PATHOPHYSIOLOGY

When the severity and/or frequency of ischemic attacks increase, the likelihood of an event is high.
Unstable angina is not well-controlled pharmacologically and imposes greater risk of a myocardial infarction.

The main objective in regulating the cardiovascular system:
- avoid HYPOtension
- avoid HYPERtension
- avoid tachycardia

Tachycardia is the WORST for CAD because:
- it increases myocardial metabolism
- may decrease coronary blood flow.

Cardiac reserve should be estimated through questioning the patient about their usual physical activities and exertional tolerance.
Perioperative and long-term cardiac risks are increased in a patient who is unable to achieve a level of strenuous activity.

The Goldman Cardiac Risk Index identifies an S3 gallop as a significant risk factor for noncardiac surgery.

Coronary artery disease is best determined through a stress ECG.

A patient that develops unexplained low cardiac output following a CABG is likely to be experiencing cardiac tamponade.
When cardiac output is low, tamponade should always be considered. During this situation, heart rate is the catalyst for cardiac output because stroke volume is limited and fixed.

A patient with peripheral vascular disease is most likely to experience a cardiac complication, rather than a renal, respiratory, or cerebral.
Myocardial oxygen supply and demand are the MOST important when managing a patient with coronary artery disease.

Oxygen demand is determined by:
- Myocardial wall tension = preload and afterload
- Heart rate- greatest increase in oxygen consumption
- Myocardial contractile state

Valvular Heart Disease

Mitral valve
- The mitral valve is situated inferiorly to the left atrioventricular annulus between the left atrium and the left ventricle. Two major leaflets are connected by commissural tissue.
- The normal mitral valve area is 4 to 6 cm².
Aortic valve
- The valve normally has 3 cusps.
  - Cusps are slightly thicker than pulmonary valves because it is subjected to greater pressure (ejection of blood from left ventricle).
  - Normal valve area is 2.5 to 3.5 cm²

Concentric hypertrophy
- Hypertrophy that occurs in response to chronic increases in intracardiac pressure.
Eccentric hypertrophy
- Hypertrophy that occurs due to chronic regurgitant volume, results in dilated ventricular wall

Mitral valve closes during ventricular systole.
- This prevents blood to back up into the left atrium.
- Mitral valve has two leaflets.

Mitral stenosis
- Reduced diastolic flow from the left atrium to the left ventricle through the stenotic/calcified lesion.
- Mitral stenosis causes the left ventricle to be chronically “underloaded.”
- Pulmonary congestion and decreased cardiac output results.
- Left atrial hypertrophy can lead to a-fib.
Anesthesia goals:
- Low normal heart rate
- Decrease afterload

Mitral regurgitation (or insufficiency)
- Left ventricular volume backs up into the left atrium.
- Volume overload of the left ventricle- eccentric hypertrophy.

- Acute MR
  - Caused by papillary muscle rupture
  - Left atrium is noncompliant.
- Chronic MR
  - Results in eccentric hypertrophy –
    - cardiac enlargement due to fluid. With gradual increases in fluid, the left atrium is able to compensate to a certain point.
    - Left atrium is able to compensate
    - v waves on PCWP tracing appear due to regurgitant volume ejected back through the incompetent valve.
Anesthesia goals:
- High normal heart rate
- Increased afterload

Aortic stenosis
- Aortic valve area is normally 2.5 – 3.5 cm².
- The valve normally has 3 cusps.
- Narrowing of the aortic valve that leads to an increased ventricular systolic pressure needed to override the outflow tract obstruction.

- Causes:
  - Valve only has 2 cusps
  - Rheumatic fever
The pressures in the left ventricle are high. In order to maintain a normal cardiac output, the ejection during systole must also increase. This results in concentric hypertrophy.

Symptomatology is not seen until the area is at least 50% constricted.
- At 1 cm², angina, syncope, and CHF appear.

Anesthesia goals:
- Maintain NSR, rate 70-80
- Avoid myocardial depression
- Maintain or slight decrease in afterload

Aortic regurgitation (or insufficiency)
- Primary ACUTE cause is infective endocarditis.
- Primary CHRONIC cause is rheumatic fever.
Secondary acute results from aortic root dissection (trauma or aneurysm)
The incomplete closure of the aortic valve results in some of the ejected blood volume into the aorta to go back into the left ventricle.

Anesthesia goals:
- High normal HR (90-100)
- Reduced SVR
- Management of aortic insufficiency is best described as decreased diastolic filling and lowered SVR.
Hypertrophic cardiomyopathy (idiopathic hypertrophic subaortic stenosis)
- Compensatory enlargement of the heart.
- Genetic
- The enlarged septum bulges into the subaortic area of the LV outflow tract. A Venturi effect during systole pulls the anterior mitral valve leaflet into the outflow tract.
- Can lead to:
  - CAD
  - valvular disease
  - ventricular shape changes
  - HTN
There is an increase in the calcium channels’ density that leads to this hypertrophy.
A left outflow tract obstruction results and mimics aortic stenosis.

Anesthesia goals:
- Increase preload
- Increase afterload (phenylephrine should be used to treat hypotension)
- Decrease contractility
- Maintain NSR and heart rate

Hypotension related to concentric hypertrophy is best treated by phenylephrine.

Nitroglycerin is appropriate for use in right heart failure.

The initial finding/symptom in >50% of patients with hypertrophic cardiomyopathy is sudden death.

Atrial contraction results in up to 75% of ventricular filling in hypertrophic cardiomyopathy.

Keep heart rate low (50-70 beats per minute) to reduce myocardial oxygen consumption and prevent myocardial ischemia with aortic stenosis.

Maintaining sinus rhythm and adequate preload are crucial with aortic stenosis.
Hypotension, tachycardia, and bradycardia are not tolerated well.
The wedge pressure may not be useful because it will underestimate the LVEDP.
Afterload reduction results in hypotension and reduced coronary perfusion because cardiac output is relatively fixed due to the stenotic lesion.
Ventricular compliance decreases and end-diastolic pressure increases.
With both aortic and mitral valve insufficiency/regurgitation, bradycardia is best avoided.
Forward flow is enhanced by reducing the afterload.
Maintaining preload can be attained with volume replacement.
Increased heart rate lowers the volume in ventricles.

***The phrase to remember for AORTIC INSUFFICIENCY/REGURGITATION is fast, full, and forward

Mitral regurgitation is the only valvular lesion that does NOT have isovolumetric contraction.
Vasodilators, volatile agents, and anticholinergics are all appropriate during a mitral valve replacement for regurgitation.
Diuretics are NOT appropriate.
The amount of regurgitant volume is lowered by a slightly elevated heart rate because it helps to decrease ventricular volume.

Right ventricular failure is worsened by increases in PVR. So, in the setting of MITRAL STENOSIS the anesthetist will want to AVOID:
- vasoconstriction
- hypoxia
- hypercarbia
- acidosis

The outflow obstruction seen in idiopathic hypertrophic subaortic stenosis (IHSS) is caused by the asymmetric hypertrophy of the interventricular septa.
- The following make the outflow obstruction worse:
  - - Hypotension
  - Decreased intraventricular volume
  - Increased contractility

Critical aortic stenosis symptomatology results from increased left ventricular systolic pressure.
- Angina, syncope, and CHF are often experienced.
- Leads to concentric left ventricular hypertrophy.
- When the disease progresses, the myocardium of the left ventricle dilates and contractility decreases.

Slower heart rates are more desirable for patients with stenotic lesions because the heart has more diastolic filling time.

Faster heart rates for regurgitant valvular issues help decrease the backward flow because it decreases the time spent in diastole.
Diastole is when the blood flows backward.

Hypertrophic cardiomyopathy is worsened by tachycardia but helped by high SVR.

Murmurs:
- Mitral stenosis-
  - opening snap that occurs early in diastole and by a rumbling diastolic murmur, best heard over the cardiac apex.
- Mitral regurgitation-
  - blowing holosystolic (heard throughout systole) murmur, best heard over the cardiac apex. The murmur typically radiates into the axilla.
- Aortic stenosis-
  - systolic murmur that is best heard in the second right intercostal space (over the aortic arch) with radiation into the neck.
- Aortic regurgitation-
  - diastolic murmur that is best heard along the left sternal border.

