Anesthesia Article by Dr Cohen

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I cut and paste the article below. You can find it in a more printable form at www.umdf.org on the right hand side of the main Library page.

Just my opinion here...but why not be safe than sorry? Seem like its not that big a deal just to ask them to use the safe meds and skip the rest. This is indicated for Neuromuscular diseases.

deb

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Anesthesia and Mitochondrial CytopathiesBruce H. Cohen, MD, Shoffner, MD, Glenn DeBoer, MDã United Mitochondrial Disease Foundation, 1998IntroductionThis article will outline some basic aspects of anesthesia and address the issue of the special risksof anesthesia in patients with mitochondrial cytopathies. The applicability of theserecommendations to a particular patient is complex and should be individualized by yourphysician. Considerations include whether the patient is undiagnosed (i.e. receiving their firstevaluation to determine whether a mitochondrial disease is present), whether the patient carriesthe diagnosis of a mitochondrial disease, and what criteria were used in making the diagnosis. Theclinical condition of the patient is probably the most important aspect of the pre-operativeevaluation. Some patients have minimal disease manifestations and are at low risk forcomplications, whereas, other patients have significant disease manifestations such as respiratorymuscle weakness, swallowing difficulties, liver disease, and heart disease, and are at high risk forcomplications.Anesthesia, often referred to as general anesthesia, is the medical procedure that renders patientsunconscious, insensible to pain and provides muscle relaxation. With local anesthesia, or regionalanesthesia, patients are awake or sedated, but do not feel pain because the pain pathways are“blocked†by the local anesthetics. Spinal anesthesia involves the use of local anesthetics ornarcotics injected around the spinal cord, causing loss of sensation below the level that themedication is injected.Intravenous AnestheticsIn ancient times orally administered extracts of poppy seeds (opium and morphine), extracts of thedeadly night shade (hyoscene and belladonna), and extracts of fermentations (alcohol) were usedfor “anesthesiaâ€. All of these drugs decrease consciousness and the awareness of pain. Atpresent, most of these drugs or their modern counterparts are administered intravenously.Thiopental is a rapidly acting barbiturate used for induction (the first part of anesthesia when theawake patient is put to sleep) of anesthesia. Propofol and etomidate are new rapidly actinginduction agents. epam (Valium) and midazolam (Versed) are drugs in the benzodiazepinecategory, which are potent hypnotics (induce a sleep-like state). Morphine, meperidine (Demerol)and fentanyl are examples of potent narcotic pain relievers (analgesics) that are used as part ofsome anesthetics.Inhalation AnestheticsThe earliest modern inhalation anesthetics were the gas nitrous oxide (also referred to as laughinggas), and ether, a potent inhalational anesthetic. Potent inhalational anesthetics are vaporsproduced from a liquid that evaporates easily. Nitrous oxide is still a basic in modern anesthesia;however, the modern potent inhalational anesthetics include halothane, enflurane, isoflurane,sevoflurane, and desflurane. The potent inhalational anesthetic agents provide all the modalitiesof general anesthesia; which include unconsciousness, analgesia and mild muscle relaxation.Anesthesia and Mitochondrial CytopathiesCohen, Shoffner, DeBoer Page 2 ã UMDFMuscle RelaxantsIn addition to the drugs that induce the sleep-like state, a group of drugs that provides musclerelaxation are often part of a modern anesthetic. These drugs interfere with the communicationbetween nerves and muscles, and induce a paralyzed state so that the patient does notunconsciously move during surgery. There are of two types of muscle relaxants; the depolarizingmuscle relaxants (succinylcholine), which causes the patient’s muscles to move before paralysisoccurs and is relatively short acting, and the non-depolarizing muscle relaxants which do notcause such movements. When patients are paralyzed with these drugs, the anesthesiologist oranesthetist must breathe for the patient by either hooking the breathing tube to a machine ormanually squeezing a “bag†often containing a mixture of oxygen, laughing gas and a potentinhalational anesthetic.Issues of Anesthesia in Mitochondrial CytopathiesModern general anesthesia consists of induction with intravenous agent and maintenance withinhalational agents and/or with intravenous agents. Muscle relaxants may or may not be used.Concerns about the side effects and possible complications associated with surgery and anesthesiaare shared by patients with mitochondrial cytopathies, their families and their physicians.The vast majority of patients with mitochondrial cytopathies have an uneventful surgery andanesthesia. Patients rarely experience a complication with a simple elective surgical proceduresuch as a muscle biopsy or gastrostomy tube placement. Patients with preoperative respiratoryproblems are at greater risk for worse problems after surgery. Similarly, those with seizures mayexperience post-operative seizures.There are a limited number of reports describing adverse events and outcomes in patients withmitochondrial diseases following surgery and anesthesia. Our knowledge about these potentialcomplications are based on these anecdotal reports. It is not possible to draw conclusions aboutthe safety of a particular anesthetic agent based on the outcome of these cases. Although it ispossible to test a particular anesthetic in a laboratory setting to see how it affects mitochondrialfunction, this work is based on animal experiments. How these animal studies relate to humans ina clinical (not laboratory) setting is impossible to determine. In reviewing these reports, a numberof inferences can be made:· Patients with mitochondrial cytopathies, on average, are “sicker†than the unaffected patientundergoing surgery and are having an operative procedure for potentially more seriousreasons than the unaffected patient.