Anesthesia: Risks, Precautions and Recommendations for Mitochondrial Disease Patients

Anesthesia poses specific risks for children and adults with mitochondrial disease. Join  us this month with Dr. Andre Mattman from Vancouver General Hospital to learn more about risks, precautions and recommendations for anesthesia use in mitochondrial disease patients.

• What are the different types of anesthesia and how/why are they used?
• What are the risks related to Mito and anesthesia, and why do they exist?
• Are there specific anesthetic agents to use or avoid?
• What precautions should children and adults who need anesthetics take?
• Recommendations for before, during and after surgical procedures requiring sedation

CLICK HERE FOR TABLE OF ANESTHETICS

LISTEN TO THE RECORDING OF THIS MEETING HERE

See the Protocol for Procedures Requiring Anesthesia from the Mito Clinician's Guide here: http://www.mitoaction.org/files/protocol-general-surgery-eating-not-disrupted.pdf

and here, the Protocol for Procdures Requiring Anesthesia when Fasting is Required http://www.mitoaction.org/files/protocol-general-surgery-eating-disrupted.pdf

MEETING SUMMARY

Introduction Dr. Mattman is a medical biochemist with a joint appointment in the Department of Pathology and Laboratory Medicine at St. Paul's Hospital and the Department of Internal Medicine at Vancouver General Hospital where he is a consultant in the Adult Metabolic Disease Clinic.  His current laboratory medicine interests focuses on testing for alpha 1 antitrypsin deficiency as well as his previous interests related to prenatal screening and heavy metal testing.  His clinical interests are in mitochondrial disease, lysosomal storage disorders and other adult inborn errors of metabolism.  As a metabolic and laboratory physician, Dr. Mattman's interest is in the effect of anesthesia on mitochondrial function as it affects his patients who have mitochondrial disease. Since he is not an anesthetist, he defers to physicians who are anesthetists when making recommendations regarding a particular plan of anesthetic management for individual cases.

Dr. Mattman's discussion will focus on the specific risks, precautions and recommendations for anesthesia use in mitochondrial patients. Protocols for procedures requiring anesthesia and the protocol for procedures requiring anesthesia when fasting is required can both be found at the MitoAction website in the Clinician's Guide section.  A chart/handout accompanies Dr. Mattman's talk and can also be found at the MitoAction web site. 

Mitochondria Mitochondria play multiple roles in the body; therefore, since anesthesia can effect mitochondria, the effects can occur on multiple levels: ATP energy production, heat generation, metabolism, cellular stress response, and calcium signaling.

Introduction to Anesthesia Anesthesia is needed for surgery in order to

• induce/provide a decreased level of consciousness
• provide a relatively pain free state for all or part of the body
• induce partial or total inhibition of muscle contractions for all or part of the body

Types of Anesthetic Agents

Induction Agent These medications are used at the outset of surgery or a procedure to quickly induce sedation in order to insert a breathing tube and they are short acting.

Maintenance Agent These are either inhalant or intravenous anesthetics that are used to sustain or maintain sedation for the length of the surgery.

Muscle relaxants.  These medications are used to prevent muscle contraction during surgery. They can be either depolarizing or non-depolarizing agents. Though they produce the same effect, they use different mechanisms to achieve the results. Non-depolarizing agents do not cause initial large scale muscle contractions.

Analgesics These medications relieve pain by means other than sedation.

Inhalational (volatile) Anesthetics This medication is a traditional means of producing sedation for surgery. It can be inhaled quickly, sedation is achieved rapidly and can be stopped quickly as well.

Intravenous Anesthetics These medications produce the same effects as the volatiles, but are given through IV lines.

Levels of Anesthesia The level of anesthesia refers to how much consciousness remains during the procedure. Light anesthesia has a minimal sedating effect allowing some consciousness. Minimal conscious sedation refers to providing light sedation and analgesics during a procedure while the patient maintains consciousness. Deep anesthesia on the other hand sedates the patient to a degree that they are unable to wake until the medication is cleared from the body.

General anesthesia During general anesthesia the body/mind as a whole is sedated and paralyzed. Analgesics take effect after the patient wakes from the sedation. General anesthesia can be inhalation or intravenous.

