydrocortisone以免影響血中cortisol濃度檢測值
8.4 敗血症病患未合併休克時，不建議使用類固醇
9 人類活性C蛋白使用
9.1 高死亡率之多重器官衰竭、敗血性休克、成
人呼吸窘迫症病患，無出血傾向時、
APACHEII score>=25、在主治醫師同意下得
以使用人類活性C蛋白(rhAPC)
10 血類製劑
10.1 無特殊禁忌症之敗血症病患在血色素7.0g/dl以下時得以
輸血
10.2 輸血目標值為血色素7.0至9.0g/dl
10.3 病患無明顯出血時、不建議以冷凍新鮮血漿來改善血液
中之凝血值
10.4不論有無出血現象，嚴重敗血症病患得以輸用血小板以
維持血小板值在5000/mm3以上(5×10-9/L)
11 呼吸器使用
11.1 呼吸器使用依本院呼吸器使用原則，及成人
呼吸窘迫症呼吸器使用原則行之
12 鎮靜劑麻醉藥品及肌肉鬆弛劑使用
12.1 嚴重敗血症病患合併呼吸衰竭及呼吸器使用時、得依
本院藥物使用規範使用鎮靜劑麻醉藥物及肌肉鬆弛劑
12.2 必要時得以會診麻醉科、以進行藥物調整及避免藥物
副作用
13 血中葡萄糖控制
13.1 敗血症病患須嚴密監測並控制血糖
13.2 血中葡萄糖控制以200 mg/dl以下為原則(有嚴格監
測時得控制在140 mg/dl以下)
13.3 必要時得以使用胰島素取代口服降血糖藥控制血糖
14 碳酸鹽治療
14.1 碳酸鹽治療得以使用於敗血症合併血流灌注所引起之酸中
毒
14.2 碳酸鹽治療酸中毒以pH值7.3以下為原則
14.3 嚴重敗血症病患得使用低劑量肝素或低分子量肝素預防深
部靜脈血栓形成
14.4 病患有出血傾向或其他禁忌症時應避免使用肝素
15 預防壓力性腸胃道潰瘍
15.1 所有敗血症病患均應預防壓力性潰瘍之產生
15.2 以使用H2 receptor抑制劑為原則，有禁忌
症或不適用者除外
16 褥瘡之預防
16.1 敗血症合併活動能力降低之病患、應預防褥瘡之產生
16.2 臨床上依預防褥瘡形成臨床技術手冊行之
16.3 褥瘡之治療、必要時可給予抗生素及施行清創手術
Epidemiology of Sepsis in the
United States from 1979-2000
Causative Organisms
Gram-positive bacteria
Gram-negative bacteria
polymicrobial infections
anaerobes
fungi
52.1%
37.6%
4.7%
1.0%
4.6%
Specific organisms causing sepsis were recorded in
51% of all discharge records over the 22-year period.
N Engl J Med 2003; 348: 1546-54.
Antimicrobial Agents in the
Management of Sepsis
Two blood culture
- one percutaneous
- one from each vascular
access >48 hrs
Begin IV antibiotics within
the first hr of recognition
of severe sepsis
Reassess antimicrobial
regimen at 48-72 hrs
Evaluate patient for a
focused infection
- one or more drugs active against
likely bacterial or fungal pathogens
- consider microbial susceptibility
patterns
- microbial and clinical data
- narrow-spectrum antibiotics
- non-infectious cause identified
- prevent resistance, reduce toxicity
and reduce cost
Crit Care Med 2004; 32: 858-73.
Vasopressor and Inotropics
Norepinephrine 4 mg/4 ml/amp (diluted by D5W)
- 0.03~3.3 μg/kg/min (2~200 μg/kg/hr)
Epinephrine 1 mg/1 ml/amp
- 0.06~0.47 μg/kg/min (3.6~30 μg/kg/hr)
Dopamine 200 mg/5 ml/amp
-2~55 μg/kg/min (0.12~3.3 mg/kg/hr)
Dobutamine 250 mg/20 ml/amp
- 2~28 μg/kg/min (0.12~1.68 mg/kg/hr)
Vasopressin 20 U/1 ml/amp
- 0.01~0.04 U/min (0.6~2.4 U/hr)
Crit Care Med 2004; 32: 1928-48.
