PREOPERATIVE MANAGEMENT OF COMMON MINOR MEDICAL ISSUES IN THE OUTPATIENT SETTING

AMBULATORY ANESTHESIA

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PREOPERATIVE MANAGEMENT OF COMMON MINOR MEDICAL ISSUES IN THE OUTPATIENT SETTING Gail A. Van Norman, MD

A number of problems are frequently encountered in an outpatient preoperative clinic that seem minor and require detection and attention in the preoperative preparation to ensure safe conduct of anesthesia and surgery. In this article several of these issues are reviewed and recommendations made with respect to appropriate management.

ENDOCARDITIS PROPHYLAXIS: PREVENTING “THE MISCHIEF” Lord Thomas Horder wrote in 1909 that “when infection is grafted upon a previously sclerosed endocardium. . .it is possible to do something to prevent the mischief. . .”.31 In 1965, the American Heart Association (AHA) issued guidelines for antibiotic treatment to prevent bacterial endocarditis, which have since undergone periodic revisions. Despite the common belief that antibiotic prophylaxis prevents cases of endocarditis, there has been no prospective study that clearly shows that it is 43 and the rationale behind recommendations for prophylaxis relies on in vitro studies, clinical experience, animal model data, and knowledge about the organisms that are most likely to produce bacteremia from a given site and those most likely to result in endocarditis. Infective endocarditis continues to cause substantial morbidity and mortality despite modern treatment, with an estimated incidence of between 4000 and 8000 new cases of endocarditis per year in the United States. Over 75% of cases of endocarditis occur in patients with preexisting cardiac abnormalities, and fewer than 20% of cases of endocarditis can be attributed to medical proce~~

From the Department of Anesthesiology, University of Washington, Seattle, Washington

ANESTHESIOLOGY CLINICS OF NORTH AMERICA VOLUME 14 NUMBER 4 * DECEMBER 1996

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Table 1. PATIENTS AND PROCEDURES FOR WHICH ANTIMICROBIAL PROPHYLAXIS OF BACTERIAL ENDOCARDITIS IS RECOMMENDED Prophylaxis is Recommended Medical Conditions

Prosthetic heart valves Previous endocarditis Most congenital heart defects (except ASD) Rheumatic or other acquired valvular dysfunction Hypertrophic cardiomyopathy Mitral valve prolapse with valve regurgitation

Procedures

Procedures causing gingival or oral mucosal bleeding, tonsillectomy, adenoidectomy, and emergency nasotracheal intubation Rigid bronchoscopy Sclerotherapy of esophageal varices, esophageal dilation Gallbladder surgery Cystoscopy, urethral dilation Urethral catheterization of infection present Prostatic surgery I and D of infected tissue Vaginal hysterectomy, vaginal delivery if affected

Prophylaxis is Not Recommended Previous CABG Mitral valve prolapse without valve regurgitation Physiologic or “innocent” heart murmurs Pacemakers or implanted defibrillators Isolated atrial secundum defect S/P complete repair VSD, PDA Previous rheumatic heart disease or Kawasaki’s disease without valve dysfunction Dental procedures not likely to cause gingival bleeding Injection of intraoral anesthetics Tympanostomy tube insertion Elective oral endotracheal intubation Flexible bronchoscopy with or without biopsy Cardiac catheterization Endoscopy with or without biopsy Cesarean section Urethral catheterization, uterine D & C, vaginal delivery, therapeutic abortion, sterilization procedures, insertion or removal of IUD-all if no infection present

ASD = atrial septal defect; CABG = coronary artery bypass grafting; D & C = dilation and curettage; I and D = incision and drainage; IUD = intrauterine device; PDA = patent ductus arteriosus; VSD = ventricular septal defect.

dures.26 With a low incidence of disease in the general population and w i t h a minority of cases attributable to medical procedures, antibiotic prophylaxis for a l l patients w o u l d be unduly expensive, b o t h in terms of dollars and treatment complications. For example, it i s estimated that use of parenteral penicillin in patients with uncomplicated mitral valve prolapse w o u l d result in more deaths f r o m anaphylaxis than w o u l d result f r o m endocarditis i f n o prophylaxis was given.14 Patients with higher endocarditis risk should be targeted for prophylaxis, but the cut off point below which the risk is too l o w to require intervention remains arbitrary. Cardiac conditions and procedures for w h i c h antimicrobial prophylaxis should be considered can be found in Table 1, and treatment recommendations are summarized in Table 2.56 Antibiotics m a y prevent endocarditis either by killing bacteria outright, by damaging them so that host defenses can destroy them, by preventing adherence of bacteria to endocardia1 structures, or by a combination of mechanisms. Bacteremia can occur as early as 30 seconds after the beginning of a dental procedure, and bacterial seeding of the endocardium occurs in animal models within

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Table 2. BACTERIAL ENDOCARDITIS REGIMENS ENDORSED BY THE AMERICAN

HEART ASSOCIATION Procedure

Recommended Regimen

Dental, oral, or upper respiratory tract: standard regimen Dental, oral or upper respiratory tract: patients at high risk and not candidates for standard regimen or unable to take oral medication Genitourinary or gastrointestinal procedures

Amoxicillin 50 mg/kg (to maximum dose 3 g) orally 1 hour prior to procedure, then 25 mg/kg 6 hours after the initial dose Ampicillin and gentamycin, 50 mg/kg (maximum dose 2 g) and 2 mg/kg (maximum dose 80 mg), respectively, IV 30 minutes prior to procedure, and repeat 8 hours after initial dose

Alternative Regimen for PCN-Allergic Patients

Erythromycin 20 mg/kg (maximum dose 1.O g) orally 2 hours prior to procedure, then 10 mg/ kg 6 hours after the initial dose Clindamycin 10 mg/kg (maximum dose 300 mg) IV 30 minutes prior to procedure, then 5 mglkg 6 hours after initial dose or

Vancomycin 20 mg/kg (maximum dose 1 g) IV 1 hour prior to procedure Ampicillin and gentamycin, 50 mg/kg (maximum dose 2 g) and 2 mg/kg (maximum dose 80 mg), respectively, IV 30 minutes prior to procedure, and repeat 8 hours after initial dose Alternative low risk regimen: Amoxicillin 50 mg/kg (maximum dose 3 g) orally 1 hour prior to procedure, then 25 mglkg 6 hours after initial dose

Vancomycin, gentamicin 20 mglkg (maximum dose 1 g) and 2 mg/kg (maximum dose 80 mg), respectively, IV 1 hour prior to procedure

minutes of a bacteremia.I5Antibiotic treatment is effective in preventing endocarditis even when antibiotic administration is delayed for one-half hour after an intravenous (IV) injection of streptococci into laboratory animals, but not when treatment is delayed for 6 hours.19,2o The AHA recommends oral administration of appropriate antibiotics at least 1 hour before indicated procedures and parenteral administrations at least 30 minutes prior to procedure^,'^, 19, 43 premised on the goal of having therapeutic plasma levels of antibiotics present at the start of procedures when bacteremia may be initiated; however, in a survey by Schwartz et a1,5690% of anesthesiologists reported that if antibiotic administration occurred after anesthetic induction they did not delay incision for an additional 30 minutes to achieve these goals. It is sometimes difficult or impossible to administer oral or parenteral antibiotics to patients (i.e., pediatric patients) prior to induction. Because of the effectiveness of antibiotics in animal models administered up to one-half hour after the onset of bacteremia, Schwartz et a1 suggested that waiting an additional half hour after antibiotic administration to start the procedure in such patients would cause undue delay in the operating room for no demonstrated benefit, and may subject the patient to unwarranted risks and expense of longer anesthetic times. The AHA does not recommend prophylaxis for orotracheal (OT) or nasotra-

