Emerging Barrier to Timely Care of Hip Fracture
Patients: A Prospective Study of Direct Oral
Anticoagulation and Time to Surgery
Marlis T Sabo, Fatima Mahdi, Leanne Reimche, Marcia Clark
About the Authors:
Marlis T Sabo is a Clinical Assistant Professor, Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary,
Alberta. Fatima Mahdi is an MD Candidate, Cumming School of Medicine, University of Calgary, Calgary, Alberta. Leanne Reimche
is a Clinical Assistant Professor, Division of General Internal Medicine, University of Calgary, Calgary, Alberta. Marcia
Clark is a Clinical Associate Professor, Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, Alberta.
Corresponding Author: marlis.sabo@gmail.com
Submitted: February 5, 2018. Accepted: June 10, 2018. Published: November 9, 2018. DOI: 10.22374/cjgim.v13i4.272
ABSTRACT
Rapid surgical management of hip fracture patients is critical to reduce morbidity and mortality.
These patients may be anticoagulated and the new direct oral anticoagulants (DOAC) may
introduce delays to treatment. Our purpose was to examine the impact of these DOAC on time
to surgical management for hip fracture patients.
Methods
A prospective audit of 55 consecutive operative hip fracture patients examined time from
diagnosis to surgery. Indications for anticoagulation were recorded.
Results
Time to surgery for the DOAC group was 66±16 hours, versus 38±21 and 25±19 hours for warfarin
and control groups, respectively (P<0.05). Anticoagulation was for atrial fibrillation in 93%.
Conclusion
Patients on DOAC faced significant delays to surgery. Given that both DOAC use and incidence of
hip fracture are expected to rise, this presents a barrier to optimized care in this vulnerable group.
RESUME
La prise en charge chirurgicale rapide des patients fracturés de la hanche est essentielle pour
réduire la morbidité et la mortalité. Ces patients peuvent être anticoagulés et les nouveaux
anticoagulants oraux directs (DOAC) peuvent retarder le traitement. Notre objectif était dexaminer
l’impact de ces DOAC sur le délai de prise en charge chirurgicale des patients souffrant dune
fracture de la hanche.
Canadian Journal of General Internal Medicine
6 Volume 13, Issue 4, 2018
Clinical Medicine: The Art and Science
Méthodes
Un audit prospectif de 55 patients consécutifs à une fracture de la hanche a examiné le temps
écoulé entre le diagnostic et la chirurgie. Les indications pour lanticoagulation ont été enregistrées.
Résultats
Le temps nécessaire à lopération pour le groupe DOAC était de 66 ± 16 heures, contre 38 ± 21 et 25
± 19 heures pour la warfarine et les groupes témoins, respectivement (p <0,05). Lanticoagulation
concernait la fibrillation auriculaire à 93%.
Conclusion
Les patients sous DOAC ont dû faire face à des retards importants avant la chirurgie. Étant
donné que lutilisation de DOAC et l’incidence de fractures de la hanche devraient augmenter,
cela constitue un obstacle à loptimisation des soins dans ce groupe vulnérable.
Almost 30,000 elderly Canadians sustain a low-energy hip fracture
each year.
1
These injuries are commonand are a major cause of
morbidity and mortality.
2,3
Early surgery reduces complications,
length of hospital stay, facilitates return to independent living,
and improves survival.
4,5
The Canadian Institute for Health
Information has a benchmark of 48 hours,
6
while the UK National
Health Service has a benchmark of 36 hours
3
from admission to
surgery for these patients. The percentage of patients receiving
surgery within 48 hours increased over time to 86% in 2016.
6
However, barriers to performing timely surgery continue, and
the definition of “timely” continues to move earlier and earlier.
7
Among the more challenging barriers to early surgery remains
the problem of anticoagulation. Previously, all patients would be
anticoagulated with warfarin, which can be reversed with vitamin
K, fresh-frozen plasma, or Octoplex®. With the increasing use
of direct oral anticoagulants (DOACs) the use of warfarin is
slowly declining in favour of these other medications.
8
This is
further fuelled by consensus statements such as the Canadian
Cardiology Society 2016 guidelines urging physicians to move
their patients to DOAC from warfarin.
9
While each DOAC has
advantages, disadvantages, and individual pharmacological
considerations, most are irreversible at this time (dabigatran has
a specific antidote, idarucizumab, which is available in Canada).