· As a general rule, patients with mitochondrial cytopathies are at greater risk than unaffectedpeople for side effects of some medications. Although some medications may interfere withenergy metabolism to some degree, complications are usually related to the clinical conditionof the patient prior to surgery.· The adverse events reported include new neurologic problems such a strokes, worsening ofthe overall neurologic status, respiratory difficulties, seizures, cardiac arrhythmias, prolongedcoma and death.Anesthesia and Mitochondrial CytopathiesCohen, Shoffner, DeBoer Page 3 ã UMDF· Hypotonia (low muscle tone), bulbar dysfunction (weakness of the muscles that protect theairway) and relatively poor ventilatory function (decreased ability to breathe deeply andcough) are common in patients with mitochondrial diseases and pose an increased risk forperioperative pneumonia. In one study of patients with typical Leigh syndrome (whichgenerally represents one of the more severe forms of mitochondrial cytopathies), respiratorydifficulties prior to anesthesia and surgery were a predictor of postoperative respiratory failureand death. In the cases reported, the patients awakened from anesthesia but deterioratedwithin a day. There did not seem to be any specific anesthetic agent or technique thattriggered these adverse events. It is not clear from this study whether the deterioration was adirect result of the surgical procedure, the anesthetic drugs, or as a result of mitochondrialfailure due to inadequate oxygen, which resulted form an unrecognized pneumonia orrespiratory failure. Understanding these factors may make anesthesia safer, but will not avoidall risks. (J Child Neurol 1990;5:137-41)· Malignant Hyperthermia (MH) is a life threatening, inherited syndrome triggered by potentinhalational anesthetic agents and/or depolarizing muscle relaxants. It is caused by abnormalincreases in muscle calcium concentrations leading to uncontrolled muscle metabolism,subsequent metabolic acidosis, muscle damage, and elevated potassium levels. Withouttreatment, MH will often result in death. Patients at risk for MH may develop the disorderwith their first anesthetic, or may have a dozen or more anesthetics without a problem, only todevelop MH with the next anesthetic. There are specific treatments available for MH if itshould develop, but the best approach is to identify patients at risk and use anesthetics that donot trigger MH. Risk factors for MH include 1) prior MH episode in the patient, 2) a familyhistory of MH and 3) muscle disease. Many patients with mitochondrial cytopathiessometimes have an associated myopathy (muscle disease), which places them at a potentialrisk for MH. There are anesthetics that are “safe†for those with or at risk for MH, but theseanesthetics may adversely affect mitochondrial function in some patients.· The risk of respiratory failure and worsening of neurologic function is often noted in patientswith mitochondrial cytopathies after “stressful†illnesses, including infections such as viral orpneumonia. Infections may be associated with surgical procedures, either as a complication ofsurgery or as the need for surgery, as in the case of a ruptured appendix. Infections, such asthe common cold, can also occur randomly around the time of surgery. Certainly surgeryitself, even if for a non-emergency condition, is a major stress. The following discussion isquite complicated but necessary in order to understand that anesthetic drugs alone should notbe considered the only element in leading to these adverse outcomes. During infections, thebody responds by making chemicals known as cytokines. Cytokines help the body fightinfection, and are also responsible for the fever, aches, chills and the overall “rotten†feelingwe get when we are ill. Cytokines induce the formation of nitric oxide. Nitric oxide (thechemical formula is NO·) is a powerful oxidant with many useful purposes in our bodies,some of which seem quite unrelated, such as forming new memories and killing bacteria.However, nitric oxide inhibits cis-acotinase (a citric acid cycle enzyme) and the ironcontainingcytochromes of the respiratory chain. Therefore, NO· in high amounts maydecrease energy production, which is ill-afforded in patients who already have an impairedability to generate energy. Nitric oxide can also interact with other chemicals in the body thatresult in damage to the mitochondrial DNA and mitochondrial structure itself. One cytokineAnesthesia and Mitochondrial CytopathiesCohen, Shoffner, DeBoer Page 4 ã UMDFknown as tumor necrosis factor (TNF), is known to be released by the body during surgery,and is also known to be a potent inhibitor of complex III. TNF has many essential functions,and serves as a natural defense against infections and cancer. In otherwise healthy people, theinhibitory effect on complex III is obviously not harmful, but may play some role in peoplewith mitochondrial diseases, who are not able to tolerate any small decrement in mitochondrialfunction. Therefore, anesthetic agents may not be responsible, at least without additionalfactors, for causing neurologic deterioration. Both the stress of surgery as well as anyassociated infections may trigger the events leading to a deterioration in susceptible patients.