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cheal (NT) intubation. This is based on two studies carried out under elective operating room conditions that demonstrated a 0% incidence of bacteremia associated with OT intubations and a 12% incidence of bacteremia associated with NT in tuba ti on^.^, 24 A recent study examined the incidence of bacteremia associated with both OT and NT intubations outside of the operating room. Whereas OT intubation did not result in bacteremia, emergency NT intubation was associated with bacteremia in 28% of cases,'z suggesting that NT intubations should be avoided for emergency intubations in patients predisposed to bacterial endocarditis or that antibiotic prophylaxis should be considered when NT intubation in such patients is the route of choice. ANTIBIOTIC PROPHYLAXIS FOR SURGERY As with antibiotic prophylaxis in patients with valvular heart disease, the benefit of a reduced incidence of postoperative infections must be weighed against the risks of antibiotic administration, which include allergic and toxic reactions, promotion of antibiotic-resistant strains of bacteria, and superinfection. Antibiotic prophylaxis is therefore recommended only for procedures with high infection rates, for surgeries involving the implantation of prosthetic material, and for surgeries or patients in whom infections are likely to be serious.',28 The choice of an appropriate regimen should include consideration of the most likely offending organisms as well as cost. For example, third-generation cephalosporins, such as cefotaxime, ceftriaxone, cefoperazone, ceftazidime, or ceftizoxime, should generally be avoided because they are expensive, have low activity against staphylococci, and their popular use promotes emergence of bacterial resistance to this class of antibiotics. With most prophylactic regimens a single dose given just prior to the procedure is adequate to provide prophylaxis.2 Short-acting drugs, such as cefoxitin, may require repeat dosing during longer procedures, and major blood loss and fluid resuscitation during the procedure may lower serum drug levels, necessitating repeat dosing.I6 A summary of suggested antibiotics for different surgical procedures is provided in Table 3. Routine antibiotic prophylaxis is not recommended for cardiac catheterization, gastrointestinal endoscopy (except endoscopic retrograde cholangiopancreatography (ERCP"), herniorrhaphy, varicose vein surgery, most plastic surgery, dental extractions, or breast surgery? MONOAMINE OXIDASE INHIBITORS Patients presenting for surgery may be under treatment for a variety of affective disorders, including depression. One class of antidepressant medications, monoamine oxidase (MAO) inhibitors, presents anesthesiologists with a treatment dilemma. Should MA0 inhibitors be routinely discontinued preoperatively? If so, how long before surgery should withdrawal of the medication be undertaken? MA0 is the principle intraneuronal enzyme responsible for the oxidative deamination of amine neurotransmitters, such as dopamine, norepinephrine, epinephrine, and serotonin. MA0 in intraneuronal tissue plays a key role in regulation of the monoamine content within the nervous system whereas MA0 in other tissues performs a defensive function in inactivating circulating monoamines. Monoamine oxidase in hepatic tissue, for example, appears to form a first line of defense against monoamines absorbed from foods, which could otherwise produce an indirect sympathomimetic response resulting in precipitous elevations in blood pressure. MA0 inhibitors are a heterogenous group of

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Table 3. ANTIBIOTIC PROPHYLAXIS IN OUTPATIENT SURGICAL PROCEDURES Operation

Orthopedic: total joint, internal fracture fixation2* Ophthalmologic

Common Pathogens

Wound infection

PID

=

Adult Dose

S. aureus, S epidermidis

Cefazolin Vancomycin

1-2 g IV 1 g IV

S. aureus, S. epidermidis, streptococcus, enteric gramnegative bacilli, Pseudomonas S.aureus, streptococcus, oral anaerobes

Gentarnycin Tobramycin Neomycin-gramicidinpolymyxin B Cefazolin

Eye drops topically over 2 to 24 hours

Cefazolin Clindamycin +_ gentamycin

1-2 g IV 600-900 mg IV 1.5 mg/kg IV

Only on high-risk

1-2 g IV

Head and Neck: entering the oral cavity, nose or pharynx6z Enteric gram-negative Abdominal: bacilli, gramgastroduodenal positive cocci Enteric gram-negative Abdominal: bacilli, enterococci, biliary tract clostridia Enteric gram-negative Abdominal: bacilli. anaerobes colorectal Gynecologic and obstetric: aboFtion3'

Recommended Antibiotics

procedures: cefazolin Only on high-risk procedures: cefazolin

1-2 g IV

Oral: neomycin and erythromycin base; parenteral: cefoxitin or cefotetan Enteric gram-negative First trimester, high risk anaerobes, Group only (i.e.,patients B streptococcus, with PID) enterococci Penicillin G or doxycycline Second trimester: cefazolin S.aureus, Group A Cefazolin streptococcus, clostridia

1-2 g IV

1-2 g IV 1 million units IV 300 mg PO

1 g IV 1-2 g IV every 8

hours

pelvic inflammatory disease.

drugs whose common action is to inactivate MAO, an enzyme distributed widely in the body. Drugs that inhibit MA0 include isocarboxazide, phenelzine, and tranylcypromine (Table 4). Therapy with MA0 inhibitors leads to accumulation of amine neurotransmitters in presynaptic terminals in neuronal tissue as well as in hepatic and gastrointestinal tissues. In addition, MA0 inhibitors cause accumulation of a false neurotransmitter, octopamine, in presynaptic sympathetic nerve terminals, which is a far less potent vasoconstrictor than other neurotransmitters released from nerve terminals.58Thus, patients on MA0 inhibitors may exhibit exaggerated orthostatic hypotension in response to stimuli that normally only cause a small decline in blood pressure. Because of the presynaptic accumulation of neurotransmitters subject to breakdown by MAO, patients on MA0 inhibitors can exhibit augmented responses to administration of indirect-acting sympathomimetic drugs, such as

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Table 4. M A 0 INHIBITORS

Reversible M A 0 inhibitors (Pharmacologic effects gone in about 24 hours) Irreversible M A 0 inhibitors (Pharmacologic effects may last u p to 2 weeks after drug is discontinued)

Generic Name

Trade Name

Tranylcypromine

Parnate/SmithKline (Philadelphia, PA)

lsocarboxazid Phenelzine Pargyline Deprenyl (selegiline hydrochloride)

MarplanlRoche (Nutley, NJ) NardillParke-Davis (Morris Plains, NJ)

Eutonyl, Eutron/Abbott (Abbott Park, IL)

