Anesthesia & Surgery for Mast Cell Patients

UPDATED 20 JULY 19

What You Should Know About Anesthesia – It Could Save Your Life

(Please see my notes at the bottom - stay tuned for updates as I research the different drug safety for us)

Introduction

Surgery is a stressful experience. For a patient with mast cell disease, that stress is compounded by the possibility of complications including anaphylaxis, cardiovascular collapse, increased bleeding and even death. Therefore, general anesthesia is considered a high-risk procedure in patients with mast cell disease. It is critical that all members of the patient’s operating team take proper precautions before, during, and after surgery to protect against potentially life-threatening mast cell activation.

Planning for surgery should begin as soon as the need for surgery arises.

It is imperative that good communication is established between the patient, referring physician, surgeon, anesthesiologist, nurses, and all others involved in the patient’s care before, during, and after surgery. The surgeon must be aware of the patient’s mast cell disease and inform themselves of the measures necessary to keep the patient as free of symptoms as possible.

Additionally, the patient should contact the anesthesiologist assigned to their care as soon as possible after surgery has been scheduled. Both regional and general anesthetics can cause life-threatening complications. An experienced anesthesiologist is aware of medications known to cause mast cell degranulation and medications that stabilize mast cells.

If the patient is satisfied that their anesthesiologist fully understands the importance of planning around the mast cell disease, it will go a long way toward calming the patient, which in turn may reduce mast cell mediator release.

Symptoms should be as well-controlled as possible in the days prior to surgery. The patient should carefully avoid known triggers of mast cell activity and should take their medications as prescribed. Those medications include H1 and H2 histamine receptor blockers such as Allegra (H1) and Zantac (H2). A mast cell stabilizer such as disodium cromoglycate or ketotifen, and medications targeting other mast cell mediators should be taken regularly if they are part of the patient’s normal drug regimen.

The patient’s complete medication list should be reviewed by the surgical team prior to surgery and any necessary medication changes should be thoroughly discussed with the patient. For example, if the patient regularly takes a medication in the family known as beta blockers for blood pressure or heart rate abnormality, a change to another drug should be considered well before surgery is scheduled.

Beta blockers are generally avoided in people with mast cell disease undergoing surgery because they interfere with an important natural control of mast cell activation.

These drugs may also interfere with the use of epinephrine, which may be required if the patient has a major release of mast cell mediators resulting in low blood pressure during surgery. Other drugs that may interfere with control of blood pressure during surgery must be carefully reviewed by the patient’s physician before the surgery.

It may be necessary to perform a “graded challenge” procedure in the hospital under the supervision of an allergist and an anesthesiologist for certain medications if there is no history of exposure to that medication. This procedure usually starts with scratching the skin with a small amount of medication followed by injection of increasing amounts with careful monitoring after each injection. Resuscitation equipment and drugs including epinephrine must be readily available during the procedure.

Precautions taken in the hours prior to surgery will help the patient go into surgery in the best possible condition

For pre-operative control of anxiety and the reduction of mast cell activity, drugs in the valium family (diazepam, midazolam, lorazepam) are usually effective. Some procedures require the patient not to take anything by mouth including medications after midnight of the night before the surgery. In this case, H1 and H2 blockers should be administered intravenously prior to the surgery. (as well as MethylpredniSOLONE) The use of corticosteroids, such as prednisone, has also been suggested although there is no evidence that the short-term use of steroids reduces the ability of mast cells to release the chemicals contained in their granules. However, corticosteroids may reduce the extent of other inflammatory reactions that result from mast cell activation.

A tube may be inserted into an artery and attached to a device allowing the anesthesiologist to vigilantly monitor blood pressure without having to periodically inflate a blood pressure cuff. In addition, a tube is inserted into a vein and securely taped in place, with intravenous (IV) fluids running to keep the patient well-hydrated in all surgeries involving general anesthesia or conscious sedation. This tube will also make it possible to immediately administer any emergency medications that may be needed.

In the operating room, the patient should not be allowed to become either too cold or over-heated. Warm blankets should be used, and all IV fluids should be warmed before they are given. In addition, there should be a minimum of noise and bustle around the patient prior to the administration of the anesthetic in order to reduce the possibility of anxiety-triggered mast cell mediator release.

