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Clinical design and application of body weight-bas

作者:pkupv   发布时间:2012-09-18 08:12:34   浏览次数:738
Clinical design and application of body weight-based
 heparin dosing nomogram

(2003,APCDC Oral Presentation)

 
1.Liang Ying, 2.Luo Hua
1.Department of Pulmonary Medicine, Beijing Anzhen Hospital, Affiliated Hospital of Capital University of Medical Science, Beijing 100029),China
2.Department of CCM, Shenzhen Hospital,PKU,China
 
 
Heparin has been used to treat and prevent pulmonary thromboembolism for more than 30 years. It is widely welcomed by the clinicians because its anticoagulation is effective and easy to be monitored. However, the effect of heparin is associated with its half-life, its dosage, the function of the platelet and the endothelium. The stead concentration of heparin is difficult to control. In present clinical practices, APTT monitoring is necessary when patients are treated with heparin, specially in PTE.
    Many results of animal experiments and human clinical trials have conformed that it is safe when APTT ratio achieves therapeutic range, 1.5 to 2.5 times the control, with the low incident of bleeding and recurrent thrombosis. Although APTT does not always properly reflect antithrombotic effect of heparin, presently, the clinicians still regard it as major index of monitoring to adjust heparin dosage.
Body weight-based heparin dosing nomogram designed by Raschke (table 1), which is recommended by ACCP in the sixth consensus conference on antithrombotic therapy, has promoted prompt heparinization during anticoagulant therapy in PTE. Whereas, it is still not convenient enough for the doctors to use in clinical practice. It will take the doctors quite a long time to calculate not only total amount of heparin dosage according to measured APTT but also diluted milliliters of heparin. It is a dull work and rather hard to handle.
To make it easy to be understanderable and memorable for the doctors, to shorten the time interval of heparin adjustment, to strengthen the antithrombotic effect, we develope a convenient nomogram (table2,3) and design a meter of heparin ,with Excel 2000 of Microsoft office, basing on heparin nomogram of Raschke as supplement.
In our meter, the horizontal axis is about body weight (kg), the left axis of ordinate is about heparin dosage (u/h ) and diluted milliliter (ml/h); The right axis of ordinate is about heparin dosage (u/h/kg) and measured aptt (s).Talking about its application, we take it for example: a patient with measured APTT 95 seconds is 70 kg weight; after we stop infusion an hour, he will receive a change of heparin dosage from initial 18u/kg/h to 15u/kg/h---what is his exact diluted infusion volumes each hour after adjustment? Finding the result with our meter is a piece of cake, which sequences that (sketch map): firstly, to line vertically across to the point of 70kg on the horizontal axis (line 1); secondly, to find the oblique line that 95 seconds belongs to, which is the line ‘‘>90 seconds ’’(line 2); Thirdly, to line vertically on the left axis of ordinate across to the point that two lines---line 1 and line 2 intersects (line 3); The number of the point that line 3 intersects the left axis of ordinate is that of heparin dosage---1125 u/h, the left number is that of heparin milliliters diluted---45ml/h.
Sketch map:                         line2(aptt)
(heparin)line3
 
                           Line1(kg)
 
 
Table 1     Body weight-based dosing of IV heparin 
          APTT(s)                                      dose change      additional action          next APTT
                   (U/Kg/h)                                                  (h)
<35 (1.2×mean normal)                  +4              rebolus with 80IU/Kg,           6     
35-45(1.2-1.5× mean normal)        +2             rebolus with 40IU/Kg,           6 
46-70(1.5-2.3× mean normal)         0                             0                              6 #
71-90(2.3-3.0× mean normal )       -2                             0                              6
>90(>3.0 ×mean normal                 -3                stop infusion 1 hour            6
    
* Initial dosing: loading, 80 IU/kg; maintenance infusion:18 IU/kg/h (APTT in 6 h).
# During the first 24 h, repeat APTT every 6 h. Thereafter, monitor APTT once every morning unless it is outside the therapeutic range. (From the sixth ACCP consensus conference on antithrombotic therapy)
 