(Anesthesiology 1997;87:420-5)· Some patients have heart rhythm problems, such as those with Kearn-Sayres, that are at riskfor severe heart electrical conduction blocks, which can lead to death. Isoflurane may be apreferred inhalational agent as opposed to Halothane, because Isoflurane causes lessdisturbances in heart rhythms. (Anesthesiology 1994;49:876-878)· Although spinal anesthesia is safe, it should be used with extra caution in patients withneuropathies or myopathies, because of the possible deleterious effects on blood pressure andrespiratory function.RecommendationsThere is no doubt that patients with mitochondrial disease can undergo general anesthesia safely,as demonstrated by untold thousands of uneventful surgeries and anesthetic exposures. Thequestion that patients and their physicians wish to know is how to further decrease the risk. Thefollowing recommendations are made with the understanding that there are little data suggestingthat any specific precautions can lower the risk of neurologic events. However, theserecommendations seem to be prudent given what is known about the effects of surgical stress,infections and anesthetic agents in patients with mitochondrial cytopathies:1. Strict attention should be made to respiratory function before, during and after surgery,especially in patients with abnormal preoperative respiratory signs and symptoms. Vigorousrespiratory physiotherapy should be standard postoperative care in any patient with pulmonarydifficulties. Early use of artificial ventilation, maintaining normal oxygenation, CO2elimination, and vigorous respiratory physiotherapy are recommended at the first sign ofrespiratory deterioration.2. There should be a heightened level of suspicion for infections such as pneumonia, whichshould be promptly treated.3. Lactated Ringer’s solution (also known as Ringer’s Lactate) should be avoided as anintravenous fluid, as it contains lactic acid.4. Normal blood glucose, body temperature, and acid-base balance should be maintained duringsurgery. Low blood glucose should be avoided. However, a high blood glucose may indicatean acute disturbance in pyruvate metabolism or oxidative phosphorylation. In this situation,the lactic acid levels may also be elevated.Anesthesia and Mitochondrial CytopathiesCohen, Shoffner, DeBoer Page 5 ã UMDF5. Avoid depolarizing muscle relaxants, although these have been used safely in many patientswith mitochondrial diseases. Anesthesiology 1979;51:343-345.6. Delay elective surgery if there is any evidence of infection.7. Potent inhalational anesthetic agents appear to be safe in the majority of people withmitochondrial diseases. In patients at risk for MH, such as those patients with myopathiesthat are often associated with their mitochondrial disease, the risks and alternative methods ofanesthesia must be considered by the physician. Certainly if there has been a previous adversereaction in the patient or family member, these agents should be avoided. (Table 1)8. Anesthesia with combinations of barbiturates, narcotics, benzodiazepines, and nitrous oxidealso pose a theoretical risk for patients with disorders of oxidative phosphorylation. (Table 2)This risk should be considered only as a potential risk unless a patient has experienced a badreaction to any of the medications. This apparent paradox between the two methods ofgeneral anesthesia must be addressed with each patient, and the anesthesiologist mustdetermine what is the safest route.9. Animal studies indicate that propofol, a new intravenous anesthetic, impairs mitochondrialfunction to a greater degree than other anesthetics. However, this drug has been used safelyas an anesthetic in many patients with mitochondrial cytopathies. There have beenobservations that prolonged continuous use (days) at high dosages to treat frequent seizurescauses a syndrome similar to mitochondrial failure, and therefore prolonged use in a patientwith a mitochondrial cytopathy may not be safe.ConclusionAn increased awareness is needed whenever a person with a mitochondrial cytopathy iscontemplating or undergoing a surgical procedure. By virtue of the illness itself, there are greaterrisks involved with every medical intervention. The safest anesthetic is not known and the choiceof anesthetic must be individualized to the patient’s particular needs. Although anesthetic agentsmay play a contributing factor in causing an adverse event associated with surgery, the illness, thestress of that illness, the surgical procedure and concurrent infections may play a larger role incausing neurologic deterioration. With additional research, more will be learned about theseproblems.

deb...mom to four great kids and wife to one amazing guy!www.LifeofLoveProject.orgwww.debwells.com