Associate Editor, Carlo Santaguida

I. Trauma

A. Basics

1. Monro–Kellie doctrine—There is a fixed volume within the skull and any increase in volume of one intracranial component will require a decrease in another component to maintain normal pressure.

2. Cerebral perfusion pressure CPP = mean arterial pressure (MAP) – intracranial pressure (ICP) = (⅔ diastolic blood pressure [BP] + ⅓ pulse pressure [PP]) – ICP.

3. No clear optimal level for CPP, but should be > 50–70 mm Hg

4. Autoregulation

a. Cerebral blood flow (CBF) pressure autoregulation is maintained at a constant level despite fluctuation of systolic BP from 50–160 mm Hg.

b. Viscosity—alteration of vessel diameter in response to changes in blood viscosity

c. Metabolic—CBF responds to brain metabolic demand.

d. Blood gas—Hypoxia leads to vasodilatation and P_a CO₂ regulates cerebrovascular tone.

B. Prevention of secondary injury

1. Cerebral edema—peaks several days following injury, generally due to cytotoxic edema. May increase ICP and decrease CPP. Steroids are of no benefit and are detrimental in traumatic brain injury.

2. Hypotension—results in compensatory vasodilatation and increased ICP. Avoided to maintain CPP. Systolic blood pressure (SBP) < 90 mm Hg is associated with a twofold increase in mortality.

3. Hypoxemia—detrimental from the resultant vasodilatation and ICP increase and lack of O₂ to neurons

4. Pyrexia—metabolism increased, resulting in larger energy requirement of brain. 10% increase in metabolism per increased degree centigrade

C. Brain oxygen monitoring—may be measured by jugular venous saturation or brain tissue oxygen tension. Jugular venous saturation < 50% or oxygen tension < 15% is threshold to treat

D. Brain death

1. Considered in presence of catastrophic central nervous system (CNS) event, no medical conditions and no drug intoxication or poisoning that may confound assessment, temperature > 34°C.

2. Clinical exam—Glasgow Coma Score (GCS) 3, absent pupillary light, corneal, oculocephalic, oculovestibular and gag reflexes, absent cough while suctioning, absent sucking or rooting reflexes and fulfill criteria of apnea test.

3. Apnea test—core body temperature > 36.5°C, SBP > 90 and euvolemia. Absence of respiratory response with P_aCO₂ > 60 or increase of 20 mm Hg from baseline

5. No CBF may be documented by cerebral angiography, transcranial Doppler or computed tomographic angiography (CTA) and may be necessary when cannot document other features above.

II. Cardiac

9. If SVT is in an unstable patient then cardioversion is indicated.

10. If stable then attempt to establish the diagnosis and treat with β-blocker (metoprolol) or Ca²⁺ channel blocker (verapamil).

B. Wide complex tachycardia

1. Wide complex tachycardia (> 0.12 seconds or 3 small squares QRS duration) is often a ventricular rhythm but may also be an SVT with aberrancy (bundle branch block), a pacemaker, or relating to AV reentrant tachycardia.

2. Ventricular tachycardia (VT) may often be caused by QT prolongation from hypomagnesia, hypokalemia, or iatrogenic (quinidine, digoxin).

3. Polymorphic VT is generally found in an unstable patient following myocardial ischemia but may be seen in Torsades de pointes when a prolonged QT interval is present. May resolve with K⁺ or Mg²⁺ replacement.

4. In the stable patient, elective synchronized cardioversion is appropriate treatment for VT. If the patient is unstable, then conscious synchronized cardioversion is recommended; defibrillation if patient is unconscious.

C. Bradycardia

1. Bradycardia—heart rate < 60. If associated P wave with every beat then it is a sinus bradycardia. Sign of increased ICP. Common in athletes or iatrogenic relating to drugs, it may be due to sick sinus syndrome in patients with heart disease.

2. If intermingled with SVT known as tachycardia–bradycardia syndrome.

3. If PR interval longer than 0.2 seconds then it is first degree AV block.

4. Second degree AV block is divided into Wenckebach and Mobitz.

5. Wenckebach is a cyclic progressive blocking of conduction at an AV node, which results in a dropped QRS, characterized by progressive lengthening of the PR interval.

6. Mobitz refers to a series of P waves that cannot conduct through an AV node.

7. Third AV degree block is a complete dissociation of P and QRS waves generally resulting in an escape junctional rhythm.

8. If the patient is symptomatic may treat with atropine, transcutaneous pacer, dopamine, or epinephrine drip. If the patient is not symptomatic but has a Mobitz or third degree AV block may need transvenous pacer.