Emergency surgery:

An emergency situation may arise in which a person with mast cell disease requires immediate surgery. Wearing a MedicAlert bracelet could be a life-saver if this happens. Inscriptions vary depending upon the patient’s specific needs, but generally include the patient’s diagnosis and drug sensitivities.

Emergency response team members can access more detailed information 24 hours a day, 7 days a week from the MedicAlert organization by dialling the toll-free number on the bracelet. MedicAlert is a non-profit organization serving patients world-wide.

There are nominal membership and annual fees with financial assistance available for those in need. For more information, please visit www.medicalert.org or dial 888-633-4298 within the U.S. or 209-668-3333 from outside the U.S.

Alternatively, there are several companies that manufacture and inscribe medical identification jewellery. These products are available on the internet and are also carried by some jewellery stores and pharmacies. It may be wise to select jewellery which provides space for a miniature version of the patient’s medical history (often supplied by the manufacturer as part of the cost) in addition to the inscription. Although these companies do not have a 24 hour information center, they do not require membership or annual fees and may be preferable for some patients.

It may also be helpful for mast cell patients to carry with them at all times emergency information, written on their physician’s letterhead, which contains a list of current medications and other instructions for treatment in the event of severe symptoms.

During surgery:

Constant attention from the anesthesiologist is required for the safety of a patient with mast cell disease during surgery, as some of the early symptoms of mast cell mediator release such as flushing, hives, and early signs of obstructed breathing can be masked by the surgical drapes covering much of the patient’s skin and by the use of an airway tube during anesthesia.

Should anaphylaxis occur during surgery, the drug thought to be responsible should be discontinued immediately and epinephrine should be administered. Airway support with 100% oxygen, IV replacement fluids to compensate for dilated blood vessels, H1 and H2 antihistamines, bronchodilators, and corticosteroids may also be given. Continuous IV epinephrine and other “vasopressor drugs” may be necessary to keep blood pressure from falling.

However, it is important to keep in mind that not all hypotensive episodes during surgery are due to mast cell degranulation and anaphylaxis. A serum tryptase level obtained during the hypotensive episode and its comparison with pre-surgery or “baseline” level may be helpful to determine whether the episode is due to mast cell degranulation.

** Note from DK: Its important to note that there are 3 types of mast cells and not all types of mast cells contain tryptase in them - thus not affecting your overall tryptase levels.

Drugs:

Records from prior surgeries should be examined and drugs tolerated in those procedures should be preferred if possible. Prior to the administration of any drugs associated with surgery, it is important that an IV is running, that epinephrine is available for immediate intramuscular (IM) or IV administration, and that emergency equipment is easily accessible in case of an adverse reaction.

IV preparations without preservative should be used!!!

Drugs to avoid include ethanol, dextran, and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and toradol (unless the patient is already successfully taking a drug in this family), polymyxin B, amphoteracin B, quinine, dextromethorphan, α-adrenergic blockers, β-adrenergic blockers, and anticholinergic drugs as well as drugs mentioned in specific categories below.

Local anesthetics – True allergic reactions to local anesthetics resulting from mast cell degranulation are thought to be rare. Skin testing and graded challenge protocols have been published and may be administered by an allergist prior to the surgery if questions arise regarding the safe use of a local anesthetic in a patient.

If possible, preservative-free local anesthetic should be used in these tests, as the preservative often present in local anesthetics can cause a mast cell reaction.

In general, local anesthetics in the “ester” group should be avoided. This group includes procaine, chloroprocaine, tetracaine, and benzocaine.

Anaphylactic reactions to local anesthetics in the “amide” group are rare. This group includes lidocaine, mepivacaine, prilocaine, bupivacaine, levobupivacaine, and ropivacaine.

Muscle relaxants - Muscle relaxants are the most likely group of the anesthetic drugs to cause anaphylaxis. Succinylcholine, D-tubocurarine, metocurine, doxacurium, atracurium, and mivacurium are more likely to cause a severe reaction than rocuronium or the so-called nondepolarizing muscle relaxants such as pancuronium or vercuronium. Some studies have reported increased numbers of anaphylactic reactions to rocuronium, however, so it may not be appropriate as the first choice for patients with mast cell disease.

