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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

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อาชั�พ

Patient profiles IV

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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