SECTION X. Other Conditions
A Allergic Reactions and Hypersensitivity
DEFINITION
In some cases, the immune response to antigen is greatly exaggerated, a situation referred to as hypersensitivity. Anaphylaxis is a life-threatening response that a sensitized person develops within minutes after administration of a specific antigen. Hypersensitivity reactions are classified as types I, II, III, and IV.
TYPE I HYPERSENSITIVITY
Type I hypersensitivity is a rapidly developing reaction that results from antigen-antibody interaction in an individual who has been previously exposed and sensitized to the antigen. The responsible antigen, referred to as an allergen, reacts with specific IgE antibodies on tissue mast cells and circulating basophils to trigger mediator release and an allergic response. A key mediator of allergic symptoms is histamine, which is described in the following section. Chemically, allergens are usually proteins, and a multitude of environmental factors, including grass, pollen, dust, mites, molds, and animal dander, can generate type I hypersensitivity reactions.
Histamine
• Histamine is a basic amine stored in granules within mast cells and basophils and secreted when allergen interacts with membrane-bound IgE or when complement components C3a and C5a interact with specific membrane receptors.
• Histamine produces symptoms of allergic reactions by acting on H1- or H2-receptors on target cells.
• The main actions of histamine in humans (via the receptors involved) are:
• Vasodilatation (H 1)
• Increased vascular permeability (H 1 and possibly H 2)
• Contraction of most smooth muscle other than that of blood vessels (H 1)
• Cardiac stimulation (H 2)
• Stimulation of gastric secretion (H 2)
• Histamine causes the cutaneous “triple response”: erythema from local vasodilatation, wheal from increased vascular permeability and protein and fluid extravasation, and flare from an “axon” reflex in sensory nerves that releases a peptide mediator.
• The pathophysiologic effects of histamine can be blocked by H 1 receptor antagonists (diphenhydramine, hydroxyzine, cyclizine, loratidine) and H 2 receptor antagonists (cimetidine, ranitidine, famotidine).
CLINICAL MANIFESTATIONS
Allergic reactions present with symptoms such as rhinitis, conjunctivitis, urticaria, pruritis, and, possibly, anaphylaxis. The term anaphylaxis refers to a severe, generalized, immediate hypersensitivity reaction that includes pruritus, urticaria, angioedema (especially laryngeal edema), hypotension, wheezing and bronchospasm, and direct cardiac effects, including arrhythmias. A shocklike state can develop from hypotension secondary to systemic vasodilatation and extravasation of protein and fluid. Clinical manifestations of an allergic reaction can occur in various combinations and usually occur within minutes of exposure to the precipitating antigen(s). In some cases, though, the onset of signs and symptoms may be delayed for an hour or longer. Signs and symptoms can be protracted and variably responsive to treatment. Biphasic anaphylaxis can also occur, in which early signs and symptoms clear, either spontaneously or after acute therapy, and symptoms reoccur several or many hours later. Generally, the severity of an anaphylactic event relates to the suddenness of its onset and to the magnitude of the challenge (i.e., the bigger the provocative stimulus, the more severe is the reaction). However, anaphylaxis can occur after exposure to minute amounts of allergen in highly sensitive individuals.
Anaphylactoid reactions are caused by mediator release from basophils, but not from mast cells, in response to a non–IgE-mediated triggering event. Such reactions present with similar clinical manifestations as those with anaphylaxis; however, it has been reported that cutaneous symptoms are more frequent and cardiovascular collapse is less frequent in patients experiencing anaphylactoid reactions versus those experiencing anaphylactic reactions.
Tryptase is a marker for mechanistic delineation of an allergic response. It is an enzyme that is released from mast cells along with histamine and other inflammatory mediators during an allergic response. A significantly elevated tryptase level (>25 mcg/L) strongly suggests an allergic mechanism. The presence of a normal tryptase level, however, does not exclude an immunologic reaction since elevated tryptase levels are not found in almost one third of anaphylactic cases. While diagnosis of anaphylaxis should not rely on a single test, the high positive predictive value of tryptase makes it useful medicolegally and for subsequent patient management.
