BARBITURATES: THIOPENTAL

QUESTION 1: Thiopental is contraindicated in:
A. porphyria congenita
B. porphyria cutanea tarda
C. acute intermittent porphyria
D. myotonia
E. chorea

QUESTION 2: Propofol compared to thiopental:
A. is less likely to provoke bronchospasm
B. if administered in equipotent doses for induction of anesthesia causes less reduction in systemic blood pressure
C. causes adrenal suppression after prolonged infusion
D. has no effect on cerebral metabolic rate
E. does not cause excitatory motor activity

QUESTION 3: The action of thiopental after injection is terminated by:
A. its elimination unchanged by the kidneys
B. its biotransformation by the liver
C. its being bound to proteins
D. its redistribution
E. being taken up in fatty tissues

ANSWER 1: (C) Thiopental is contraindicated in patients with acute intermittent porphyria.  The other porphyrias listed as options are not associated with enzyme induction

ANSWER 2: (A) excitatory phenomena after propofol induction occur at about the same frequency as with thiopental, however, bronchospasm appears to occur less frequently.  In equipotent doses, propofol produces a dose-dependent decrease in blood pressure that is more pronounced than with thiopental administration.  Propofol and thiopental cause a similar decrease in cerebral metabolic rate.  Adrenal suppression occurs after the administration of etomidate.

ANSWER 3: (D) The action of thiopental is terminated by redistribution.  The drug is bound to protein, and various concomitant drugs may interfere with binding.  It is taken up in fatty tissues, but that is not the mechanism of terminating its effect.

VOLATILE ANESTHETICS

QUESTION 1: The current theories of the mechanism of general anesthesia suggest that all volatile anesthetics: (select all that apply)
1. act at a specific receptor
2. act primarily in the reticular activating system
3. depress release of neurotransmitters
4. affect synaptic transmission

QUESTION 2: The MAC value for isoflurane is: (select all that apply)
1. highest in the young
2. decreased at age 70 compared to age 20
3. decreased at lowered body temperature
4. decreased by administration of 70% nitrous oxide

QUESTION 3: A patient is to have a cholecystectomy.  The anesthesiologist decides to use sevoflurane in oxygen as the sole anesthetic agent, with no other medications administered.  Approximately what concentration of sevoflurane will be required to prevent movement in response to intubation?
A. 1.75%
B. 2.25%
C. 3%
D. 4%
E. 5%

ANSWER 1: (4) It is thought that all volatile anesthetics affect synaptic transmission.  Excitatory synapses are depressed by general anesthetics while inhibitory synapses may be depressed or potentiated.  There is no specific receptor konwn for volatile anesthetics, and no definite location within the CNS is thought to be responsible for their actions.

ANSWER 2: (1, 2, 3, 4) The MAC value is highest in the very young child and decreases as one gets older.  It is also decreased by lower body temperature.  Nitrous oxide in 70% concentration decreases MAC for a given agent.

ANSWER 3: (C) MAC is defined in terms of the prevention of movement in response to skin incision.  The concentration necessary to prevet movement in response to a greater stimulus, such as intubation, is approximately 1.5 times the values for MAC.

REFERENCE:

McGraw-Hill Specialty Board Review

COPD

QUESTION 1: A patient with obstructive lung disease has an altered anesthetic induction with an insoluble agent because of:
A. decreased cardiac output
B. increased perfusion
C. increased PCO2
D. uneven ventilation
E. decreased minute volume

QUESTION 2: A patient has chronic obstructive pulmonary disease requiring the constant administration of oxygen.  He is dypsneic at rest and can walk at the most 20 feet before needing to rest.  He is scheduled to undergo an exploratory laparotomy because of small bowel obstruction.  He would be classified by the American Society of Anesthesiologists as a physical status:
A. III
B. IIIE
C. IVE
D. V
E. VE

Here's your COPD patient.  Have fun intubating him!

(Beards are wierd)

ANSWER 1: (D) The patient with chronic obstructive lung disease has a prolonged induction due to ventilation/perfusion mismatching.  The cardiac output is usually not decreased.  The increased PCO2 does not directly affect the uptake of the agent.  Decreased minute ventilation is not a factor.

ANSWER 2: (C) This patient would be classified as physical status IV because he has an incapacitating systemic illness.  Because the patient is to undergo an emergency procedures, "E" is added to the physical status.

