What are the pros and the cons of antifibrinolytics during cardiac surgery? —ashaddadin@hotmail.com

Dr. Richard Prielipp responds:

Use of the lysine analogue, Amicar (epsilon-amino-caproic acid), specifically inhibits fibrinolysis which may be triggered by exposure of the patient's blood to the artificial surfaces of the CPB circuit. To be most effective, Amicar probably needs to be administered BEFORE the hemostatic stress initiated by CPB. The dosing is controversial, but probably requires both a loading dose, and a constant infusion during the cardiac operation. Most studies suggest that use of Amicar is associated with a reduction in mediastinal bleeding after surgery, but it is difficult to correlate this with an actual reduction in transfusion of blood, or use of blood coagulation products. Amicar does have the feature of being available as a generic compound, and thus, is quite inexpensive (on the order of 20 dollars to treat one patient).

By contrast, Aprotinin, is a more broad-based serine-protease inhibitor, and has multiple, complex effects modulating multiple coagulation, inflammatory, and complement pathways. The effects are generally considered "more potent" than Amicar, and some studies do show an actual reduction in the use of blood after surgery--- especially in redo cardiac operations. However, in the USA, Aprotinin is rather expensive, and a full-dose regimen may cost $1,500 - $2,000 dollars per patient. There is really little evidence that either compound is associated with a documented increase in the incidence of early bypass graft thrombosis, but this remains a concern. One note of caution -- once you commit to a therapy, you need to "stick with it." Do not mix the two agents together in any one patient.

Is it safe to use IV/IM clonidine hydrochloride for epidural route? —lrey@urbis.net.il

Dr. Richard Rosenquist responds:

The only injectable preparation available in the USA is Duraclon. It only has indications for epidural administration from the FDA. It is preservative free and has been used intrathecally in some publications as well. As far as I can determine through searches and discussions with our pharmacy, there is no form that is indicated for IV or IM use. The injectable form available in the USA is safe for epidural administration.

What is the lowest platelet count at which patients in labour can be offered epidural analgesia? —khussain@gofree.indigo.ie

Dr. Joy Steadman responds:

The truth is: no one really knows. Some institutions have an artificial cutoff at 100,000. However, studies using the Platelet Function Analyzer show that as soon as the platelet count falls below 150,000, clot function in the PFA begins to fail. Yet everyone who does obstetric anesthesia has no problem with platelet counts below 150K but above 100K. Perhaps other questions must be asked:

1) Is this a patient with stable ITP or TTP or Lupus? A chronic platelet count of 60,000 may be fine to place an epidural.
2) Does this patient have a really terrible airway AND other risks for a bad outcome with general anesthesia (i.e. morbid obesity, severe preeclampsia, cardiomyopathy, longstanding diabetes, etc) In that case I personally talk with and really educate the patient about the various risks and benefits. The hypothetical risk of an epidural hematoma is less frightening to me than the risk of a lost airway and death.
3) Does the patient have a really strong desire to have an epidural and a really good reason. A woman dying from her liver transplant rejection may just want to be awake and alert for the birth of her child, whereas someone who heard that epidurals are great and happens to have a platelet count of 22,000 doesn't really necessarily need an epidural.
4) Remember that even surgeons like the platelet count to be above 50,000 before they do something invasive.

I am an anesthesiologist in M�xico. There has been an explosion here in the use of the Cox-1 and Cox-2 inhibitors, both in prescription use and outside the medical establishment, often without controIs. Are there cardiovascular side effects that we should be keeping an eye out for? —berny47_2000@yahoo.es

Dr. David Lubarsky responds:

Cox-1 and Cox-2 have different side effects. Unlike Cox-1 inhibitors like ibuprofen (Motrin) or ketorolac (Toradol), Cox-2 drugs such as paracoxib (Bextra) do not have any effects on platelets, and, are therefore a better choice to use in the perioperative period. Unlike ketorolac, cox-2 drugs do not have gastric ulceration as a significant side effect, so do not have to be as carefully monitored in that regard (e.g. ketorolac has a imitation as to how long one should remain on the drug postoperatively, and the dosing regimen is age dependent). Unfortunately, no cox-2 drugs are available in IV form, nor has their efficacy been established in the treatment of postoperative pain. Ketorolac remains the only IV NSAID with a perioperative pain management indication. However, in my opinion, it is likely that studies currently being done will demonstrate that cox-2 drugs do help with perioperative pain management.