Induction drugs - These are medications given to initiate anesthesia. It is rare for mast cell activation to occur in response to the use of propofol, ketamine, or the benzodiazepine drugs such as midazolam.

Inhaled anesthetics - Sevoflurane is an inhibitor of mast cell activation and is less likely to cause liver damage than other inhaled anesthetics in this family. * NOTE: It is important to note that while the induction drugs may be safe, the drugs to bring you OUT of anesthesia can cause the reactions, as many of these drugs are newer and no information is available for them (yet).

Opiates and opioids - Oral opioid drugs for pain relief may be tolerated by some mast cell disease patients, but their use should be approached with caution, beginning with very small doses. All drugs in this category are capable of causing mast cell mediator release.

Summary

Surgery for a person with mast cell disease involves exposure to drugs and conditions that may trigger extensive mast cell degranulation. It should be emphasized that it is often impossible to predict or avoid the risk of adverse events which may occur in surgery due to the administration of drugs and the procedure itself.

The risk can be reduced, though, if the mast cell disease is brought to the attention of everyone involved in the patient’s care and measures are taken to reduce the possibility of mast cell mediator release. Careful planning is important, beginning from the time a need for surgery has been defined and continuing through the immediate pre-operative period, anesthesia, surgery, and recovery. The choice of drugs is of major importance, and the anesthesiologist, the surgeon, the nursing staff, the patient’s physician, and the patient should form a working team to ensure that surgery presents the fewest possible dangers for the patient.

On a side Note from DK: (other meds that can affect you) UPDATED!

With the surgery quickly approaching and meeting 2 anesthesia doctors I was given a list of drugs for me to research to see if I may be able to tolerate them. I've had to research the pathology of the drugs and any inactive ingredients in them that may affect us. There's literature the ansethesia docs use, however there are many that aren't well tested. Below are some of the drug options I was given and the results that I have found. I will update this section as I research other drugs. Drugs in Red are "use extreme caution or should be avoided". Drugs in Blue are "use caution but generally tolerated."

Bupivacaine is often used in epidurals and is a local anesthetic This drug has been reported to induce Hypersensitivity reactions and anaphylaxis on some occassions. Bupivicaine has either methylparababen or sodium metabisulfite as preservatives. So if you are sensitive to sulfur - better to avoid this drug.

There are drugs that are considered safe for Mast cell patients - such as amikacin, bupivicaine, and fetanyl. However, they have the preservatives in them para-aminobenzoic acid or methylparaben - those may act as allergens able to induce anyphylaxis and Kounis anaphylaxis-associated syndrome. It must be remembered that simultaneous exposure of several allergens has an additive effect on multi-sensitized mast cells and basophils.

Where some patients may tolerate it, the more sensitized patients may NOT be able to due to the fact that it has been reported to increase and induce anaphylactic shock and Kounis anaphylaxis-associated coronary syndrome (Journal of Pharmacology, Pharmacotherapeutics) May/June 2014

Histamines and Antibiotics

There is a subset of CFS/IBS/FM patients that are histamine sensitive. The probable cause according to the model is overgrowth of histamine producing bacteria, for example, some (not all) strains of Escherichia coli ,Lactobacillus sp., Proteus morganii, Proteus sp. , Pseudomonas reptilivora and Streptococcus sp. With CFS we see massive overgrown of bacteroidetes — the species that tag-team to cause this to happen, vary from patient to patient.

A reader asked about antibiotics and histamine interactions. That is a good question which I have not attempted to research and very relevant if you have a MD willing to prescribe antibiotics AND have histamine issues.