Local, regional & spinal anesthesia.  Local anesthesia is that in which pain control is administered to only a small localized part of the body. Regional anesthesia affects a region of the body, but not the entire body. Spinal anesthesia is a form of regional in which a local agent is introduced into the spinal fluid leading to a loss of sensation and function in the lower half of the body.

Commonly Used Anesthetic Agents

Propofol This is an intravenous agent which can be used for induction or maintenance. One possible side effect which is particularly important for Mito patients to be aware of is called propofol related infusion syndrome (PRIS). This syndrome causes metabolic acidosis, cardiac failure with conduction abnormalities and kidney failure.

Etomidate  This is used as an induction agent but can have a transient impact on adrenal function. It has been shown to cause abnormal electrolytes in some MELAS patients following surgical use.

Midazolam This is a sedative which is also used as an induction agent. There are no particular reports/research which indicate side effects for mito patients.

Halothane, Sevoflurane, Desevoflurane, Isoflurane These inhalant anesthetics can cause something called anesthetic induced preconditioning (APC). This is a phenomenon whereby a brief exposure to a volatile anesthetic can protect the heart from potential ischemia. Halothane is associate with a greater predisposition to malignant hyperthermia (to be discussed later) than other volatiles.

Nitrous Oxide (Laughing gas) This inhalant is a fairly weak agent and has few if any reports of untoward effects.

Succinylcholine A depolarizing muscle relaxant, this agent may trigger hyperkalemia and/or malignant hyperthermia in patients with myopathy.

Vecuronium & Rocuronium Both of these depolarizing muscle relaxants are relatively short acting and have few reports of significant side effects.

Atracurium, Pancuronium, Cisatracurium These also are nondepolarizing  muscle relaxants which have been known to cause prolonged weakness post operatively if the dose exceeds patient requirements; mito patients should be aware of this.

Sodium Thiopental This barbiturate is used as an intravenous induction agent (short acting) which decreases blood flow to the brain while maintaining normal brain oxygen utilization (useful in those with a brain injury).

Ketamine This is a short acting anesthetic which causes amnesia, analgesia, and lack of awareness and pain. Not much has been reported/written about untoward effects.

Fentanyl Because this analgesic depresses respirations, patients need to be monitored carefully after surgery especially if the patient had respiratory problems beforehand.

Bupivaccaine, Lidocaine Both are local anesthetic agents. Bupivacaine induced myopathy is characterized by abnormal mitochondrial function and long term use of lidocaine has shown to decrease ATP. For these reasons, both agents should be used with caution or avoided by Mito patients.

The Impact of Anesthesia (and Surgery) on Mitochondrial Function

Anesthetic agents themselves may impair mitochondrial electron transfer chain function directly. These medications may also exacerbate cellular dysfunction that results from ETC dysfunction causing energy deficits and or reactive oxygen species generation (ROS).

Persons with poor health or multiple health problems prior to surgery can expect to have more problems after surgery or be more prone to  bad/poor outcomes than those who enter surgery in good health and have few if any health problems. Beyond that, surgery itself generates an inflammatory response locally which in turn generates inflammatory cytokines which can act systemically.  These inflammatory cytokines can impair mitochondrial ETC, exacerbate cellular dysfunction, and generate ROS. A common complication of surgery is infection, and infection can maximize production of inflammatory cytokine.

Malignant Hyperthermia  MH is a cellular level condition which is caused by the loss of regulation of normal muscle contraction. These "out of control" contractions then lead to high body temperature and muscle damage as well as high potassium and Creatinine kinase levels in the blood.  This severe side effect (MH) occurs in sensitive patients as a response to depolarizing muscle relaxants and volatile inhalants (especially halothane). Recent studies have shown that mitochondrial patients may not be more prone to this side effect than others (it had been thought that they were particularly sensitive). Nevertheless, Succinylcholine and halothane are generally avoided in Mito patients.

Propofol Related Infusion Syndrome (PRIS) This syndrome is caused by prolonged administration of Propofol to patients who might be particularly susceptible.  The syndrome causes heart, muscle and kidney disease along with lactic acidosis. From 18-50% of patients who develop PRIS die. Those more prone include: children, those receiving high doses for long periods of time, infection at the time of surgery, high catecholamine/cortisol states (stress response hormones), low carbohydrate/high fat loading, and underlying metabolic disease(i.e., Mito).  It is noteworthy that propofol has been used as an induction agent in Mito patients with no ill results, but it is still not recommended.