TYPE II HYPERSENSITIVITY
Type II hypersensitivity reactions result when IgG and IgM antibodies bind to antigens on cell surfaces or extracellular tissue components such as basement membrane. The antigen-antibody reaction activates the complement cascade, causing production of C3a and C5a, which attract PMNs and macrophages, and production of the C5b5789 membrane attack complex that inserts into target cell membranes. Examples of type II hypersensitivity reactions include transfusion reactions, autoimmune hemolytic anemia, myasthenia gravis, and Goodpasture’s syndrome.
TYPE III HYPERSENSITIVITY
Type III hypersensitivity represents immune complex disease, in which antigen-antibody complexes deposit in tissues and cause injury. Normally, immune complexes are cleared by the mononuclear phagocyte system shortly after their formation. In some situations, however, immune complexes persist and deposit in tissues. Protracted infections or autoimmune processes can lead to type III reactions. The mechanism of tissue injury is similar to that in type II reactions, involving activation of complement and recruitment of phagocytes. Systemic lupus erythematosus, rheumatoid arthritis, and glomerulonephritis are examples of immune complex diseases.
TYPE IV HYPERSENSITIVITY
Type IV hypersensitivity is also referred to as delayed-type hypersensitivity. By strict definition, type IV reactions require at least 12 hours after contact with antigen. Migration of antigen-specific CD4 + lymphocytes to the reaction site is followed by cytokine release and a local inflammatory response. Contact hypersensitivity is one form of type IV reaction and occurs where skin has come into contact with antigen. Contact dermatitis and the response to poison ivy are examples of contact hypersensitivity. Another form of type IV hypersensitivity is granulomatous hypersensitivity, in which chronic infection leads to the formation of granulomas in tissues. Granulomatous diseases include tuberculosis, sarcoidosis, and Crohn’s disease.
DRUG REACTIONS
INCIDENCE
Predicting who will react adversely to a drug or combination of drugs is difficult. Fortunately, life-threatening adverse reactions to drugs and products used during anesthesia and surgery are very uncommon, with the overall incidence estimated to be 1 in every 5000 to 10,000 anesthetics.
ETIOLOGY
Adverse reactions to anesthetic agents have been found to be two thirds immune-mediated (anaphylactic reactions); the other one third was classified as anaphylactoid reactions. Of anesthetic drugs that triggered anaphylactic reactions, neuromuscular blocking agents (NMBAs) do so most frequently. Anaphylactic and anaphylactoid reactions occurred more frequently in female patients, which is thought to be due to chemical epitopes that NMBAs and many cosmetics have in common. This observation may also explain why many patients generate an allergic response to NMBAs on their first exposure to the drug.
Persons who have an increased allergic tendency are termed atopic and exhibit a genetic predisposition to such events. Atopic patients frequently present with some history of hay fever, rhinitis, asthma, or food or drug allergy. A generalized history of allergy does not necessarily predispose a patient to anaphylactic or anaphylactoid reactions to anesthetic drugs. If a patient has a history of sensitivity to a particular anesthetic drug, such as a muscle relaxant, that individual may well be at increased risk for allergic responses to other agents in that class.
Anaphylactic reactions to local anesthetics are uncommon; ester local anesthetics are more likely than amide agents to elicit an allergic response. Ester local anesthetic metabolites, such as para-aminobenzoic acid, have been identified to be responsible for this higher incidence of allergic response. Local anesthetic solutions containing methylparaben and propylparaben as preservatives may induce allergic responses in susceptible individuals. Thus, administration of preservative-free local anesthetic solutions may reduce the likelihood of an allergic response. Recent theories suggest that allergies to various antioxidants and certain sulfite components may be responsible for some degree of allergic reactions to local anesthetic preparations.