Drug allergy syndrome may be connected to the drug impact on histamines. “When oral tolerance tests were performed, only doxycycline was tolerated whereas levofloxacin, clarithromycin, nimesulide and tramadol caused mild urticaria [ hives]”

Fosfomycin Tromethamine – “…suppressed the release of histamine in a dose-dependent manner…We concluded that some antibiotics, particularly fosfomycin, have the capacity to suppress histamine release mediated by various secretagogues, suggesting they may possess an anti-allergic property as well as a bactericidal activity. ”
Polymyxin B ( derived from the bacterium Bacillus polymyxa.) “…suppressed the release of histamine in a dose-dependent manner. (**NOTE: From DK: Its important to note that its derived from bacteria and should be avoided by mast cell patients as its a trigger for many of us. Some institutions claim its safe while others do not. However, due to HOW its derived I would recommend avoiding it unless you've been successful in using it in the past. )

Tetracycline

Tetracyclines reduces histamines

Minocycline reduces histamine
“…suppressed the release of histamine in a dose-dependent manner. ”
Doxycycline reduces histamine

Macrolides

rapamycin – “Bouts of scratching induced by the histamine-dependent… were significantly reduced”
Inhibitory action of roxithromycin on histamine release and prostaglandin D2 production from beta-defensin 2-stimulated mast cells

Beta-lactams.

UPDATED!! 20 Jul 19. Beta-lactams should be avoided due to cross sensitivities (same line as cephlasporins/cyclosporins) and the penicillin connection. AMINOGLYCOSIDES are in the flouroquinilone family and are listed to be avoided.) I changed them from Blue to red as they can indeed incite reactions. It should be noted to do your homework on drugs as one site can say they're okay - where another will say they are not. -OR- they belong to a known group/class of drug that are known to cause reactions. I found this repeatedly in my research before my surgery. Hopefully my research will help you and your doctors make the best choices. REMEMBER!! Be your own advocate. If you need help, dont hesitate to ask, or ask you local pharmacist. But this is a list of the common ones.

Original text:

“beta-lactams* and aminoglycosides*, none had the capacity to enhance antigen-induced histamine release,”

Aminoglycosides

“beta-lactams* and aminoglycosides*, none had the capacity to enhance antigen-induced histamine release,”

Cephalosporin

Cefaclor etc – appears to increase histamine

Penicillin

Amocixillin —Anti-Amoxicillin Immunoglobulin E, Histamine-2 Receptor Antagonist Therapy and Mast Cell Activation Syndrome Are Risk Factors for Amoxicillin Anaphylaxis.
“penicillin treatment directly elicited rapid histamine release.”

Fluoroquinolones

“levofloxacin… induces histamine release from the connective tissue-type mast cells distributed mainly in the liver, somewhat in the cutaneous tissue, through the activation of pertussis toxin-sensitive G proteins.”

Intra-opererative Induction drugs

Generally considered safe are Ketamine, Midazolam, and Propofol.

Inhailed Anesthetics:

Sevoflurane as it can inhibit mast cell activation and is less likely to cause liver damage than other inhailed anesthetics.

Bottom Line

Two of the families of antibiotics (tetracycles and macrolides) that inhibits histamine release are very important in Dr. Jadin’s protocol.

Note: Fentanyl has mast cell activating preservatives. Please see above written literature on the subject. ANSEF (although listed safe here) is another name for Cepholosporin which is also listed off limits to us. See literature above. Please use discernment when selecting your meds with you doctors. Do your research on the subject and MAKE SURE before you go under!! Some of the drugs itself may be okay, but the preservatives used to make them are harmful or the drug to bring you out of anesthesia may be the trigger. Those drugs do not have enough study to annotate whether they are safe for mast cell sufferers or not. And I do not know either at this time.

Be sure to avoid drugs that interfere with Mitochondria as well, the more mitochondrial damage you take on the further your body makes metabolic changes to compensate. This process will further throw your methylation cycles further out of whack thus creating more histamine/inflammation issues. ESPECIALLY if you have an MTHFR gene mutation.

This is an incomplete list but does cover some common families of antibiotics, anesthetics and mitochondrial damaging drugs. If there are additional ones that you wish me to research, just add a comment to this post!

This does not replace doctors care, however BE you're OWN advocate for ultimate safety. Nobody knows your body better than YOU. Hopefully you'll find this information extremely helpful in getting started with your team of doctors.

Good Luck!!

Love and Light,

Happy Healing