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Anticoagulated patients are common, and the amount of available oral anticoagulants is becoming more diverse and confusing. Anticoagulation is the cornerstone in the treatment of thrombosis and thromboembolic complications in a variety of diseases. Lixiana, Pradaxa, Eliquis and Xarelto are some of these pretty-sounding drugs that many doctors know but find it difficult to keep up.
So if you work in an emergency room, anaesthesia or intensive care, there's a good chance you will be facing an anticoagulant patient with potentially critical bleeding that could require urgent treatment... And this leaves you with the following questions:
- What is a critical bleed (apart from obvious massive bleeding)? Does this bleeding need imminent reversal?
- Do I need any laboratory testing before?
- What treatment should I actually give the patient?
If you do not have a guideline in your institution, it may be time to create one, and the following publication is indeed very useful for this purpose!
The 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants very nicely summarises current evidence and expert opinion on these issues. But the very best are their excellent figures, providing all the answers you need: simple and very understandable!
What is a Critical Bleeding?
|Acute Exacerbations in Patients with IPF,Kim Respiratory Research 2013, 14:86|
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The authors look at this topic point for point and review current literature in an easy to understand sort of manor. They define major blood loss when it leads to a heart rte of >110/Min or a systolic blood pressure of less than 90mmHg, or simply said: when bleeding becomes haemodynamic relevant. In general it is recommended to have a major haemorrhage protocol at hand (1D) and all staff should be trained to recognise major blood loss early (1D).
Here's a summary of the recommendations made by the British Committee for Standards in Haematology (BCSH):
In Major Haemorrhage....
Red Blood Cells RBC
- Hospitals must be prepared to provide emergency Group 0 red cells and group specific red cells (1C)
- Patients must have correctly labelled samples taken before administration of emergency Group 0 blood (1C)
- There is NO indication to request 'fresh' or 'young' red cells (under 7d of storage, 2B)
- Note: The optimum target haemoglobin concentration (Hb) in this clinical setting in general is NOT established. Current literature shows a tendency towards restriction towards 70-90g/L, but the BCSH makes no recommendations therefore (see blow)
Cell Salvage (e.g. cell saver)
- 24h access to cell salvage should be available in cardiac, obstetric, trauma and vascular centres (2b)
- Use haemostatic tests regularly during haemorrhage, every 30-60min, depending on severity of blood loss (1C)
- Measure platelet count, PT, aPTT (1C)
- Note: The BCSG does not recommend TEG and ROTEM at this stage
Fresh Frozen Plasma FFP
- Use FFP in a 1:2 ratio with RBC initially (2C)
- Once bleeding is under control administer FFP when PT and/or aPTT is >1.5 times normal (recommended dose 15-20ml/kg, 2C)
- The use of FFP should not delay fibrinogen supplementation if necessary (2C)
- Supplement fibrinogen when levels fall below 1.5g/L
Prothrombin Complex Concentrates PCC
- Do not use PCC
- Keep the platelet count >50 x 10^9/L (1B)
- If bleeding persists give platelets if count falls below 100 x 10^9/L (2C)
Tranexamic Acid TA
- Give tranexamic acid as soon as possible to patients with, or at risk of major haemorrhage (Recommended dose: 1g IV over 10min, followed by 1g IV over 8h, 1A)
- Note: TA has no known adverse effects
- Note: Aprotinin is not recommended
Recombinant Activated Factor VIIa (Novo Seven)
- Do not use
Specific Clinical Situations
- Fibrinogen levels increase during pregnancy to 4-6g/L
- In major obstetric haemorrhage fibrinogen should be given when levels are <2.0g/L (1B)
- Use restrictive strategy for RBC transfusion is recommended in most patients (1A)
- Transfuse adult trauma patients empirically with a 1:1 ratio of FFP : RBC (1B)
- Consider early use of platelets (1B)
- Give tranexamic acid as soon as possible (Dose 1g over 10min and then 1g over 8h, 1A)
Prevention of Bleeding in High-Risk Surgery
- Use tranexamic acid (Dose 1g over 10min and then 1g over 8h, 1B)
Hunt B et al. British J Haemat, July 6 2015
Read more HERE:
Great Review on Transfusion, Thrombosis and Bleeding Management
Restricitve Transfusion Threshold in Sepsis, the TRISS Trial
Transfusion: Harmful for Patients Undergoing PCI?
These guidelines outline the nature and properties of biofilms and and their implications on mostly chronic infections caused. As biofilms are very common in critically ill patients it is important to know what specific problems you might encounter, how to proceed and perform a proper diagnosis and what are the essential bits and pieces in the prevention and treatment of biofilm infections.
The article is OPEN ACCESS: Clin Microbiol Infect. 2015 Jan 14. pii: S1198-743X(14)00090-1.
ARISE and ProCESS had been published before (read here) and both of them showed no difference between EGDT and 'usual care'.
ProMISe included 1251 patients with severe sepsis or septic shock that were admitted to a total 56 hospitals in the UK. Again classical EGDT with measurement of continuous central venous oxygenation was compared to so called 'usual treatment'. It's remarkable to notice that in the 'usual treatment' group about half of the patient didn't get a central line and central venous oxygenation wasn't even measured in the ones who got one. And here's the result:
There was no difference in 90-day mortality and no differences in secondary outcomes. In contrast EGDT actually increased costs.
