Dept Of Anesthesiology & Critical Care, University Of Pennsylvania School Of Medicine

The American Society of Regional Anesthesia guidelines for regional anesthesia/analgesia when anti platelet or anticoagulants are being used

The American Society of Regional Anesthesia has taken a leadership position in defining the role of the regional anesthesia in the presence of various and changing forms of anticoagulation.  Their first consensus conference was in 1998 and the 2nd in 2003.  Conclusions from the 2nd conference often differed from those of the 1998 conference mostly because of increasing experience. Antiplatelet medications: Neuraxial regional anesthesia and NSAIDs – no contraindications, d/c clopidogrel 7 days in advance.  Unfractionated Heparin S.Q.: No contraindications, consider delaying heparin until after block if technical difficulty is expected.  Unfractionated Heparin I.V.: Heparinize 1 hr after neuraxial technique, remove catheter 2 – 4 h after last heparin dose.  LMWH, twice daily dosing: Do not start until 24 h plus after surgery, remove neuraxial catheter 2 h before first LMWH dose.  LMWH, single daily dosing:  Give first dose 6+ h after surgery, second dose 24+h after the first dose.  Neuraxial catheter may be safely maintained, catheter removed 10 – 12 h after LMWH and 2- 4 h prior to next dose; postpone LMWH if block placement is traumatic.  Warfarin: Document normal INR after discontinuation of drug (prior to neuraxial technique); remove catheter when INR < 1.5.  Note that at present the UPHS Anesthesia Pain Service is more conservative with respect to LMWH and Neuraxial blocks.  Note that data from Europe with respect to LMWH and Neuraxial complications may not approximate the United States experience as the dosing regimens have been proven to be significantly different with respect to the degree of anticoagulation.

            The major concern for regional anesthesia in the presence of anticoagulation is related to bleeding into the subdural or epidural space and resulting paraplegia.  However peripheral blocks may also be associated with hematoma formation.  The consensus conference document reviewed several reported cases.  In the cases they reviewed the neurologic deficits associated with peripheral bleeding resolved within 6 – 12 months.  The reported cases of bleeding occurred with psoas compartment or lumbar sympathetic block.  In some cases the bleeding was detected because of a fall in hemoglobin and not neurologic changes.

REF: Horlocker TT et al: Regional anesthesia in the anticoagulated patient: defining risks (the second ASRA consensus conference on neuraxial anesthesia and anticoagulation).  Regional Anesth Pain Med 2003;28:172-197

David S. Smith, M.D., Ph.D.

Anti Coagulants And Neurologic Complications

Epidural hematomas in patients on LMWH --

            Chan and Bailin (1) report the formation of a spinal epidural hematoma 3 days after a lumbar puncture in an 80 year old woman who presented with a hip fracture.  Her pre op medications included aspirin 81 mg QID and her pre op INR was 0.9.  Three attempts were required for the lumbar puncture and the CSF was initially blood tinged.    On the first post operative day she was started on SQ enoxaparin, 30 mg BID.  On the afternoon of the third post operative day she complained of low back pain together with weakness and numbness of the right upper and lower extremities.  A CT scan was negative for bleed or infarct.  Her aspirin was restarted.  She later complained of increasing bilateral lower limb numbness, with some changes on her neurologic exam including decreased DTRs some decreased LE strength and decreased sensation to touch.  She was started on IM ketorolac 30 mg for pain.  On the fourth post op day she had lost sensation below the umbilicus and was unable to move either lower extremity.  An MR showed a T12 – L3 epidural hematoma with acute cord compression.

            SreeHarsha CK et al (2) report that following epidural analgesia a patient developed a spinal hematoma that caused acute paraplegia.  The patient was a 78 year old woman admitted for total knee replacement.  The surgery was done with combined spinal and epidural analgesia at L2 – L3.  The epidural catheter was left in for post operative pain control.  The patient was placed on LMWH 10 hours after surgery (10 mg SQ) and she received a second dose 12 hours later.  The patient tested positive for occult blood in the stool and the LMWH was stopped. On the 2nd postoperative day she complained of severe back pain with was treated with oral analgesics.  Two hours later she complained of difficulty moving her lower extremities.  Exam revealed complete motor paralysis of both lower extremities and decreased sensation below L1.  An MRI showed a linear mass consistent with an epidural hematoma extending from T10 – L3.