The severity of aortic valvular regurgitation is graded angiographically after contrast injection into the aortic root as follows:
- 1+: small amount of contrast material enters left ventricle during diastole, but is cleared from left ventricle during systole
- 2+: left ventricle is faintly opacified by contrast media during diastole and not cleared during systole
- 3+: left ventricle is progressively opacified
- 4+: left ventricle is completely opacified during the first diastole and remains so for several beats

**Note: recognize there are four grades for aortic valvular regurgitation reflecting the severity of the problem.

Both systolic and diastolic murmur occur in the patient with patent ductus arteriosus.
- The murmur is more intense during systole than during diastole, so that the murmur ebbs and flows, creating a machine-like sound

Congenital Heart Defects

OUTFLOW OBSTRUCTION	LEFT-TO-RIGHT SHUNT	RIGHT-TO-LEFT SHUNT (↓ LUNG FLOW)	RIGHT-TO-LEFT SHUNT (↑ LUNG FLOW)
Coarctation of the aorta (LV)	Ventricular septal defect	Tetralogy of Fallot	Transposition of the great vessels
Pulmonic valve stenosis (RV)	Patent ductus arteriosus	Pulmonary atresia	Truncus arteriosus
	Atrial septal defect	Tricuspid atresia

Obstructive lesions
- Pulmonic valve stenosis restricts right ventricular output and leads to concentric hypertrophy.

Left-to-right shunts
- Normal higher pressures of the left side push blood to the right side, which increases fluid in the lungs.
- When the shunt is large, flow is dependent on PVR and SVR.
  - Increased SVR favors left-to-right shunting
  - Increased PVR favors right-to-left shunting
- Air bubbles can cause cerebral or coronary embolism.

Right-to-left shunts with decreased lung flow
- Tetralogy of Fallot
  - Needs an increase in afterload during anesthesia

Symptoms:
- Right to left shunts- cyanosis
- Outflow obstruction and increased blood flow defects- congestive heart failure

Cardiac Conduction and Rhythm Abnormalities

The cardiac electrical system is precise and stimulates a muscular response. When the timing is off or there is an abnormality, pathophysiology ensues.
- First degree heart block- PR interval is longer than 0.2 seconds
- Second degree type I (Wenckebach) – PR interval gets progressively longer until a QRS complex is dropped
- Second degree type II- NSR with a dropped QRS complex
- 3^rd degree- the ‘P’ waves and ‘QRS’ complexes are independent of each other

Cardiovascular and Peripheral Vascular Complication

Hypertension is the most common cardiovascular disease process seen in surgical candidates.

Atrial natriuretic peptide (ANP) is released from the atria in response to volume overload.

Hypertension increases both the risk and severity of CAD, CVA, renal failure, CHF, etc.

2 types:
- Primary– no identifiable cause
- Secondary– pheochromocytoma, coarctation of the aorta, renal artery stenosis, etc.

Left ventricular hypertrophy results from chronic hypertension. This increase in size also increases the oxygen requirements for the heart. The enlargement of the heart due to HTN is termed concentric hypertrophy.
- Leads to ↓ in function (Ejection fraction) and filling (Stroke volume)

Patients with chronically untreated HTN require higher pressures to perfuse organs due to autoregulation shifts.
- Under anesthesia, MAP should be kept within 20% of their normal. The reason is two-fold:
  - Autoregulation of vital organ blood flow has increased
  - Those with long-standing HTN often experience a profound hypotensive response after induction.

BLOOD PRESSURE CATEGORY	SYSTOLIC mm HG		DIASTOLIC mm HG
NORMAL	LESS THAN 120	And	LESS THAN 80
ELEVATED	120-129	And	LESS THAN 80
HTN STAGE 1	130-139	Or	80-89
HTN STAGE 2	140 OR HIGHER	Or	90 OR HIGHER
HTN CRISIS	HIGHER THAN 180	And/or	HIGHER THAN 120

2017 American Heart Association/American College of Cardiology guidelines

Infectious Disease

Prophylaxis to infective endocarditis in patients with valvular heart disease:
- Dental, oral, respiratory, or esophagus procedures
  - Amoxicillin/Ampicillin or Clindamycin (PCN allergy)
- GI/GU procedures
  - Ampicillin + gentamicin
  - Vancomycin + gentamicin (allergy to PCN)

Pericardial Disease

Pericarditis is inflammation of the sac surrounding the heart- pericardium.
- Diffuse ST-segment elevation in multiple leads
- Differentiated from myocardial infarction because of a pleural association.
  - Pain exacerbated with position changes
  - Pain relieved by sitting or leaning forward

- Acute pericarditis
  - treated according to the symptoms and cause.
- Chronic pericarditis
  - Hardens the pericardium
  - Limits diastolic filling → both SV and CO ↓
  - Congestion/edema
  - Pressures in the heart begin to equalize (pulmonary, wedge pressures, CVP)
  - Cardiac output is dependent on heart rate.

- Cardiac tamponade
  - Accumulation of fluid in the pericardium that causes filling to become impaired. Cardiac pressures (e.g. pulmonary artery, PCWP, right atrial pressure) begin to equalize.
  - As with chronic pericarditis, cardiac output is heart rate dependent.
  - Beck’s triad:
    - Hypotension
    - Jugular venous distention
    - Distant muffled heart sounds
  - Pulsus paradoxus– > 10 mm Hg decrease in SBP with inspiration.

Cardiomyopathy and Heart Failure

The major compensatory mechanism associated with CHF is the activation of the renin-angiotensin-aldosterone system.
The progressive structural changes in the peripheral vasculature and in the remodeling of the left ventricle are influenced by the RAA and sympathetic nervous system.
The combination of an inodilator and a beta-adrenergic agonist results in synergistic inotropic effects.
Both dobutamine and amrinone have favorable effects on the myocardial oxygen balance.
Fluid overload can cause an S3 heart sound.
Severe CHF patient will exhibit an increase renin and angiotensin production.

Terazosin

Spironolactone

Amlodipine

Lisinopril

Losartan

Alpha1 blocker

Aldosterone competitive antagonist

Calcium channel blocker

ACE inhibitor

ARB

The inability to pump enough blood or because of elevated pressure leads to heart failure.
- This is the result of an ineffective pumping of the left ventricle to meet the metabolic demands of the body.

The renin-angiotensin-aldosterone system helps control:
- blood pressure
- blood volume

- Renin → angiotensinogen → Angiotensin I
- Angiotensin converting enzyme (ACE) helps Angiotensin I → Angiotensin II

Angiotensin II has many pharmacologic actions including potent vasoconstriction action as well as stimulating aldosterone release from the adrenal gland.

Doppler electrocardiography assesses left ventricular compliance and is the best indicator of diastolic function.

Patients with congestive heart failure compensate by a(n):
- Increased preload
- Increased sympathetic activity
- Activation of renin-angiotensin-aldosterone system
- Release of arginine vasopressin
- Ventricular hypertrophy

Concentric hypertrophy leads to a decrease in left ventricular wall tension.
Higher filling pressures are required to produce the same work from the ventricles.

Decrease in afterload is best in congestive heart failure.

In the absence of significant valvular dysfunction, venous return is the major determinant of both right and left ventricular preload.

The Frank-Starling curve relates left ventricular filling pressure to left ventricular work.
- Left ventricular filling pressure can be reflected by:
  - left ventricular end-diastolic volume
  - left ventricular end-diastolic pressure
  - left atrial pressure
  - pulmonary artery occlusion pressure
  - in some instances, central venous pressure
- Left ventricular work can be represented on the y-axis by:
  - left ventricular stroke work index
  - stroke volume
  - cardiac output
  - cardiac index
  - arterial blood pressure

Inotropy refers to the force and velocity of ventricular contractions when preload and afterload are held constant.
Chronotropy refers to the heart rate.
Dromotropy refers to the conduction of impulses along conductive tissue.
Bathmotropy refers to muscular excitation in response to a stimulus.
Lusitropy refers myocardial relaxation or diastole. A decrease in lusitropy is seen with the aging myocardium

RESPIRATORY

Pathophysiology

FEV₁	Indication of airway obstruction
FEV₁/FVC	Restrictive vs obstructive diseases
FEF _{25 TO 75%}	Small airway resistance
DL_COPPO	Postoperative pulmonary complications in lobectomies

Pain is known to increase pulmonary vascular resistance.
Etomidate is the anesthetic agent best tolerated in patients with pulmonary hypertension.
When the upper airway becomes obstructed and inspiratory effort continues, high negative intrathoracic, transpleural, and alveolar pressures are created. This enlarges the pulmonary vascular volume and subsequently the interstitial volume. The lymphatics are overwhelmed and ooze interstitial fluid into alveoli. This causes hypoxia, which in turn, leads to even more accumulation of pulmonary fluid. The pulmonary edema stimulates the J receptors and tachypnea ensues.
Basilar crackles are the traditional hallmark of early pulmonary edema. By the time these are present, the fluid has overfilled the alveoli and spilled into the bronchioles.
Interleukin-8 is the main cytokine involved in both acute respiratory distress syndrome and aspiration pneumonitis.

