Multi-center research of small-sized polymyxin B hemoperfusion

Naohiro Wada Department of Pediatric Nephrology Shizuoka Children’s Hospital Shizuoka, JAPAN

polymyxin B immobilized fiber column

Polystyrene/polypropylene (9/1) conjugated fiber

Covalent linkage

Polymyxin B Polymyxin B LPS =Endotoxin Polysaccharide Lipid A Lipid A + Anandamide 2-arachidonylglycerol (endocannabinoids) Gram –positive bacterial infection also effective

Crus DN et al (Crit Care 2007;11:R47) “Effectiveness of polymixin B immobilized fiber column in sepsis: a systematic review” Review : meta-analysis Favorable effect : MAP, dopamine use, PaO2/FiO2 ratio, mortality Consideration : publication bias, lack of blinding Cruz DN et al (JAMA 2009;301:2445-2452) “Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock. The EUPHAS Randomized Controlled Trial.”

PMX 20R PMX 05R Priming volume 135 ml 40 ml Length 225 mm 135 mm Diameter 63 mm 55 mm

PURPOSE

The effectiveness and safety of small-sized polymyxin B hemoperfusion in the severe septic shock children.

Retrospective analysis in three units.

Complete count survey in the units.

Units: pICU, Nagano Children’s Hosp.

Neonatal section, Kurashiki Central Hosp.

Nephrology section, Shizuoka Children’s Hosp.

PATIENS

Septic shock Definitions for sepsis and organ dysfunction in pediatrics

(Pediatr Crit Care Med 2005;6:2-8)

Cases : 36 (male 24, female 12) Age : 1.6

±

2.6 y (0m-10y : median 0.32 y) Weight : 6.5

±

5.5kg (1.2kg~28kg : median 5.0kg

）

Data (at the time of treatment) sBP (mmHg) 77

±

24 HR ( /min) 144

±

33 WBC (10 3 /mm 3 ) 8.3

±

6.9

Plt (10 4 /mm 3 ) 8.6

±

8.3

BUN (mg/dl) 19.0

±

17.1

Cr (mg/dl) 0.80

±

0.67

PELOD : 35

±

11 (predictive mortality : 94.6%) Frequency : once 11 twice 25

Bacterial culture detected 22 E.coli

Klebsiella Pseudomonas Serratia MSSA MRSA GBS Streptococcus 2 ( blood 2) 2 ( blood 1

、

ascites 1) 3 ( blood 2

、

urine 1) 1 ( blood) 5 ( blood 5) 4 ( blood 2

、

2 3 ( blood 3

）

( blood 2

）

sputum 2) Endotoxin

（

before treatment

）

detected not detected not done 11 (1-714

：

mean 150.6

土

227.4

；

median 49.9) 9 16

Qb 28.3

±

15.0 ml/min (5

－

80) 6.2

±

4.0 ml/min/kg (0.97

～

16.2

：

median 5.7) Anticoagrant Nafamostat mesilate : 36 (100%) 0.40

±

0.18 mg/kg/hr, (0.1

～

1.0, median 0.41) Priming Blood

＋

Albumin/FFP albumin saline 34 1 2

（

2y:9.9kg)

（

7y:26kg, 14y:18kg) Concurrent therapy

（

overlapped

）

CH(D)F ECMO 36 (100%) 4 ( 11%)

Blood access (excluded ECMO route access) jugular v.

femoral v.

subclavian v.

20 10 2 Catheter size

（

DL) (excluded ECMO route access) 17G 16G 15G 6 Fr 6.5Fr

7 Fr 1 4 8 Fr 13 10 Fr 1 1 2 2 8 10 9 8 7 6 5 4 0 5 10 15 20 25 boby weight(kg)

※17G=4.5Fr, 16G=5Fr, 15G=5.5Fr

30

Changes in blood pressure before and end of treatment

(before therapy = 1) 1 0.9

0.8

0.7

0.6

1.6

1.5

1.4

1.3

1.2

1.1

>1

：

30/52 (57%) 1.09

±

0.23

pre post

2 1.8

1.6

1.4

1.2

1 0.8

0.6

Changes in blood pressure

( before therapy = 1) pre just after Tx pre 2nd Tx just after 2nd Tx 24hrs after Tx 48hrs after Tx

Changes in HR

(before therapy = 1) 1.6

1.4

1.2

1 0.8

0.6

0.4

pre just after Tx pre 2nd Tx just after 2nd Tx 24hrs after Tx 48hrs after Tx

0.5

1 0 3.5

3 2.5

1.5

2

Change in WBC and platelet

before and 24hrs after treatment (before therapy = 1) WBC 2 0 1 3 4 7 5 6 Platelet pre post pre post

PROGNOSIS

Death : 18/36 (mortality rate 50%) < 7 days 14 (39%) 8

～

28 days 2 29 days< 2 PELOD 40< : 19 cases Death : 9 /19

（

47

％）

(predicted mortality rate: 99% and more

）

Comparison of death group and living group

number Age (y) Weight (kg) Systolic BP (mmHg) HR (/min) PELOD WBC (10 3 /mm 3 ) Plt (10 4 /mm 3 ) BUN (mg/dl) Cr (mg/dl) Death 18 1.5

±

2.6

6.1

±

4.9

73

±

24 139

±

34 35.9

±

7.9

7.2

±

6.5

8.6

±

8.6

19.0

±

17.6

0.89

±

0.71

Living 18 1.7

±

2.8

6.8

±

6.3

81

±

24 149

±

32 33.8

±

13.3

9.2

±

7.2

8.7

±

8.3

19.0

±

17.3

0.72

±

0.63

ns ns ns ns ns ns ns ns ns ns

Conclusion

Polymyxin B hemoperfusion treatment was possible to be effective to the septic shock children safely even at low body weight and contributed to the prognosis improvement. However, other therapies effect to the mortality, randomized control trial and definite indication are necessary for the effectiveness of polymyxin B hemoperfusion itself.

CHDF + PMX-DHP

PMX

－

DHP Double lumen CHDF

CH(D)F + PMX-DHP

Q B 1 CH(D)F

CH(D)F + PMX-DHP

Q B 1 Q B 2 CH(D)F PMX-05R QB1>QB2

CH(D)F + PMX-DHP

Q B 1 CH(D)F