1. Review the potential relationship between anesthetic management and immune function.

2. Examine how choice of anesthetic management might influence cancer recurrence and other long-term outcomes.

3. List the risks associated with anesthetizing a child with a URI undergoing elective surgery.

4. Discuss the clinical predictors of anesthetic complications in the pediatric patient with a URI.

5. State the risk factors for perioperative adverse respiratory events in children with URIs.

Does Anesthetic Management Affect Long-term Outcome?
Daniel I. Sessler, MD, Professor and Chair, Department of Outcomes Research, Cleveland Clinic, Cleveland, OH

Introduction: ≈25 yr ago—anesthetic mortality ≈1 in 10,000 (in relatively healthy patients coming for small operation); volatile anesthetics included halothane, enflurane, and isoflurane; often delivered by copper kettles (required accurate calculation for correct dose); automatic blood pressure cuffs unavailable; pulse oximetry not yet invented; end-tidal gas monitoring unavailable; anesthetic training less sophisticated (compared to now); available drugs were also less sophisticated; present day—anesthetic mortality ≈1 in 200,000 (anesthesia has made bigger improvements in outcome than has any other specialty)

Hypothermia: unwarmed surgical patients invariably become hypothermic; initial redistribution hypothermia occurs; unwarmed patients become increasingly hypothermic, to temperature of ≈34°C, depending on length of operation; with simple warming techniques (eg, forced air) normothermia can be maintained; surgical wound infection— detected 1 to 3 wk after surgery; never previously considered anesthetic complication; even today, surgeons do not consider wound infection anesthetic complication (instead, attributed to poor surgical technique); but hypothermic patients have 3 times greater risk for surgical wound infection and stay in hospital 20% longer; morbid myocardial outcomes—hypothermia triples risk; events typically occur 2 to 3 days after anesthesia and surgery; blood loss— also increased with hypothermia; occurs during surgery and anesthesia; related to tissue hypothermia, not core hypothermia; recent meta-analysis shows each degree of hypothermia increases blood loss by 16%; consequently, mild hypothermia significantly increases need for allogeneic transfusion (can save life, but also toxic; associated with numerous and severe immunologic complications)

Transfusion medicine: meta-analysis finds because of complications, transfusions double mortality risk; Food and Drug Administration (FDA) allows blood to be stored ≤42 days; stored blood degrades and promotes inflammatory reaction when transfused; study found difference in survival continues to accrue up to ≈6 mo; showed patients given older blood die at higher rate 5 mo after surgery; even 7 yr after surgery, substantial and statistically significant difference between patients given older blood and those given fresh blood

β-blockers: Mangano (1996) showed perioperative atenolol reduced mortality; PeriOperative ISchemic Evaluation (POISE) trial (2006) confirmed β-blockers reduce risk for nonfatal myocardial infarction (MI); trial also showed large increase in number of strokes, consequently increasing mortality; concluded that atenolol reduces risk for MI, but does so at expense of causing strokes, therefore worsening mortality (studies evaluated different populations, different drugs, and different doses); β-blockers cause long-term outcomes; Monk (2005) published study linking anesthetic depth with mortality (association only; not causal); overall mortality ≈5% in year following surgery; in patients >65 yr of age, mortality 10%; half of mortality from cancer

Potential protective effects of regional analgesia: cancer recurrence usually lethal; therefore, preventing recurrence essential; traditionally thought that localized cancer either removed completely or not (patient either cured or has relapse); now known that at time of diagnosis, no matter how early, cancer already widely disseminated (blood sample shows cancer cells; especially true during surgery); important to remove primary tumor, because peripheral tumor inhibited by removal of primary tumor; provides window of opportunity for host to manage circulating tumor cells; host defense, more than cancer surgery itself, determines recurrence; natural killer cells most important host defense for cancer (infectious analogue of neutrophils); actions by anesthesia provider in context of cancer surgery can impair natural killer cell function; three perioperative factors impair host defense, 1) cancer surgery (stress response to surgical tissue injury), 2) volatile anesthetics, and 3) opioids