Obstructive Diseases

ASTHMA

Reactive airways: asthma, COPD, emphysema, viral upper respiratory illness.
Asthma involves an increased responsiveness of the trachea and bronchi to various stimuli that leads to widespread narrowing of the airways. Symptoms include dyspnea, cough, and wheezing.
Asthma can be caused by an allergic response (IgE) to antigens or by nonantigenic stimuli (like exercise, temperature, etc.). The release of mediators leads to inflammation, capillary leakage in airways, increased mucous secretion, and bronchial smooth muscle contraction.
The most common physical finding of asthma is expiratory wheezing due to obstructed airflow and points to a prolonged expiratory phase.
Asthma treatment centers around beta-2 agonists. Selectivity for beta-2 is key especially in those patients with CAD where tachycardia would be detrimental. Other medications: corticosteroids, anticholinergics, cromolyn sodium, leukotriene modifiers.
Avoid histamine-releasing anesthetics like morphine and atracurium. Respiratory depression increases with opioid administration, so titrate carefully.
Intraoperative management of bronchospasm:
- Check the ETT and listen to breath sounds, increase the FiO₂ to 100%, and deepen the anesthetic.
- Causes of bronchospasm:
  - Kinked ETT; bronchoconstriction; hypoxemia; “light” anesthesia.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Emphysema, chronic bronchitis, and bronchitis from asthma.
Progressive increased breathing resistance.
Loss of elastic recoil or obstruction of small or large conducting airways causes airflow limitation.
Symptoms are cough, dyspnea, and wheezing.
Chronic bronchitis (classically “blue bloaters”)
- Cough with sputum, recurrent infection, and airway obstruction.
- Airway lumen is decreased, causing more resistance to gas flow because of mucus and inflammation.
Emphysema (classically “pink puffers”)
- Progressive dyspnea and cough.
- Enlargement of air spaces due to elastic and collagen destruction
- Air trapping
Causes: smoking, exposure, genetics (alpha-1 antitrypsin deficiency)
- Mast cells cause bronchoconstriction; degranulate to release histamine.
Hypoxic drive becomes the main stimulus for breathing because prolonged hypercapnia desensitizes respiratory chemoreceptors.
Because atelectasis and poorly ventilated areas are common, hypoxic pulmonary vasoconstriction helps to redirect blood to better ventilated areas. When given 100% oxygen, hypoxic pulmonary vasoconstriction decreases and leads to an increased V/Q mismatch.
Smoking cessation
- After 48 hours, carboxyhemoglobin levels decrease.
- After 4-6 weeks, postoperative pulmonary complications decrease.
- After 2-3 months, improved ciliary function, improved pulmonary mechanics, and reduced sputum production.

Morphine causes histamine release and could lead to hyperactive airway reflexes. Therefore, it is generally avoided in a patient with COPD.
Volatile anesthetics can depress hyperactive airway reflexes. The CRNA should avoid medications that can cause a histamine release, like morphine, atracurium, and mivacurium.
Carbon dioxide retention a late finding of status asthmaticus.
Emphysema is an example of an obstructive disease.
Sedation should be used with caution. GETA can still be used but there is an increased chance of postoperative ventilation. Neuraxial techniques are not recommended above T6 sensory level due to the risk of decreasing expiratory reserve volume, impairing the cough effort, and creating anxiety.
Thiopental is the anesthetic agent that is most associated with wheezing after intubation in the asthmatic patient.
Methylergometrine (ergot derivative for postpartum bleeding) can cause bronchoconstriction. Desflurane (along with Isoflurane) is a mild respiratory irritant. Atracurium can cause histamine release and lead to asthma exacerbation. Esmolol is a selective beta-1 agonist and is preferred as opposed to nonselective beta agonists that could lead to bronchoconstriction.

Restrictive Dieseases

Smoking causes decreased ability to cough up secretions, increased mucoid secretions, increased lung compliance, and increased pulmonary compliance.
Scoliosis, aspiration, and obesity are examples of restrictive respiratory disease.
Pulmonary restrictive disease may be due to acute intrinsic restrictive lung disease (aspiration), chronic extrinsic restrictive lung disease (obesity, scoliosis, etc.), and others. COPD is an obstructive lung disease.
FEV₁/FVC ratio is normal with restrictive pulmonary disease.
Restrictive disease corresponds to a preoperative pulmonary function test that shows a low FEV₁ along with a normal FEV₁/FVC ratio.
Pulmonary edema is an example of an acute intrinsic disorder of restrictive pulmonary disease.
Pregnancy and ascites are two chronic extrinsic diseases of restrictive pulmonary disease.

NEGATIVE- PRESSURE PULMONARY EDEMA

Negative-pressure pulmonary edema is caused by an acute airway obstruction. A laryngospasm is typically the cause.
- Breathing against a closed glottis creates a more negative pressure in the lungs.
- Greater hydrostatic pressure between interstitial space and pulmonary circulation results.
- This leads to fluid accumulation from the blood to the lungs.
- Treated with PEEP. This is typically self-correcting.

ASPIRATION PNEUMONIA

The risk of aspiration pneumonitis increases when:
- Gastric volume is greater than 25 mL AND
- Gastric pH is less than 2.5
Adult respiratory distress syndrome (ARDS), also known as aspiration pneumonitis (Mendelson’s syndrome), is the most serious complication of aspiration.

INFECTIOUS DISEASES

ASPIRATION
- When gastric (or esophageal, nasal, or oral) content enters the lungs.
- The amount and pH of the content that is aspirated directly correlates with morbidity and mortality. (MENDELSON’S SYNDROME)
- Prevention
  - NPO status
  - Bicitra and H-2 antagonists decrease pH
  - Metoclopramide (gastric prokinetic) increases motility
  - Nasogastric tube for drainage/suction
  - Rapid sequence induction with cricoid pressure
- Treatment
  - X-ray- fluffy infiltrates
  - Immediate suctioning
  - Positive end-expiratory pressure
  - No antibiotics unless there is a high likelihood of gram negative or anaerobic microbes were aspirated
- PNEUMONIA
  - The most common risk factor of acute respiratory distress syndrome (ARDS) is pneumonia that leads to sepsis.

Pulmonary Vascular Complications

Pulmonary embolus is generally associated with a decrease in PaO₂ with a decrease in ETCO₂. Bronchospasm would explain the peak inspiratory pressure increase.
With venous air embolism, PaO₂ and SaO₂ decrease while PaCO₂ increases and ETCO₂ The changes in arterial and end-tidal gases occur secondary to the increase in dead space. In addition, nitrogen is detected ill the end-tidal gases.
In the event of a venous air embolism, the surgeon should flood the operative field with saline while the CRNA discontinues nitrous oxide, administers 100% oxygen, and aspirates the air with a central venous catheter.
Place the patient in the left lateral decubitus position with a slight head down (Trendelenburg) tilt if venous air embolism is suspected.
The first signs of a PE are tachycardia and a decreasing PETCO₂ (PaCO₂ – ETCO₂) waveform and value. With a massive PE, abrupt and unexplained hypotension with loss of ETCO₂ and tachycardia are classic signs. Increases in PAPs and CVP are seen along with decreased SBP and DBP. Bronchospasm is common. There are also EKG changes, like right axis deviation, incomplete/complete RBBB, or peaked T waves.
Pulmonary edema is classified as either cardiogenic (high pressure, hydrostatic) or noncardiogenic (altered or increased permeability). Cardiogenic is the most common form and the other three choices are examples.

Altered Airway Anatomy

PULMONARY EDEMA
- Caused by increased pulmonary hydrostatic pressure OR increased alveolar-capillary membrane permeability.
- Negative pressure pulmonary edema results from breathing against a closed glottis (i.e. laryngospasm)
- Diagnosis
  - Auscultating basilar crackles
  - Cephalization of vessels and bilateral symmetric ground-glass opacities are common findings on x-ray. Cephalization is the redistribution of blood into the upper lobe vessels. Can also be described as having a “whited-out” appearance.
- LARYNGOSPASM
- BRONCHOSPASM

Loud snoring due to upper-airway obstruction along with a blunted respiratory drive are characteristic of obstructive sleep apnea patients. A thorough history from the sleeping partner is key. Patients may also experience dry mouths. Complications with this condition in the perioperative period may involve hypertension, arrhythmias, myocardial infarction, hypoxia, pulmonary edema, and stroke. The vulnerability for obstruction warrants minimal opioids/sedatives to be given.
Elevations in pulmonary blood flow and pulmonary artery vasoconstriction from persistent hypoxia can lead to pulmonary hypertension. Upper airway obstruction leading to periods of apnea/awakening causes hypercarbia and daytime sleepiness.