The perioperative management of DOAC medications is
controversial. Patients undergoing major orthopaedic surgery
are considered to have high bleeding risk.
8
The safe performance
of surgery will depend on the surgeon, type of surgery,
7
type of
anaesthetic,
7
the specific DOAC, and the patients renal function.
8
Perioperative management of DOAC for elective surgery is
mapped out,
8,10–15
but confusion exists regarding management
in emergent situations.
Our purpose was to determine the time from radiographic
diagnosis to procedure start time for hip fracture patients on
DOAC compared with those on warfarin or on no anticoagulation.
We hypothesize that patients on any form of anticoagulants will
face significant delays to surgery, but that those on DOAC will
wait longest.
Methods
All patients presenting to our institution during the study
period with a low-energy surgically-treated hip fracture were
included prospectively from January – March 2017. Time from
diagnosis to surgery was defined as the number of hours from
the time stamp on the initial radiographs to the procedure start
time from the official OR record. Demographic data, important
comorbidities, indications for anticoagulation and its dosing,
INR (international normalized ratio), GFR (glomerular filtration
rate), type of surgery and type of anaesthesia were recorded for
each patient.
A difference of 24 hours in time to surgery was felt to be
the minimum clinically important difference (MCID). Based on
data from a pilot retrospective audit and this MCID, a minimum
of three patients in each group provided 80% power to detect a
24-hour difference. Data was collected for 3 consecutive months
to ensure that we achieved this sample size, and also obtained
enough information to draw conclusions about our secondary
outcomes.
Statistical analysis of the demographic data (descriptive
statistics) and comparison between groups was performed
(one-way ANOVA). Data was not adjusted for other medical,
non-medical, or non-surgical delays, and the single patient on
clopidogrel was excluded from intergroup comparisons. Ethics
approval was sought and obtained from the local research ethics
board (REB 16-1324).
Results
A total of 55 patients, 41 females and 14 males with average age
79.3 ± 12.9 years were included. A total of 14 (25%) were taking
Canadian Journal of General Internal Medicine
Volume 13, Issue 4, 2018 7
Sabo et al.
either warfarin (8), apixaban (5), or clopidogrel (1). (While not
strictly an anticoagulant, Plavix® use can also introduce delays
to surgery.) There was no significant demographic difference
between the three groups (Table 1). The warfarin group had a
significantly higher admission INR (P<0.0001).
Distribution of fractures types showed 47% had a neck of
femur fracture, 44% were had an intertrochanteric fracture,
and 9% had a subtrochanteric fracture. The type of procedures
performed for these fractures is shown in Table 2. The most
common procedures were cephalomedullary devices and
hemiarthroplasties.
Time to surgery for patients on apixaban was 66±16 hours,
longer than those on warfarin (38±21 hours) and those not
anticoagulated (25±19 hours) (P<0.05). Four of the eight patients
on warfarin were chemically reversed using Octoplex® with a
mean time to surgery of 36.6±12.7, while all warfarin patients
received vitamin K pre-operatively. Use of Octoplex® was at
surgeon discretion. No patient in either anticoagulated group
faced delays for any medical reason beyond the time required
to correct their anticoagulation.
Indication for anticoagulation was atrial fibrillation (93%), or
valve disease (7%). The apixaban was used within FDA guidelines
in 4 of 5 patients, and the last patient could not be confirmed
due to inability to achieve an accurate pre-operative weight.
Discussion
Nearly one-quarter of the study population presented on
anticoagulants, with the 9% on DOAC experiencing a substantial
delay to surgery compared to the other groups. Four patients on
warfarin were chemically reversed using Octoplex®, potentially
reducing the delays faced by the warfarin group. The delays
observed in the warfarin and DOAC groups are consistent
with previous reports from other studies.
17
Patients on warfarin
experienced delays to surgery despite the availability of a
rapid antidote, similar to other studies.
3,18,19
Waiting for INR
normalization can cause delays without reducing the risk of
bleeding or other complications.
17
In this cohort, initiation of
Octoplex® was associated with failure of INR to correct within
48 hours using vitamin K alone. Although the clinical need for
anticoagulation could be viewed as a marker of greater medical
comorbidity, this did not appear to add further medical delays
to treatment in this cohort.
