รายนามผู้นิพนธ์ นพ. ธนชัย พนาพุฒิ รพ.ขอนแก่น รศ.นพ.สมนึก ดำรงกิจชัยพร
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รายนามผู้��นพนธ์�
นพ . ธ์นชั�ย พนาพ�ฒิ รพ.ขอนแก่�นรศ.นพ. สมน�ก่ ดำ�ารงก่จชั�ยพร รพ.รามาธ์บดำ�รศ.ดำร. บ�ณฑิต ถิ่$นคำ�ารพ คำณะสาธ์ารณส�ขศาสตร� ม.ขอนแก่�น
WHO perspectiveEmerg Infect Dis 1997;3(2):223-8
“Emerging Infectious Disease”
Rationale and Background
166 102 100 143 358
23342840
5709
0
1000
2000
3000
4000
5000
6000
2535 2536 2537 2538 2539 2540 2541 2542
Patients
Death
145113
19470 0
Leptospirosis patients 2535-2542, ThailandLeptospirosis patients 2535-2542, Thailand
232
Anicteric Weil’s disease
LEPTOSPIROSIS LEPTOSPIROSIS
Mortality Rate
Barbados 10 %Hawaii 10 %Trinidad 8 %Korea 5 %Thailand 5 %
Literature review : Risk Factors for Death Literature review : Risk Factors for Death
Only few retrospective studies
OLIGURIA Elizabeth Daher et al 1999
Literature review : Risk Factors for Death Literature review : Risk Factors for Death
No prospective study
Objectives
To determine
1. Prognostic factors of death in leptospirosis.
2. Mortality rate among admitted patients.
3. Overall survival time.
To determine
1. Prognostic factors of death in leptospirosis.
2. Mortality rate among admitted patients.
3. Overall survival time.
Study Design Study Design
Prospective Cohort study
Conceptual framework Conceptual framework
FactorsHx: Age, Sex Duration before Admission Hemoptysis Hemorrhagic symptom Neurological symptom Previous antibiotic usePE: Tachypnea Crepitation Hypotension OliguriaLab : Hct, Wbc, Platlet Cr, K, CPK, TB, SGOT
Outcome
Death
Survivor
Rx
Materials & Methods IMaterials & Methods I
• Inpatient unit, Department of medicine, Khon Kaen Hospital
• June to December 2542
• 121 patients with Leptospira Ab positive (Dip-stick IgM test)
Materials & Methods IIMaterials & Methods II
Exclusions
Known localized infections
Septicemia, Malaria
Rickettsia
Inclusions
Age > 15
Acute FUO within 10 days
Fever with hepatorenal involvement
Initial Evaluation Initial Evaluation
1. History and Physical Examination.
2. Lab: CBC, BUN, Creatinine, Electrolyte,
LFT, CPK
Leptospira titer (Dip-stick IgM specific test)
Hemoculture, Malaria, Rickettsial Ab (IgM)
Chest x-ray
3. Urine volume, Modified APACHE II score
Study design overview Study design overview
AdmissionOutcome - Dead - Alive
Follow up
Treatment 2 weeks
PGS 6mu/day or Doxycycline 200 mg/day
Statistical Analysis
Risk estimation : Survival analysis
Outcome, start, event, censoring observation
Univariate - Kaplan-Meier estimate
- Logrank Test
Multivariate - Cox Regression Model
(Backward, Likelyhood ratio test)
Hazard ratio (95%CI) - Magnitude of risk
Risk estimation : Survival analysis
Outcome, start, event, censoring observation
Univariate - Kaplan-Meier estimate
- Logrank Test
Multivariate - Cox Regression Model
(Backward, Likelyhood ratio test)
Hazard ratio (95%CI) - Magnitude of risk
RESULT
S
Patient profiles I
18
42
2521
15
051015202530354045
16-25 26-35 36-45 46-55 >55
Age
Age (year)
Average age 38 years (16 - 73 )
No.