In terms of cardiovascular issues, there are relatively few other side effects. There is some effect on renal blood flow regulation that, to my knowledge, has not been shown to impact perioperative renal outcomes.

The FDA has recently reported arrhythmias and fatalities at droperidol doses as low as 0.25 mg. Given that many of us have used this drug thousands of times at adult doses of 0.625 mg without any problem, should this new report change our practice? —jroberts@mayohospital.com

Dr. David Lubarsky responds:

Only if you fear the legal profession. And you should. The black box warning, paraphrased, says that you should not use droperidol unless all other therapies are not working. AND everyone getting droperidol should have a 12 lead EKG to rule out a pre-existing prolonged QT interval. Since patients have arrhythmias and heart problems in the perioperative period, if you have given droperidol, you will get blamed.

The whole point of the FDA accumulating information is to detect trends/issues that are not apparent to the individual practitioner.

I think our national society, though, should have insisted on a thorough review of low dose droperidol PRIOR TO THE ISSUANCE OF THE BALCK BOX WARNING and considered collecting data on the use of low dose droperidol. The likelihood of that happening now is extremely low. Given the generic nature of the drug, the fact that medico-legal risk would be incurred, and that patients would need an informed consent that reiterates the black box warning that they could die from receiving droperidol makes it exceedingly unlikely that a study will be done that allows droperidol to find its way back into our practice.

What are the current recommendations regarding discontinuing Plavix (clopidogrel) prior to an epidural for vascular surgery? Can it be continued, like aspirin, up to the day of surgery? —chcost@aol.com

Dr. David Lubarsky responds:

The current recommendations are 10-14 days for discontinuation of Plavix prior to an epidural for vascular surgery.

What is the current recommendation for discontinuing Sulphasalazine before elective surgery (TURP)? —kwetny@usa.net

Dr. Kathryn McGoldrick responds:

I am not aware of any blanket recommendation to discontinue sulphasalazine preoperatively. However, a preop CBC may be helpful because the drug has (very rarely) been associated with agranulocytosis, thrombocytopenia, hemolytic anemia, and even aplastic anemia. Occasional hepatotoxicity and pulmonary eosinophilia have also been reported. One should also be aware that the drug may impair the hepatic metabolism of oral anticoagulants and may reduce the serum levels of digoxin.

What are the relevant anesthetic issues concerned with patients on naltrexone? —tyctoc@idx.com.au

Dr. Richard Rosenquist responds:

Could you please tell me if epinephrine is used in ankle blocks, and if not, what the disadvantage is? —Lynn Schable

Dr. Richard Rosenquist responds:

Epinephrine is not appropriate for use in ankle blocks. There is a significant risk of causing severe vasoconstriction and reduced blood flow to the foot. This may result in significant ischemia and tissue damage.There is little risk of absorbing toxic levels of local anesthetic from an ankle block and if long duration is desired, using plain bupivacaine will provide a long lasting block without the need for epinephrine.

Many of our elderly hip fracture patients are on Plavix for ischemic heartor brain disease. When they present for ORIF or bipolar arthroplasty mypractice has been to give them spinal anesthesia. However, we have noticedthese patients have significantly increased intraoperative hemorrhagecompared to patients who are not on antiplatelet agents and even those whoare mildly coumadinized (INR<2). Are there any guidelines with regard tocentral neuraxial block for patients on this potent platelet inhibitor? —eungkim67@yahoo.com

Dr. Ronald Olson responds:

There is very little data on this. We stop the clopidogrel between 7 and 14 days preoperatively. Individual cases must balance the presumably decreased risk of spinal hematoma from stopping early, with the increased risk of stroke or MI. Thus if the risk of embolism or thrombosis is high, we only stop for 7 days; if the risk is small, we stop between 10 and 14 days preop. Anesthesiologists have legitimate differences in opinion on this.