D. Other electrocardiogram (ECG) findings

1. Digoxin—gradual downward curve of ST segment; causes multiple dysrhythmias and AV blocks

2. Hypocalcemia—increased QT interval

3. Hypokalemia—U-wave

4. Hyperkalemia—peaked T-wave

5. Hypothermia—J-point elevation

7. Quinidine toxicity—prolonged QT interval, notched P wave, wide QRS, ST depression

8. Subendocardial ischemia—ST depression

9. Transmural ischemia—ST elevation

10. Pericarditis—flat or concave ST segment elevation often in all leads

11. Brugada syndrome—right bundle branch block with ST elevation in V1–V3 predisposes to sudden cardiac death

12. Long Q-T syndrome—QT interval is > 50% of cardiac cycle, predisposes to arrhythmias

13. Wellens syndrome—T wave inversion in V2–V3 due to anterior descending coronary artery stenosis

14. Subarachnoid hemorrhage (SAH)—shows peaked T wave and ST depression

15. Pulmonary embolism—Most frequent ECG changes are nonspecific ST and T changes (66%), tachycardia (63%), and rarely the classic “S1Q3T3.”

E. Cardiac medications

1. Antiarrhythmics—class 1 (Na⁺-channel blockers), class 1A (quinidine and procainamide; may lead to reversible K+-channel blockade resulting in prolonged QT), class 2 (β-blocker), class 3 (K⁺-channel blocker such as amiodarone, sotalol), class 4 (Ca²⁺-channel blockers)

2. Adrenergic receptors – α₁-receptor stimulation leads to vasoconstriction. β₁ receptors increase cardiac rate (chronotropy) and strength of contraction (inotropy). β₂ receptors vasodilate.

3. Dopamine receptor—leads to vasodilatation in cerebral, renal, coronary, and mesenteric vasculature

4. Dobutamine—β₁ agonist, mild β + α₂ agonist, inotropic, causes peripheral vasodilation (reduces afterload), increases cardiac output (CO) with a reflex decrease in systemic vascular resistance (SVR), no change in BP. Side effects include tachycardia if hypovolemic. Contraindications include hypertrophic cardiomyopathy. Dose is 5–15 μg/kg/min up to 40.

5. Dopamine—causes renal, splanchnic, and cerebral vasodilation, increased renal Na⁺ excretion independent of blood flow and vasoconstriction with higher doses. Useful with cardiogenic or septic shock. Doses are 1–2 μg/kg/min for renal effect and selective vasodilatation. Doses of 5–10 μg/kg/min have more β₁ effect leading to higher stroke volume; 10–20 μg/kg/min for α₁ and β₁ effects. Side effects include tachydysrhythmias.

6. Epinephrine—Strong β₁, moderate β₂ + α₁, drug of choice for anaphylaxis. α₁ effects predominate over β₂ at higher doses. Dose is 3–5 mL of 1:1000 or 2–4 μg/min. Side effects include myocardial ischemia, dysrhythmia, and acute renal failure.

7. Phenylephrine—Mostly a₁ effects with minimal effects on inotropy and chronotropy.

8. Norepinephrine—Agonist for α₁ and β₁ receptors, may lead to reflex bradycardia following increase in MAP. Drug of choice in septic shock. Dose is 8–70 μg/min. Use with dopamine 1 μg/kg/min for renal protection. Contraindications include renal failure.

9. Vasopressin—noradrenergic pressor, appropriate for late vasodilatory shock

11. Furosemide—a diuretic that increases SVR and decreases CO. Diuresis occurs in 20 minutes–2 hours. Nonsteroidal antiinflammatories (NSAIDs) may block the response. Use for early oliguric renal failure. Dose is 1 mg/kg. Side effects include ototoxicity, hypokalemia, hypomagnesemia, hypochloremia, and metabolic alkalosis. Contraindications include sulfa allergy, hepatorenal syndrome, and edema from nephrotic syndrome.

12. Glucagon—increases heart rate and contractility independent of its β effect. It reverses a β-blocker overdose to help as an inotrope, but not a chronotrope. Consider use with electromechanical dissociation. Dose is 1–5 μg up to 1–20 μg/h mixed with 10 mL saline intravenously (IV). Side effects include hypokalemia and hyperglycemia.

13. Labetalol—blocks α and β receptors to lower BP and does not increase heart rate or change CO. Dose is 2 mg/min or 20–80 mg every 10 minutes up to 300 mg IV.