Patient profiles II
Male 94.2 %
Female 5.8 %
Sex
Patient profiles III
• เก่ษตรก่รรม 774. %• ก่รรมก่ร 11.3 %• ร�บจ�างทั่�$วไป 35. %• ราชัก่าร 35%• คำ�าขาย 2.6 %• ไม�ไดำ�ประก่อบอาชั�พ 17. %
อาชั�พ
Patient profiles IV
• ขอนแก่�น 669.%
• จ�งหว�ดำอ.$น 33.1 % : – มหาสารคำาม ก่าฬสนธ์��– ชั�ยภู�ม หนองคำาย– หนองบ�วลำ�าภู� นคำรราชัส�มา– ส�รนทั่ร� อ�ดำรธ์าน�– สก่ลำนคำร นคำรราชัส�มา
ทั่�$อย��
Presenting symptoms
Presenting symptoms Non-survivors Survivors (n = 17) (n =104)
Fever 100.0 100.0 Myalgia 100.0 95.2Headache 88.2 89.4Chill 77.0 77.7Hemoptysis 29.4 22.5Jaundice 88.2 49.0*Conjunctival suffusion 52.9 52.9Hypotension 94.1 44.2*Tachypnea (RR > 28/min) 70.6 18.3*Oliguria (urine<400cc/day) 76.5 12.5*
*p < 0.05
Laboratory values Non-survivors Survivors(n = 17)
(n =104)
Hematocrit (%) 29.1 + 5.4 32.7 + 6.6*Leukocyte count (109/L) 16.5 + 6.7 12.7 + 5.2*Platelet count (109/L) 56.0 + 61.1 68.7 + 65.6Urea nitrogen (mg/dl) 93.0 + 42.5 62.1 + 35.2*Creatinine (mg/dl) 7.8 + 2.5 4.6 + 2.9*Sodium (mmol/l) 131.7 + 7.4 133.5 + 5.2Potassium (mmol/l) 4.7 + 1.5 3.5 + 0.6*Bicabornate (mmol/l) 13.3 + 3.8 18.1 + 3.9*Albumin (g/dl) 2.7 + 0.4 3.0 + 0.5*Total bilirubin (mg/dl) 15.5 + 10.8 9.1 + 9.9*Aspartate aminotransferases (IU/L) 131.8 + 123.5 75.6 + 56.6*Creatinine kinase (IU/L) 941.4 + 1092.6 367.8 + 454.9*
p < 0.05
Laboratory values on admission
Organs involvementOrgans involvement
Thrombocytopenia 78.6 %Acute renal failure 74.2 %Acute hepatitis 65.3 %Hypotension 51.6 %Congestive heart failure 28.2 %Pulmonary hemorrhage 9.1 %ARDS 3.4 %
Thrombocytopenia 78.6 %Acute renal failure 74.2 %Acute hepatitis 65.3 %Hypotension 51.6 %Congestive heart failure 28.2 %Pulmonary hemorrhage 9.1 %ARDS 3.4 %
Outcome Outcome
Admission Outcome Follow up
Treatment 2 wk
121 Dead 17Alive 104
Alive 104
Median follow up time 9 day (4-36)
Outcome Outcome
Admission Outcome Follow up
Treatment 2 wk
121 Dead 17Alive 104
Alive 104
Mortality rate 1.4 per 100 patient-days(95%CI: 0.9 - 2.3)
Associated Causes of Death
Causes of death N %
Pulmonary hemorrhage 8 47.1 Complicated renal failure 3 17.6Multiple organs failure 3 17.6ARDS 2 11.8Irreversible shock 1 5.9
Kaplan-Meier survival estimate
0 10 403020
0.00
1.00
0.75
0.50
0.25
analysis time (days)
121
104
Pro
bab
ilit
y o
f su
rviv
al
Kaplan-Meier survival estimate
0 10 403020
0.00
1.00
0.75
0.50
0.25
analysis time (days)
121
104
91.4% at 1 week82.7% at 2 week
Pro
bab
ilit
y o
f su
rviv
al
Age (year) < 28 29-48 > 48Delay time >4 daysPrevious antibiotic useHemoptysisHemorrhagic symptomsNeurological symptoms Tachypnea (resp. rate > 28/min)*Bilateral pulmonary rales*Hypotension (dopamine use)*Oliguria (urine < 400cc./day)*
Age (year) < 28 29-48 > 48Delay time >4 daysPrevious antibiotic useHemoptysisHemorrhagic symptomsNeurological symptoms Tachypnea (resp. rate > 28/min)*Bilateral pulmonary rales*Hypotension (dopamine use)*Oliguria (urine < 400cc./day)*
Univariated analysis
Hct < 32%*Wbc counts > 13,000/mm3*
Platlet counts < 100,000/mm3
Creatinine > 5 mg/dl*Hyperkalemia (K > 5 mmol/l) *Total bilirubin > 9 mg/dlAspartate aminotransferase > 80 IU/L*Albumin < 2.9 g/dl*Creatine phosphokinae > 440 IU/L*Modified APACHE II score > 15*