 
Table 2 Initial dose of heparin  (80u/kg)
 

                     bolus        milliliters

weight(kg )    u nits       *2ml/ampule
< 50                      4000                 0.6
51-58                   4400                  0.7
59-66                   5040                  0.8
67-74                   5680                  0.9
> 75                      > 6000              1.0
 
Table 3  A convenient nomogram of weight-based heparin infusion
             
22 u/kg/h   20u/kg/h   18u/kg/h   16u/kg/h     15u/kg/h  
 weight(kg)           u (ml)     u (ml)      u (ml)         u (ml)         u (ml)
< 50        1100(44)  1000(40)    900(36)   800(32)    750(30)
 51-58     1210(48)  1100(44)    990(40)   880(35)    825(33)
 59-66     1386(55)  1260(50)    1134(45) 1008(40)   945(37)
 67-74     1540(61)  1400(56)    1260(50)   1120(44) 1050(42)
> 75         1650(66) 1500(60)    1350(54)   1200(48) 1125(45)
 APTT                   < 35s                   34—45s               4670s               71—90s                > 90s
·* sodium of heparin 2ml/ampule,
Dilution:sodium of heparin 12500units in 500ml of 0.9 % N.S (equal to 25u/ml)
· Initial dosing; loading, 80 IU/kg; Maintenance infusion:18U/Kg/h(During the first 24 h, repeat APTT every 6 h. Thereafter, monitor APTT once every morning unless it is outside the therapeutic range.)
Three to five days of heparin therapy later, to examine the numbers of platelet.
The horizontal axis is about body weight (kg), the left axis of ordinate is about heparin dosage (u/h) and diluted milliliter (ml); The right axis of ordinate is about heparin dosage (u/h/kg) and measured aptt (s).
By our experience, it is quicker to find the result of heparin dosage with the meter than to calculate basing on Raschke nomogram. It is also easier to comprehend for the doctors and nurses. It makes the nurses keep good cooperation with the doctors and lessen their burden in emergent case by applying the meter themselves. In our meter, the most accurate unit of heparin dosage is 5 u, the most accurate milliliter is 1 ml. There is not obvious difference between dosing results of the meter and Raschke nomogram. Furthermore, we think it is feasible that 12500 units of heparin are diluted by 500 ml of 0.9% NS in most of patients without chronic cardiologic and pulmonary diseases. It is equal to 25 u of heparin in 1 ml of NS. For the patients with left heart failure, we suggest that infusion amount of the NS should be controlled each day and diluted ratio of heparin should be changed.
In summary, our nomogram and meter feature that :
   the three-line method to find the dosage number of heparin, without dull calculation ,is easy to understand and handle;
   1 to 2 minutes spend on looking up the units and milliliters of heparin is time- saving;
   errors during manual calculation is avoided;
④ more and more patients who receive heparin therapy will be benefit from it.
 Whether our nomogram and meter are become popular in clinical practice or not needs further improvement and evaluation.
 
 
References :
1.      Fernandez F, Nguyen P ,van Ryn J, et al. Hemorrhagic doses of heparin and other glycosaminoglycans induce a platelet defect. Tthromb Res 1986;43:491-495
2.      Hirsh J, van Aken WG, Gallus AS. Heparin kinetics in venous thrombosis and pulmonary embolism. Circulation 1976; 53:601-695
3.      Basu D, Gallus A, Hirsh J, et al. A prospective study of the value of monitoring heparin   treatment with the activated partial thromboplastin time. N Engl J Med 1972; 287:325-327
4.      Young E, Pruis M, Levine MN, et al. Heparin building to plasma proteins: an important mechanism for heparin resistance. Thromb Haemost 1992;67:639-643
5.      Hyers TM , Agnelli G, Hull RD, et al. Antithrombotic   therapy for venous thro boembolic disease. Chest,2001,119:176s-193s
 







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