Eldepryl (Somerset,Tampa, FL)

ephedrine and dopamine, which cause release of preformed endogenous vasoconstrictors. When vasoactive medications are needed, the use of direct-acting drugs, such as methoxamine, is therefore 64 The actions of some exogenously administered catecholamines (epinephrine, norepinephrine, isoproterenol, methoxamine) appear to be affected less by MA0 inhibitors, probably because catechol-0-methyltransferase (COMT) and neuronal uptake in part offset the accumulation of these drugs in the absence of MAO. MA0 inhibitors are not specific for monoamine oxidase, and may inhibit the metabolic degradation of a wide variety of drugs. The effects of MA0 inhibitors on enzymes in the liver and gastrointestinal tract lead to predictable side effects; problematic effects of these drugs include hepatotoxicity and peripheral neuropathy. The ingestion of tyramine-containing foods may lead to hypertensive crisis in patients taking MA0 inhibitors because tyramine is no longer deactivated in the gastrointestinal tract and it stimulates release of norepinephrine from sympathetic nerve endings. Such foods include cheese, chicken liver, chocolate, avocados, figs, broad beans, beer, and wine. Hypertension resulting from ingestion of these foods is effectively treated with phent~lamine.~~, 65 There is conjecture that MA0 inhibitors may also inhibit other hepatic enzymes and that slower metabolism of various agents may play a role in the exaggerated depressant effects of opioids and barbiturates as well as magnified effects of antihistamines, anticholinergics, and tricyclic antidepressants. Prolonged responses to succinylcholine have been reported, perhaps due to an inhibition of plasma anticholinesterase.8 Accumulation of norepinephrine in the CNS may explain the observation that animals given MA0 inhibitors have higher requirements for anesthetic volatile The administration of meperidine to patients who are taking MA0 inhibitors can result in hyperpyrexia, muscle rigidity, seizures, coma, hypotension, and respiratory depression?O,55, 64 This reaction may be due to an increase in cerebral serotonin secondary to MA0 inhibitors and potentiated by meperidine, which blocks neuronal uptake of serotonin. There is evidence from animal studies that serotonin inhibitors prevent this febrile response.64Dantrolene may be effective in treating skeletal muscle rigidity and symptoms of hypermetabolism following an overdose of an MA0 inhibitor.% The inhibition of MA0 is often irreversible or so slowly reversible that the attenuation of the effects of MA0 inhibitors depends on regeneration of this enzyme. Enzyme regeneration can take up to 2 weeks after discontinuance of irreversible MA0 inhibitors. MA0 activity rises more rapidly after discontinuation of trancypromine because this MA0 inhibitor does not bind to the enzyme irreversibly. Pharmacologic effects of trancypromine are not detectable 24 hours after the drug is discontinued.21,33, 47

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Recommendations Traditionally, anesthesiologists have been taught to discontinue MA0 inhibitors 2 to 3 weeks prior to elective surgery, although there are no controlled studies to support this recommendation. Although significant adverse drug reactions have occurred in small numbers of patients receiving MA0 inhibitors, the true incidence of these events is unknown. There are now several clinical reports indicating the safety of continuing MA0 inhibitors in the perioperative period, but the reports include only small numbers of patients. It is the current recommendation of many authors that MA0 inhibitors not be discontinued prior to surgery and that an anesthetic technique should be chosen to avoid sympathetic stimulation." General anesthesia may be preferable to regional techniques if hypotension cannot be controlled or reliably mitigated. Meperidine should be avoided in patients who are taking MA0 inhibitors. LATEX ALLERGY

Although the clinical syndrome of latex allergy was recognized as early as 1979,5l it did not become a significant problem until the late 1980s. At that time, the Centers for Disease Control published recommendations for universal precautions for prevention of viral transmission in the health care setting.*2a In response to a global shortage of gloves in 1988, hundreds of new glove factories opened abroad, resulting in a worldwide glut of gloves by 1989. Gloves produced in factories that were new to glove manufacturing were then subjected to prolonged storage; these circumstances may have resulted in products more likely to produce sensitization to latex during ~ s e . 2The ~ number of cases of anaphylactic shock during surgery and gynecologic procedures has increased since the 1980s. Currently, 8 out of 10 anaphylactic reactions occurring during surgery in children are due to latex and mucosal or serous membrane exposure to latex in sensitized patients carries a high risk of With the ubiquity of latex-containing products in the operating room, it is imperative that anesthesiologists be knowledgeable about potential hypersensitivity reactions to latex and be prepared to minimize anesthesia-related exposure to latex in the sensitized patient. Reactions to latex can be broadly classified as contact dermatitis, contact urticaria, and systemic reactions. Characteristics of these reactions are summarized in Table 5. The overall prevalence of latex allergy has not been determined, but several populations appear to be at particular risk for reactions. Healthcare workers and hospital employees may experience progressive sensitization to latex because of repeated occupational exposure. In one study, 7.4% of doctors and 5.6% of nurses of 512 surveyed hospital workers were allergic to latex.60Sixty-seven percent of latex-allergic hospital workers had a history of atopy. Monert-Vautrin et a P found that atopy and frequent exposure to latex are independent risk factors for latex allergy, which synergistically produce a latex allergy risk of 36% in individuals who have both characteristics. Certain medical populations have significant risks for latex allergy and anaphylaxis. In children with myelodysplasia or spina bifida, the incidence is as high as 28%.46Patients requiring frequent urinary catheterization may also be at risk for developing hypersensitivity to the latex present in some catheters. Bananas, avocados, and chestnuts have all been shown to cross-react with latex, and allergies to these foods have all been associated with latex allergy. Other foods implicated include apricots, celery, figs, grapes, papayas, passion

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Table 5. GLASSfFlCATlONS OF REACTIONS TO LATEX

Reaction

Presentatlon

Onset

Mechanism

Contact dermatitis Macular or vesicular Variable, peaks at 48 T-cell mediated rash confined to hours after area of skin exposure contacted 10 to 30 minutes after IgE-mediated immune Contact urticaria Wheal-and-flare response or contact reaction or pruritus, nonimrnunologic erythema f release of vesiculation histamine Systemic reaction Rhinrtis, conjunctivitis, 15 minutes to 2 hours IgE-mediated mast asthma, after induction of cell degranulation anesthesia generalized pruritus or urticaria, anaphylaxis

fruit, peaches, and pineapples.%’Finally, occupationa1 exposures to latex may predispose to latex allergy, which has been reported in gardeners, restaurant workers, cleaners, and workers in the rubber industry.2q Tests to determine latex hypersensitivity have been problematic from the standpoints of accuracy and safety. In vivo skin prick tests (SPT) or intradermal tests are difficult to standardize for antigen, and both have been reported to produce anaphylaxis. In vitro testing by enzyme-linked immunosorbent assay (ELISA) and radioallergosorbent test (RAST) can be unreliable. Both types of tests have good sensitivity @So/,), but ELISA has a low specificity (59”L). They do not distinguish between patients who are likely to experience localized reactions from those at risk for severe, life-threatening episodes. Routine preoperative testing of at-risk populations remains controversial. The efficacy of pharmncologic prophylaxis, such as the administration of steroids and HI and H2 blocking agents in patients at risk for latex allergy,.has not been established, despite case reports of uneventful surgery in pretreated patients with prior latex-induced anaphylaxis. The risk of serious untoward reactions to these medications and the monetary cost is low when compared with the significant potential morbidity and cost of treatment and sequellae of anaphylaxis. Perioperative management of the patients with possible latex allergy relies heavily on a careful history and on the provision of an essentially latex-free environment for patients a t risk. PIanning for the perioperative care of patients with latex allergy should include measures to make the maintenance of a latexfree environment straight-forward and routine. It i s useful to compile a notebook of product information regarding Iatex content of equipment and supplies used in the operating room st) that if questions arise unexpectedly relevant information is readily available. Signs to identify sensitivities can facilitate adherence to maintenance of a latex-free environment by all personnel. Identifiers on doors, beds, and charts should include a statement that the patient has latex sensitivity and should caution against the use of latex gloves or other latex-containing materials. A cart of latex-free supplies for use during the perioperative care can make the maintenance of a latex-free environment more manageable. A checklist of acceptable (”safe”) and unacceptable (“unsafe”) materials can be useful in managing patients. Anesthesia and surgical equipment that may pose some risk for the latex-allergic patient are included in Table 6, together