It has become difficult to ignore these three trials!
Our conclusion: The classical EGDT therapy has ended here and now... but EGDT will keep its central role in the treatment of septic patients!
- Identify septic patient quickly, start screening for patients if indicated
- Administer antibiotics within the first our of recognition of sepsis
- Start IV-fluid therapy immediately
- Take (blood) cultures as quick as possible, but do not delay antibiotic treatment
- Aim for a reasonable mean arterial pressure (e.g. 65mmHg)
- Aim for a sufficient urinary output (0.5ml/h)
- Central venous pressure (CVP) certainly and most probably central venous oxygenation (ScvO2) are not parameters to measure fluid responsiveness
- Lactate remains an issue of debate
- Simple: Whatever the physician feels is best!
ProMISe Trial, Mouncey et al. N Engl J Med. 2015 Mar 17.
BIJC Review on ARISE and ProCESS
Picture displayed taken from the Ice Cream Trilogy by Wright, Pegg and Frost
As these guidelines are open access it can be considered mandatory Free Open Access Meducation FOAMed. Below is a summary of the Recommendations according to specific patient groups.
It's interesting to notice that digoxin still plays a role in patients with heart failure, especially when looking at the findings of Turakhia et al. in JACC, Aug 19 2014.
J Am Coll Cardiol. 2014;64(21):2246-2280 OPEN ACCESS
BIJC post on dixogin in critical care
Little Christmas Present: Open Access 'Anaesthesia' Supplement on Transfusion, Thrombosis and Bleeding Management
The supplement consists of multiple review articles which are kept nice and short and are perfect for reading in between...
In Conclusion: Reading highly recommended!
On following website you can find a list of all articles including links to the full text:
Anaesthesia, Vol. 70, Issue Supplement s1, January 2015: Transfusion, Thrombosis and Bleeding Management
- Platelets must be stored at room temperature
- Because of the risk of bacterial growth the shelf life of platelet units is only 5 days
- Maintaining a constant pool of platelets for clinical work is extremely difficult and resource-intensive
- Transfusion related risks are notable (e.g. febrile reaction 1/14, allergic reactions 1/50, bacterial sepsis 1/75'000)
When it comes to their usage intensivists often have a different approach than haematologists and guidelines mostly vary from hospital to hospital, from country to country. However, instead of searching all the literature yourself you might consider reading the article by Kaufman RM et al. published just this month in the Annals of Internal Medicine.
A panel of 21 specialists, covering almost all areas of medicine involved in handling platelets, performed a systematic review by looking up publications from 1900 to 2013. From 1024 identified studies, 17 RCTs and 53 observational studies were included in the review. The result of their work are guidelines on the use of platelets including their grade of recommendation. Short:
- Platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypo proliferative thrombocytopenia < 10 x 109 cells/L (Grade: strong recommendation; moderate-quality evidence)
- Platelets should be transfused prophylactically for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L (Grade: weak recommendation; low-quality evidence)
- Prophylactic platelet transfusion is recommended for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L (Grade: weak recommendation; very low-quality evidence)
- Prophylactic platelet transfusion is recommended for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L (Grade: weak recommendation; very low-quality evidence)
- Routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass (CPB) is NOT recommended. Platelet transfusion for patients having CPB who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction is NOT recommended (Grade: weak recommendation; very low-quality evidence)
- Recommendations for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous) cannot be made (Grade: uncertain recommendation; very low-quality evidence)
It is remarkable to see that after a century of intense research we are left with some moderate-quality evidence and lots of low quality evidence and therefore weak recommendations. I guess guidelines will continue to vary from doctor to doctor, hospital to hospital... country to country.
Kaufman RM et al. Ann Intern Med, Nov 11, 2014: Open access article
Despite this the debate has continued and remains highly controversial. This is nicely reflected in recent guidelines regarding the timing of supplemental PN. While the European Society for Clinical Nutrition and Metabolism (ESPEN) recommends PN within 24-48h in patients who are expected to be intolerant to enteral nutrition (EN), the American Society for Parenteral and Enteral Nutrition (ASPEN) recommends postponing the initiation of PN until day 8 after ICU admission.
In order to clarify things a little Bost et al. have now published a systematic review on the timing of parenteral nutrition in critical care (Open access). From 3520 initially screened articles only four randomised controlled trials and two prospective observational studies remained after critical appraisal.
"In conclusion it seems to be reasonable to assume that in critically ill patients, when full enteral support is contraindicated or fails to reach caloric targets, there are no clinically relevant benefits of early PN compared to late PN with respect to morbidity or mortality end points.
Considering that infectious morbidity and resolution of organ failure may be negatively affected through mechanisms not yet clearly understood and acquisition costs of parenteral nutrition are higher, the early administration of parenteral nutrition cannot be recommended."
The Review in one short sentence: Early PN has no advantage over late PN, but might be actually harmful.
Bost et al. Annals of Intensive Care 2014, 4:31
ESPEN Guidelines on parenteral nutrition, 2009
A.S.P.E.N. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient
BIJC.org on: Starting early PN weakens the critically ill
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