How to Prepare for Surgery

Because surgery and anesthesia have the potential for negative effects on mitochondrial function, there are important considerations for patients and their doctors to consider.  First, they should ask if there is a definite need for surgery. Sometimes the answer is a clear yes or no, but other times the answer is not so clear. In these cases the risks and the benefits of surgery need to be weighed carefully noting that the risks of surgery are greater than normal for Mito patients.  If the risks of avoiding surgery are too great, then proceed with caution keeping in mind which anesthetic agents might be associated with greater risks for Mito patients.

Impact of Anesthetic Agents on Mitochondrial Function & Mito Disease

Propofol Evidence indicates that this drug interferes with ATP generation and fatty acid metabolism. PRIS, a serious side effect, is a risk after prolonged use above a certain dosage level.

Halothane At higher doses volatile anesthetics can reduce oxidative phosphorylation and can cause arrhythmias.

Etomidate There have been some cases of unusual patient sensitivity.

Sevoflurane, Isoflurane Complex I has been shown to be the most sensitive step in oxidative phosphorylation which is inhibited by volatile anesthetics. There are studies, however, that show the use of these agents Mito patients without incidence.

Nitous oxide  There are no studies which show problems with this drug's use.

Sussinylcholine There has been one case of a patient with Mito disease getting hyperkalemia after the use of this drug; there has also been one case report of MH.

Rocuronium and other nonpolarizing muscle relaxants These are commonly used short term anesthetics and have been used without incidence.  There are some reports of having to use higher doses due to interactions with anti-seizure medications.

Ketamine There are no  reports of untoward reactions related to Mito patients use.

Fentanyl/Remifentanyl Used at the clinical concentrations, there are no reports of incidents, but at higher doses there may be inhibition of the Electron Transport Chain complexes  III, IV and IV.

Bupivacaine, Lidocaine There have been studies showing that these drugs induce changes in the mitochondria, loss of mitochondrial membrane potential and impaired ATP synthesis.

Summary and Recommendations

All patients, but especially those with mitochondrial disease, should weigh the risks and benefits of surgery, keeping in mind the increased risk of complications for those with Mito. Pre-surgical anesthesia consultation should occur and the anesthetist should always be informed of the patient’s medical condition(s).

When at all possible, surgery should be planned (ie, planned C-Section rather than spontaneous birth). If swallowing problems exist, decrease gastric acididty and volume prior to surgery by fasting (if possible). Patients are at higher risk for post op respiratory complications if they have respiratory problems before surgery and respiratory depressants should be minimized. Cardiac signal conduction abnormalities are more common in mito patients and will be exacerbated by both the surgery and anesthesia. Use the most appropriate anesthesia -one that is cardiovascularly stable.  Because Mito patients are more prone to  hypo or hyper glycemia, glucose fluctuations should be minimized. Try to be scheduled for the first surgery of the day in order to minimize fasting. Start IV glucose preop, monitor glucose during surgery and give insulin if needed. Keep body temperature stable in order to minimize requirements for oxidative phosporylation. Use IV fluids (generally Ringer's Lactate is avoided), and monitor electrolyte balance both before, during and after surgery, especially sodium and potassium. MELAS patients are particularly prone and use of Etomidate would theoretically make this worse.

Total IV anesthesia using propofol should be avoided and volatile anesthetics with a lower predisposition to MH (like sevoflurane) should be used.  Ketamine/Nitrous Oxide may be the preferred option for procedural  sedation. Regional anesthetics shgould be avoided if possible. Of the muscle relaxants, Succinylcholine is generally avoided and nonpolarizing muscle relaxants should be minimized if the patient has myopathy.

Submitted by

Joanne M.Turco, RN, MS, Cristy Balcells RN MSN 

 Please join us!

MitoAction meeting details

Friday December 2nd, 2011

Noon eastern time/9 am Pacific ( find your time zone)

by toll-free teleconference

1-866-414-2828, participant code 017921# All are welcome!

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This meeting will be recorded and posted here along with a summary following the meeting.  To find summaries from other presentations, go to the blog page