GENETIC RESPIRATORY DISORDERS

PULMONARY HYPERTENSION
- Can be genetic or due to secondary causes
- When pulmonary systolic pressure is greater than 25 mm Hg at rest and 30 mm Hg during exercise.
- Pulmonary circulation has high flow and low resistance. The right ventricle accommodates changes in volume better than pressure. During periods of increased flow, vessels can accept an increase in flow up to 3-5 x normal without a change in PA pressures.
- Pressure overload in the right ventricle leads to hypertrophy. The thin-walled right ventricle thickens and cannot distend as easily. Right ventricular failure results and tricuspid regurgitation may be seen.
- Treatment
  - Oxygen supplementation to keep SpO₂ > 90%
  - Diuretics
  - Anticoagulation
  - Calcium channel blockers
    - Nifedipine and hydralazine can decrease pulmonary vascular resistance and improve survival rates.
  - Intraoperative
    - Nitroglycerin, sodium nitroprusside, prostaglandin E, phentolamine, and isoproterenol.
    - Avoid hypercarbia and hypoxemia
    - Avoid increased PEEP
  - Intraoperative monitoring
    - PA catheter directly measures the PA pressure and right atrial pressure, along with an indirect assessment of the left ventricular volume.
    - CAUTION: patients with pulmonary HTN are at increased risk of pulmonary artery rupture; TEE is safer.
  - Nitric oxide
    - Crosses into vascular smooth muscle with the help of nitric oxide synthetase on arginine and stimulates guanylate cyclase.
    - Cyclic guanosine monophosphate (cGMP) is formed to produce smooth muscle relaxation and vasodilation.
    - Its mechanism of action is the same as the other nitrovasodilators. However, because it is administered inhalationally, the systemic effects of hypotension are bypassed.
  - CYSTIC FIBROSIS
    - Genetic mutation that affects the cells that produce mucus, sweat, and digestive juices.
    - Very thick mucus secretions are retained and can cause pulmonary infections, airway obstruction, airway collapse.
    - Keep patient hydrated so that secretions are humidified.
    - Avoid anticholinergics.
  - ALPHA 1 ANTITRYPSIN DEFICIENCY
    - Hereditary condition that leads to increased risk of COPD, liver disease, skin problems, and blood vessel inflammation.
    - Alpha-1 antitrypsin proteins are made in the liver to help protect the lungs.

Central Nervous System

Cerebrovascular Diseases

Ischemic injury to the brain is very likely due to the high oxygen consumption and dependence on aerobic glucose metabolism.
The most effective method for protecting the brain during focal and global ischemia is hypothermia.
Hyperventilation decreases PaCO₂ resulting in the diversion of blood to an ischemic region of the brain. Succinylcholine could cause hyperkalemia, depending on the patient’s amount of inactivity. Nitroprusside would cause cerebral steal and shunt blood away from the ischemic regions because they have no tone.

Cerebrovascular insufficiency – an inadequate supply of blood flow, oxygen, and/or glucose to the brain.

Focal ischemia – a more localized issue resulting from vasospasm, trauma, hemorrhage, embolus, or plaque formation.

Global ischemia – occurs when the brain is not perfused, i.e. respiratory failure or cardiac arrest.

NEURODEGENERATIVE DISEASES

MYASTHENIA GRAVIS

Autoimmune disease where antibodies attack acetylcholine receptors or other postsynaptic neuromuscular junction proteins.
Triggers a complement-mediated damage to the postsynaptic membrane which results in lysis of junctional folds.
90% of patients have a thymoma, thymic hyperplasia, or thymic atrophy.
Weakness of skeletal muscles that worsens with activity or repetition. Symptoms effect those muscles that innervate bulbar, limb, ocular, and respiratory muscles.
Treatment
- Pyridostigmine increases acetylcholine amounts at the NMJ.
- Corticosteroids and nonsteroidal immunosuppressive drugs target the immune dysregulation and decrease binding of acetylcholine receptors by antibodies.
- Thymectomy

PARKINSON’S DISEASE

Progressive loss of dopamine in the nigrostriatum (extrapyramidal system).
An overriding GABA activity leads to thalamic and brain stem inhibition resulting in dyskinesia, rigidity, postural instability, and tremor.
Treatment
- Anticholinergics, MAOIs, carbidopa/levodopa, COMT inhibitors, and dopamine-receptor antagonists
Avoid phenothiazines, droperidol, Haldol, and metoclopramide because their antidopaminergic activity can make symptoms worse.

ALZHEIMER DISEASE

The hallmarks of Alzheimer’s disease are progressive impairment of memory, judgment, decision-making, and emotional lability.
Cholinesterase inhibitors slow the progression.
Sedatives can increase confusion and agitation.
Expect postoperative cognitive impairment for several days.

AMYOTROPHIC LATERAL SCLEROSIS (ALS)

The most prevalent motor neuron disease.
Rapidly progressing disorder of the upper and lower motor neurons and results in muscular weakness, atrophy, fasciculation, and spasticity. Progressive respiratory muscle weakness makes patient an aspiration risk.
Avoid succinylcholine; NDNMBs should be used sparingly.

NEUROLEPTIC MALIGNANT SYNDROME

Neuroleptic malignant syndrome can be precipitated by Compazine and phenothiazines.
- A rare complication of antipsychotic therapy that is related to dopamine blockade in the brain. Muscle rigidity, hyperthermia, rhabdomyolysis, autonomic instability, and altered consciousness occur.
- Meperidine and metoclopramide can also lead to NMS.
- Dopamine blockade in the basal ganglia and hypothalamus and thermoregulation impairment.
- Mimics malignant hyperthermia. Dantrolene is somewhat effective. Bromocriptine is also effective.

HUNTINGTON’S DISEASE

Congenital genetic disease caused by a trinucleotide (CAG) repeat on chromosome 4.
Symptoms
- Begins with a rapid phase of chorea and evolves into bradykinesia. Progressive dementia and mood-altered states of apathy and depression are also seen.

EPILEPSY

A neurologic disorder that causes sudden recurrent episodes of sensory disturbance, loss of consciousness, or convulsions, with abnormal electrical activity in the brain.
A seizure is the result of an excessive discharge of neurons.

MYELIN DISEASES

MULTIPLE SCLEROSIS

Reversible demyelination at different spots in the brain and spinal cord.
Chronic inflammation leads to scarring, or gliosis.
Known for the relapse and remission cycle.
Hyperthermia can cause an exacerbation of symptoms due to decreasing nerve conduction. It may only take an increase of 0.5^o C to completely block conduction.
Spinal may exacerbate disease.
Avoid succinylcholine if paralysis is present.
Anesthesia
- Supplemental corticosteroid administration may be warranted.
- Avoid hyperthermia.
- Spinal anesthesia is not advised.

GUILLAIN-BARRE SYNDROME

A disorder that results in a sudden onset of ascending motor paralysis, areflexia, and variable paresthesias.
Motor neuron impairment that affects speech and swallowing along with respiratory muscle paralysis is a common finding.
Immunologic reaction against the myelin sheath of peripheral nerves; commonly follows a viral infection.

NEUROPATHIES

Psychiatric Disorders

SCHIZOPHRENIA

Excessive brain dopamine.

Spinal Cord Disorders

Autonomic hyperreflexia is a reflex sympathetic discharge in the spinal cord below the injury. It can develop after the acute phase of spinal shock. Common triggers include pain, any noxious stimuli, bladder surgery, and bowel surgery.
Regional anesthesia and deep general anesthesia are effective in preventing hyperreflexia.
Spinal shock causes vasodilation below the level of injury. The cardioaccelerator fibers are T1-T4 and provide sympathetic output to the heart. An injury in this area will leave unopposed vagal activity- resulting in bradycardia.
Autonomic hyperreflexia is a reflex sympathetic discharge in the spinal cord below the injury. It can develop after the acute phase of spinal shock. Common triggers include pain, any noxious stimuli, bladder surgery, and bowel surgery.
Regional anesthesia is preferred for patients at risk of autonomic hyperreflexia. Deep general anesthesia is also effective in preventing hyperreflexia.
Hypotension and bradycardia are expected when the spinal cord is transected at the T4 level.
Spinal shock causes vasodilation below the level of injury. The cardioaccelerator fibers are T1-T4 and provide sympathetic output to the heart. An injury in this area will leave unopposed vagal activity- resulting in bradycardia.