Table 1: Demographic Data and Preoperative Laboratory Values
Demographic
(Mean)
No Anticoagulants
[n=41]
Warfarin
[n=8]
Apixaban
[n= 5]
Total
[n=55]
Age 77.3±14.0 84.5±5.8 87.2±7.4 79.3±12.9
Gender 30 F
11 M
7 F
1 M
4 F
1 M
41 F
14 M
Patients with Dementia 17 4 2 23
GFR
(>60 is normal)
79.3±20.2 57.5±21.1** 61.0±18.1 74.7±21.6
Serum creatinine 71.3±37.4 88.6±24.0 83.8±19.1 74.6±34.5
Anaesthetic type 13 GA
27 Spinal
1 Epidural
1 GA
7 Spinal
2 GA
2 Spinal
1 Epidural
16 GA
36 Spinal
2 Epidural
INR at admission 1.08±0.1 2.4±0.7* 1.4±0.2 1.3±0.55
INR at Surgery NA 1±0.2 1.3± 0.2 1.3±0.2
GFR = glomerular filtration rate; GA = general anaesthesia; INR = international normalized ratio.
*Denotes statistical significance P<0.05. **Denotes difference between warfarin and no anticoagulant groups (P<0.05).
No patient in any group had a GFR < 30. The 1 patient on Plavix is reflected in the Total (n=55) column only.
Table 2: Distribution of Types of Surgery
Type of Surgery Number of Patients (%)
Intramedullary Nail
Short
Long
30 (55)
21
9
Hemiarthroplasty 15 (27)
Total Hip Arthroplasty 4 (7)
Internal Fixation
Cannulated Screws
Cannulated Screws + Dynamic
Hip Screw
6 (11)
3
3
Total 55 (100)
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8 Volume 13, Issue 4, 2018
Emerging Barrier to Timely Care of Hip Fracture Patients
The incidence of patients with operative hip fractures on
DOAC in this cohort was 9%, which is higher than earlier reports
of 1%,
17
reflective of increased adoption of guidelines advocating
a switch from warfarin to a DOAC. It is reasonable to conclude
that DOAC use will overtake that of warfarin, making the problem
of DOAC and emergent surgery more pressing in the future.
As the number of hip fracture patients on DOAC increases,
important differences in care delivery may be encountered.
Large cohort studies demonstrate that mortality in hip fracture
patients starts to rise after 24 hours from time to diagnosis to
surgical treatment. Pilot data from an ongoing multicenter
trial suggests that mortality can be decreased by even more
rapid surgery (within 6 hours of presentation).
20
An antidote
is available for only one DOAC (dabigatran) currently, but was
not available at the time of this audit. While other antidotes will
eventually become available, an already vulnerable population
is exposed to increased risk of death due to hip fracture in the
meantime. Based on the Thrombosis Canada guidelines for
apixaban, 34% of this cohort would have “high bleeding risk
surgery, requiring 3 days delay, while the remaining 66% had
moderate bleeding risk” surgery, and could have been operated
after 2 days.
15
It is not clear at this time what the optimal balance
of risk of surgical delay versus risk of proceeding in the face of
active and irreversible anticoagulation is.
Selection of a minimum clinically important difference of
24 hours was influenced by the metrics already collected in the
local health region. The smallest unit recorded for length of stay
is a day. A clinically important effect size must be larger than
the normal ebb and flow of patients and operating room access.
Interestingly, unlike the Tran study,
17
capacity issues were not
a prominent problem in this cohort. While the data was not
corrected for non-medical or non-surgical delays, few patients
were affected by such delays. The vast majority of patients were
treated in a priority fashion as operating theatre access allowed.
This is a small prospective cohort study, but it has some
strengths. Because it was performed at a single site over a short
period of time, it avoids heterogeneity arising from different
operating theatre access and different practice patterns. There
was sufficient power to address our primary outcome, but
sweeping conclusions about our secondary outcomes are not
possible. Furthermore, this audit was not designed to examine
longer-term end-points such as complications, survival, or length
of stay between groups.
In summary, patients on DOAC faced clinically significant
delays to surgery in this prospective cohort. Nine percent of this
cohort was on a DOAC, a higher prevalence than prior reports.
Future work will need to relate the observed delays to patient
outcomes, as well as assessment of the economic impact of
these agents, especially in a time of health spending constraints.
Given that DOAC are here to stay, evidence-based guidelines
on management of these medications in a context in which
even a 2-day delay may adverse affect patient survival will be of
tremendous value to patients and their surgeons going forward.
Collaboration between internists, anesthetists and surgeons will
be vital to achieving this.
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