            Aharma S et al (3) reported a thoracic hematoma after placement of a high epidural catheter in anticipation of cardiac surgery.  The 60 year old patient had been on LMWH (enoxaparin 40 mg SQ QD) and the catheter was placed 10 hours the last LMWH dose.  Five hours after catheter placement the patient complained of backache and was given oral acetaminophen.  The following morning the patient complained of weakness in both lower extremities.  MRI showed an extradural hematoma extending from T1-T4.

            In this final example, Varitimidis reported an epidural hematoma that appeared to be associated with epidural catheter removal.  The patient was a 68 year old man who presented for total knee replacement which was done using epidural anesthesia (uncomplicated placement).  The epidural catheter was left in for post operative analgesia.  Six hours after surgery LMWH (tinzaparin sodium containing 4500 IU of anti factor Xa) was injected SQ into the abdominal wall and continued with a once daily injection.  The epidural catheter was removed on the third post operative day, 12 hours after the daily dose of LMWH.  The following day (post operative day 4) the patient started complaining of muscle weakness and low back pain.  This progressed to loss of bowel and bladder function.  An MRI 26 hours after the first symptoms showed an epidural hematoma extending from T12 – L3.

1)      Chan L, Bailin MT: Spinal epidural hematoma following central neuraxial blockade and subcutaneous enoxaparin. J Clin Anesth 2004;16:382-385

2)      SreeHarsha CK, Rajasekaran S, DhanasekaraRaja P: Spontaneous complete recovery of paraplegia caused by epidural hematoma complicating epidural anesthesia: a case report and review of the literature.  Spinal Cord 2006;44:514-517

3)      Sharma S et al: Epidural hematoma complicating high thoracic epidural catheter placement intended for cardiac surgery.  J Cardiothor Vasc Anesth 2004;18:759-762

4)      Varitimidis S et al: Epidural hematoma secondary to removal of an epidural catheter after a total knee replacement.  J Bone Joint Surg Am  2007;89:2048-50

Epidural hematomas in patients on clopidogrel (plavix) –

            Unlike LMWH, I was not able to find isolated case reports of epidural hematomas associated with clopidogrel and an anesthetic intervention.  However, I was able to find several case reports of clopidogrel together with LMWH that were associated with epidural hematomas after spinal-epidural or spinal anesthesia (1,2).  I also found three reports of spinal hematoma formation in patients taking clopidogrel who had not received spinal or epidural needle insertion (3,4,5).

1)      Litz R, Gottschlich B, Stehr SN: Spinal epidural hematomas after spinal anesthesia in a patient treated with clopidogrel and enoxaparin.  Anesthesiology 2004;101:1467-70

2)       Tam NLK, Pac-Soo C, Pretorius PM: Epidural hematoma after a combined spinal-epidural anaesthetic in a patient treated with clopidogrel and dalteparin.  BJA 2006;96:262-5

3)       Steet RCS et al: Spontaneous epidural hematoma presenting as cord compression in a patient receiving clopidogrel.  Eur J Neurol  2005;12:811-813

4)       Sung JH et al: Clopidogrel-induced spontaneous spinal epidural hematoma.  J Korean Med Sci 2007;22:577-9

5)       Karabatsou K et al: Non traumatic spinal epidural hematoma associated with clopidogrel.  Zentralblatt fur Neuoshirurgie 2006;67:210-2

David S. Smith, M.D., Ph.D.

Avoiding epidural hematoma related paralysis

The increasing use of platelet inhibitors (clopidogrel, Plavix) because of drug eluting stents makes careful drug history taking even more important then previously to avoid placing epidural catheters or performing subdural punctures on patients who might not clot quickly if a vessel is entered.  As prevention of deep vein thrombosis is now a national patient safety goal and as fewer insurance companies compensate for the costs associated with treating post operative blood clots, expect more aggressive post operative DVT prophylactic therapy including the use of low molecular weight heparin (Lovenox).  Thus prior to discussing post operative epidural analgesia with a patient it is necessary to know the post operative DVT prophylaxis planned by the surgical service.  In general these guidelines follow the ASRA guidelines regarding conduct of regional anesthesia in the anticoagulated patients (Reg Anesth Pain Med 2003;28:172-197). The following is the position of the UPENN Anesthesia Pain Service with respect to these issues: 