Intercranial Tumor

Congenital Abnormalities (e.g. Cerebral Palsy)

Down’s syndrome patients may have the following pathophysiological features:
- Atrial/Ventricular septal defects
- Chronic pulmonary infections
- Mental retardation
- Tracheoesophageal fistula
- Hypotonia
- Seizures
- Difficult intubation
  - Large tongue and small mouth
  - Short neck
  - Subglottic stenosis
  - Atlantoaxial instability from weak ligaments
  - Irregular dentition
- Trisomy 21 (or Down’s syndrome) is associated with atlantoaxial dislocation from cervical spine instability.

Seizure Disorders

Increased levels of normeperidine, a meperidine metabolite, have been associated with seizures. Normeperidine produces CNS stimulation, manifesting as myoclonus and seizures.
Patients being treated with antiepileptic drugs have increased dose requirements for thiopental, propofol, midazolam, opioids, and nondepolarizing neuromuscular blocking drug. Possible explanations for altered dose requirements for drugs administered during anesthesia include increased hepatic P-450 enzyme activity as a result of stimulating effects of antiepileptic drugs, alterations in the number and/or responsiveness of receptors, and interactions with endogenous neurotransmitters.
The likelihood of a seizure is increased when the seizure threshold is lowered. On the other hand, seizures are less likely when the threshold is raised. Acidosis makes it less likely that a seizure will occur.
The likelihood of a seizure is increased when the seizure threshold is lowered. On the other hand, seizures are less likely when the threshold is raised. Acidosis and hypoventilation make it less likely that a seizure will occur. Also, propofol increases the seizure threshold.

Intercranial Hypertension

Because the cranial cavity is the area encompassed by the skull, the elements contained are precise. Any increase in one area must be compensated by another. The brain makes up the largest portion (80%), followed by blood (12%), and then cerebrospinal fluid (8%).
Cushing’s triad is an increase in ICP and results in a reflex increase in blood pressure, a reflex decrease in heart rate, and irregular respirations.

Thermoregulation

A drop in temperature of 1^oC alters cerebral blood flow 5-7%.

Musculoskeletal

Skeletal muscle contains actin, myosin, and troponin.
Calcium combines with troponin in skeletal or cardiac muscle to initiate contraction.
The primary signaling chemical is acetylcholine, whose formation is catalyzed by choline acetyltransferase from acetyl coenzyme A and choline.
Acetylcholine is stored in vesicles that reside either in the active zone or away from the active zone in a reserve pool.
The process of acetylcholine mobilization and release utilizes calcium signaling; therefore, any impediment to that signaling can cause weakness.
- Examples:
  - Hypocalcemia and hypermagnesemia
  - Eaton-Lambert syndrome- antibodies against calcium channels
Acetylcholinesterase hydrolyzes acetylcholine into choline and acetic acid. Choline then reenters the presynaptic nerve terminal to be reused.

Myopathies / Metabolic Complications

MALIGNANT HYPERTHERMIA

The ryanodine receptor in the sarcoplasmic reticulum is responsible for the calcium release during the excitation-contraction coupling of muscles. The defect results in sustained contractions with increased metabolic activity because of unsequestered calcium.

TREATMENT FOR MH IS DANTROLENE.
- calcium channel blocker that decreases the release of calcium to contractile proteins.
- The dose is 2.5 mg/kg and may be repeated to a max of 10 mg/kg.
- A vial of dantrolene is 20 mg and needs to be diluted with 60 mL of sterile water.
- Dantrolene should be repeated every 10-15 hours for three days. This is because the half-life of dantrolene.

One of the earliest signs/symptoms is unexplained increase in ETCO₂. Hyperthermia is a late finding.

Triggering agents:
- succinylcholine
- volatile anesthetics

Neuromuscular Diseases

Succinylcholine should be avoided because of hyperkalemia in the setting of paresis or paralysis, as seen in advanced multiple sclerosis.
- Patients being treated with corticosteroids may require intravenous corticosteroid supplementation during the perioperative period. Spinal anesthesia can exacerbate symptoms of multiple sclerosis.

Myasthenia gravis is characterized by weakness and easy fatigability of skeletal muscles. The weakness can be asymmetric, confined to one group of muscles, or generalized. Easy fatigability of skeletal muscle in myasthenia gravis is caused by autoimmune destruction of nicotinic acetylcholine receptors at the neuromuscular junction.
- Destruction of post-synaptic acetylcholine receptors.
- The acetylcholine receptors are functionally weakened by immune-mediated destruction, blockage, or inactivation. There are circulating antibodies found in an overwhelming majority of these patients, however, the amount of these antibodies does not indicate the severity of the disease.
- The onset of myasthenia gravis is often ocular, resulting in ptosis and diplopia.
- Edrophonium is an anticholinesterase agent that increases the concentration of acetylcholine at the neuromuscular junction. This would improve the muscle strength of myasthenia gravis patients.

Diphenhydramine is a medication that is given for an acute exacerbation of Parkinson’s
- Avoid drugs with antidopaminergic activity:
  - phenothiazines
  - butyrophenone
  - metoclopramide

Symptoms of Parkinson’s disease can be treated with antihistamines or anticholinergics.

Hydrocephalus is a common comorbidity of myelomeningocele.

Skeletal Diseases

In rheumatoid arthritis, cricoarytenoid arthritis and C1-C2 instability may lead to anesthetic difficulties.
Rheumatoid arthritis patients may have cervical spine involvement, TMJ synovitis, cricoarytenoid arthritis manifested by hoarseness, pericarditis, aortic regurgitation, pulmonary fibrosis, peripheral nerve compression, hepatitis, anemia, and drug-induced side-effects associated with aspirin and/or steroid therapy
Scleroderma results in progressive fibrosis of the gastrointestinal tract that leads to lower esophagus and small intestine hypomotility.
Scoliosis is the lateral curvature of the spine.

Musculoskeletal Disorders (Genetic and Acquired)

Myotonic dystrophies (like Steinert’s disease):
- persistent contracture (myotonia) after voluntary contracture of skeletal muscle or following electrical stimulation.
- This results from abnormal calcium metabolism-
- ATP-driven pumps fail to return calcium to the sarcoplasmic reticulum (SR) thus the unsequestered calcium remains available to produce sustained skeletal muscle contraction.
- Steinart’s disease presents facial weakness, sternocleidomastoid atrophy, ptosis, dysarthria, dysphagia, and myotonia.

Lambert-Eaton myasthenic syndrome (LEMS):
- proximal skeletal muscle weakness that typically affects the lower extremities.
- A defect in the motor nerve terminal causes a decreased release of acetylcholine.
- The decreased release of acetylcholine is thought to be due to antibodies directed against the voltage-gated calcium channel.

Duchenne’s muscular dystrophy:
- Symmetric proximal muscle weakness that is manifested as a gait disturbance.
- Fatty infiltration typically causes enlargement (pseudohypertrophy) of muscles, particularly the calves.
- Progressive weakness and contractures eventually result in kyphoscoliosis.
- Concerns: succinylcholine-induced hyperkalemia, gastroparesis, and pulmonary secretion retention.
- Decreased cardiac function.

Know the following associations:

Lambert-Eaton myasthenic syndrome = Small-cell carcinoma of the bronchi

Myasthenia gravis = Normal prejunctional acetylcholine level

Duchenne muscular dystrophy = X-linked disease

Malignant hyperthermia = Ryanodine receptor

Rheumatoid arthritis = Atlantoaxial instability

Steinart’s disease = Myotonia followed by muscle atrophy

Genetic Musculoskeletal Disorders

Endocrine

Thyroid and Parathyroid Disorders

THYROID

Hyperthyroidism
- Decreased T3
- Decreased T4
- Increased PTH
Hypothyroidism
- Decreased T3
- Increased TSH
- Decreased T4
Decreased cardiac output may speed the rate of induction with an inhalation anesthetic, but hypothyroidism does not significantly decrease MAC.
Potential problems with the anesthetic management of the hypothyroid patient include hypoglycemia, anemia, hyponatremia, hypothermia, and difficulty during intubation because of an enlarged tongue.
Clinical manifestations of hypothyroidism include weight gain, cold intolerance, muscle fatigue, lethargy, constipation, hypoactive reflexes, and depression.
Thyroid storm is characterized by hyperpyrexia, tachycardia, and hypotension. The onset is usually 6 – 24 hours after surgery but can occur intraoperatively. Unlike MH, thyroid storm is not associated with muscle rigidity, elevated creatinine kinase or a marked degree of acidosis.