Hct < 32%*Wbc counts > 13,000/mm3*
Platlet counts < 100,000/mm3
Creatinine > 5 mg/dl*Hyperkalemia (K > 5 mmol/l) *Total bilirubin > 9 mg/dlAspartate aminotransferase > 80 IU/L*Albumin < 2.9 g/dl*Creatine phosphokinae > 440 IU/L*Modified APACHE II score > 15*
Univariated analysis
Independent Risk Factors for DeathIndependent Risk Factors for Death
Risks Cox-regression Model Haz. Ratio 95%CI p*
Hypotension 10.3 1.3-83.2 0.029(Need Dopamine)Oliguria (<400 cc/d) 8.8 2.4-31.8 0.001Hyperkalemia 5.9 1.7-21.0 0.006Pulmonary rales 5.2 1.4-19.9 0.015
* p-value from partial likely hood ratio test
ConclusionsConclusions
1. Mortality rate 1.4 per 100 patient-days (95%CI: 0.9-2.3)
2. Overall survival timeat 1 week was 91.4%at 2 week was 82.7%
3. Hypotension, oliguria, hyperkalemia and pulmonary rales were the significant independent risk factors for death in leptospirosis.
1. Mortality rate 1.4 per 100 patient-days (95%CI: 0.9-2.3)
2. Overall survival timeat 1 week was 91.4%at 2 week was 82.7%
3. Hypotension, oliguria, hyperkalemia and pulmonary rales were the significant independent risk factors for death in leptospirosis.
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ขอขอบคำ�ณ
Suggestions Suggestions1. Urine volume record (ml.)2. Clinical close monitoring in 1st week3. District hospital : referral indication
3.1 urine < 200 ml./12 hr. or3.2 pulmonary rales. or
3.3 hypotension4. Tertiary center
4.1 Early dialysisurine <200 ml/12hr or K > 5 mmol/l
4.2 Early intubation: tachypnea and rales
4.2 ICU care for pulmonary complication4.3 Intermediate care of leptospirosis
• Serovas N (%)• L. Sejroe 21 (60.0)• L. Bratislava 8 (22.8)• L. Bangkoki 3 (8.4)• L. Pyrogenes 2 (5.8)• L. Copenhageni 1 (2.9)• L. Icterohaemorrhagia 1 (2.9)• L. Sejroe+L.Bratislava 2 (5.8)• L. Sejroe+L.Pyrogenes 1 (2.9)• total 35
• Serovas N (%)• L. Sejroe 21 (60.0)• L. Bratislava 8 (22.8)• L. Bangkoki 3 (8.4)• L. Pyrogenes 2 (5.8)• L. Copenhageni 1 (2.9)• L. Icterohaemorrhagia 1 (2.9)• L. Sejroe+L.Bratislava 2 (5.8)• L. Sejroe+L.Pyrogenes 1 (2.9)• total 35
Serovars of LeptospirosisSerovars of Leptospirosis
Antibiotic use before admission 59 (48.7 %)
Antibiotic use in hospital
Antibiotic N %
PGS 64 52.9Doxycycline 31 25.6PGS + Doxycycline 10 8.3PGS + 3rd cephalosporin 16 13.2
Pulmonary Hemorrhage
Frank hemoptysis or bloody fluid in ET
with 2 of 3
1. Hct drop > 3%
2. CXR show alveolar infiltration with normal cardiothoracic ratio.
3. No clinical congestive heart failure
Acute Respiratory Distress syndrome
1. No clinical of congestive heart failure: JVP < 4 cm. or CVP<12 cm.2. Gas index: PO2/FiO2 < 2003. CXR : diffuse alveolar pattern with normal cardiothoracic ratio.4. Pw < 18 cm.
1. No clinical of congestive heart failure: JVP < 4 cm. or CVP<12 cm.2. Gas index: PO2/FiO2 < 2003. CXR : diffuse alveolar pattern with normal cardiothoracic ratio.4. Pw < 18 cm.
Congestive Heart Failure
1. JVP > 5 cm. or CVP > 15 cm.2. S3 gallop or pulmonary rales3. CXR : diffuse alveolar pattern cephalization increase cardiothoracic ratio
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