Here is the recommendation published on the ASA website

Would you please send me information about the infusion of xylocaine and atracurium (combination) in intravenous regional anesthesia. —MOIS@cyberia.net.lb

Dr. David Lubarsky responds:

I have never heard of such a practice.

Dr. Beverly Philip responds:

I do not know about infusing atracurium as part of intravenous regional anesthesia.

My hospital has recently implemented the use of generic propofol. I am unfamiliar with many of the subtle and not so subtle differences as compared with Diprivan. In which patients, or situations should I avoid the generic substance. Also is a history of allergy to "sulfa" drugs a contraindication to using propofol with bisulfites? —dnigus@pol.net

Dr. Beverly Philip responds:

The issue is not with the propofol itself, but with the preservative in the less expensive formulation, metabisulfite. The FDA has stated repeatedly that the two formulations of propofol, by the two different companies, are equivalent, and the FDA does not support restrictions or other cautions about use.

What is the opinion of the Advisory Board on current guidelines concerning the use of standard heparin 5000 u pre-operatively as well as low molecular weight heparins pre-operatively and subsequent regional techniques, i.e. spinal/epidural. There are few reports of spinal hematomas but no guidelines. I have recently been giving enoxaparin sc 40 mg 12 hours pre-operatively, but I do not know if that time delay will be losing the anti-thrombotic effect.

Dr. Douglas Coursin responds:

The simple answer to your question is to use the low molecular weight heparin (LMWH) that your institution has available (i.e. dalteperin, enoxiparin, nadroperin, tinzaparin, or others). Doses vary as to what source you use, see below for general recommendations. Timing of the doses are similar to dosing unfractionated heparin. Low-molecular-weight heparins are given subcutaneously usually 1 - 2 hours before surgery. LMWHs are usually administered once daily in normal risk patients, but high risk patients (such as yours with a prior history of DVT/PE or undergoing cancer surgery) should receive their doses earlier in the preop period and receive higher daily single doses or be dosed twice daily. Some studies show that LWMHs are better than low-dose unfractionated heparin at preventing venous thromboembolism and cause fewer wound hematomas.

Some recommended doses:

A couple of good refs:

1. Weitz J. Drug Therapy - LMWH. NEJM 1997; 337:688-698
2. Horlocker TT and Heit JA. Anesth Analg 1997; 85:874-885

Two other important issues in this patient are:

1. The use of neuraxial blocks in patient who are on or will receive low molecular weight heparin (LMWH). Look to the PDR for a boxed warning about this. Also see Recommendations for Neuraxial Anesthesia and Anticoagulation at <http://www.asra.com>, look under items of interest and follow the table of contents.

Also see -

• Tryba M. European practice guidelines: thromboembolism prophylaxis and regional anesthesia. Regional Anesthesia & Pain Medicine. 23(6 Suppl 2):178-82, 1998
• Horlocker TT. Wedel DJ. Neuraxial block and low-molecular-weight heparin: balancing perioperative analgesia and thromboprophylaxis [see comments]. [Review] [27 refs] Regional Anesthesia & Pain Medicine. 23(6 Suppl 2):164-77, 1998
• Horlocker T T, Wedel, D. Spinal and Epidural Blockade and Perioperative Low Molecular Weight Heparin: Smooth Sailing on the Titanic 1998; 86:1153-1155. 