PARATHYROID

Parathyroid gland function and PTH secretion are inhibited by chronic and severe hypomagnesemia. PTH secretion is also reduced with hypercalcemia as can occur with Paget’s disease, malignancy, and chronic immobility.
Parathyroid hormone is the principal regulator of calcium homeostasis. It increases serum calcium by promoting bone resorption, limiting renal excretion, and enhancing GI absorption.
Hypoparathyroidism is usually due to deficiency of parathyroid hormone following parathyroidectomy.

Pituitary Disorders

Also known as the hypophysis
Master endocrine gland
Located in the center of the brain; more specifically, it is enclosed within a bone cavity of the sphenoid called the sella turcica.
Pituitary stalk connects the pituitary to the hypothalamus
Hypothalamus helps to regulate the pituitary
- Gathers signals related to pain, emotions, water, energy, etc. to help the pituitary
- Hormones are also regulated by a negative-feedback loop
2 parts to pituitary
- Anterior lobe (adenohypophysis)
- Posterior lobe (neurohypophysis)
Neuronal cells, called osmoreceptors, are excited by small increases in ECF osmolarity. These cells send nerve signals to control their firing and secretion of ADH. In addition to increased osmolarity, two other stimuli increase ADH secretion: decreased arterial pressure and decreased blood volume. Nausea is a potent stimulus for ADH release, which may increase to as much as 100 times normal after vomiting. Also, drugs such as nicotine and morphine stimulate ADH release.
The syndrome of inappropriate antidiuretic hormone secretion is a disorder characterized by a high circulating vasopressin level relative to plasma osmolarity and serum sodium concentration. Hormone-induced water reabsorption causes expansion of intracellular and extracellular fluid volumes, hemodilution, and weight gain. The urine is hypertonic relative to plasma, and urine output is typically low.

Adrenal Disorders

Pancreatic Disorders

Diabetes mellitus:
- Impairment of carbohydrate metabolism caused by an absolute or relative deficiency of insulin or insulin responsiveness.
Diabetic ketoacidosis (DKA):
- Type 1 DM
- Individuals with an initial diagnosis of type 2 diabetes mellitus can later develop type 1 diabetes.
- Long-term complications of diabetes:
  - Hypertension, coronary artery disease, myocardial infarction, congestive heart failure, diastolic dysfunction, peripheral and cerebral vascular disease, peripheral and autonomic neuropathies, and renal failure.
- Ketoacidosis is a common cause of metabolic acidosis. If the diabetic patient has insufficient insulin to block the mobilization and metabolism of free fatty acids, the metabolic byproducts are ketones. They cause metabolic acidosis with an increased unmeasured anion gap.
Hypoglycemia is a stress that activates the sympathetic nervous system leading to diaphoresis, hypertension, hunger, and a feeling of impending doom.
- Each milliliter of 50% glucose will raise the blood glucose of a 70-kg patient by approximately 2 mg/dL.
Hyperosmolar hyperglycemic nonketotic diabetic coma is caused by deficient insulin response to glucose stimulation, but there is enough endogenous insulin to prevent ketoacidosis. This disorder usually occurs in elderly patients unable to take fluids by mouth or in those unable to recognize thirst signals. Severe dehydration concentrates serum glucose. Blood glucose may reach 1,000 mg/dL. The marked hyperosmolality may lead to coma and seizures. The increased plasma viscosity produces a tendency to intravascular thrombosis.
Subcutaneously administered insulin has an onset of action of 15 – 30 minutes, a peak effect at 1 – 3 hours and a duration of 5 – 7 hours. Insulin has a very short plasma half-life of only about 7 minutes when administered intravenously.

Others (Thymus, Hypothalamus, Androgen, and Metabolic – Related)

MULTIPLE ENDOCRINE NEOPLASIA

MEN type I tumors are found in the pancreas, pituitary gland, and parathyroid gland.
MEN type II consists of medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism (type IIa) or multiple mucosal neuromas (type IIb or type III).

ADDISON’S

CONN’S

CUSHING’S

GRAVES’

ADRENAL INSUFFICIENCY

HYPERALDOSTERONISM

HYPERCORTISOL

HYPERTHYROIDISM

Patient’s with Addison’s disease (adrenal insufficiency) are likely to experience hypotension.

PHEOCHROMOCYTOMA

Patients with pheochromocytoma should be alpha blocked first, then beta blocked. If β-blockade is initiated first, catecholamine will produce unopposed α-stimulation and severe vasoconstriction. This may explain the paradoxical hypertension produced in a few patients treated with labetalol.
Pheochromocytoma accounts for about 0.1% of all cases of hypertension and has an incidence of malignancy of 10 – 15%.
A decrease in both red cell mass and plasma volume contributes to the severe chronic hypovolemia seen in patients with pheochromocytoma.
Deep anesthesia should be obtained prior to intubation to reduce the catecholamine response. Anticholinergic and sympathomimetic drugs are generally avoided as they will worsen the imbalance of autonomic tone. Because histamine provokes catecholamine release, atracurium should also be avoided. Although droperidol has α-blocking properties, it has been associated with hypertensive crises in some patients.

Hepatic

Infectious Diseases

Kupffer cells phagocytize bacteria
The most common cause of drug-induced hepatitis is alcohol.
Elective surgery should be delayed in those with acute hepatitis until liver tests are normal.

need more infectious dz - Hepatitis patho?

Biliary Tract and Bilirubin Disorders

Acute intermittent porphyria produces the most serious symptoms (systemic hypertension and renal dysfunction) which affects the central and peripheral nervous system.

The defective enzyme is porphobilinogen deaminase.

Avoid triggers agents such as:

- etomidate
- barbiturates
- ketamine
- calcium channel blockers
- ketorolac
- amiodarone

Increase in plasma alkaline phosphatase means bile duct cellular damage (most commonly from biliary obstruction).

Cirrhotic Disorders

Portal circulation (venous) is markedly lower.
Hepatic arterial flow is maintained or increased.
Oxygen supply in the liver is maintained.
Total hepatic blood flow is decreased.

Avoid decreases in hepatic artery flow and oxygen delivery. This is achieved by optimizing arterial blood pressure and avoiding hypotension.

These patients are described as being in a hyperdynamic state
- Increased cardiac output
- Decreased portal blood flow
- Low plasma osmotic pressure.

Portal hypertension – Excessive hydrostatic pressure in the portal vein.

Decreased blood flow to the liver is the cause for drugs to be prolonged in the patient with cirrhosis.

The most common major complication of cirrhosis is ascites.

Major cause of morbidity and mortality is massive bleeding from gastroesophageal varices.

Lab findings:
- Increased total bilirubin
- Increased AST and ALT
- Decreased albumin
- Increased PT

Albumin is a good indicator of chronic liver disease but not acute. This is because the half-life is 20 days.

Cirrhosis causes an increase in volume of distribution and lower plasma concentrations for drugs that are water-soluble. In addition, the cirrhotic liver will lead to longer elimination times.

- How does this affect dosing?
  - Dosage may need to be increased for loading but repeated doses for maintenance may need to be smaller.

Hepatovascular Abnormalities

The liver receives 1500 mL/min of blood flow, or 25% of total cardiac output.

	HEPATIC ARTERY	PORTAL VEIN
BLOOD FLOW	25%	75%
OXYGEN TO LIVER	50%	50%
VASODILATING RECEPTORS	Beta-2 Dopaminergic Cholinergic	Dopaminergic
VASOCONSTRICTING RECEPTORS	Alpha-1	Alpha-1

When the SNS is activated, the hepatic artery is vasoconstricted.

Beta blockers reduce blood flow and decrease portal pressure.

The liver acts as a reservoir and holds 500 mL of blood normally.

Anemia, thrombocytopenia, and leukopenia may occur in cirrhosis.

Renal

Intrinsic Kidney Disorders

Glycosuria is the result of either a low tubular threshold for glucose (normally 180 mg/dL) or hyperglycemia.
Decreased renal perfusion is the most important stimuli for renin secretion.
Diabetes insipidus
- No ADH or ineffective; results in large diuresis
Syndrome of Inappropriate ADH (SIADH)
- Too much release of ADH

Acute Kidney Injury

Decreased erythropoietin production, decreased red cell production, and decreased cell survival are thought to be responsible for anemia

Acute kidney injury (AKI) is occurs with a decline in GFR and results in inability of the kidneys to excrete nitrogenous wastes.

Most current and consensus definition for acute kidney injury:
- Increase in serum creatinine by 0.3 mg/dL within 48 hours OR
- Increase in serum creatinine ≥ 1.5 times baseline OR
- Urine volume < 0.5 mL/kg/hr for 6 hours

Serum creatinine does NOT rise until GFR drops < 50 mL/min.