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Table 6. ANESTHESIA AND SURGiCAL EQUIPMENT RELEVANT TO THE CARE OF THE LATEX-ALLERGIC PATlENT Safe

Glass syringes* Oral airways Paper EKG electrodes Some oximeter probes Vinyl gloves Neoprene gloves, etc. 0, nasal cannulae Plastic disposable masks LMAs Plastic anesthesia circuits (except reservoir bag) Endotracheal tubes (Mallinckrodt, St. Louis, MO,Sheridan, Argyle, NY) Esophageal stethoscopes Tape foam, durapore, transpore, paper, tegaderm Stopcocks or unidirectional valve “Needleless” IV injection systems Surgical supplies Jackson-Pratt Drains Hernovacs Feeding tubes Silastic NG tubes

Unsafe Rubber headstraps Most toothguards Tourniquets; BP cuffs, other extremity tourniquets, penrose drains, rubber blood draw tourniquets Rubber anesthesia masks Latex (elastic) strap on plastic 0, masks Anesthesia circuit reservoir bag; plastic reservoir bags from hand ventilation sets are safe Bandaids Eschmark bandage Rubber stoppers on vials Latex injection ports on 1Vs and epidural injection ports Ventilator bellows-can be rinsed in water before use to reduce particulate latex Surgical supplies Penrose drains Red rubber catheters Red rubber NG tubes Rubber-shods or suture bolsters Rubber bands Chest tube drainage system tubing (wrap with webril) Elastoplast Fogerty catheters Ear tubes Bulb syringes

*Rubber-tipped plunger syringe systems may not be safe i f medications are no\ used immedialeiy after they are drawn into them. BP = blood pressure; LMAs = laryngeal mask airways; NG = nasogastric.

with a list of acceptable equipment and substitutes. Several specific items warrant further commentary. Gloves used during care of the latex-allergic patient should be latex-free. Several studies have shown that latex glove brands vary widely in antigenicity, and powder from latex gloves has been shown to produce symptoms due to aerosolized latex. Alternatives include neoprene gloves or styrene-butadiene block polymer gloves. Perforation of latex injection ports on N bags or tubing or the perforation of rubber stoppers on multiple-dose vials can lead to micro-embolization of latex fragments into injectable solutions and must be avoided. Covering the latex injection ports with tape prior to use serves as a reminder to inject medications only via a syringestopcock or a nonlatex-containing unidirectional valve. The rubber stoppers on multiple-dose vials can be removed or single-use ampules of drug can be substituted. There are no reports of problems from rubber-tipped plunger syringes when drugs are freshly drawn and administered, but prolonged contact of drug with the plunger may “leach” latex into the

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solution in the syringe. Glass syringes avoid the issue of latex exposure, and have been recommended by Holzman et aLw A simple measure to prevent prolonged direct skin contact with rubberbased materials in blood pressure cuffs and tourniquets is to wrap the skin under the material with soft cotton, such as Webril (Kendall, Mansfield, MD). Rubber tubing attached to a blood pressure cuff should be wrapped with cotton at the end near the patient. Finally, postanesthesia care unit nurses and floor nursing staff must be alerted so that measures to maintain a latex-free environment will be adhered to in the postoperative period. Patients with latex allergy should be encouraged to obtain and wear a medic-alert tag to notify healthcare providers of their hypersensitivity. Preoperative medication with steroids and HI and H, blockers is practiced in many centers as an additional safeguard in minimizing the risks of a serious reaction. Although probably useful, and at least nonharmful, it should be recognized that such a treatment regimen does not prevent all manifestations of anaphylaxis in other situations where potentially offensive agent must be administered to sensitized individuals. For example, use of a prophylaxis regimen consisting of 50 mg of oral prednisone, 50 mg of intravenous (IV) diphenhydramine, and 300 mg oral cimetidine reduced the severity and frequency of a response to radiocontrast dye in susceptible individuals but did not entirely prevent reactions." Thus, prophylactic medications may be helpful but do not diminish the need to provide a latex-free environment for affected individuals. Table 7 summarizes recommendations for anesthetic care for patients with latex allergy. LACTATING MOTHERS UNDERGOING ANESTHESIA Because of an increase in recent years in the popularity of breast feeding, it is now common for anesthesiologists to be faced with questions from lactating mothers. Does breast feeding after undergoing an anesthetic pose any health risks to the infant? Will any affects from intraoperatively administered drugs be seen in the baby? Should mothers avoid breast feeding their babies after anesthesia, and if so, for how long? Lactating mothers may produce 500 to 1000 cc of breast milk every 24 hours, and although the intervals between feedings vary, they usually do not exceed 6 hours during the day. A prolonged interval between feedings can lead to severe maternal discomfort if milk is not otherwise expressed. Breast feeding holds advantages for mothers and infants, including the provision of nutritional, antimicrobial, and immunologic supplementation to the infant, as well as emotional benefits to both mother and baby. Anesthesia and surgery can interfere with normal lactation and breast feeding in a number of ways. Maternal perioperative stress or malaise can lead to inhibition of lactation before and after surgeryj2 Lactation may be impaired perioperatively because of dehydration secondary to fasting, nausea, and vomiting or direct inhibition of lactation by drugs administered in the perioperative period. Drugs given in the course of anesthetic care can have persistent effects on the mother that impair her ability or desire to nurse and effects on infants via passage of drugs in the breast milk. Human milk is a suspension of fat in a protein-carbohydrate solution, with several different types of protein in breast milk theoretically capable of binding drugs and acting as transport proteins. Lipid-soluble drugs can be compartmentalized into milk lipid and water soluble drugs may be carried in the aqueous phase of breast milk. Excretion of drugs into breast milk occurs via several mechanisms, including reverse pinocytosis, carrier-mediated transport, and pas-

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Table 7. RECOMMENDATIONS FOR ANESTHETIC CARE OF THE PATIENT WITH LATEX ALLERGY Relevant Preoperative History

History of neural tube defects Patients who require chronic bladder catheterization Occupational exposure with additional history of atopy (health care, latex industry) History of allergy to balloons, gloves, glove powder, dental dams History of anaphylaxis during surgery, bladder catheterization, gynecologic procedures

Preoperative Preparation

Consider preoperative treatment with steroids, HZ blockers Suggested dosing: dexamethasone 8 mg or 0.1 mglkg IV; diphenhydramine50 mg IV; ranitidine 0.5-1 .O mgm Be sure OR staff and recovery room staff are alerted to patient’s latex allergy

Preparation of the OR

Remove latex-containing equipment and supplies from the operating room Have anesthesia ventilator bellows rinsed in water Have cart of latex-free supplies available in the room Have available medications for treatment of possible anaphylaxis: epinephrine, prednisone, histamineblocking agents Draw up medications in glass syringes or plan to draw up medications for immediate use in regular syringes Tape all latex injection ports on IV equipment to prevent injection through ports

Preparation of the Patient Before Induction

Wrap areas of skin that might contact latex with cotton, such as webril (i.e., skin in contact with BP cuffs, tourniquets, etc.)

