Anesthesia and Immunity

Anesthesia and Immunity

• Anesthesia's effects on the immune system have been under investigation for over 30 years.
• There is no conclusive understanding of how anesthetics affect immune function.
• Anesthesia, given during surgery, impacts immune function.
• Immune dysfunction after anesthesia may lead to increased perioperative complications such as infection, poor transplant outcomes, and cancer recurrence.

Innate vs Adaptive Immunity

• Innate immunity is a primitive defense mechanism involving intact skin and mucous membranes.
• Perianesthesia procedures like CL insertion, intubation, and surgical incisions can compromise these barriers.
• Neutrophils, macrophages, and natural killer cells are key players.
• Inflammation is initiated by innate immune cells.
• Histamine release leads to vasodilation, increased blood flow, and capillary permeability.
• The result of inflammation is the destruction of microbes, tissue repair, and activation of adaptive immunity.
• Adaptive immunity has characteristics: delay, specificity and memory.
• CD4 helper lymphocytes use T-cell receptors to recognize antigens.
• Cellular immunity is activated by CD8 cells that target infected body cells, defending against bacteria and viruses.
• B lymphocytes promote humoral immunity, secreting antibodies into the plasma that attack microbes.

Stress Response

• The perianesthesia period can trigger a neurohormonal stress response, including fear, anxiety, and surgical pain.
• The hypothalamus and SNS are activated, which increases plasma levels of cortisol and catecholamines.
• Cortisol enters immune cells and binds to receptor molecules, causing global immune suppression.
• Catecholamines impair immune function by interacting with alpha and beta receptors and shifting T helper cell subtypes, diminishing effective cellular immune response.

Associated Risks

• Elevated perioperative cortisol and catecholamine levels cause a catabolic state, resulting in hyperglycemia.
• Protein, fat, and starch are metabolized into glucose molecules, leading to hyperglycemia.
• Elevated glucose activates endothelial cells lining blood vessels, decreasing lymphocyte function and immune cell movement to infection sites.
• Large surgeries can cause hypothermia, fluid shifts, and affect vascular perfusion.
• Mild hypothermia during surgery may cause vasoconstriction.
• Tissue hypoxia impairs neutrophil-mediated oxidative killing, inhibiting collagen deposition and delaying wound healing.
• Hypothermia impairs the function of immune cells.

Inflammatory and Allergic Risks

• Surgical tissue damage causes a localized inflammatory response.
• Proinflammatory biochemicals are activated by cell damage, including prostaglandin E2 and interleukin 6 (IL-6).
• Surgical intervention-related inflammation relates to the invasiveness of the procedure.
• Depression of adaptive immunity is proportional to the level of innate immune system activation.

Anesthetic Agents: Opioids

• Opioid effects on immune function have conflicting reports.
• Mu opioid receptors in the heart and autonomic pathways activate the parasympathetic (vagal) response, reducing sympathetic outflow, impacting immune function.
• Vagal activation through acetylcholine can impair innate immune cell-driven inflammation.
• Pain reduction from opioids lowers circulating catecholamine and cortisol levels.
• Effective pain management is vital for autonomic balance and immune protection.

Anesthesia Types

• Neuraxial anesthesia reduces the stress response compared to general anesthesia.
• Neuraxial anesthesia reduces postoperative pain, a potent stress response activator and immunosuppressor.
• Neuraxial anesthesia may prevent or lessen perioperative immune dysfunction.

Improving Outcomes

• Interventions can reduce metabolic stress from surgery.
• Manage pain using regional anesthesia and analgesia when possible.
• Prescribe drugs to limit inflammation (COX inhibitors, Decadron).
• Avoid hyperglycemia in patients susceptible to immune suppression.
• Prevent hypothermia.
• Adequate tissue perfusion and oxygen/nutrient delivery for circulating immune cells are necessary.
• Maintain the arterial pressure based on patient history.
• Maintain oxygen saturation to maintain arterial values with normal range.
• Use minimally invasive surgical approaches.
• Prescribe antibiotics before incision where possible.
• Reduce invasive instrumentation.
• Use aseptic techniques.
• Avoid blood transfusions in at-risk patients.
• Surgical Invasiveness = Immune depression in perioperative period.
• Transient immune function depression unlikely to cause complications in healthy populations but may increase risk in high-risk populations undergoing major surgery.

Hypersensitivity

• This is an exaggerated immune response to an antigen.
• Type I is an antigen-antibody reaction in previously sensitized individuals.
• Type II involves IgG and IgM antibodies binding to cellular antigens, triggering complement activation.
• Type III involves antigen-antibody complex deposition in tissues, causing injury.
• Type IV involves delayed hypersensitivity (e.g., contact dermatitis), appearing 12+ hours after contact.
• Type V involves autoantibodies binding to stimulate target cells.