Acute tubular necrosis is the most common cause of AKI in surgical patients.

AKI causes:
- Prerenal– increase in BUN associated with kidney hypoperfusion or ischemia
- Intrinsic– primary kidney insult due to ischemia, nephrotoxins, and kidney parenchymal diseases.
  - Most likely nephrotoxins:
    - antimicrobials
    - chemotherapeutics
    - radiocontrast
    - NSAIDs
    - endogenous heme pigments myoglobin and hemoglobin
- Postrenal– downstream obstruction

Chronic Kidney Disease

End-stage renal disease (ESRD) means the kidney dysfunction would be fatal without renal replacement therapy. These patients have < 25% GFR.

Uremic syndrome is an extreme form of chronic renal failure where GFR is < 10%. The kidneys are unable to regulate the volume and composition of ECF and excrete waste products.

Common electrolytes problems:
- Hyperkalemia
- Hyper- or hypocalcemia
- Hyperphosphatemia
- Hypermagnesemia
- Hyponatremia
- Metabolic acidosis

Glomerular filtration rate is normally 125 mL/min; renal insufficiency begins at 50 mL/min.

Chronic anemia is due to decreased production of erythropoietin. Creatinine is a waste product of the muscles that is filtered out by the kidneys. Its normal range is 0.7 to 1.3.

Chronic renal failure is associated with:
- glomerular filtration rate 15 mL/min
- hemoglobin 6 g/dL
- pruritus

REFERENCE: Barash Clinical Anesthesia 9^th edition, pages 1355-1364

Hematologic

Anemias

Sickle cell disease anesthesia management includes adequate hydration, saturation, normothermia, normal acid base balance, proper positioning, and analgesia that may interrupt intraoperative and postoperative crisis.
The three components of the Virchow triad- stasis (anesthesia), hypercoagulability, and vessel-wall injury (surgery)- lead to venous thrombosis. Malignancy/cancer would be responsible for the hypercoagulability component. Others that are classified as a stasis component are immobility, bed rest, CHF or cor pulmonale, and prior venous thrombosis.
The plasma half-life of most clotting factors is around 1.5 to 3 days, except for the initiating factor VII (6 hours) and the cofactors V and VIII (8-12 hours).
Chronic anemia leads to the following compensatory mechanisms:
- Decreased blood viscosity; increased cardiac output; increased 2,3 DPG levels; rightward shift of oxyhemoglobin dissociation curve; and increased dissolved O₂ in the plasma volume.

Hemoglobin Disorders

Coagulation Disorders

Gastrointestinal

Esophageal / Gastric Disorders

The difference between the lower esophageal sphincter (LES) pressure and gastric pressure is “barrier pressure,” which is more important than the LES tone in the production of gastroesophageal reflux.

The adult esophagus extends from the cricopharyngeal sphincter at the level of the C6 vertebra to the gastroesophageal junction.
- An inner circular layer surrounded by an outer longitudinal layer makes up the musculature.
- The upper third of the inner circular muscle is striated and the lower two-thirds are smooth.

The major physiological derangement in gastroesophageal reflux is a reduction in LES pressure.

The tunica muscularis is composed of two distinct layers of smooth muscle:
- inner circular layer
- outer longitudinal layer.

The autonomic innervation of the gastrointestinal tract functions through two distinct regions containing autonomic ganglia:
- Submucosal (Meissner’s) plexus
- Myenteric (Auerbach’s) plexus.

Gastric pH in the fasted patient ranges from 1.6 – 2.2

Gastroparesis, or delayed gastric emptying, greatly increases the risk of vomiting and pulmonary aspiration perioperatively.

Most common symptoms:
- Nausea
- Abdominal pain
- Early satiety (fullness)
- Vomiting

Gastroparesis is associated with:
- Diabetes mellitus (MOST COMMON)
  - Autonomic neuropathy due to chronic hyperglycemia that affects the vagus nerve.
- Obesity
- Pregnancy
- Opioids
- Trauma
- Pain
- Anxiety

FACTORS THAT AFFECT LOWER ESOPHAGEAL SPHINCTER TONE

INCREASE TONE

NO CHANGE IN TONE

DECREASE TONE

DRUGS:

-Anticholinesterases

-Cholinergics

-Succinylcholine

-Antacids

-Metoclopramide

-Metoprolol

HORMONES/ NEUROTRANSMITTERS:

-Acetylcholine

-Alpha stimulation

-Gastrin

-Serotonin

-Histamine

-Pancreatic polypeptide

DRUGS:

-Histamine-2 antagonists

-Nondepolarizing muscle relaxants

-Propranolol

DRUGS:

-Inhaled anesthetics

-Opioids

-Anticholinergics

-Thiopental

-Propofol

-Beta agonists

-Ganglion blockers

-Tricyclic antidepressants

HORMONES:

-Secretin

-Glucagon

CONDITIONS/ OTHER:

-Cricoid pressure

-Obesity

-Hiatal hernia

-Pregnancy

Gastroesophageal regurgitation (GERD)

- Irritation to the esophageal lining caused by stomach acid or bile

Hiatal hernia

- Part of the stomach is pushed up through the diaphragm; caused by intraabdominal pressure

Achalasia

- Nerve damage to the esophagus creates difficulty in the passage of food to the stomach

Peptic ulcer disease

- A sore that develops in the esophagus, stomach, or small intestine

ACID-BASE BALANCE

MEASURE	NORMAL
pH	7.35-7.45
PaCO₂	35-45 mm Hg
HCO₃	22-26 mEq/L

IMBALANCE	pH	PaCO₂	HCO₃
Respiratory acidosis	↓	↑ >45	↑ (compensatory)
Respiratory alkalosis	↑	↓ < 35	↓ (compensatory)
Metabolic acidosis	↓	↓ (compensatory)	↓ >26
Metabolic alkalosis	↑	↑ (compensatory)	↑ <22

Nasogastric suction is a cause of metabolic alkalosis.

Metabolic alkalosis can be a result of vomiting and laxative & diuretic abuse.

Ketoacidosis is a common cause of metabolic acidosis. If the diabetic patient has insufficient insulin to block the mobilization and metabolism of free fatty acids, the metabolic byproducts are ketones. They cause metabolic acidosis with an increased unmeasured anion gap.

Four common causes of metabolic acidosis:
- ketoacidosis
- lactic acidosis
- renal failure
- toxic dose of salicylates.

When the pH is decreased (acidosis) and its due to the bicarbonate level being low (acidosis), the lungs compensate by hyperventilating to decrease CO2.

Pancreatic (Exocrine) Disorders

The exocrine function of the pancreas is to release enzymes that aid in digestion. Pancreatic juice is secreted in to the duodenum of the small intestine by acinar cells.

The 3 types of enzymes are:
- amylose
- trypsinogen
- lipase.

Pancreatitis has MANY possible causes but alcohol abuse is the most common. Pain is the most associated with pancreatitis. These patients also suffer from nausea, vomiting, and fever. Hypotension is common as hypovolemia occurs due to the loss of plasma proteins.

Pancreatitis is associated with:
- Dehydration
  - Patients lose fluids externally (vomiting) and internally (fluid builds up around the pancreas in response to inflammation and within the lungs).
- Hypocalcemia
  - Usually involves malnutrition and/or low circulating albumin levels
- Hyperglycemia
  - Alpha and beta cells are injured
- Adult respiratory distress syndrome

Pancreatic tumors

Ductal adenocarcinomas
Insulinomas (most common functioning tumor)
Zollinger-Ellison syndrome
Duodenal neoplasm that releases too much gastrin
Linked with MEN type 1
Gastrinoma

INTESTINAL

The small intestine’s main objective is to absorb nutrients while also aiding in digestion. The small intestine also plays a major role in the immune system.
The large intestine’s primary goal is to store and expel waste. The right colon helps to absorb water and sodium.
The parathyroid hormone acts on the intestine to absorb calcium.
Scleroderma leads to hypomotility of the lower esophagus and small intestine due to the progressive fibrosis of the GI tract.

Tumors / Secreting Lesions

Carcinoid tumors are derived from enterochromaffin or Kulchitsky cells and arise from the different embryonic divisions of the gut.

- Foregut: lungs, bronchi, or stomach
- Midgut: small intestine, appendix, and proximal large bowel
- Hindgut: distal colon or rectum.

Serotonin is the most common carcinoid hormone; others include:

corticotrophin
histamine
dopamine
substance P
neurotensin
prostaglandins
kallikrein

Carcinoid symptoms can be verified by urinary 5-HIAA testing.

