Intra-operative use of anti-fibrinolytics during neurosurgical procedures
Primary brain tumours can contribute to significant haemostatic dysfunction with consequent bleeding complications or thrombo-embolic events, which may have catastrophic impact on a patient’s outcome post surgery.(1,2) The disturbance of haemostasis may not be detectable on routinely performed tests of coagulation, namely activated partial thromboplastin time (APTT), prothrombin time (PT) and platelet count.(2)
Anti-fibrinolytics are agents that interfere with the formation of plasmin from its precursor plasminogen.
Plasmin is a fibrinolytic enzyme and a reduction in plasmin levels causes inhibition of fibrinolysis. Aprotinin has been shown to reduce blood loss in patients with intra-cranial meningiomas and vestibular schwannomas (3) and tranexamic acid to reduce intracerebral haematoma growth.(4) These benefits have been demonstrated without an increase in thrombo-embolic events.(2) Tranexamic acid is now routinely administered to poly-trauma patients with significant haemorrhage either pre-hospital or in emergency departments to reduce blood loss.(5)
In lieu of national guidance regarding the use of these agents in neurosurgical procedures we seek to understand how anti-fibrinolytics are being used by neuro-anaesthetists/intensivists/surgeons in both elective and emergent neurosurgical procedures.
Dr N. Talbot
Dr H. Church
Dr H. Krovvidi
University Hospitals Birmingham NHS Foundation Trust
References
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2169692&tool=pmcentrez&rendertype=abstract 2. Gerlach R, Krause M, Seifert V, Goerlinger K. Hemostatic and hemorrhagic problems in neurosurgical patients. Acta Neurochir (Wien) 2009;151:873–900
Available from: http://dx.doi.org/10.3171/jns.2003.98.6.1208
pressure control for intracerebral hemorrhage. Neurosurgery 2005;57:837–43
(CRASH-2) a randomised, placebo-controlled trial. West Indian Med J [Internet] Elsevier Ltd; 2010;59:612–24 Available from: http://dx.doi.org/10.1016/S0140-6736(10)60835-
Intra-operative use of anti-fibrinolytics during neurosurgical procedures
Which neurosurgical unit do you currently work in?
| ABERDEEN | 1 | 0.56% |
| BARTS and THE LONDON | 12 | 6.67% |
| BELFAST | 1 | 0.56% |
| BIRMINGHAM | 10 | 5.56% |
| BRISTOL | 16 | 8.89% |
| CAMBRIDGE | 1 | 0.56% |
| CHARING CROSS | 1 | 0.56% |
| CORK | 1 | 0.56% |
| DUNDEE | 3 | 1.67% |
| EDINBURGH | 4 | 2.22% |
| GLASGOW | 8 | 4.44% |
| HULL | 1 | 0.56% |
| KING’S COLLEGE | 1 | 0.56% |
| LIVERPOOL | 13 | 7.22% |
| MANCHESTER (SALFORD) | 19 | 10.56% |
NATIONAL 8 4.44%
| NEWCASTLE-UPON-TYNE | 17 | 9.44% |
| NOTTINGHAM | 8 | 4.44% |
| OXFORD | 1 | 0.56% |
| PLYMOUTH | 13 | 7.22% |
| PRESTON | 1 | 0.56% |
| PRINCESS ROYAL / BRIGHTON | 4 | 2.22% |
| QUEENS, ROMFORD | 2 | 1.11% |
| SHEFFIELD | 12 | 6.67% |
| SHEFFIELD CHILDRENS | 1 | 0.56% |
| SOUTHAMPTON | 9 | 5.00% |
| ST GEORGE’S | 12 | 6.67% |
180 response(s)
What is your current role within that organisation
| Consultant Neuro-Anaesthetist | 158 | 87.78% |
| Consultant Anaesthetists | 32 | 17.78% |
| Consultant Neuro-Intensivist | 46 | 25.56% |
| Consultant Intensivist | 13 | 7.22% |
| Trainee (Anaesthesia / ICM) | 1 | 0.56% |
| other (please specify below) | 2 | 1.11% |
| Other Answers | 2 | 1.11% |
Other Answers:
cons pain paediatric neuro
180 respondent(s), showing percentage as a maximum of 100% per answer (multiple checkbox selection)
In the last 6 years have you ever used any of the available anti-fibrinolytics to reduce bleeding during neurosurgical procedures?
| Yes | 131 | 72.78% |
| No | 49 | 27.22% |
180 response(s)
In what circumstances have you used anti-fibrinolytics?
| Prophylactically / routinely | 54 | 42.19% |
| In response to bleeding | 99 | 77.34% |
| At surgeon’s request | 42 | 32.81% |
| As part of a clinical trial | 10 | 7.81% |
| Other – please specify | 5 | 3.91% |
| Other Answers | 7 | 5.47% |
Other Answers:
in accordance with nice guidelines where ebl is expected to exceed 500mls inadequate platelet function on-going treatment of major trauma patient who already received txa loading and was coming to theatre for neuro and other surgery polytrauma rotem guided trauma
where there is expected major blood loss
128 respondent(s), showing percentage as a maximum of 100% per answer (multiple checkbox selection)
All neurosurgical operations may benefit if haemostasis inadequate from a haematological cause rather than a surgical one!