Avoiding known causal agents (particularly those that induce histamine release), combined with careful selection and application of additional drugs, can reduce risk of adverse reactions. A thorough history and discussion with the patient or the patient’s guardian can usually reveal the potential for untoward drug effects and alert the anesthesia provider to avoid suspicious agents. Patients frequently mistake drug sensitivity or an unpleasant response for an allergy. This is especially true with local anesthetic solutions containing epinephrine or administered with opioids. Careful investigation and cautious interviewing techniques are usually beneficial in clarifying these questionable areas. Reviewing past procedural notes and anesthesia records, and possible consultation with an allergist when appropriate, can further help in determining situational specifics and facilitate appropriate planning. The administration of H 1– and H 2-receptor antagonists pre-emptively may prevent allergic reactions in many cases when a known or suspected sensitivity is present.
TREATMENT
Patients who do not appear to have life-threatening symptoms on initial presentation may nonetheless progress to life-threatening anaphylaxis. Early administration of medications may be beneficial in halting this progression. Standard therapy for non–life-threatening situations includes the following:
1. Epinephrine: The initial adult dose may range from 100 to 500 mcg subcutaneously or intramuscularly. This dose may be repeated every 10 to 15 minutes as needed up to a maximum of 1 mg per total dose. The dose in children is 10 mcg/kg up to a maximum of 500 mcg per total dose. The total dose can be repeated every 15 minutes for two doses and then every 4 hours as needed. There is evidence that more rapid systemic absorption and higher peak plasma levels occur after intramuscular administration than after subcutaneous administration.
2. Diphenhydramine: 1 to 2 mg/kg or 25 to 50 mg/dose (parenterally).
3. Glucocorticoids may also be administered. However, the efficacy of glucocorticoids in treating acute anaphylaxis or in reducing a late anaphylactic reaction has not been clearly established.
Life-threatening anaphylaxis requires immediate administration of epinephrine and may require other immediate measures for support of cardiorespiratory status. Cardiopulmonary resuscitation (CPR) should be instituted if there is loss of circulation or respiration. Oxygen (100%) should be administered and the airway secured. Hypotension should be addressed by administration of vasopressors and infusions of large volumes of intravenous fluids and/or colloids to compensate for peripheral vasodilation and intravascular fluid loss. Bronchospasm should be treated with inhaled bronchodilators, theophylline, or both.
Patients experiencing anaphylaxis may not always respond adequately to one injection of epinephrine. Epinephrine has a rapid onset, but a short duration, of action. At the same time, mediator release from mast cells and basophils may be prolonged, producing biphasic or protracted anaphylaxis. Moreover, patients who are taking β‑adrenergic blocking agents may not respond to epinephrine and may require substantial fluid replacement. For patients with life-threatening anaphylaxis who are poorly responsive to initial doses of epinephrine, more frequent or higher doses may be required. If the patient does not respond to subcutaneous epinephrine, intravenous administration of epinephrine must be initiated. Bolus doses of 50 to 100 mcg should be titrated to effect. Epinephrine infusion should initially be administered at 1 mcg/min, which can be increased to 2 to 10 mcg/min. For refractory cardiorespiratory arrest in children, the initial intravenous epinephrine dose is 10 mcg/kg. Subsequent doses of 100 mcg/kg can be administered every 3 to 5 minutes, and, if the patient is still refractory, the dose may be increased to 200 mcg/kg.
A good clinical response represents resolution of the allergic reaction. If there is partial resolution or concern about biphasic anaphylaxis, continuous monitoring is suggested. Additional history might reveal previous episodes of anaphylaxis or asthma. Antihistamines may be useful in the treatment of anaphylaxis, particularly for symptoms of urticaria and angioedema. An H 1 receptor antagonist, alone or in combination with an H 2 receptor antagonist, may be useful in reversing hypotension refractory to epinephrine and intravascular fluid replacement. Glucocorticoids, such as 200 mg of intravenous hydrocortisone, may reduce the risk of recurring or protracted anaphylaxis, although direct clinical evidence for this has not been clearly established.
TRANSFUSION REACTIONS
INCIDENCE
Because of advances in technological capabilities and quality-control practices, blood transfusion reactions are, fortunately, not a common occurrence. The relative risk of an allergic transfusion reaction of mild severity (urticaria and pruritus) is approximately 1 in 500, whereas a fatal hemolytic reaction occurs in approximately 1 in 250,000 to 600,000 transfusions administered nationally.
