This study analyzed 190 courses of heparin treatment given to 170 consecutive patients admitted to the coronary care unit between November 18, 1996, and April 2, 1997. The baseline characteristics of the patients are presented in Table 1. Of the 190 heparin treatments given, 133 (70%) were prescribed for patients who presented with non-ST-elevation acute coronary syndromes, and 181 (95%) were administered concomi- tantly with acetylsalicylic acid. In 61 cases (32%), a weight-adjusted loading dose and infusion were prescribed to initiate heparin therapy; in the other cases, there was no adjustment for body weight.


Table 1. Baseline Characteristics



Mean ±
SD or No.


(%)





Characteristic



All
Treatment Courses (n


= 190)



Without
Noncompliant Interventions (n


= 96)



With
Noncompliant Interventions (n


= 94)




p

Value



Age (yr)




65

±


13*




66

±
14f




65

±


12$



0.91



Sex
(no. and


%

of
men)



115 (68)*




59


(68)f



56 (68)$



0.96



Weight (kg)



74 ±14*




74

±
14f



74 ±15$



0.73



Diagnosis on admission



Unstable angina



90 (47)



47 (49)



43 (46)



0.77



Non-ST-elevation MI



43 (23)



14 (15)



29 (31)


0.01



ST-elevation MI



49 (26)



29 (30)


20 (21)


0.21



Other



8 (4)


6 (6)


2 (2)



0.29



Weight-based heparin dosing



61 (32)



29 (30)



32 (34)


0.68



Starting infusion rate, U/kg per hour



Adjusted for body weight



14.9 ±2.5



15.0 ±2.8




14.8

±
2.1


0.80



Not adjusted for body weight



14.1 ± 2.7




14.3

±
3.0




13.8

±
2.3



0.27



Concurrent medication



Alteplase



15 (8)



4 (4)


11 (12)


0.10



Streptokinase


21 (11)



7 (7)



14 (15)



0.15



Acetylsalicylic acid



181 (95)



91 (95)



90 (96)



0.97



Warfarin



14 (7)


6 (6)



8 (9)



0.75



Ticlopidine



35 (18)



13 (14)



22 (23)


0.12



SD= standard deviation, MI = myocardial infarction. *Data calculated and presented on the basis of170 patients. fData calculated and presented on the basis of 87 patients. $Data calculated and presented on the basis of 83 patients.

Data regarding the efficiency of the protocol in achieving therapeutic aPTT values are summarized in Table 2. The duration of heparin infusion was 87 ± 62 h (median 74 h). The mean infusion rate by the time therapeutic aPTT was achieved was 917 ± 231 U/h (12.6 ± 2.8 U/kg per hour; median 960 U/h). Therapeutic values of aPTT were achieved during heparin infusion for 187 (98%) of the treatment courses. On average, 21 ±18 h (median 17 h) elapsed from the time the infusion was initiated until aPTT values reached therapeutic levels, and only 92 (48%) of the treatment courses led to therapeutic aPTT values within 24 h. Patients spent only 63% ± 23% of the time in the therapeutic range (aPTT between 45 and 75 s). Supratherapeutic values of aPTT (above 75 s) at any time during the infusion period were observed for 131 (69%) of the treatment courses. In total, 587 interventions were performed, 190 by physicians and 397 by nurses. Overall, half of the treatment courses (94 of 190) included heparin dosing adjustments that were not compliant with the approved protocol (Table 3), and there were a total of 96 noncompliant modifications.
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Table 2. Attainment of Therapeutic Values for Activated Partial Thromboplastin Time (aPTT)


Mean
±


SD
or No.


(%)

of
Treatment Courses



Clinical Parameter


All
Treatment



Without


With



p

Value



Courses (n


= 190)



Noncompliant Interventions (n


= 96)



Noncompliant Interventions (n


= 94)


Heparin infusion rate (U/h)*



917

±


231



907

±


211


930 ± 255


0.024


Duration of heparin infusion (h)


87 ± 62


79 ± 46


96 ± 74


0.25


Therapeutic aPTTf at any time during
infusion


187 (98)


95 (99)


92 (98)


0.99


Time to reach therapeutic aPTTf (h)

21 ± 18


18 ±16


25 ± 19


0.43



Therapeutic aPTTf reached within


24

h


92 (48)


56 (58)


36 (38)


0.009



aPTT


> 75

s
at any time during infusion


131 (69)


65 (68)


66 (70)


0.82



%

of
time in aPTT zones



<45

s (subtherapeutic)

22 ± 22


18 ±19


26 ± 24


0.017



45-75

s
(therapeutic)


63 ± 23


68 ± 21


57 ± 23


0.001



>75

s (supratherapeutic)


16 ±17


14 ±16



17

±


18


0.21


SD = standard deviation.



*Rate of heparin infusion when target aPTT is reached. fTherapeutic aPTT


= 45-75

s.

Of the 190 interventions performed by physicians, 27 (14%) were noncompliant with the protocol. In close to half of these cases, heparin was reinitiated (after a period of discontinuation) at a different infusion rate than specified by the protocol.
Of the 397 interventions performed by nursing personnel, 69 (17%) were noncompliant with the protocol. Miscalculations or misreading of the protocol were the source of noncompliant adjustments in 32 (46%) of these 69 cases. In addition, 27 (39%) of the noncompliant adjustments were due to unauthorized interventions, such as lack of modification of the infusion rate as specified by the protocol or an unwarranted change in heparin dosing regimen.

Table 3. Physicians’ and Nurses’ Compliance with Heparin Protocol


No.

(%)*


No. of treatment courses with


at least one noncompliant


94 (49)



dosing adjustment (n


= 190)


No. of interventions


587


By nurses


397 (68)


By physicians


190 (32)


Dosing adjustments noncompliant with
protocol


96


By nurses


69 (72)


By physicians


27 (28)


No. of noncompliant interventions by
nurses


69


No increase or decrease in infusion
rate when needed


16(23)


No change in dosing regimen despite
physician’s order


3 (4)


Unauthorized increase or decrease in
infusion rate


8 (12)


aPTT measured too early


4 (6)


Infusion initiated late


6 (9)


Miscalculation or misreading of
infusion rate


32 (46)


No. of noncompliant adjustments by
physicians


27


Reinitiation of infusion at inadequate
rate


12 (44)


Loading dose given with streptokinase


7 (26)


Unwarranted loading dose


1 (4)


Unwarranted lack of loading dose


6 (22)


Unwarranted change in infusion rate


1 (4)



aPTT
= activated partial thromboplastin time.



*Percentages in each section of the table are calculated using the
nvalue in the


first row of the section as the


denominator.

Patients for whom noncompliant dosing adjustments were made spent less time in the therapeutic aPTT range than patients for whom all interventions were compliant with the protocol (57% ± 23% vs 68% ± 21%, p = 0.001) (median 58% vs 72%) and more time in the subtherapeutic zone (26% ± 24% vs 18% ± 19%, p = 0.017) (median 19% vs 11%) or the supratherapeutic zone (17% ± 18% vs 14% ± 16%, p = 0.21) (median 12% vs 10%). Finally, a smaller proportion of patients whose heparin infusion rate was adjusted inappropriately reached therapeutic aPTT levels within 24 h (38% vs 58%, p = 0.009).
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Category: Diseases / Tags: acute coronary syndromes, heparin, titration protocol

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