at the start of a crani for excision of a large meningioma, I gave tranexamic acid. I decided against apotinin as I do not think there is enough evidence that is safe or effective in this circumstance
Complex spine surgery with expected blood loss > 500 ml Intra-operative haemorrhage Haematological advice for known coagulopathy
Craniotomy for tumours known to be vascular in nature or where patient has been recently anti-coagulated or where auto-anticoagulation is evident.
Have used prophylactically in meinigiomas / procedures likley to bleed in Jehovah’s Witness patients. In response to blleding in meningiomas / AVMs / large spinal procedures
Major bleeding in urgent cranioplasty, in response to prolonged “oozing” and in major spinal surgery which may not be appropriate to this survey
major spinal surgery (i.e. anything more than lumbar disc/decompression) I routinely use tranexamic acid. For intracranial surgery only when major haemorrhage occurs. Not in neurovascular procedures
multi level lumbar laminectomy (!)
multilevel spinal surgery meningioma surgery
Neurosurgery – craniotomy for tumour and spinal surgery with large resection soft tumour.
Neurovascular-AVM resection Spine-fixation,Adult deformity,tumour Meningiomas
No details. I use in some arthroplastys but have not considered transfer of practice to neuro routine practice
Paediatric brain tumour resection, Malignant Spine decompression.
Patients with high alcohol intake preoperatively, emergency surgery
Pedicle screws fixation,Meningiomas,Spinal tumours
Polytrauma with head injury, bleeding tumours.
Post fossa craniotomy Anterior fossa meningioma surgery major spinal instrumentation
Posterior fosaa tumour surgery with difficult to contol haemorrhage – as part of major transfusion protocol
Posterior fossa bleeding in a child
Posterior fossa craniotomy for microvascular decompression of trigeminal nerve.
Posterior fossa tumour bleeding not cotrolled by surgeon.
primary brain tumours ( usually complex meningioma ) with either excessive bleeding or ROTEM suggestion of fibrinolysis
Routine use of TXA for paediatric craniofacial surgery. Use of TXA as part of CRASH-3 trial – as this trial is ongoing I would not routinely give TXA for TBI prophylactically. I would use TXA if any neurosurgical patient (including TBI) lost a significant amount of blood. I have a low threshold for using TXA if the patient has other markers of haemostatic dysfunction, e.g. a history of liver disease, recent antiplatelet usage, thrombocytopaenia.
SAH aneurysm coiling – peri-procedural rupture
Spinal fixation Intracerebral AVM bleeding intraoperatively Intracerebralaneurysm clipping bleeding intraoperatively Amputation above knee
trans-sphenoidal pituitary sirgery for non-functioning adenoma. Slow but constant ooze – normal coag (INR/APTT and platelets) Tranexamic acid 1g tried “empirically”
Trauma case with heavy intra cranial bleeding (and extra cranial injuries)
TXA once in tumour surgery. Also used by a colleague for a bleeding aneurysm. NB we are a children’s hospital, we don’t get many aneurysms!
Use of tranexamic acid in patient bleeding from spinal surgery. Patient went on to have angiogram and embolisation of bleeding vessel. No sequelae
Where massive blood loss is anticipated. E.G. Major spinal surgery for metastatic tumours and large meninigioma surgery.
Have you used Tranexamic acid
| Yes | 124 | 96.88% |
| No | 3 | 2.34% |
Other Answers 1 0.78%
Other Answers:
more than 6 yrs ago also aprotinine
128 response(s)
When administering tranexamic acid do you usually use
| Bolus only | 82 | 65.60% |
| Bolus plus infusion | 36 | 28.80% |
| Infusion only | 1 | 0.80% |
| Other Answers | 5 | 4.00% |
| No Answer | 1 | 0.80% |
Other Answers:
with additional bolus top up
bolus plus infusion for polytrauma occasionally with infusion slow bolus
sometimes an infusion too
124 response(s) , 1 No Answer(s)
1g sometimes followed by another 1g (If long procedeure or if major blood loss during major spinal procedures where prophylactic dose given.
Would you usually continue the infusion post operatively?
| Yes | 14 | 11.57% |
| No | 66 | 54.55% |
| N/A | 26 | 21.49% |
| Other Answers | 7 | 5.79% |
| No Answer | 8 | 6.61% |
Other Answers:
dependent on degree of confidence in haemostasis have on one occassion, but not usually
if bleeding risk continues if going to critical care
if trauma and within window of trauma infusion only if ongoing haemostatic failure
sometimes
113 response(s) , 8 No Answer(s)
For how long?