In this editorial, Horlocker and Wedel recommend that in patients receiving neuraxial technique:

1. The smallest effective dose of LMWH should be administered perioperatively. The FDA has recently approved enoxaparin 40 mg once daily as an alternate dosage regimen for thromboprophylaxis after total hip arthroplasty. Single daily dosing results in a true trough in anticoagulant activity, during which time needle placement and catheter removal can occur.
2. LMWH therapy should be delayed as long as possible: a minimum of 12 h and, ideally, 24 h postoperatively. This is within the FDA-approved dosage schedule and is particularly true for patients with indwelling catheters.
3. Antiplatelet or oral anticoagulant medications administered in combination with LMWH may increase the risk of spinal hematoma. Education of the entire patient care team is necessary to avoid potentiation of the anticoagulant effects.
4. The risk of spinal hematoma in patients with indwelling catheters who receive LMWH is almost certainly increased. Removal of the catheter before initiating LMWH therapy may be a compromise that provides superior analgesia for 24 h but eliminates the risk of concomitant epidural analgesia and LMWH therapy.
5. Catheter removal should occur when anticoagulant activity is low. Twice daily dosing of LMWH results in two peaks and no trough of anti-Xa activity. Skipping the evening dose of LMWH before an anticipated morning removal of the epidural catheter is unlikely to significantly increase the risk of thromboembolic events, but it should provide safe conditions for catheter removal.

Finally, all patients undergoing neuraxial block require repeated neurologic evaluations. A dilute local anesthetic or opioid solution permits the accurate assessment of neurologic status.

I recently had a 16 yr old patient with a prolonged response to mivacurium; turns out he was most likely homozygous for the atypical trait per enzymeanalysis. I have searched for a thorough information source for the family, but have come up short. Any suggestions? —stanleythor@home.com

Dr. David Lubarsky responds:

Can tramadol be used as an adjuvant with opioids? If so, what are the advantages?—viswanatha_m@usa.net

Dr. Beverly Philip responds:

Dr. Richard Rosenquist responds:

There are a large number of references available through a search of this topic on MD Consult. Two references regarding the use of clonidine for opiate withdrawal include:

1. Effective Medical Treatment of Opiate Addiction NIH Consensus Statement 1997 Nov 15(6):1
2. Acute detoxification of opioid-addicted patients with naloxone during propofol or methohexital anesthesia: a comparison of withdrawal symptoms, neuroendocrine, metabolic and cardiovascular patterns. Crit Care Med 2000 Apr;28(4):969-76.
   
   

Dr. Richard Rosenquist responds:

Morphine is preferred over meperidine for PCA pumps in almost all settings. This is due to morphine’s demonstrated ability to provide analgesia when used in a PCA delivery system and a reduced incidence of adverse side effects when using morphine instead of meperidine. Meperidine has the potential for extremely dangerous drug interactions, most notablywith MAOI anti-depressants. In addition, the metabolite of meperidine(normeperidine) can accumulate and produce seizures. This adverse side effect is primarily related to dose and duration of treatment. However, ithas been reported to occur in relatively short timeframes and with doses that do not appear excessive. These complications have been described in anumber of publications.

A good review of this in the pediatric setting maybe found in:

Golianu B, Krane EJ, Galloway KS, Yaster M, WB Saunders. Pediatric Acute Pain Management. Pediatric Clinics of North America June 2000; 47(3):559-87

A brief case series description in adults may be found in:

Stone PA, Macintyre PE, Jarvis DA. Norpethidine toxicity and patient controlled analgesia. Br J Anaesth 1993 Nov;71(5):738-40

Special thanks to Lynne Alexander, Beth McLendon and the Pharmacy Department at Duke University for the following answer:

Beth McLendon, Pharm. D. responds:

According to the literature, biguanides should not be given perioperatively due to the potential for lactic acidosis. There was no published literature that documents a direct interaction between metformin andanesthetics.

The package insert states that metformin "should be withheld for any surgical procedure, except minor procedures not associated with restricted intake of food and fluids and should not be restarted until the patient's oral intake has resumed and renal function has been evaluated as normal". Metformin is not metabolized by the liver, therefore renal function is essential for the patient to clear the drug from the body. The package insert also has a special warning for patients scheduled for radiologic studies, in which metformin should be withheld for 48 hours after the procedure and only restarted once the patients renal function hasbeen evaluated as normal.

References:

1. Anesthesiology 1997;87(4):1003-1005.
2. Peters A. Exp & Clin Endocrine & Diabetes 1995;103(4):213-8.
3. Ritter MM. Biguanide and elective anesthesia. Anaesthesist. 1998 Jun;47(6):522.