Immune Reactions

• Alloimmunity is a response against tissues from the same species.
  • Can result in transient neonatal disease, transfusion reactions, and transplant graft failure.
• Autoimmunity is an abnormal response to self-antigens, causing self-antibody production and tissue damage due to innate/adaptive immune system dysfunction.
  • Chronic inflammation, seen more commonly in women, is a classic sign.
  • 80 types of autoimmune disorders include Grave's Disease, Hashimoto Thyroiditis, Multiple Sclerosis, Rheumatoid Arthritis, SLE, Type I Diabetes.
• Drug reactions are life-threatening but uncommon during anesthesia/surgery (1 in 5,000-10,000 anesthetics).
  • Allergy risk may vary by region.
  • Immune-mediated reactions cause 63% of perioperative hypersensitivity reactions.

Allergic Reactions

• Ester local anesthetics have a higher chance of triggering allergies than amide agents.
• Ester LA metabolites, such as para-aminobenzoic acid, are responsible for the allergy.
• Preservatives like methylparaben and propylparaben in LA solutions might stimulate responses.
  • Using preservative-free solutions may reduce allergy risk.
  • Adverse reactions are correlated with accidental intravascular injection or epinephrine absorption.
• "Atopic" patients are prone to allergies, indicating a genetic component.
• Prior allergy to hay fever, rhinitis, asthma, or specific foods or drugs may indicate risk.

Latex Allergy

• It is an IgE-mediated reaction to proteins in natural rubber latex (NRL) from the rubber tree Hevea Brasiliensis.
• Latex gloves, syringes, and catheters, made from NRL, can cause allergies.
• Latex allergies lead to redness/itching, asthma, and anaphylaxis.
• Early diagnosis and management are crucial.

Common Latex Containing Equipment

• Mattresses, rubber gloves, adhesive tape, urinary catheters, electrode pads, wound drains, stomach and intestinal tubes, condom urinary collection devices, protective sheets, enema tubing kits, rubber pads, fluid circulating warming blankets, hemodialysis equipment, Ambu bags, bulb syringes, elastic bandages, Ace wraps, medication vial stoppers, stethoscope tubing, Band-Aids, exam gloves, patient controlled analgesia syringes and tourniquets.
• Anesthesia equipment includes rubber masks, electrode pads, head straps, rubber tourniquets/airways, teeth protectors, bite blocks, blood pressure cuffs, breathing circuits/bags, ventilator hoses/bellows/tubes, latex cuffs, injection ports, multidose vial stoppers, suction catheters and injection ports.
• The general population has a low incidence of latex allergy around 1.0% to 6.7%.
• High-risk groups include healthcare workers (8-16%), and children with conditions requiring multiple latex exposures (24-64%).

Populations at Risk

• Workers with latex exposure
• Individuals with asthma, dermatitis, or eczema
• Patients requiring repeated bladder catheterization
• Those allergic to foods like bananas, avocados, kiwi,chestnuts
• Patients with unexplained anaphylaxis or those with multiple surgeries as children
• Women who are exposed via obstetric/gynecological procedures.

Allergies vs Exposure

• Foods which trigger latex allergies include: avocado, banana, figs, cherimoya, chestnut, eggplant, and kiwi, mango, melon, papaya, passion fruit, pineapple, potato, tomato, and wheat.
• Latex exposure occurs when products touch the skin, mucous membranes, or bloodstream.
• Airborne latex proteins exist on glove powder.
• Inhaled latex-containing dust can also cause allergic reactions.
• Type I causes immediate hypersensitivity.
• Type IV causes delayed hypersensitivity.
• Irritant contact dermatitis is a non-allergic reaction.
• Latex allergy management includes identification, and patient/healthcare worker protection.
• A multidisciplinary committee is needed with representatives across medical departments. The focus should be on at-risk patient identification, higher-risk employee determination, allergy accommodation and provide employee/patient education.

Anaphylaxis and Precautions

• Successful management of high-risk patients needs early diagnosis and treatment of type I hypersensitivity.
• Preoperative assessment includes allergy history, occupation, symptoms (itchy eyes, runny nose, sneezing), asthma after latex contact, fruit allergy, and spina bifida.
• Healthcare providers should inform Type I allergy patients that they will be monitored by an allergist, need to wear an allergy bracelet and keep an epinephrine auto-injection kit.
• Non-latex safe facilities should prep procedure room night before to reduce latex particles with priority scheduling for the morning.
• All anesthesia staff need to know if a patient has an allergy.
• Latex allergy needs to be documented.
• ALL items containing latex MUST be removed from the patient care area and only non-latex gloves, catheters, IV equipment, surgical tape, tourniquets, ventilation equipment and medication containers should be used.
• Latex in syringe plungers has a low likelihood of any allergic reaction.
• Vial stoppers should only be punctured once.
• Stopcocks eliminate need to inject medications via intravenous tubing latex ports.
• Non-latex substitutes might not protect well against bloodborne pathogens.