Role of Corticosteroid in the
Management of Septic Shock
Treat patients who still require vasopressors despite
fluid replacement with hydrocortisone 200-300 mg/day
for 7 days divided in 3-4 doses or by continuous
infusion
(Grade C)
High dose of corticosteroids (> 300 mg/day) should
NOT be used in severe sepsis or septic shock.
(Grade A)
Crit Care Med 2004; 32: 858-73.
Role of Corticosteroid in the
Management of Septic Shock
In the absence of shock, corticosteroids should NOT
be administrated for the treatment of sepsis
(Grade E)
The use of ACTH stimulation test to identify responders
(>9 μg/ml increase in cortisol 30-60 mins post-ACTH
administration) and to continue therapy is optional.
Should NOT wait for ACTH stimulation results to
administer corticosteroids
(Grade E)
Crit Care Med 2004; 32: 858-73.
Mechanical Ventilation of
Sepsis-induced ALI/ARDS
High tidal volume that are coupled with high plateau
pressures should be avoided in ALI/ARDS.
- reduce tidal volume over 1-2 hrs to 6 ml/kg predicted
body weight
- maintain inspiratory plateau pressure <30 cmH2O
- maintain SaO2/SpO2 88-95%
- anticipated PEEP settings at various FiO2 requirements
FiO2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0
PEEP 5 5 8 8 8 10 10 12 14 14 14 16 18 20-24
(Grade B)
Crit Care Med 2004; 32: 858-73.
Intensive Insulin in Critical
Ill Patients
After initial stabilization of patients with severe sepsis
- maintain glucose <150 mg/dl by continuous infusion of
insulin
- monitor blood glucose every 30-60 mins and then q4h
(Grade D)
In patients with severe sepsis, a strategy of glycemic
control should include a nutrition protocol with the
preferential use of the enteral route.
(Grade E)
Crit Care Med 2004; 32: 858-73.
Intensive Insulin in Critical
Ill Patients
- prospective, randomized, controlled trial
- adults admitted to SICU (N= 1,548) who were receiving MV
adults admitted to MICU (N= 1,200) who were considered
to need ICU care for at least 3 days
- 50 IU actrapid HM/ 50 ml NS infused by pump (max. dose
50 IU/hr)
- intensive insulin (blood glucose ~80-110 mg/dl)
conventional treatment (blood sugar ~180-200 mg/dl)
- primary endpoint: ICU mortality/in-hospital mortality
N Engl J Med 2006; 354: 449-61.
Intensive Insulin in Critical
Ill Patients
Surgical ICU
Mortality
RRR
ARR NNT P value
ICU death
8.0% vs 4.6%
42.5% 3.4%
29
<0.04
In-hospital
death
10.9% vs 7.2%
33.9% 3.7%
27
0.01
26.8% vs 24.2% 9.7% 2.6%
38.1% vs 31.3%* 17.8% 6.8%
14
0.31
0.05
In-hospital 40.0% vs 37.3% 6.8% 2.7%
death
52.5% vs 43.0%* 18.1% 9.5%
10
0.33
0.009
Medical ICU
ICU death
* patients who stayed in the ICU ≥3 days
N Engl J Med 2001; 345: 1359-67.
N Engl J Med 2006; 354: 449-61.
Advances in Therapy for
Severe Sepsis and Septic Shock
Time-sensitive intervention
Mortality reduction (ARR)
Early goal-directed therapy
16% (P= 0.009), NNT= 6
Drotrecogin alfa (activated)
for high-risk patients
13% (P= 0.001), NNT= 8
Low-dose steroids
10% (P= 0.023), NNT= 10
Low tidal volume ventilation
10% (P= 0.005), NNT= 10
Tight blood sugar control
3.4% (P= 0.005), NNT= 29
N Engl J Med. 2001; 345: 1368-77.
N Engl J Med. 2001; 344: 699-709.
JAMA 2002; 288: 862-71.
N Engl J Med. 2000; 342: 1301-8.
N Engl J Med. 2001; 345: 1359-67.
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