Dr. David Lubarsky responds:

There are several articles addressing the use of beta blockers in patients at risk for ischemia undergoing non-cardiac surgery. Poldermans et al. in a NEJM article (reviewed in AnesthesiaWeb) gives the best example of how to use beta blockers. Beta blockade prior to surgery for several days and then throughout the perioperative period will lessen ischemia, MI, and death 10 fold in at risk patients (defined by dobutamine stress echo). However, the patient set studied excluded those with severe wall motion abnormalities in the screening dobutamine stress echo test - meaning that most patients with unstable angina probably had additional cardiac workup and intervention and were not part of the study. As for actual use of metoprolol. Gentle titration (1-2 mg every 3-5 minutes monitoring the heart rate) prior to surgery and administration to a resting rate of 50-60 is appropriate in those who can tolerate the effect without dropping their blood pressure significantly. Although B1 specific, patients with severe COPD/asthma may still suffer from the lack of total B1 specificity. In my experience, using judicious but fairly liberal patient selection, I have not encountered pulmonary problems using the drug in this fashion.

Dr. David Lubarsky with advice from Dr. TJ Gan responds:

In general multimodal therapy is always superior. Middle ear surgery responds well to histamine receptor antagonists (e.g. hydroxyzine). A full review of combination antiemetics will be published by Dr. Habib et al in June in the Journal of Ambulatory Surgery.

Dr. Charles Coté responds:

Dr. Richard Rosenquist responds:

Dr. Katherine McGoldrick responds:

Plavix is an inhibitor of platelet aggregation. As long as the patient gives no history of easy bleeding or bruising while on this drug, we feel comfortable proceeding with regional anesthesia. If there is a tendency toward bleeding/bruising I would wait 10 days after discontinuing the medication to be on the safe side.
I have no information on "pletal" and was unable to find it in the PDR.

Dr. Beverly K. Philip responds:

The issue is not with the propofol itself, but with the preservative in the less expensive formulation, metabisulfite. The FDA has stated repeatedly that the two formulations of propofol, by the two different companies, are equivalent, and the FDA does not support restrictions or other cautions about use.

Dr. Beverly Philip responds:

The issue is not with the propofol itself, but with the preservative in the less expensive formulation, metabisulfite. The FDA has stated repeatedly that the two formulations of propofol, by the two different companies, are equivalent, and the FDA does not support restrictions or other cautions about use.

Dr. Katherine Grichnik responds:

We do not use Halothane at our institution any longer so I have no source for finding out this information. I searched the web but found no manufacturers.

Dr. Richard Rosenquist responds:

I don't think that there is any good indication for the use of intradermal morphine in the postoperative setting. Subcutaneous morphine has been used successfully in a wide variety of settings with reasonably good absorption. This is especially true in the setting of chronic administration for cancer pain. There is not a great deal of data regarding the use of intradermal morphine and I would not recommend it for pain control in the acute postoperative setting. There are many other methods with significantly more predictable results

Dr. Richard Rosenquist responds:

These are both appropriate indications for the use of epidural steroids. As far as sciatica is concerned, the most likely candidate is one with pain of less than one years duration, without significant neurologic deficit, clear radicular pattern and with imaging studies that confirm the history and physical examination. Patients with lumbar spinal stenosis are somewhat more controversial. Patients with a clear history of pain, neurogenic claudication and the absence of significant neurologic deficit are the best candidates. As with sciatica, shorter duration of symptoms and agreement of the history, physical and imaging studies are the best candidates. A good review of the topic may be found in the article by Steven E. Abram:

• Abram SE. Treatment of Lumbosacral Radiculopathy with Epidural Steroids, Anesthesiology 1999: 91(6): 1937-41.

Dr. Richard Rosenquist responds:

The duration of any respiratory depressant effects will be dose-dependent. If the dose of intrathecal or epidural fentanyl is small, e.g. 10 - 25 ug intrathecally, the patient can safely be sent to the floor 1-2 hours after the drug is administered. Even larger doses will only last 4-6 hours and patients may then be sent to the floor. This is similar for small epidural doses of the drug. If significantly larger doses of drug are administered, they may need to be monitored for a longer period of time although these doses are not commonly given.