Octreotide, along with lanreotide, are long-acting synthetic analogues of somatostatin. These medications are best to treat hypotension during a resection of metastatic carcinoid tumor.

Carcinoid heart disease usually affects the RIGHT side with fibrous thickening of the endocardium causing retraction and fixation of the tricuspid valve. If the left side of the heart is involved, that generally means that the lungs are involved. Lung metabolism of serotonin evidently prevents involvement of the left side of the heart.

Anesthetic Considerations:

- Prevent hypotension
- Refrain from catecholamine administration
- Avoid histamine-releasing drugs (like morphine, atracurium)

MALABSORPTION

Primary clinical signs of malabsorption syndromes involving the small intestine:
- Unexplained weight loss
- Steatorrhea
- Diarrhea
- Others:
  - Anemia
  - Bone loss
  - Menstrual disturbance
- Deficiencies in fat-soluble vitamins (A, D, E, and K)

REFERENCE: Nagelhout Nurse Anesthesia 7^th edition, pages 770-805

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Immune

Infectious Disorders (e.g., HIV, AIDS)

Acquired immune deficiency syndrome (AIDS) is the final stage of infection caused by the human immunodeficiency virus (HIV).

Hypersensitivity Disorders (Allergic Response) Type I-V

A hypersensitivity reaction or intolerance refers to an immune system response to a foreign environmental antigen that causes an altered T-cell and antibody response upon reexposure to the antigen. It requires prior sensitization and can be immediate or delayed.
- NSAIDs are the most frequent trigger of anaphylaxis followed by:
  - beta-lactams and non-beta-lactam antibiotics
  - proton pump inhibitors.

- NDNMBs account for 58.2% (rocuronium at 43.1%) of anaphylactic reactions during anesthesia.
  - Latex is responsible for 16.7%
  - Antibiotics are responsible for 15.1%
  - Opioids are responsible for 1.3%

**Of drugs used in ANESTHESIA that triggered anaphylactic reactions, neuromuscular blocking agents (NMBAs) did so most frequently, with rocuronium implicated in more than 40% of cases.

Penicillins are responsible for the most anaphylactic reactions in the antibiotics class, followed closely by cephalosporins. The rest are far less frequent.

Latex anaphylactic reactions are the second most common cause during surgery and anesthesia, only behind neuromuscular blocking agents.

An H₁-receptor antagonist, alone or in combination with an H₂-receptor antagonist, may be useful in reversing hypotension refractory to epinephrine and intravascular fluid replacement.

Epinephrine, antihistamines, and corticosteroids are routinely given during anaphylaxis/anaphylactic reactions.

Mild-to-moderate bronchospasm can be treated with a beta -2 adrenergic agonist. Moderate-to-severe bronchospasm should be treated with intravenous aminophylline (a phosphodiesterase inhibitor), subcutaneous terbutaline (a beta-2 receptor agonist), or both.

The most important mediators of anaphylaxis:

histamine
leukotrienes
BK-A
platelet-activating factor

They increase vascular permeability and contract smooth muscle

TYPE 1

Immediate hypersensitivity, occurring within 15-30 minutes
- After the initial exposure, T cells stimulate B cells to produce specific IgE antibodies that bind onto mast cells and basophils.
- Upon second exposure, IgE receptors lead to degranulation of the cells and release of mediators, like histamine, heparin, proteolytic enzymes, etc.

Histamine is the most important mediator of type 1 reactions.

Tryptase is released from mast cells significantly during this response. Serial serum total mast cell tryptase (MCT) is the gold standard for differential diagnosis of anaphylaxis.

Anaphylaxis
- Severe type 1 reaction
- Risk factors for severe reactions include:
  - cardiovascular disease
  - asthma
  - advanced age
  - mast cell disorders
  - beta blockers/ACEIs

Anaphylaxis involves:
- angioedema
- systemic vasodilation
- hypotension
- 3^rd spacing
- bronchospasm
- dysrhythmias

Epinephrine is the definitive treatment.
- Decreases the degranulation of mast cells and basophils and its vasoactive properties
- Alpha-1 stimulatory effects support BP
- Beta-1 increases the inotropic and chronotropic myocardial response
- Beta-2 causes bronchodilation

Also needed for treatment:
- IV fluid resuscitation
- Vasopressin
- Methylene blue
- Glucagon

Second-line treatment
- Antihistamines (both H-1 and H-2)
- Bronchodilators
- Corticosteroids

TYPE 2

AKA Cytotoxic
Primarily mediated by IgM or IgG
Examples: type 1 diabetes, myasthenia gravis, transfusion reactions

TYPE 3

AKA Immune complex hypersensitivity
Results from the immune system to effectively rid the body of antibody-antigen complexes.
It is also IgG and IgM antibodies but the antigen is soluble.
Examples: serum sickness, systemic lupus erythematosus (SLE), and rheumatoid arthritis

TYPE 4

AKA Cell-mediated or delayed-type hypersensitivity
Can take anywhere from 24 hours to 14 days to manifest.
Primary mediators are T lymphocytes and monocytes and macrophages, and it does not involve antibodies.
Example: TB skin test

TYPE 5

Result of IgG autoantibodies
Example: Graves disease

AUTOIMMUNE DISEASES

The immune system can recognize and avoid destruction of host cells. This is called self-tolerance.

Autoimmunity is an abnormal response to self antigens resulting in production of self antibodies or autoantibodies and damage to self tissues due to dysfunction of the innate and/or adaptive immune systems.
- Graves disease
- Hashimoto thyroiditis
- Multiple Sclerosis
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Type 1 diabetes mellitus

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Other Conditions

Cancer

BURNS

Initial therapy of burn victims focuses on fluid resuscitation and airway management.

The burn patient will first experience a loss of vascular and endothelial integrity.
Inhalational injury to a burn patient’s airway greatly increases mortality.
The hallmark in the reduction in cardiac output after a major injury is 24 hours.
The initial phase of a major burn injury results in third-spaced edema and the inflammatory response (burn shock). After 24-72 hours, the hypermetabolic phase begins where the major mediators are catecholamines and corticosteroids.

All of the following are considered to be major burns:

- A 2^nd -degree burn involving more than 10% of the TBSA in adults or 20% at extremes of age;
- A 3^rd -degree burn involving more than 10% of the TBSA in adults;
- Any electrical burn
- A burn complicated by smoke inhalation.

Succinylcholine is OK in burn patients until 24 hours after the incident.

- Cholinergic receptor up-regulation occurs after a burn injury, with proliferation of acetylcholine receptors throughout the muscle membrane.
- Succinylcholine can cause potassium release from the entire muscle membrane rather than from discrete endplate junctions, leading to hyperkalemia and cardiac arrest.

The dose of nondepolarizing muscle relaxants in burn patients is increased.

- Up-regulation of acetylcholine receptors.
- Massive fluid shifts producing significant changes in volume of distribution.
- Qualitative decrease in receptor sensitivity.

TRAUMA

Airway

Airway management involves a rapid-sequence induction with manual in-line stabilization for tracheal intubation.

Even with known cervical injury, oral tracheal intubation can be performed as safely as the nasal route.
The gum elastic bougie has been used with great documented success in trauma airways.
It is the provider’s choice/discretion on whether to use direct laryngoscopy or video laryngoscopy as the current evidence shows no difference in attempts or time required.
Ventilatory strategies involve lower tidal volumes (6 mL/kg) to limit possible lung injury.

Resuscitation

For those hypotensive trauma patients, a crystalloid bolus has been proven to increase blood pressure and decrease mortality. Vasopressors in a hypotensive setting (as first-line treatment) and preloading crystalloid in a normotensive patient is not indicated.

Resuscitation is centered on the administration of “hemostatic” blood products.

Massive transfusion is:
- 10 units of whole blood in 24 hours
- > 150 mL/hr of blood loss
- Transfusion of > 5 units of whole blood in 3 hours
Transfusion ratios of PRBCs, FFP, and platelets of 1:1 improved outcomes.

The ideal resuscitative fluid for hemorrhagic shock is blood.

Neurologic

The main cause of death in trauma is neurologic injury. Hypotension and hypoxemia can have detrimental effects with traumatic brain injury (TBI). Therefore, maintaining cerebral perfusion pressure is vital.
No improvements or benefits seen with decompressive craniectomy, ventriculostomy catheter, or steroids.
Mannitol has been proven to decrease ICP but can lead to renal failure. Hypertonic saline dodges the renal risk but must be given in a central line.
Post-traumatic seizure prophylaxis for 7 days after the injury is recommended. Both phenytoin and levetiracetam are appropriate.

Substance Disorder

Alcohol
Nicotine
Other

I. BASIC SCIENCES