| Standards of Monitoring AAGBI.pdf |
HIP FRACTURES AND DVT BY DR SHIV KUMAR SINGH
In hip fractures,
the death rates of 4% to 6% during hospitalisation and 14% to 36% at 1 year are
notably higher than the 1% to 1.3% for patients undergoing total hip or knee
replacements.
A British study looking at 580 consecutive patients with
femoral neck fractures reported fatal pulmonary embolism in 4% of patients not
receiving prophylaxis.
DELAY IN PRESENTATION TO THE HOSPITAL AFTER HIP
FRACTURE AND DELAY IN TIME TO SURGERY ARE ASSOCIATED WITH A SIGNIFICANTLY
INCREASED RISK OF DVT.
One study showed that the incidence of DVT in
patients who did not present to the hospital until more than 48 hours after hip
fracture was 55%, compared with 6% in those presenting sooner than 48 hours.
In another study of 61 consecutive patients admitted for hip fracture,
62% of those who waited to undergo surgery at least 48 hours after hospital
admission had preoperative venographic evidence of DVT.
These studies
imply that the risk of venous thrombi-embolism (VTE) in hip fracture patients
starts at the time of injury rather than after surgical repair.
VTE
PROPHYLAXIS CAN BE BROADLY CLASSIFIED IN TWO CATEGORIES: MECHANICAL AND
PHARMACOLOGIC
MECHANICAL PREVENTION
Mechanical VTE prophylaxis
includes intermittent pneumatic compression devices (TED stocking), graded
compression stockings, and venous foot pumps.
Studies of mechanical
thromboprophylaxis in hip fracture patients are few, but a Canadian prospective
randomized study of the effectiveness of TEDS in 231 patients with hip fractures
found a DVT rate of 12% in the control group vs 4% in the group using TEDS a
statistically significant difference.
PHARMACOLOGIC PREVENTION
ASPIRIN
In the Pulmonary Embolism Prevention (PEP) trial, 13,356
patients who underwent surgery for hip fracture were randomized to receive
either aspirin 160 mg daily or placebo, starting preoperatively and continuing
for 35 days postoperatively.
Additional forms of thromboprophylaxis
were used if the treating physician deemed it necessary, and these included
low-dose unfractionated heparin in 18% of patients, low-molecular-weight heparin
in 26%, and graded compression stockings in 30%.
The use of aspirin
reduced the incidence of DVT by 29% and pulmonary embolism by 43% , despite a
small but statistically significant increase in the risk of gastrointestinal and
wound-related bleeding.
The PEP trial results come with a caveat,
however, as a subgroup analysis of patients who also received
low-molecular-weight heparin showed no statistically significant difference
between aspirin and placebo in the rate of symptomatic VTE.
WARFARIN
The largest was a prospective randomized controlled trial of
194 hip fracture patients who received aspirin 650 mg twice daily, or warfarin
titrated to an international normalized tatio (INR) goal of 2.0 to 2.7, or
placebo.
Prophylaxis began immediately after surgery and continued for
21 days or until hospital discharge.
Venographic evidence of VTE was
found in 20% of the warfarin group, 41% of the aspirin group, and 46% of the
placebo group.
The incidence of proximal DVT or pulmonary embolism or
both was 9% with warfarin, 11% with aspirin, and 30% with placebo.
There were no significant differences with respect to adverse bleeding outcomes
among the three groups. This trial, in addition to two others comparing warfarin
to placebo, shows relative risk reductions of over 60%.
HEPARINS
One prospective, double-blind, randomized controlled trial compared 90 hip
fracture patients who received either low-dose unfractionated heparin (5,000 U
every 8 hours) or the low molecular-weight heparin dalteparin (5,000 U daily).
Venography showed DVT in 14% of patients on unfractionated heparin and
in 32% of those taking dalteparin. Also, 14% of patients taking dalteparin had a
lung scan with a high probability of pulmonary embolism, whereas none of those
taking unfractionated heparin did. Both of these findings were statistically
significant. No significant difference was observed with respect to bleeding
complications.
In a randomized controlled study of the effects of
dalteparin vs placebo on DVT in 82 hip fracture patients, no difference in
bleeding events was seen; however, dalteparin 5,000 U daily resulted in a
statistically significant 50% decrease in the incidence of DVT.
A study
of enoxaparin vs dalteparin in 197 hip fracture patients found no significant
difference in the frequency of DVT or bleeding complications.
FONDAPARINUX
The Pentasaccharide in Hip-Fracture Surgery study
(PENTHIFRA) compared fondaparinux, a synthetic inhibitor of factor Xa, with
enoxaparin.