            Patients receiving anticoagulants for DVT prophylaxis or antiplatelet drugs post cardiac stenting are at a small, but real, risk of epidural hematoma if epidural catheters are placed or removed.  This includes the use of low molecular weight heparin (LMWH), unfractionated heparin or antiplatelet drugs such as clopidogrel (Plavix), NSAIDs or aspirin.  In addition it appears that the risk of harm increases with dose and with duration of therapy or when more than 1 anticoagulant is used.  Consequently:

1)      Patients who are taking LMWH or clopidogrel are not candidates for post operative epidural analgesia.  There is some data to suggest that the use of low-dose once a day LMWH is safe to use in patients with an epidural.  However the dosing used in the United States is commonly moderate to high dose, or twice a day dosing, both of which are contraindications to epidural use.

2)      Patients taking clopidogrel for whom an epidural catheter is desired should be taken off the drug for 7 days prior to the planned epidural catheter placement.

3)      Patients taking LMWH for whom an epidural catheter is desired should be taken off the drug for 12 hours if on once a day dosing or 24 hours if on twice a day dosing before epidural catheter insertion.

4)   Patients in whom an epidural catheter has been placed should not be started on LMWH or clopidogrel until the epidural catheter is removed.

David S. Smith, M.D., Ph.D.

Heparin contamination -- newest findings

A series of adverse anaphylactic like reactions, mostly in dialysis patients, led to recall of Baxter Pharmaceutical brand Heparin in January, 2008.  Raw material for this heparin was sourced in China and a contaminate was suspected.  Baxter is the source for about half of the heparin used in the United States.  A supply loss of this magnitude is serious considering the ubiquity of heparin use.  Two papers from overlapping groups of investigators have used complex chemical techniques to identify the contaminate (an oversulfated chondroitin sulfate, not found in nature) and have linked this contaminate to direct activation of the kinin-kallikrein pathway in human plasma and the potential production of bradykinin, a potent vasoactive mediator.  This contaminate also generates C3a and C5a which are potent vasoactive mediators.

            Of particular interest is the speed of investigation and publication.  The first notification from the Centers for Disease Control of a potential problem was January 7, 2008.  The Heparin recall is dated January 17 and the research described above was done, the papers written, accepted and available online about 14 weeks later.  Clearly the nearly 29 investigators listed as authors, in roughly 8 laboratories made this work their first priority.

            Considering the nature of the contaminate and the fact that the authors have proposed screening techniques it is unlikely that this particular contaminate will re-occur however certain lesions can be learned.  1) The importance of reporting adverse or unexpected reactions to the FDA Medwatch web site (http://www.fda.gov/medwatch/ ).  The initial reports related to heparin came from the Missouri Department of Health to the FDA.  2) Be alert to unusual responses to medications.  The symptoms that occurred are not typical for heparin (hypotension, generalized sensations of warmth, numbness or tingling in the extremities, shortness of breath, chest tightness, and nausea.  3) Be prepared to treat the unexpected.  Though most patients recovered with cessation of the Heparin there may be as many as 103 deaths.

1)      Guerrini M et al: Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events.  Nature Biotechnology.  April 23, 2008 Advance online publication DOI 10.1038/nbt1407

2)      Kishimoto TK et al: Contaminated heparin associated with adverse clinical events and activation of the contact system.  NEJM April 23, 2008 Published on line DOI 10.1056/NEJMoa0803200

3)      MMWR: Acute allergic-type reactions among patients undergoing hemodialysis – multiple states 2007 – 2008.  MMWR Weekly 2008;57:124-125

            4)   Perrone M: FDA probes deaths from contaminated heparin.  Charleston Gazette. April 9, 2008

David S. Smith, M.D., Ph.D.

An engineer's personal encounter with an OR fire

Fourteen year's ago Dennis Parker lost his son as a consequence of an OR airway fire.  His first person account was recently published in AORN connections and is reproduced here.

Download an_engineers_commitment_to_safety_in_the_or_pp_1_89.pdf

Reprinted with permission from AORN connections (September 2007) newsletter. Copyright 2007 AORN, Inc., 2170 S Parker Rd, Suite 300, Denver, CO 80231.  All rights reserved

Who is my doctor?