After Surgery

Alert all personnel that the patient is latex allergic Alert signs on the patient bed regarding latex allergy may be helpful If the patient does not already possess a medic-alert tag, arrange for one to be ordered

sive diffusion. Many, if not most, drugs administered during the course of an anesthetic can cross into breast milk, with data on drug excretion in breast milk suggesting that passive diffusion is responsible for the transfer of most The dose of drug received by an infant via breast milk and the resulting plasma level reached in the infant are determined by maternal, mammary, and infant pharmacokinetics. The maternal plasma concentration of unbound drug available for diffusion into breast milk depends on factors such as dose, route, frequency of administration, plasma protein binding, volume of distribution, metabolism, and clearance. Highly lipid-soluble drugs may be concentrated in milk (i.e., morphine has a milk to plasma ratio of 2.46), but because lipid-soluble drugs are largely partitioned outside the plasma in the mother, little is available in plasma to diffuse into milk. Only 0.4% of a maternal dose of morphine is 42 Water-soluble drugs pass ultimately excreted in breast milk, for e~ample.~, freely into breast milk and are present in equal concentrations with plasma. Drugs that are protein-bound do not diffuse readily into breast milk.9 Human

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milk has a pH of 7.09, and weak acids generally achieve a lower concentration in milk than weak bases9,42 Timing of a maternal drug dose may also affect milk concentrations. Drug concentrations in milk vary over time, and trough milk levels may lag behind trough plasma concentrations? The dose of a drug delivered to an infant via breast milk is determined by both the concentration of the drug in breast milk and the volume of milk consumed. The oral bioavailability of the drug and the infant clearance of the drug are other major determinants of the infant’s plasma concentration. Infant absorption and elimination of drugs differ from adults because reduced selective permeability of the gut to drugs, delayed gastric emptying, and reduced amounts of bile salts can lead to a bioavailability of some drugs, which approaches Hepatocyte immaturity and decreased renal clearance also may decrease drug elimination, especially in premature infants, and predispose infants to the toxic effects of drugs to which they are exposed?,42 Drugs given in the perioperative period can be broadly divided into preoperative medications, such as anxiolytics, drugs related to anesthetic management, antibiotics, and postoperative medications, such as analgesics and antiemetics. A summary of commonly used agents can be found in Table 8. Antibiotics

Of all drugs administered to nursing mothers, antibiotics have been most clearly demonstrated to have potentially significant negative effects on breastfed infants. Cutaneous reactions to antibiotics appear to be rare in neonates, but individual antibiotics have some specific and significant problems. Sulfonamides are traditionally contraindicated in nursing mothers because of the theoretical risk of kemicterus, which has never been demonstrated, and the very real threat that they will precipitate hemolytic anemia in infants with glucose-6-phosphate dehydrogenase deficiency, which has been demonstrated in several cases.37 Ampicillin is associated with oral candidiasis in nursing infants. Choramphenicol is associated with several adverse reactions in neonates. The “gray baby” syndrome, consisting of cardiovascular collapse and toxic bone marrow suppression, is dose-related and would appear unlikely in nursing infants of chloramphenicol-treated mothers because exposure is small; however, idiosyncratic bone marrow aplasia is not dose-related, and is theoretically possible after even minute exposure? Prernedications

Benzodiazepines are excreted into breast milk, with diazepam the most well-known of the group. Both diazepam and its metabolites appear in breast milk in significant quantities. Weight loss, lethargy, and electroencephalogram changes have all been reported in the breast-fed infant of a mother taking diazepam, 10 mg three times a day.37Subsequent studies have shown plasma levels in breast-fed neonates that are high enough to account for these effects and to raise the possibility of competition for hepatic conjugation, with resultant hyperbilirubinemia.= Some authors recommend that women who are nursing should not receive dia~epam.~, 42 Lorazepam and midazolam and its metabolites are excreted in breast milk in quantities that are low enough to result in insignificant absorption by infants. Histamine-2 receptor antagonists cimetidine, ranitidine, and famotidine all pass freely into breast milk, and although no adverse effects have been reported

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Table 8. DRUGS COMMONLY USED DURING ANESTHESIA AND SURGERY: EFFECTS ON BREAST-FEEDING MOTHERS AND THEIR INFANTS Reported Effect on Infant or Effect on Lactation Antibiotics Sulfonamides Ampicillin Chloramphenicol Prernedication Diazepam Lorazepam, midazolam Histamine-2 receptor agonists Cimetidine, ranitidine, famotidine Anticholinergic agents Atropine, hyoscine Glycopyrrolate 0pioids Morphine, methadone, fentanyl, sufentanil, alfentanil

Induction agents Thiopentone Propofol Etomidate, ketamine, methohexital Inhalation agents Halothane, isoflurane, enflurane, sevoflurane, desflurane Local anesthetics Lidocaine, bupivacaine

Antiemetics Metaclopramide, droperidol, ondansetron Neuromuscular Blocking Agents Cholinergic agents Neostigmine, physostigmine, edrophonium

Miscellaneous drugs Ephedrine Nonsteroidal anti-inflammatory agents

Kernicterus, hemolytic anemia in G-6-PD deficient infants Oral candidiasis Theoretical concerns regarding “gray baby” syndrome and idiosyncratic bone marrow suppression Infant weight loss, lethargy, and electroencephalogram changes No neonatal effects reported, but concerns have been raised about their effects on neonatal CNS function No neonatal effects reported. Famotidine is excreted less freely in breast milk than cimetidine or ranitidine Inhibition of lactation and theoretical concerns regarding CNS depression in neonates Effects unknown One study reports a statistically significant association between breast milk opioids and neonatal apnea, bradycardia, and cyanosis. Most studies have found opioids to be safe for use in breast-feeding patients. One report of neonatal drowiness No reported ill effects Effects unknown Halothane is excreted in breast milk but no neonatal effects have been reported. Levels with other inhalation agents have not been studied. Both found in small amounts in breast milk. Oral bioavailability is low and no neonatal effects have been reported. Antidopaminergic effects raise concerns regarding the effect on neonatal CNS, but no adverse effects have been reported. All agents pass poorly in breast milk and are very poorly absorbed in the gastrointestinal tract.

Breast-fed infants of mothers treated with neostigmine for myasthenia gravis have shown no ill effects. Specific information on other cholinergic agents is lacking. One report of irritability and interrupted sleep in a breast-fed infant Ibuprofen appears safe. Information about ketorolac is minimal. Theoretical risk of Reye’s syndrome, platelet dysfunction, acidosis, or hypoprothrombinemia in neonates.