Cancer surgery: Ben-Eliyahu (1999) showed that, in rats, natural killer cell function in blood and spleen decreased after surgery for ≤1 day (by 1 wk, natural killer cell function had recovered); without surgery, injection of breast cancer line resulted in relatively few tumors in lung; after surgery, “you get lots and lots of [tumors]”; stress response to surgical tissue injury impairs natural killer cell function and facilitates metastases in rats

Volatile anesthetics: halothane (and other volatile anesthetics) substantially increases lung tumor retention; impair natural killer cell function and, therefore, facilitate metastases in rats

Opioids: via central and peripheral mechanisms, impair natural killer cell function and, therefore, increase lung tumor retention (substantial increase)

Theory: regional anesthesia and analgesia reduce stress response to surgery, eliminate or reduce need for volatile anesthetics, and eliminate need for opioids; if true, this will facilitate maintaining good natural killer cell function; hypothesis—regional anesthesia and analgesia reduce risk for cancer recurrence; additional studies—study of rats that had major surgery with either general anesthesia or general anesthesia combined with spinal anesthesia showed factor of 3 difference in lung tumor retention; evidence suggests regional anesthesia and analgesia may be protective against cancer recurrence; limited human evidence in breast cancer shows women receiving general anesthesia and opioid analgesia far more likely to have cancer recurrence than those who had paravertebral analgesia combined with general anesthesia; similar data from prostate cancer patients who received either general anesthesia and opioid analgesia or epidural anesthesia combined with general anesthesia followed by epidural analgesia; results showed men given general anesthesia had higher recurrence risk

Summary: maintaining normothermia reduces infection risk by factor of 3, decreases risk for morbid myocardial outcomes by factor of 3, and reduces blood loss and allogeneic transfusion requirement; prolonged storage of red blood cells worsens outcome, causes major complications, and increases mortality (difference preserved ≤7 yr after surgery); β-blockers reduce perioperative myocardial events, but (in selected patient populations, doses, and drugs) increase risk for stroke and mortality; regional anesthesia and analgesia may reduce risk for cancer recurrence (speculative)

The Upper Respiratory Tract Infection (URI) Dilemma in Pediatric Ambulatory Anesthesia
Linda J. Mason, MD, Professor of Anesthesiology and Pediatrics, Loma Linda University School of Medicine, and Director, Pediatric Anesthesiology, Loma Linda University Medical Center, Loma Linda, CA

Decision to postpone elective surgery: must include both scientific and human/emotional considerations (eg, parents may have taken time off from work for surgery; scheduling surgery between episodes of URI challenging); risk factors include acute purulent URI, fever >38.5°C, and lower respiratory tract infection (eg, rales, rhonchi, and wheezing); parents best monitor for determining whether child has URI; important to ask parents whether child sick, whether anyone else in family sick, and whether child had contact with sick children

Noninfectious causes: allergic rhinitis (seasonal or perennial); vasomotor rhinitis (emotional [eg, crying]; temperature)

Infectious causes: viral infections—nasopharyngitis (common cold); flu syndrome (usually lower respiratory tract); laryngotracheal bronchitis (infectious croup); viral exanthems—measles; chickenpox; acute bacterial infections— streptococcal tonsillitis

Risk of anesthetizing child with URI: child <1 yr of age has decreased time to desaturation during apnea; hypoxemia, bronchospasm, and atelectasis increased with endotracheal intubation; possible increased risk for laryngospasm (Schreiner—yes; Tait and Knight—no); airway hyperreactivity exists for 6 wk after viral infection; Coté recommends postponing elective surgery in obviously ill child to avoid compound effects of systemic illness, coughing, and surgical incision

Minimizing risks: Tait (1998)—looked at use of laryngeal mask airway (LMA) compared to endotracheal intubation in children with URI scheduled for elective surgery; found risk for laryngospasm equal, but risk for bronchospasm higher in intubated group; Lakshmipathy (1996)—looked at environmental tobacco smoke as risk factor for pediatric laryngospasm; all cases occurred on emergence; higher incidence if source of passive smoke maternal; found risk 10 times greater than risk seen in normal population