1. Palmer CM, Voulgaropoulos D, Alves D. Subarachnoid fentanyl augments lidocaine spinal anesthesia for cesarean delivery. Regional Anesthesia. 20(5):389-94, 1995
   Link to Abstract
   
   
2. Liu S, Chiu AA, Carpenter RL, Mulroy MF, Allen HW, Neal JM, Pollock JE. Fentanyl prolongs lidocaine spinal anesthesia without prolonging recovery. Anesthesia & Analgesia. 80(4):730-4, 1995
   Link to Abstract
   
   
3. Belzarena SD. Clinical effects of intrathecally administered fentanyl in patients undergoing cesarean section. Anesthesia & Analgesia. 74(5):653-7, 1992.
   Link to Abstract

1. Ropero-Miller JD, Goldberger BA. Recreational Drugs: Current Trends in the 90s. Clinics in Laboratory Medicine 1998;18:727.
   
2. Saum CA, Inciardi JA. Rohypnol Misuse in the United States. Substance Use and Misuse 1997;32:723.
   
3. Cirimele V, Kintz P, Mangin P. Determination of Chronic Flunitrazepam Abuse by Hair Analysis using GC-MS-NCL. Journal of Analytical Toxicology 1996:20:596

1. Butterworth J, James R, Prielipp RC, Cerese J, Livingston J, Burnett DA. DO shorter-acting neuromuscular blocking drugs or opioids associate with reduced ICU or hospital LOS after coronary artery bypass grafting? Anesthesiology 1998;88:1437-46
   
2. Smeulers NJ, Wierda JM, van den Broek L, Gallandat Huet RC, Hennis PJ. Effects of hypothermic cardiopulmonary bypass on the pharmacodynamics and pharmacokinetics of rocuronium. J Cardiothoracic and Vascular Anesthesia 1995;9:700-5
   
3. Hudsen RJ Thompson IR Pro: The choice of muscle relaxants in important in cardiac surgery. Fleming N. Con: The choice of muscle relaxants in important in cardiac surgery. J Cardiothoracic and Vascular Anesthesia 1995;9:768-74

1. Haas DA, Harper DG. Ketamine: A Review of Its Pharmacologic Properties and Use in Ambulatory Anesthesia. Anesth Prog 39:61-68; 1992
   

Dr. Richard Rosenquist responds:

The information regarding antibiotic prophylaxis is somewhat limited, but I will tell you how we practice. We do not give routing antibiotic prophylaxis for our postoperative epidurals or our epidural steroid injections. On the other hand, if we are putting in a percutaneous epidural that we intend to tunnel and use for a prolonged period of time, we do provide antibiotic prophylaxis. We choose an antibiotic to cover the skin flora that are commonly associated with epidural skin tract infections.

Dr. Richard Rosenquist responds:

I think that in most settings, it is better to use a low or moderate concentration of local anesthetic at a higher infusion rate in order to get greater spread. A higher concentration of local anesthetic will provide an denser block, but, postoperatively, analgesia rather than anesthesia is desired. The higher infusion rate provides greater spread, while the lower concentration provides a greater margin of patient safety.

Given the higher cost of desflurane and sevoflurane, and the reported failure of the isoflurane-switch-to-desflurane-
for-the-last-1/2-hour technique, where do these agents fit in today's cost effectiveness medicine times?   -- Brad Stone MD

Dr. Lubarsky Responds:
Expensive agents work when:

1. You use very low flows. At 1L/min, sevoflurane and desflurane cost about $5/hour, and isoflurane costs about $2-3/hr. Pennies a minute difference.
2. You use the more rapid recovery to move patients out faster, decrease peak staffing in the PACU. This could allow you to recover much greater labor savings.
3. Your ORs routinely run overtime, and the few saved minutes at the end of each case add up to real OR labor savings.
4. You want to go home an average of about 3 minutes earlier for each case you do in a particular room. Although the HMO's don't agree, our time IS valuable!