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in nursing infants, many authors urge caution in the use of these drugs in nursing Atropine and hyoscine have an elimination half-life of 2 to 4 hours, and result in inhibition of milk production in mammals in which they have been studied: 35 the effects of glycopyrrolate are unknown. Anticholinergic drugs should probably be avoided in lactating women whenever possible. Morphine is excreted in minimal amounts in breast milk after a single dose, but repeated doses may have accumulative effects on breast-fed infants.42 Methadone has been safely used in nursing mothers on methadone programs? Fentanyl secretion into breast milk has not been reported, but its short half-life would likely lead to minimal amounts being excreted in milk despite its lipid solubility. Fentanyl also has very poor oral bioavailability, suggesting that it would be poorly absorbed by a breast-fed infant.42Sufentanil secretion in breast milk has also not been reported, but would be presumably minimal because of its short half-life. Alfentanil has been shown to be excreted, but because of its short half-life and high protein-binding, it has been shown to be safe in infants.42 It should be noted that in one study of neonatal apnea a statistically significant association was found between neonatal apneic episodes and the presence of opioids in breast milk, although neonatal plasma levels were not analyzed? Anesthetic Induction Agents

Thiopental levels in breast milk have been studied following induction doses in women undergoing cesarean section and were found to be negligible.35,42 Accumulation can occur in milk after repeated doses or infusions: and neonatal drowsiness has been reported." Propofol is found in low levels in breast milk after induction and maintenance anesthesia, and is cleared rapidly from the neonatal cir~ulation?~, 42 No information is available about methohexital, ketamine, or etomidate. lnhalational Agents

Excretion of halothane in breast milk was studied in a lactating anesthetist and were detectable in trace amounts after she had worked in the operating room for 5 hours administering halothane to patientsj2 No information is available about the excretion of isoflurane, enflurane, or desflurane in breast milk following general anesthesia. Neurornuscular Blocking Agents and Reversal Agents

Both depolarizing and nondepolarizing muscle relaxants are minimally excreted in breast milk and cannot be absorbed from the infant gastrointestinal tract.4z Some publications have raised questions about whether cholinergic agents should be used for reversal of neuromuscular blockade in nursing mothers. There are no studies documenting levels of these agents in breast milk. In one study, six infants whose mothers were treated with high-dose neostigmine for myasthenia gravis were breast fed without adverse effects." The excretion of pyridostigmine has been documented to occur only in small quantities, and when considered together with its poor absorption from the gut, it appears safe

PREOPERATIVE MANAGEMENT OF COMMON MINOR MEDICAL ISSUES

to use in breast-feeding physostigmine.

669

No data are available for edrophonium or

Local Anesthetics

Lidocaine concentrations in breast milk following IV infusion and epidural administration has been studied and found to be small. Poor oral bioavailability makes lidocaine theoretically safe to use in nursing mothers. Bupivacaine levels in breast milk after epidural bolus or infusion administration appear to be insignificant?2 Antiemetics

Data available on the excretion of metoclopromide in breast milk indicate that the amount is significant, but no adverse affects have been shown in nursing infants of mothers who received metoclopromide during deli~ery.~, 25 There is little information about the excretion of droperidol, but its long half-life suggests that it should be avoided in nursing mothers until more is known. Miscellaneous Drugs

Ephedrine passes freely into breast milk, and at least one report suggests irritability and interrupted sleep in one breast-fed infant after a maternal dose of 30 mg.9 Nonsteroidal anti-inflammatory agents related to ibuprofen have been shown to be secreted in breast milk in such small amounts that it is unlikely to be harmful to nursing infants.35Aspirin, however, is excreted in high concentrations, and because of risks of Reye's syndrome, platelet dysfunction, and hypothrombinemia in infants, should not be used in nursing mothers. Breast milk concentrations of ketorolac after oral administration are very low whereas maternal concentrations suggest almost 100% absorption from the gut. Concentrations after parenteral administration have not been studied but presumably would be similar to those measured after comparable oral dosing. Recommendations for Preoperative Preparation and Anesthetic Management

Mothers should be informed that all drugs administered to them may cross into breast milk in small quantities, and that only those with minimal risks to the infant will be used in anesthesia. If possible, the timing of operation should allow breast feeding shortly beforehand. Dehydration of the mother before surgery by prolonged fasting without IV fluids should be avoided. Premedication can safely include therapeutic doses of midazolam and opioids. HZreceptor antagonists should be avoided unless strongly indicated. Thiopental can safely be used for induction, but repeat dosing or infusion should be avoided. Propofol can safely be used for both induction and maintenance anesthesia. All muscle relaxants appear to be safe, as are all inhalational agents. Postoperative analgesia can be achieved with opioids, ibuprofen, and regional techniques using local anesthetics and epidural opioids.

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Breast feeding may resume after minor surgery within several hours with no significant risks to the baby. Some authors recommend that prior to major surgery the mother can elect to express breast milk to be saved and used to feed her baby postoperatively until she has recovered. After major surgery it is reasonable to recommend that the mother express breast milk when she is able to do so and discard the first postoperative milk.9 OUTPATIENT SURGERY IN PATIENTS WITH MALIGNANT HYPERTHERMIA SUSCEPTIBILITY OR MASSETER MUSCLE SPASM Patients with malignant hyperthermia susceptibility (MHS) or history of masseter muscle rigidity (MMR) after succinylcholine pose particular problems in the outpatient setting. Should such patients have prophylactic dantrolene therapy for MH? What special precautions should be taken with anesthetic agents and equipment? Under what circumstances should outpatient anesthesia not be undertaken? Is postoperative hospitalization needed in MH-susceptible patients, patients with history of MMR, or patients who experience MMR during anesthetic induction in the outpatient setting? Many of these issues are most appropriately addressed at the time of the preoperative visit. Epidemiology of MH and MMR The incidence of MH is about 1 in 40,000 in adults and 1 in 15,000 in children, with episodes of MH being rare under age 3, and most common between ages 3 and 30.% The male-to-female ratio of reported cases is 2.Z:l.59 MH is associated with myopathic conditions, such as Duchenne’s muscular dystrophy, myotonia congenita, and congenital muscular dystrophy; There appears to be a weaker association with strabismus.3*The mortality rate from MH approached 70% when the condition was first reported, but has declined to around 7%, probably due to greater awareness, earlier diagnoses, and effective therapy.38 Several studies have shown that MMR after succinylcholine may be an early warning sign of MH, although development of MH may be delayed minutes to hours after the episode of MMR.54Approximately 50% of children with MMR after succinylcholine test positive for MHS using the in vitro halothane-caffeine contracture test.3 The incidence of MHS in adult patients with previous MMR in one study is about 25%. Two of six patients with MHS developed acute MH after an episode of MMR, indicating that episodes of MMR in adults as well as pediatric patients are important indicators of an increased probability that the patient will develop MH.3

Features of MH and MMR Although the first reported case of MH occurred during halothane anesthesia,I7MH has been reported following use of succinylcholine and all inhalational anesthetic agents, including i~oflurane’~ and sevoflurane.’* To evaluate patients who may have a history suggestive of an aberrant response to anesthesia in the past, anesthesiologists must be familiar with the signs and symptoms of MH and MMR.