14. Nitroglycerine—relaxes arteries (> 200 μg/min) and veins (< 50 μg/min) and increases coronary blood flow. Use with myocardial ischemia/infarction (if normotensive), pulmonary hypertension, and heart failure. Dose is 10–200 μg/min. There is decreased tolerance with intermittent infusion (12 hours on/12 hours off) or N-acetylcysteine that replenishes sulfhydryl groups in vessel walls. Side effects include methemoglobinemia that causes cyanosis with a normal blood gas when it is >10% (70% is usually fatal). Treat with methylene blue, 2 mg/kg IV over 10 minutes. Contraindications include increased ICP and closed-angle glaucoma.

15. Sodium nitroprusside—dilates arteries and veins, increases stroke volume, and does not change heart rate. Drug of choice for hypertensive emergencies. Dose is 2–3 μg/kg/min for < 72 hours. Side effects include cyanide toxicity, especially in smokers with decreased thiosulfate. Cyanide is converted to thiocyanate in the liver and is excreted from the kidneys. Symptoms include headache, nausea, vomiting, weakness, hypotension, lactic acidosis, and tolerance to nitroprusside. Keep the cyanide < 5 μg/mL. Prevent toxicity by mixing with 1% thiosulfate solution. Also try to keep the B₁₂ level normal. Thiocyanate toxicity causes acute renal failure, mental status changes and occurs with levels >10 mg/dL. Contraindications include B₁₂ deficiency and renal failure.

F. Cardiopulmonary resuscitation (CPR)—30% survive and 10% recover to baseline. Postresuscitation injury is caused by poor reflow from vasoconstriction (treatment is with Ca²⁺-channel blockers or Mg²⁺) and reper-fusion injury by free radicals. Consider giving MgSO₄ 2 g IV over 20 minutes to prevent “no reflow” from vasoconstriction. Consider Ca²⁺– channel blockers when not hypotensive. Steroids and barbiturates have not been shown to be of value. Prognosis is related to the ischemic time before and during CPR. 30% of patients in postresuscitation coma regain consciousness. After 48 hours, only 2–7% of patients still in a coma recover; after 7 days, none recover.

G. Air embolism—associated with dyspnea, substernal chest pain, millwheel murmur, focal neurologic deficits, and cardiorespiratory failure. May be diagnosed with echocardiography (presence of air, ventricular dilatation, pulmonary artery hypertension), end tidal CO₂ (fall in end-tidal CO₂), computed tomography (CT) scan, and pulmonary angiography. The most sensitive monitor is the precordial Doppler. Treated with left lateral decubitus position, nitrogen washout (high flow O₂), hyperbaric O₂, or aspiration of air from venous circulation. Mortality rate is 15%.

A. Oxygenation

1. O₂ content = 1.34[Hb g/dL] × O₂ saturation + (0.003 × PaO₂) = O₂ mL/100 mL

2. O₂ delivery = O₂ content × CO. Normal 520–570 mL/min/m²

3. O₂ uptake = CO × (arterial O₂ content – venous O₂ content). Normal 110–160 mL/min/m²

4. O₂ extraction ratio = Uptake/Delivery × 100 (22–32%)

5. If the O₂ extraction ratio exceeds 60%, uptake becomes dependent on delivery.

6. All tissues increase O₂ extraction in the face of decreased blood flow except the coronary circulation, which is always at its maximal extraction rate (flow dependent).

7. Mixed venous O₂ is measured in the pulmonary artery, and normal is 68–77%. It is lower with hypoxemia, increased metabolic rate, decreased CO, and anemia.

8. Lactate increases if the O₂ delivery is less than the metabolic demand and the cells are forced to use anaerobic glycolysis. Normal blood level is < 2 mmol/L, and > 4 mmol/L is abnormal.

9. Lactate may be elevated without hypoxemia, but with hepatic insufficiency (decreased clearance), thiamine deficiency (interferes with glucose metabolism), infection (endotoxin release affects glucose metabolism), and respiratory alkalosis.

10. The plateau of the oxygen–hemoglobin dissociation curve begins at PO₂ 60 mm Hg, and O₂ saturation 90%. Below this point, the O₂ saturation drops much more quickly with decreases in O₂ pressure.

11. Bohr effect

a. Right shift—occurs in tissues and there is decreased O₂ affinity. A right shift occurs with increases in H⁺, CO₂, temperature, and 2,3-diphosphoglycerate (DPG).

b. Left shift—occurs in the lung and there is increased O₂ affinity. A left shift occurs with decreases in H⁺, CO₂, temperature, and DPG, as well as with banked blood (due to decreased DPG). Hemoglobin has less affinity for O₂ in the tissues where there are higher H⁺ and CO₂ levels.