This large multicenter, randomized, double-blind trial of
1,711 hip fracture patients excluded patients if an epidural catheter was
planned for more than 6 hours postoperatively, if the patient had surgery more
than 48 hours from the time of admission, or if the serum creatinine level was
greater than 2 mg/dL.
Fondaparinux 2.5 mg daily subcutaneously was
started 6 to 8 hours after surgery, and the second dose was given at least 12
hours after the first to prevent VTE, while enoxaparin 40 mg subcutaneously was
begun on average 12 hours before surgery and restarted 12 to 24 hours after
surgery.
Despite no differences in clinically relevant bleeding rates,
the incidence of total VTE was significantly lower in the fondaparinux group (8%
vs 19%, P <.001).
ANTICOAGULATION AND NEUROAXIAL BLOCKADE
If
the first dose of anticoagulant is given immediately on presentation, how does
this influence the timing of surgery?
This largely depends on which
pharmacologic agent is used.
An agent with a short halflife, such as
low-dose unfractionated heparin 5,000 U, would allow hip fracture surgery to be
performed safely under neuroaxial blockade (spinal or epidural anesthesia) after
6 to 8 hours without increasing the risk of epidural hematoma.
If a
prophylactic dose of a low-molecular-weight heparin such as dalteparin or
enoxaparin is used, the surgery could be performed safely as early as 12 hours
after the dose is given.
With fondaparinux, however, it may not be safe
to proceed under neuroaxial blockade, even at 24 hours, as it has a half-life of
18 hours.
RESTARTING VTE PROPHYLAXIS AFTER SURGERY
The current
American Society of Regional Anesthesia (ASRA) guidelines provide no guidance
with regard to fondaparinux dosing, but common sense dictates waiting at least 6
hours after surgery to restart it, as was done in PENTHIFRA.
The ASRA
guidelines do, however, allow once-daily prophylactic use of
low-molecular-weight heparin in patients with an epidural catheter, but they
recommend not removing the catheter until 12 hours after the heparin dose is
given. And once the catheter is pulled, one must wait 2 hours to give another
dose of heparin.
DURATION OF PROPHYLAXIS
The table outlines the
dosing regimens, duration of treatment, and recommendations from the ACCP for
the commonly used prophylactic agents
In hip fractures,
the death rates of 4% to 6% during hospitalisation and 14% to 36% at 1 year are
notably higher than the 1% to 1.3% for patients undergoing total hip or knee
replacements.
A British study looking at 580 consecutive patients with
femoral neck fractures reported fatal pulmonary embolism in 4% of patients not
receiving prophylaxis.
DELAY IN PRESENTATION TO THE HOSPITAL AFTER HIP
FRACTURE AND DELAY IN TIME TO SURGERY ARE ASSOCIATED WITH A SIGNIFICANTLY
INCREASED RISK OF DVT.
One study showed that the incidence of DVT in
patients who did not present to the hospital until more than 48 hours after hip
fracture was 55%, compared with 6% in those presenting sooner than 48 hours.
In another study of 61 consecutive patients admitted for hip fracture,
62% of those who waited to undergo surgery at least 48 hours after hospital
admission had preoperative venographic evidence of DVT.
These studies
imply that the risk of venous thrombi-embolism (VTE) in hip fracture patients
starts at the time of injury rather than after surgical repair.
VTE
PROPHYLAXIS CAN BE BROADLY CLASSIFIED IN TWO CATEGORIES: MECHANICAL AND
PHARMACOLOGIC
MECHANICAL PREVENTION
Mechanical VTE prophylaxis
includes intermittent pneumatic compression devices (TED stocking), graded
compression stockings, and venous foot pumps.
Studies of mechanical
thromboprophylaxis in hip fracture patients are few, but a Canadian prospective
randomized study of the effectiveness of TEDS in 231 patients with hip fractures
found a DVT rate of 12% in the control group vs 4% in the group using TEDS a
statistically significant difference.
PHARMACOLOGIC PREVENTION
ASPIRIN
In the Pulmonary Embolism Prevention (PEP) trial, 13,356
patients who underwent surgery for hip fracture were randomized to receive
either aspirin 160 mg daily or placebo, starting preoperatively and continuing
for 35 days postoperatively.
Additional forms of thromboprophylaxis
were used if the treating physician deemed it necessary, and these included
low-dose unfractionated heparin in 18% of patients, low-molecular-weight heparin
in 26%, and graded compression stockings in 30%.