“It is unfortunately common for a patient to be caught up in a parade of tests, treatments and subspecialists with no physician clearly responsible for the whole problem.  Patients find themselves required to be their own physicians, making lonely decisions about high technology matters that doctors have trouble figuring out.  On occasion the patient is cared for by a “team” and cannot figure out the politics of responsibility and leadership – with the result that despite so many caregivers, the patient may be essentially alone at critical junctures.” From Chapter 5, The mysterious relationship between doctor and patient. In Cassell EJ: The Nature of Suffering and the Goals of Medicine (2^nd edition), Oxford University Press, 2004 page 65

David S. Smith, M.D., Ph.D.

Intraoperative awareness - potential causes and decreasing the risk

AIMS is a large, anonymous, multicenter, reporting system of anesthesia incidents that is in widespread use in Australia and parts of Asia.  Bergman et al examined the data base when there were 8372 abstracted reports collected between 1988 and 2001.  The authors queried on the keyword “awareness.”  Using specific definitions of awareness they found 81 reports of which there were 50 cases of definite awareness and 31 with a high probability of awareness.  They could find no obvious cause for awareness in 13 (16%) of the cases. Low inspired volatile agent concentration appeared to be responsible for 36 (44%) of the 81 cases.  In 14 of these cases there was no agent monitor present.  Five of these cases appeared to be due to prolonged attempts at intubation and four cases were due to reducing delivered anesthetic secondary to hypotension or cardiovascular instability.  Thirty two cases were due to inadvertent paralysis of an awake patient.  Case review suggested that inattention or distraction were contributory in 20 cases, haste in 14 and fatigue in 5.

            This study covers a later period than did the closed claims analysis study of awareness (Domino KM et al: Anesthesiology 1999;90:053-61).  In my opinion, at least in the United States, the 1988 – 2001 period is reasonably similar to current practice yet awake paralysis persists and in Bergman et al awake paralysis was the most common cause for awareness.  Picking up the wrong syringe (a paralytic instead of the desired drug) was a recurrent cause of awareness.  Keeping syringes of paralytic drugs away from other drugs might help reduce this problem.  The authors expressed particular concern about the incidents of awareness with no apparent cause.   Two of the 13 cases had agent analyzers and apparently adequate doses of volatile agent.  Two cases occurred during ECT when no volatile agent is typically used.

            Neither this study nor the closed claims study allows calculation of incidence since the total number of cases from which these reports are drawn is not known.  In addition reporting is voluntary and the threshold for reporting most likely varied from practitioner to practitioner.  Finally if patient report was the major source of information then there was most likely underreporting as most patients do not volunteer awareness information unless repeatedly asked.  However, despite these weaknesses, this paper provides an intensive study of a serious of events providing conclusions as to cause and approaches for decreasing the risk of the occurrence of awareness.

            The authors presented eight suggestions based on their data that they feel will help reduce awareness (table 4 modified):  1) Check the anesthesia machine before each use; ensure a correctly mounted and filled vaporizer. 2) When using a volatile agent use an end-tidal agent monitor.  Use a low level alarm set for a sufficient volatile agent concentration to prevent awareness. 3)  Provide further hypnotic doses for repeated intubation attempts. 4) Be aware of the potential for awareness in hypovolemic patients receiving low concentrations of anesthetic.  Restore appropriate anesthetic concentration as soon as possible. 5) Routinely use a peripheral nerve stimulator and ensure sufficient anesthetic concentration until muscle power returns. 6) When using total intravenous anesthetics, ensure a patent intravenous line and periodically check the infusion pump to confirm drug administration. 7) Clearly label all drug syringes immediately when they are drawn up.  Check this label carefully before administration.  Do not rely on recognition of syringe size to confirm its contents.  Consider newer methods of ensuring that the correct drug is given. 8) Consider a depth of anesthesia monitor, if not routinely then for selected cases.

Bergman IJ et al: Awareness during general anesthesia: a review of 81 cases from the Anesthetic incident monitoring study (AIMS).  Anaesthesia 2002;57:549-556

David S. Smith, M.D., Ph.D.