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671

The characteristics of MMR are described and discussed elsewhere in this publication. The classic features of MH include tachypnea in spontaneously breathing patients, hemodynamic lability, and tachycardia in the early phase, followed by diaphoresis, and possibly, generalized muscle rigidity. The episode may be accompanied by patient cyanosis and mottling, and hypermetabolism develops with resultant hypoxia, hypercarbia, electrolyte abnormalities, and respiratory and metabolic acidosis. Temperature elevation often occurs late, and temperatures exceeding 42°C have been reported. Ventricular arrhythmias, cardiac failure, renal and hepatic failure, rhabdomyolysis, myoglobinuria, disseminated intravascular coagulation, and neurologic injury can all complicate MH. Recrudescence has been reported hours after succinylcholine administrationJ8

Preoperative Management of Patients Susceptible to MH There are no reports to date of perioperative deaths of MH-susceptible patients if the patient was previously diagnosed with MH and the anesthesiologist was aware of that fact.%Eliciting a history of MH or of adverse experiences with anesthesia in family members is critical to the safe preparation of patients for general anesthesia. Prophylactic treatment of patients with dantrolene is controversial because pretreatment is expensive (approximately $350 for IV medication for an averagesized adult) and can be associated with muscle weakness and respiratory compromise, particularly in myopathic patients. Symptoms of weakness, dizziness, and fatigue are more pronounced in patients with MHS following prophylactic treatment with dantr0lene.6~ MH has been reported in patients following dantrolene prophylaxis, but is rare% and may not represent actual cases of MH.45 Anesthesia with nontriggering agents without prophylactic dantrolene therapy appears to be safe in patients with known MHS.3s,45 If prophylaxis is elected the patient can receive dantrolene 2.5 mg/kg IV 15 to 30 minutes prior to surgery. Oral administration of dantrolene is possible, but the regimen that offers the most consistent serum levels of drug involves giving dantrolene 5 mg/kg in 3 to 4 divided doses every 6 hours, with the last dose timed to occur 4 hours before surgery. Oral administration would necessitate either admission on the night prior to surgery or commencement of oral dosing at home preoperatively. In one study examining serum levels and. side effects of orally-administered dantrolene, 7 of 10 tested patients experienced significant side effects of drowsiness and weakness! Because many MH-susceptible patients have myopathic disease, concern has been raised about the possibility of respiratory compromise with dantrolene dosing, and it is recommended that dantrolene be administered in a monitored setting. The comparable cost of an oral prophylaxis regimen versus IV-administered dantrolene is $4 versus $350, respectively. With the additional cost of preoperative hospitalization, the cost-effectiveness of oral administration is questionable at this time despite the lower cost associated with the oral dosing of the drug itself. Preoperative sedation is an important part of the anesthetic care patients with MHS because stress by itself has been associated with episodes of MH. Benzodiazepine premedication can be started orally on the night before surgery and continued with oral administration of the sedative on the day of surgery. In small children, premedication with oral midazolam can be given on the morning of surgery. In preparation for anesthetizing the MH-susceptible patient, it is preferable

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Table 9. A SUMMARY OF DRUGS COMMONLY USED IN THE OPERATING ROOM: RELATIONSHIP TO EPISODES OF MH Potential Triggering Agents

All volatile inhalational agents: halothane,

enflurane, isoflurane, sevoflurane, desflurane Depolarizing muscle relaxants: succinylcholine,decamethonium Others: haloperidol, trimeprazine, promethazine

Safe Agents

Nitrous oxide

Barbiturates Narcotics Antipyretics Antihistamines Antibiotics Local anesthetics Nondepolarizing muscle relaxants Propranolol Droperidol Propofol

Controversial Agents

Calcium Potassium Ketamine Catecholamines Phenothiazines Etomidate

to have an anesthesia machine available for use with patients with MHS that have not been exposed to volatile anesthetic agents. When no such machine is available the vaporizers should be removed from an anesthesia machine, and the tubing, ventilator bellows, CO, absorption cannister, and reservoir bag replaced with unused components. The machine is then flushed with high-flow ~ ~10 minutes or more to eliminate residual volatile oxygen, 10 L / m i n ~ t e sfor agents: A list of safe anesthetic agents can be found in Table 9. In addition to standard intraoperative monitoring of electrocardiogram, blood pressure, and SaO,, monitoring of ETCO, concentrations are necessary to the appropriate management of any patient with MHS undergoing general anesthesia, as is temperature monitoring. Anesthetic induction can be carried out with barbiturates, propofol, narcotics, or combinations thereof, and muscle relaxation should be achieved using nondepolarizing muscle relaxants. Etomidate for use in induction in MHS patients is controversial because of evidence in pigs that it enhances the onset of MH.45There is a report of a case of MH that may have been triggered by the use of pancuronium,61and one author suggests that this may be due to the mild sympathomimetic effects of pancuronium. Vecuronium has been recommended as a safe alternative because of fewer cardiovascular side effects. Atracurium has also been shown to be safe.%Some authors raise concern about the potential triggering effects of the stress of laryngoscopy and intubation, and suggest that fiberoptic instrumentation should be used for all cases in which MH-susceptible patients are to be intubated. No case reports directly address this issue. Postoperative Planning

Should all patients with suspected or confirmed MHS be admitted postoperatively? In one retrospective study of 285 children with known MHS who underwent a total of 406 procedures, no cases of MH developed intra- or postoperatively. Ten children did develop hyperpyrexia, which was believed to be unrelated to MH, and did not receive subsequent treatment with dantro1ene.61 In one series of three patients who developed possible mild MH reactions after a nontriggering anesthetic technique, all developed fever within 5.5 hours of the

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673

end of anesthesia.Z7The longest reported period of time before development of fulminant MH following a triggering technique is 11 hours.* It appears that routine hospital admission for MHS patients following nontriggering anesthetic techniques is probably unwarranted, particularly if the patient is observed prior to discharge for a period of about 6 hours. Treatment of MH Episodes

Preoperative preparation for anesthetizing the MH-susceptible patient should include preoperative preparation to treat an acute episode of MH in the unlikely event that it should occur. Familiarity with an appropriate treatment protocol in advance will enhance the likelihood of a successful treatment outcome; treatment of MH is summarized in Table 10. A practical consideration in the treatment if MH is the logistics of administering the requisite dantrolene in an emergency situation. The IV formulation comes in 70-cc vials containing 20 Table 10. TREATMENT OF MH Remove all triggering agents Discontinue triggering anesthetic agents and conclude and treat hypermetabolism surgery ASAP. Increase gas flow rates to prevent hypoxia. Carry out endotracheal intubation if not already done and administer 100% oxygen. Hyperventilatewith nonheated gas to reduce hypercarbia and facilitate cooling. Treat hyperthermia with active cooling with chilled IV fluids, lavage of the surgical wound, bladder, rectum, and stomach with cooled irrigation fluid, and apply ice or cooling blankets to the patient’s body surface. Peritoneal lavage and cardiopulmonary bypass with cooling can be considered in extreme cases. Maintain urine output with diuretics and osmotic agents. Monitor glucose, K+,and arterial blood gases. HCO, (1-2 mg/kg), insulin, and glucose can be considered for treatment of acidosis and hyperkalemia. Volume expansion should be started. Third-space distribution of fluids in damaged muscle can be significant. Monitoring

Placement of an arterial line for frequent blood sampling. PA catheter or CVP is usually unwarranted. Urinary catheterization is necessary to monitor urine output and watch for myoglobinuria.

Pharmacologic treatment

Begin dantrolene 2.5 mg/kg IV in repeated doses up to 10 mg/kg. Treat definitively and treat early. Continue dantrolene after abatement of the acute episode, 1 mg/kg IV every 6 hours, to be gradually tapered over 24 to 72 hours. Treat other complications symptomatically. Lidocaine and procainamide have been useful for treatment of ventricular arrhythmias. Note that calcium administration for treatment of hyperkalemia is contraindicated

CVP

=

central venous pressure; PA

=

pulmonary artery.