The use of aspirin
reduced the incidence of DVT by 29% and pulmonary embolism by 43% , despite a
small but statistically significant increase in the risk of gastrointestinal and
wound-related bleeding.
The PEP trial results come with a caveat,
however, as a subgroup analysis of patients who also received
low-molecular-weight heparin showed no statistically significant difference
between aspirin and placebo in the rate of symptomatic VTE.
WARFARIN
The largest was a prospective randomized controlled trial of
194 hip fracture patients who received aspirin 650 mg twice daily, or warfarin
titrated to an international normalized tatio (INR) goal of 2.0 to 2.7, or
placebo.
Prophylaxis began immediately after surgery and continued for
21 days or until hospital discharge.
Venographic evidence of VTE was
found in 20% of the warfarin group, 41% of the aspirin group, and 46% of the
placebo group.
The incidence of proximal DVT or pulmonary embolism or
both was 9% with warfarin, 11% with aspirin, and 30% with placebo.
There were no significant differences with respect to adverse bleeding outcomes
among the three groups. This trial, in addition to two others comparing warfarin
to placebo, shows relative risk reductions of over 60%.
HEPARINS
One prospective, double-blind, randomized controlled trial compared 90 hip
fracture patients who received either low-dose unfractionated heparin (5,000 U
every 8 hours) or the low molecular-weight heparin dalteparin (5,000 U daily).
Venography showed DVT in 14% of patients on unfractionated heparin and
in 32% of those taking dalteparin. Also, 14% of patients taking dalteparin had a
lung scan with a high probability of pulmonary embolism, whereas none of those
taking unfractionated heparin did. Both of these findings were statistically
significant. No significant difference was observed with respect to bleeding
complications.
In a randomized controlled study of the effects of
dalteparin vs placebo on DVT in 82 hip fracture patients, no difference in
bleeding events was seen; however, dalteparin 5,000 U daily resulted in a
statistically significant 50% decrease in the incidence of DVT.
A study
of enoxaparin vs dalteparin in 197 hip fracture patients found no significant
difference in the frequency of DVT or bleeding complications.
FONDAPARINUX
The Pentasaccharide in Hip-Fracture Surgery study
(PENTHIFRA) compared fondaparinux, a synthetic inhibitor of factor Xa, with
enoxaparin.
This large multicenter, randomized, double-blind trial of
1,711 hip fracture patients excluded patients if an epidural catheter was
planned for more than 6 hours postoperatively, if the patient had surgery more
than 48 hours from the time of admission, or if the serum creatinine level was
greater than 2 mg/dL.
Fondaparinux 2.5 mg daily subcutaneously was
started 6 to 8 hours after surgery, and the second dose was given at least 12
hours after the first to prevent VTE, while enoxaparin 40 mg subcutaneously was
begun on average 12 hours before surgery and restarted 12 to 24 hours after
surgery.
Despite no differences in clinically relevant bleeding rates,
the incidence of total VTE was significantly lower in the fondaparinux group (8%
vs 19%, P <.001).
ANTICOAGULATION AND NEUROAXIAL BLOCKADE
If
the first dose of anticoagulant is given immediately on presentation, how does
this influence the timing of surgery?
This largely depends on which
pharmacologic agent is used.
An agent with a short halflife, such as
low-dose unfractionated heparin 5,000 U, would allow hip fracture surgery to be
performed safely under neuroaxial blockade (spinal or epidural anesthesia) after
6 to 8 hours without increasing the risk of epidural hematoma.
If a
prophylactic dose of a low-molecular-weight heparin such as dalteparin or
enoxaparin is used, the surgery could be performed safely as early as 12 hours
after the dose is given.
With fondaparinux, however, it may not be safe
to proceed under neuroaxial blockade, even at 24 hours, as it has a half-life of
18 hours.
RESTARTING VTE PROPHYLAXIS AFTER SURGERY
The current
American Society of Regional Anesthesia (ASRA) guidelines provide no guidance
with regard to fondaparinux dosing, but common sense dictates waiting at least 6
hours after surgery to restart it, as was done in PENTHIFRA.
The ASRA
guidelines do, however, allow once-daily prophylactic use of
low-molecular-weight heparin in patients with an epidural catheter, but they
recommend not removing the catheter until 12 hours after the heparin dose is
given. And once the catheter is pulled, one must wait 2 hours to give another
dose of heparin.
DURATION OF PROPHYLAXIS
The table outlines the
dosing regimens, duration of treatment, and recommendations from the ACCP for
the commonly used prophylactic agents