Symptoms of Anaphylaxis

• Awake patients may report itchy eyes, generalized pruritus, shortness of breath, sneezing, wheezing, nausea/vomiting, faintness, abdominal cramping, diarrhea, and impending doom.
• Anesthetized patients may exhibit facial edema, hives (urticaria), rash, skin flushing, bronchospasm, laryngeal edema, edema, hypotension, tachycardia, and cardiac arrest.

Treatment

• Discontinue latex products + suspected cause.
• Administer 100% oxygen.
• Discontinue anesthetic drugs during induction.
• Start epinephrine as soon as possible.
• Maintain fluid balance.
• Administer H1/H2 blockers to alleviate symptoms.
• Administer a corticosteroid to help prevent or control the late-phase reaction.

HIV

• More than 1.2 million people in the U.S. live with HIV, but 1 in 8 are unaware.
• Annual HIV diagnoses decreased by 19% from 2005-2014.
• It is most common in gay/bisexual men, especially young African Americans.
• The rate of HIV diagnoses was 19% lower in 2014, compared with 2005.

Transmission

• Heterosexuals and IV drug users are still at risk from HIV.
• In 2015: heterosexual contact accounted for 24% of HIV diagnoses.
• The majority of HIV diagnoses are due to heterosexuals or IV drug use.
• HIV is a common form of secondary/acquired immune deficiency, existing in two types: HIV-1 and HIV-2.
  • HIV-1 is more prevalent and causes pathology.
  • An HIV infection alters T-cell function and causes cytotoxicity which leads to CD4 cell depletion, increasing the risk of infections.

HIV: Perioperative Management Considerations

• Anesthetic plans account for underlying conditions: respiratory impairment and alterations inneuronal function/cognitive dysfunction with peripheral neuropathy.
• Environmental factors include ETOH, drug addiction, and Hepatitis C co-infections.
• Monitor side effects of antiretroviral therapy, lipodystrophy, dyslipidemia, and insulin resistance, along with the risks of atherosclerosis, coronary artery disease, and nutritional impairment.

HIV Interactions and Precautions

• Protease inhibitors used may decrease the metabolism of opioids, NSAIDs and benzodiazepines- increasing the risk of overdose.
  • Titrate with caution at reduced doses.
• Many clinicians avoid regional anesthesia to reduce the risk of unintentional needlestick injuries for the safety of staff.
• Preoperative patients exams require thorough assessment through physical, labs and imaging. - Consider medical management with adherence to antiretroviral therapy, monitor CD4 cell count and viral load. - Organisms not often pathogenic may cause harm, and meticulous control measures are crucial. - Immune compromise increases the risk of TB and varicella.
• Maintain Meticulous attention to aseptic technique
  • Anesthesia gas machines and their components need maintenance, cleaning, and disinfection with each use.
• New disposable circuits and HME filters must be used.

HIV Complications

• Infections and metabolic disorders can impair oxygenation during HIV infections.
• Pulmonary infections can impair gas exchange and create VQ mismatch.
• Chronic diarrhea leads to dehydration and hypovolemia.
• Pain syndromes, neuropathies, and muscle weakness can be issues.
• Wasting syndrome, from food absorption issues, exist, and neurologic changes such as PNS/CNS impairment occur due to effects of the disease, infections and treatment.
• Discomfort with peripheral or autonomic neuropathies affects CV stability.
• AIDS dementia affects motor and cognitive function.
• Other complications include Non-Hodgkin lymphoma, Kaposi Sarcoma and opportunistic infections: PCP, CMV, toxoplasmosis and fungus.

Pregnant Patients with HIV

• Perinatal transmission accounts for 80% of pediatric AIDS cases reported in the U.S.
• Unique challenges exist.
  • Anemia occurs in later stages.
  • Elective C-section reduces the risk of HIV transmission from mother to baby.
  • C-section complications with exaggerated results from immunosuppression.
  • Pain should be managed with perioperative pain modalities and chronic opiate/NSAID syndromes should have multimodal treatments.

Safe Practice

• All should self-protection through OSHA regulations: minimizing exposure to all blood-borne pathogens and immediate responses in cases of exposure and AANA details on infection control practices

HIV Postexposure

• In 2001 there was 57 documented cases of HIV seroconversion associated with occupational. exposure among healthcare professionals.
• Percutaneous injury from a hollow-bore needle is a common mechanism of occupational HIV transmission.
• Risk is 0.3% after percutaneous and 0.09% after mucous membrane exposures with suture needles are not implicated.
• Low risk with exposure to nonintact skin and exposure to infected fluid/tissues
• Postexposure prophylaxis (PEP) soon after occupational exposure decreases HIV infection risk.