12. Oximetry detects red oxyhemoglobin and infrared deoxyhemoglobin in a photodetector. Pulse oximetry samples only pulsatile vessels (arteries) because it detects volume fluctuations. It is not affected by most skin tissue thickness, pigments, or nail polish. Oximetry becomes less accurate when the O₂ saturation is below 70%.

13. Nasal cannula providing 100% O₂ at 1–6 L/min produces a FiO₂ of 0.21–0.46.

14. The maximum FiO₂ that can be achieved with a nasal cannula is 46%. This is with 6 L/min minute ventilation, and it is even less with tachypnea.

15. Standard mask providing 5–10 L/min of 100% O₂ can produce a FiO₂ of 40–60%. This level is lowered with increased respiratory rates caused by inhalation of ambient air.

16. Partial rebreather mask (no ambient air allowed, rebreathing done into mask) at 5–7 L/min provides a FiO₂ of 75%.

17. Nonrebreather mask (no ambient air allowed, exhaled breath is not reinhaled) at 4–10 L/min provides a FiO₂ of 100%.

1. Anatomic dead space (= 150 mL) includes the trachea, bronchi, and distal parts of the respiratory tree that are not used for gas exchange.

2. Physiologic dead space includes the alveoli where gas is not equilibrating with the capillary blood.

3. Total dead space normally makes up 20–30% of minute ventilation. In the normal alveoli, the arterial and expired PCO₂ are equal because no dead space is present.

4. Increased dead space is caused by overdistended alveoli (COPD and positive end-expiratory pressure [PEEP]), destroyed alveolar–capillary interface (emphysema), or decreased blood flow (congestive heart failure, pulmonary embolus).

5. The O₂ pressure in the alveolus— (P_A O₂) = FiO₂ (Pb – P_water) – (P_a CO₂/RQ) = 0.21 (713 mm Hg) – P_a CO₂/0.8, where Pb is atmospheric pressure and RQ is the respiratory quotient.

6. The A-a gradient is the alveolar to arterial O₂ gradient (P_AO₂ − P_aO₂). The P_AO₂ = FiO₂ (Pb – P water) – (P_a CO₂/RQ) and is normally 100 mm Hg at FiO₂ of 0.21 producing an A-a gradient of 10–20 mm Hg. The normal A-a gradient increases 6 mm Hg for each 10% increase in FiO₂ and is 60–70 mm Hg at a FiO₂ of 1.0. Increased FiO₂ causes an increased A-a gradient because there is less hypoxic vasoconstriction in the poorly ventilated areas.

7. In hypoxemia if the A-a gradient is normal, there is likely no primary cardiopulmonary problem so consider neuromuscular or central nervous system (CNS) causes. If there is an increased A-a gradient and the venous PO₂ is > 40 mm Hg, the problem is caused by increased dead space or shunting. If the venous PO₂ is < 40, the problem is caused by decreased blood flow or a high metabolic rate.

8. Hypercapnia can be caused by increased production of CO₂ from sepsis, trauma, burns, increased carbohydrate intake, and acidosis.

9. RQ = VCO₂/VO₂ and is the ratio of molecules of CO₂ created for each O₂ used. Normal is 0.8; carbohydrates are 1, proteins are 0.8, and lipids are 0.7. Therefore, an increased carbohydrate load creates more CO₂ molecules to expel.

10. Hypercapnia can also be caused by hypoventilation with a normal A-a gradient as with sleep apnea, myasthenic syndrome, Guillain–Barré syndrome, phrenic nerve injury, peripheral neuropathy, muscle weakness (from decreased phosphate or Mg²⁺, sepsis, and shock), opiates, and lidocaine.

C. Pulmonary disorders

1. Acute lung injury (ALI)—defined as lung inflammation resulting in increased pulmonary capillary permeability. Characterized by bilateral chest infiltrates with pulmonary capillary wedge pressure (PCWP) < 18 mm Hg (or no suspected heart failure) and PaO₂/FiO₂ between 201 and 300 mm Hg

2. Acute respiratory distress syndrome (ARDS)—more severe ALI with worsening hypoxia (PaO₂/FiO₂ < 200 mm Hg). There is diffuse alveolar damage. Protein leaves vascular space losing colloid osmotic pressure gradient, which prevents fluid reabsorption from alveoli. The alveoli fill with inflammatory fluid. Acute onset and may persist for weeks. Causes include sepsis, aspiration, infectious pneumonia, trauma, burns, and pancreatitis. Mortality rate is over 30%.