ETIOLOGY
The mechanism responsible for most transfusion reactions involves ABO incompatibility. Transfusion of incompatible blood type causes recipient antibodies to react with donor red blood cells, causing their destruction and the potential for significant consequences. Disseminated intravascular coagulation, renal failure, and death are not uncommon following this type of reaction. Since the most common cause for a major hemolytic transfusion reaction is human error, it should never be assumed that another person is solely responsible for checking blood that one is preparing to administer to a patient.
Transfusion reactions are frequently masked, or at least delayed appreciably, during anesthesia. Hallmark symptoms of cardiovascular instability, such as hypotension, as well as fever, hemoglobinuria, and bleeding diathesis are indicative of a transfusion incompatibility and should be immediately treated.
LATEX ALLERGY
Allergies to latex-containing products continue to be a source of significant problems for specific populations. Healthcare workers and certain patients, particularly those with congenital neural tube defects and those who have undergone multiple surgical procedures, have shown particular sensitivity to latex-containing products.
It has been estimated that approximately 0.8% of the general population has some form of sensitivity to latex. Atopic persons who react with skin dermatitis and who are allergic to certain fruits (particularly kiwi and bananas) should be further evaluated for latex allergy. Healthcare workers and patients who experience frequent exposure to devices and products that contain latex also exhibit such allergic reactions. The incidence of healthcare worker allergy to latex-containing products ranges between 8% and 25%. The most frequent clinical manifestations of latex reactions include some form of contact dermatitis, type I hypersensitivity reaction with the potential for anaphylaxis, or type IV hypersensitivity reaction.
Preventive procedures and recommended protocols have been established for the management of latex allergies that can have significant anaphylactic consequences. The incidence of latex allergies has increased proportionately with the 10-fold increase in medical glove usage to accommodate universal precautions and barrier protection during anesthesia, surgery, and obstetric care. Using gloves that do not contain latex (e.g., gloves processed from polyvinyl or neoprene) can prevent this source of latex exposure. While skin prick, patch testing, and radioallergosorbent tests for latex allergy are available, all present various challenges in qualifying a conclusive diagnosis. The American Association of Nurse Anesthetists (AANA) Latex Protocol provides a detailed plan to avoid and treat latex allergic responses (See Appendix 3).
B Geriatrics
DEFINITION
Geriatrics is the branch of medicine that deals with the physiologic effects of aging and the diagnosis and treatment of persons who are 65 years of age or older. In 2006, nearly 37.3 million persons were older than 65 years of age and made up 12.4% of the general population. Persons reaching age 65 have an average life expectancy of an additional 18.4 years (19.8 years for females and 16.8 years for males).
ETIOLOGY
Human organ function shows a linear decline with age. The rate constant for this decline is slightly less than 1% per year of the functional capacity present at age 30 years. As a consequence, a 70-year-old geriatric patient may have a 40% decrease in the function of any specific organ compared with that present at the age of 30 years.
CLINICAL MANIFESTATIONS
Clinical manifestations include an increased prevalence of age-related, concomitant disease (hypertension, renal disease, atherosclerosis, myocardial infarction, chronic obstructive pulmonary disease, cardiomegaly, diabetes, liver disease, congestive heart failure, angina, cerebrovascular accident). The commonly age-related anatomic and physiologic changes that occur are listed in the following box.
Common Age-Related Anatomic and Physiologic Changes
General Changes
• Decreased organ function
• Increased body fat
• Decreased blood volume
• Loss of protective reflexes
• Decreased ability to retain body heat
• Decreased lean body mass
• Decreased skin elasticity
• Collagen loss
• Decreased intracellular water
Cardiovascular Changes
• Impaired pump function
• Prolonged circulation time
• Myocardial fiber atrophy
• Hypertension
• Impaired cardiac adrenergic receptor quality
• Increased peripheral vascular resistance
• Decreased cardiac output
• Decreased organ perfusion
• Left ventricular hypertrophy
• Coronary artery disease
Pulmonary Changes
• Increased lung compliance
• Decreased forced expiratory volume
• Increased closing volume
• Decreased resting arterial oxygen tension
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