Clinical predictors of anesthetic complications in ≈2000 children with URIs (Parnis, 2001): majority had intravenous (IV) induction; 40 patients did not proceed to surgery; majority of adverse events involved airway (eg, coughing, bronchospasm, upper-airway obstruction); predictors of adverse events (eg, laryngospasm, airway obstruction) include airway management (eg, orotracheal or nasotracheal intubation), parents’ belief that child has cold, child snoring, passive smoking, sputum (moist or productive cough), thiopental induction (vs propofol), and not administering neostigmine to reverse nondepolarizing muscle relaxation; factors that were not predictors of adverse events include cold in previous 6 wk and surgery canceled in previous 6 wk due to URI; concluded that children who have cold, who snore, who are passive smokers, or who have nasal congestion or productive cough have higher risk for airway complications; intubation increases risk (decreased with LMA or face mask); propofol safest induction agent; muscle relaxants should be reversed (if nondepolarizing); cancel any nonurgent surgery if patient febrile (>38.5°C), wheezing, suffers malaise, or very young (<1 yr), especially if airway instrumentation needed

Risk factors for perioperative adverse respiratory events in children with URI (Tait, 2001): younger population than in Parnis study; URI defined by any 2 symptoms (eg, rhinorrhea, sore or scratchy throat, sneezing, nasal congestion, malaise, cough, or fever >38°C) and confirmation by parent; canceled in presence of severe URI, lower respiratory tract infection, or bacterial infection; adverse events included laryngospasm, bronchospasm, breath- holding, O2 desaturation; laryngospasm and bronchospasm equal in all groups; children with active or recent URI had higher incidence of O2 desaturation and overall adverse respiratory events; also had higher incidence of severe coughing, breath-holding, and secretions that persisted for 4 wk; predictors of adverse events include copious secretions, endotracheal intubation in child <5 yr of age, history of prematurity, nasal congestion, paternal smoking, history of reactive airway disease (postpone for ≥4 wk if child has asthma, especially if intubation required), surgery involving airway (higher risk in tonsillectomy); concluded that children with active or recent URI at increased risk for adverse respiratory events if child has history of reactive airway disease, requires surgery involving airway, has history of prematurity, exposed to environmental tobacco smoke, has nasal congestion or copious secretions, or requires placement of endotracheal tube (ETT); also concluded anesthetic agent can make difference (sevoflurane induction and maintenance had lower incidence of complications than switching to another agent after induction); with careful management, children can undergo elective procedures without increased morbidity; underlying viral myocarditis possible, but postponing for few weeks will not alter risk for arrhythmias (postpone for respiratory complications)

Additional risk factors for adverse events: in children with colds emerging from anesthesia (Homer, 2007); excluded patients with reactive airway disease, history of prematurity <1 yr of age, and chronic lung disease; variables included sex, weight, use of premedication, airway devices, URI variables (eg, passive smoking; symptoms present with recent URI); outcome variables included coughing, desaturation, laryngospasm, and duration of O2 administration in recovery; highest-risk areas included deep tracheal extubation (compared with face mask; LMA use intermediate), URI 2 to 4 wk prior to anesthesia (intermediate risk <2 wk; 4 to 6 wk protective); benzodiazepine premedication increased adverse respiratory events; low-grade fever mildly protective

Pretreatment with bronchodilator: in afebrile American Society of Anesthesiologists’ (ASA) physical status type I or II child with active or recent URI (within 6 wk), undergoing surgery lasting <3 hr, and receiving either albuterol or inhaled anticholinergic drug (eg, ipratropium), results showed no decrease in adverse airway events

Glycopyrrolate: study showed no difference in outcomes in reducing perioperative adverse respiratory events, but shorter discharge times and decreased nausea and vomiting; however, more agitation in recovery room, more redness and flushing, and more tachycardia

Conclusions: risk associated with anesthesia, even without URI; child with URI has increased risk for airway complications (anesthesia provider must decide level of risk he or she willing to take); must wait 4 to 6 wk to decrease risks; tailor anesthetic to decrease risks (eg, propofol; face mask or LMA instead of ETT), but risks cannot be reduced to zero; anticholinergic drugs have not been shown to decrease risks; use good judgment and common sense; informed consent of parents essential when deciding to proceed or cancel; document discussions with parents in chart