7. Heliox—a combination of helium and O₂ that results in a reduction of turbulent air flow. Greatest benefit in acute upper airway obstruction

E. Paralytics, sedatives, muscle relaxants

1. Side effects—decreased ability to clear pulmonary secretions even with suctioning (increased risk of pneumonia and mucous plug) and increased risk of venous thromboemboli

2. Halothane—causes central depression and bronchodilation

3. Vecuronium—a nondepolarizing blocker, has the least histamine release, dose is 0.1 mg/kg, duration is 30 minutes

4. Pancuronium—a nondepolarizing blocker, dose is 0.01 to 0.05 mg/kg every hour, duration is 1 hour, side effects include tachycardia

5. Succinylcholine—a depolarizing blocker, short acting, increases the K⁺ level; contraindicated with hyperkalemia, hemiplegia, or other neurologic disorders associated with weakness

6. Reversal agents—used to counteract muscle paralysis of competitive acetylcholine receptor blockade. The local acetylcholine levels are increased by acetylcholinesterase inhibitors such as neostig-mine 2.5–5 mg/70 kg. Pretreat with atropine (0.6–1.5 mg/70 kg) to prevent bradycardia from the increased parasympathetic stimulation by the increase in acetylcholine levels. Onset may be delayed 15–30 minutes.

7. Haloperidol—does not cause respiratory depression or hypotension (unless used with propranolol). Dose is 3–5 mg IV up to 10 mg, wait 20 minutes and double the dose. If this is ineffective, change agents or add benzodiazepines. There are less extrapyramidal side effects with the IV route. This condition is associated with neuroleptic malignant syndrome characterized by hyperthermia, muscle rigidity autonomic dysfunction, and confusion. This condition may occasionally be fatal and should be treated with dantrolene. Haloperidol also lowers seizure threshold.

8. Diazepam—1–10 mg IV

9. Lorazepam—0.04–0.05 mg/kg, good amnestic

10. Midazolam—1 mg IV every 3 hours up to 0.15 mg/kg or 0.4 μg/min, good amnestic

11. Morphine—increases histamine release and worsens asthma

K. Mechanical ventilation

1. Four modes—volume-, pressure-, time-, or flow-cycled

2. Volume-cycled—Ventilation is entirely dependent on preset tidal volume, respiratory rate, and inspira-tory flow.

a. Controlled mechanical ventilation—Ventilation is only dependent on rate and tidal volume settings, which is appropriate if the patient is not making respiratory efforts.

c. Intermittent mandatory ventilation—Preset tidal volume and rate is delivered at a regular interval and patient may breathe spontaneously as well.

3. Flow-cycled—pressure support once the patient triggers a breath, a preset pressure is delivered until flow tapers

4. Tidal volume—normally at 5–6 cc/kg in humans

5. Rate—Start at 12 for adults.

6. Sigh—a breath 1.5 × tidal volume, not shown to be of benefit

7. Monitoring lung mechanics—assess without mechanical ventilation. Test lung volume for elastic recoil and expiratory flow rate for resistance.

8. Proximal airway pressure—The peak end-inspiratory pressure is proportional to the inflation volume, the resistance of the airways, and the lung and chest wall compliance. It is proportional to R + 1/C, where R is airway resistance and C is lung and chest wall compliance.

a. At a constant volume, an increased inflation pressure is due to either increased resistance or decreased compliance.

b. The plateau pressure is proportional to 1/C.

c. Increased plateau pressure is due to decreased compliance. Increased peak pressure with no change in plateau pressure is due to increased airway resistance.

d. Increased peak and increased plateau pressures are due to decreased lung/chest wall compliance. Compliance = Volume change/Pressure change = tidal volume/plateau pressure cm H₂O. Normal is 0.05–0.07 L/cm H₂O.

9. Acute respiratory failure—usually caused by pneumonia, edema, and COPD. These do not respond to steroids or bronchodilators. If the patient is not on a ventilator, check for airway obstruction at the bedside with a peak expiratory flow rate (positive if >15% increase noted). If the patient is on a ventilator, assess the peak inspiratory pressure.

10. If there is a sudden respiratory deterioration:

a. Peak pressure increased with normal plateau pressure—likely increased airway resistance. Treat with suction or bronchodilation.

b. Peak and plateau pressure increased—likely decreased compliance or auto PEEP (with obstructive lung disease). Likely due to pneumothorax, atelectasis, edema, or abdominal distension

c. Peak pressure decreased—assess for air leak

11. PEEP should help increase compliance and decrease plateau pressure. In determining efficacy, be sure to subtract the PEEP setting from the measured plateau pressure to obtain the correct value.