24
Have you used Aprotinin?
| Yes | 17 | 13.71% |
| No | 94 | 75.81% |
| Other Answers | 6 | 4.84% |
| No Answer | 7 | 5.65% |
Other Answers:
not for a while not for years
not in last 6 years not in the last 5 years not since it was removed from formulary!!
post cardiac surgery not neurosurgery
117 response(s) , 7 No Answer(s)
When administering aprotinin do you usually use
| Bolus only | 7 | 23.33% |
| Bolus plus infusion | 7 | 23.33% |
| Infusion only | 2 | 6.67% |
| Other Answers | 7 | 23.33% |
| No Answer | 7 | 23.33% |
Other Answers: don’t give it.
historical. no longer use it due to thrombotic risk
never given intraoperatively never use never used it not used recently
this was for accoustic nerve tumours, before there was “evidence” that aprotinine increased mortality
23 response(s) , 7 No Answer(s)
When requested by surgeon – standard intra-op dose (as per cardiac anaesthesia), from memory – 8 vials rapidly infused.
Would you usually continue the infusion post operatively?
| Yes | 1 | 3.33% |
| No | 15 | 50.00% |
| N/A | 3 | 10.00% |
| Other Answers | 1 | 3.33% |
| No Answer | 10 | 33.33% |
Other Answers: v v rarely used
20 response(s) , 10 No Answer(s)
For how long?
Have you used Epsilon-aminocaproic acid ?
Yes 2 1.61%
| No | 119 | 95.97% |
| Other Answers | 2 | 1.61% |
| No Answer | 1 | 0.81% |
Other Answers:
never given intraoperatively not in uk
123 response(s) , 1 No Answer(s)
When administering epsilon-aminocaproic acid do you usually use
| Bolus only | 2 | 40.00% |
| Other Answers | 1 | 20.00% |
| No Answer | 2 | 40.00% |
Other Answers: v v v rarely used
3 response(s) , 2 No Answer(s)
What infusion dose do you use? (if applicable)
Would you usually continue the infusion post operatively?
| N/A | 1 | 20.00% |
| No Answer | 3 | 60.00% |
2 response(s) , 3 No Answer(s)
For how long?
Have you used any other anti-fibrinolytic agent ?
| No | 121 | 98.37% |
| Other Answers | 2 | 1.63% |
Other Answers:
ddavp iv asa – neuroradiology: coiings
123 response(s)
When using anti-fibrinolytics do you routinely?
Yes No No Answer
| Perform near patient clotting assays
such as TEG, ROTEM, etc |
40
|
76
|
7 |
| Specifically monitor renal function
post-operatively |
31
|
80
|
12 |
| Specifically monitor for seizures | 19 | 90 | 14 |
116 response(s)
Does your department have a written protocol for administering these agents?
Yes 9.36%
No 125 73.10%
| Don’t know | 18 | 10.53% |
| Other Answers | 12 | 7.02% |
Other Answers:
apart from nice guidelines, major haemorrhage protocols and trauma guidelines, no as part of massive tranfusion protocol ed protocol for trauma/ major haemorrhage not neurosurgery hopefully hari will write one!
in process in trauma yes only for major trauma only for trauma patients not neuro only in trauma! protocol only for trauma
yes – within the major trauma and major haemorrhage guidelines. not specifically for management of neuro cases outside of these 2 domains.
171 response(s)
I do use these drugs for major spines but I dont clasify that as neurosurgery. If I encountered a large meningioma with likelihood of bleeding then I would use it but fortunately I encounter neurosurgical beeding rarely now. Surgery has got better.
I have extensive experience of treating major traumatic haemorrhage in the military and have a low threshold for aggressive early management of haemorrhage. The use of TXA is part of this “bundle”.
I have once given a surgeon dilute TXA solution to put in a bleeding tumour bed (after excision) on cotton wool. Appeared to work well – and substantially reduces systemic effects. I never use TXA without demonstrating a least a little increase in thrombolysis with the rotem. I suspect, that a lot of dilutional coagulopathy is “treated” with TXA I do worry about cerebral microvascular occlusion with TXA. That’s not particularly well known and difficult to demonstrate, especially after craniotomy when minor cognitive dysfunction is overshadowed by the pathology itself and the effects/damage of surgery.But it’s been know for decades. I think, in very big or vascular tumours, preoprative embolizatin of tumour vessels is far more effective that treating a hypothetical hyperfibrinolysis with TXA
I hope that this write up from this survey will take the opportunity to advertise the NICE guidelines for the use of fibrinolytics in surgery
I use Tranexamic acid in major orthopaedic spinal cases but never in cranial surgery (which I do but I am not classed as a “neuroanaesthetist”).
Use occasionally for tumour resections or major spinal fixations. Stopped using aprotinin after concerns about renal impairment post op.
Dr N. Talbot
Dr H. Church
Dr H. Krovvidi