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mg of dantrolene, 3.0 g of mannitol, and sodium hydroxide to raise the pH to 9.5 when the vial is reconstituted with 60 cc of sterile water. The solution must be mixed in sterile water, and is v e y dificult to dissolve. For a 70-kg adult, the dose (2.5 mg/kg) is 520 cc of dantrolene over 5 minutes. This is the mean dose required to reverse unequivocal or probable MH without sequelae in a multicenter study.39 The mixing of this much dantrolene will require the full time efforts of three or four people, and treatment of an episode of MH will require commandeering many extra personnel. After an acute episode of MH, ICU monitoring is indicated for at least 24 hours because of the possibility of recruds~ence.~~, 54 MH Testing There are no absolute indications for muscle biopsy and testing, but general guidelines have been suggested and are summarized in Table 11. Recent advances in genomic studies may aid in the development of a test involving the identification of chromosomal markers for MH. At the present time, however, the caffeine-halothane contracture test is considered the ”gold standard” for determining MHS, with a sensitivity of 100% and specificity of 78%.41Reports of false-negative tests in patients with fulminant MH episodes have occurred, and a negative test does not therefore support the use of triggering anesthetic techniques in those patients who have had episodes of classic MH.4’ Testing for MHS is useful because positive results identify reliably those patients and families who are MH-susceptible. In patients with questionable histories, the test is reasonable to identify patients and families who are probably not MH-susceptible and who might otherwise have difficulty obtaining medical insurance coverage or might be unfairly disqualified from certain occupations, such as military service.” 41 The caffeine-halothane contracture test involves using a fresh muscle sample and measuring the contracture response to an electrical stimulus before and after exposure to halothane and combined halothane and caffeine. Strict criteria have been established for testing, requiring 500 mg of muscle harvested from the vastus muscles of the leg or rectus muscles of the abdomen. Stretching of the harvested muscle must be avoided, and testing must occur within 5 hours

Table 11. INDICATIONS FOR MUSCLE BIOPSY AND TESTING IN MH Subjects who whould be considered for MHS testing

Patients with possible MH reactions or suggestive signs, such as MMR, elevated CPK, or myoglobinuria after general anesthesia with triggering agents Patients with suspected myopathy Siblings and close relatives of an MH-susceptible patient Only one parent of a patient with MHS if the first parent tests positive The second parent of a patient with MHS only if the first parent tests negative

Subjects who do not need MHS testing

Patients with full-blown clinical MH

CPK

=

creatinine phosphokinase.

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675

of excision. Anesthesia for muscle biopsy should avoid triggering techniques, and patients should not be pretreated with dantrolene. Avoidance of calciumchannel blocking agents during the surgery is rec~rnmended.~~ The amount of muscle required makes the test inappropriate to carry out in small (preschoolaged) children, as a child should have a lean body mass of more than 20 kg prior to muscle biopsy.38A list of centers complying with the standardization protocol for the caffeine-halothane contracture test follows this article in an appendi~.~" In general, the cost of testing is not covered by health insurance carriers. The Malignant Hyperthermia Association of the United States staffs a hotline 24 hours a day that is able to advise and prepare medical personnel regarding questions of diagnosis and treatment of MH. The telephone number is 203-847-0407.

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48. Miller RD, may WL, Eger E I The effects of alpha-methyldopa, reserpine, guanethidine, and iproniazid on minimum alveolar anesthestic requirement (MAC). Anesthesiology 29:115>1158, 1968 49. Moneret-Vautrin DA, Laxenaire MC, Bavoux E: Allergic shock to latex and ethylene oxide during surgery for spina bifida. Anesthesiology 73:556-558, 1990 50. Moneret-Vautrin DA, Beaudouin E, Widmer S, et a1 Prospective study of risk factors in natural rubber latex hypersensitivity. J Allergy Clin Immunol92:668-677, 1993 51. Nutter A F Contact urticaria to rubber. Br J Dermatol 101:597-598,1979 52. Ownby DR, Tomlanovich M, Sammons N, et al: Anaphylaxis associated with latex allergy during barium enema examinations. Am J Roentgen01 156:903-908,1991 53. Patrick MJ, Tilstone WJ, Reavey P: Diazepam and breast-feeding. Lancet 1:542-543, 1972 54. Ranklev-Twetman E: Malignant hyperthermia: The clinical syndrome. Acta Anaesth Belg 41:79-82, 1990 55. Rogers KJ: Role of brain monoamines in the interaction between pethidine and tranylcypromine. Eur J Pharmacol 14:8&88, 1971 56. Schwarz RE, Lowe DA, Stayer SA, et al: Bacterial endocarditis prophylaxis: What is recommended and what is practiced? J Clin Anesth 6 5 9 , 1994 57. Setlock MA, Kelly KJ: Anaphylaxis on introduction of anesthesia associated with latex allergy [abstract]. Anesthesiology 73A1043, 1991 58. Stoelting RK: Drugs used in the treatment of psychiatric disease. In Stoelting RK (ed): Pharmacology and Physiology in Anesthetic Practice. Philadelphia, JB Lippincott, 1987, pp 359-364 59. Strazis KP, Fox A W Malignant hyperthermia: A review of published cases. Anesth Analg 77297-304, 1993 60. Turjanmaa K Incidence of immediate allergy to latex gloves in hospital personnel. Contact Dermatitis 17:270-275, 1987 61. Waterman PM, Albin MS, Brian-Smith R Malignant hyperthermia: A case report. Anesth Analg 59220-221, 1980 62. Weber RS,Raad I, Fransenthaler R, et al: Ampicillin-subactim vs clindamycin in head and neck oncologic surgery: The need for gram-negative coverage. Arch Otolaryngol Head Neck Surg 118:1159-1163, 1992 63. Wedel DJ, Quinlan JG, Iaizzo P A Clinical effects of intravenously administered dantrolene. Mayo Clin Proc 70241-246, 1995 64. Wells EG, Bjorksten A R Monoamine oxidase inhibitors revisited: A review article. Can J Anaesth 36364-74, 1989 65. Wood M, Wood A: Drugs and Anesthesia: Pharmacology for Anesthesiologists. Baltimore, Williams & Wilkins, 1982, pp 627-630 66. Yentis SM, Levine MF, Hartley EJ: Should all children with suspected or confirmed malignant hyperthermia susceptibility be admitted after surgery? A ten year review. Anesth Analg 75:345-350, 1992

Address reprint requests to Gail A. Van Norman, MD Department of Anesthesiology University of Washington Box 356540 Seattle, WA 98195

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Appendix CENTERS COMPLYING WITH THE STANDARDIZATION PROTOCOL FOR THE CAFFEINE-HALOTHANE CONTRACTURE TEST

Bowman Gray School of Medicine Winston-Salem, NC 27157 Thomas E. Nelson, PhD

Mayo Clinic Rochester, MN 55901 Denise Wedel, MD

Cleveland Clinic Foundation Cleveland, OH 44106 Glenn E. DeBoer, MD Hiroshi Mitsumoto, MD

University of California Davis, CA 95616 Gerald Gronert, MD

Hahnemann University Philadelphia, PA 19102 Henry Rosenberg, MD University of Massachusetts Worcester, MA 01605 Barbara Waud, MD University of Minnesota Minneapolis, MN 55455 Paul Iaizzo, PhD Northwestern University Chicago, IL 60611 Steven Hall, MD Silas Glisson, PhD

University of California Los Angeles, CA 90024 Jordan Miller, MD Uniformed Services University of Health Sciences Bethesda, MD 22014 Sheila Muldoon, MD University of Nebraska Omaha, NE 68105-1065 Dennis Landers, MD, PhD University of South Florida Tampa, FL 33612 Julius Bowie, MD