REFERENCES:

McGraw-Hill Specialty Board Review

REGIONAL ANESTHESIA: BLOCKS

QUESTION 1: The stellate ganglion:
A. is a fusion of the inferior cervical and first thoracic ganglia
B. receives fibers whose cell bodies are located primarily at the C4-C7 levels of the spinal cord
C. is primarily a parasympathetic ganglion
D. lies at the level of the fifth cervical vertebra
E.. may be blocked with little danger of complications

 

 

QUESTION 2: The most superior approach to the brachial plexus involves placing the needle:
A. between the lateral head of the sternocleidomastoid muscle and the anterior scalene muscle
B. between the medial and lateral heads of the sternocleidomastoid muscle
C. between the anterior and posterior scalene muscle
D. between the anterior and middle scalene muscle
E. on the first rib

QUESTION 3: The obturator nerve:
A. is unimportant in arthroscopic surgery of the knee
B. supplies motor innervation to the adductor muscles of the hip
C. supplies sensory innervation to the skin overlying the patella
D. is derived from the first and second sacral roots
E. supplies sensory innervation to the lateral aspect of the knee

(answers at bottom of post) 

___________________________________________________________________________________________________________________________________

REGIONAL ANESTHESIA: BLOCKS

*This is a summary/overview of Regional Blocks based on Nagelhout Nurse Anesthesia.  Please click on the NYSORA link (www.nysora.com) to read step-by-step procedures.  Future posts will focus more indepth on individual blocks*

*Click on photos to start familiarizing yourself with nerve anatomy*

-Permits the patient to retain upper airway and pharyngeal reflexes while providing surgical anesthesia.

-Block of SANS results in increased gastric and intestinal motility causing the stomach to empty sooner

-Hypotension that develops from regional may cause increased nausea and vomiting

-Should not be considered an alternative to securing the airway.  If airway cannot be secured in a safe manner regional should be avoided

ABSOLUTE CONTRAINDICATIONS:

• patient refusal*
• uncorrected coagulation deficiencies
• infection at site of block
• severe bleeding with or without hypovolemia or potential for severe bleeding
• trauma and other conditions that cause contracted volume states can result in significant hypotension and tachycardia after initiation of regional
• hypovolemic shock
• abruptio placentae with or without fetal distress

RELATIVE CONTRAINDICATIONS:

• patient age – recommended in neonates; peds provides postop pain management à but should be avoided in children who are unable to tolerate loss of feeling and strength in legs (age 3-9; anxiety)
• pts who have difficulty understanding the procedure or who are uncooperative
• history of headaches or backaches
• pts with chronic neurologic disorders
• history of documented LA allergy (a true allergy is rare) – reaction may be d/t a preservative or PABA (para-aminobenzoic acid) a metabolic product of LA hydrolysis.  Or may be from LA that contains epinephrine.  If they are allergic to an ester, choose and amide.  Premedicate with H1 & H2 blocker.
• history of Mobitz type I, Mobitz type II or 3^rd degree heart block without a pacemaker
• patients with fixed-volume cardiac states (unable to respond to changes in SVR by increasing SV as a means of maintaining CO

COMPLICATIONS:

• CV problems are the most critical immediate complications
• respiratory and GI consequences
• immediate and delayed complications
• Immediate: potential of intravascular injection à CNS toxicity (tingling of lips, strange taste in mouth, ringing in ears, visual disturbances, seizures); cardiac dysrhythmia (ventricular); respiratory and CV collapse
• Complications with Continuous peripheral nerve blocks: nerve injury, bleeding requiring surgical intervention, catheter-associated infection, dyspnea, pneumothorax, LA toxicity, local inflammation at catheter insertion site, equipment failure (broken needles, broken/sheared catheters, glass in the epidural and SA space, injection of wrong drugs)

Techniques used for Regional Blocks:

1. Peripheral nerve stimulators
2. Ultrasound-guided

UPPER-EXTREMITY BLOCKS:

4 Primary approaches to block the brachial plexus:

1. Axillary

2. Interscalene

3. Supraclavicular

4. Infraclavicular

*Axillary is most frequently used

BRACHIAL PLEXUS ANATOMY:

Brachial plexus is a large network of nerves that extend from the neck through the xilla and innervate the upper extremity

(click image to enlarge)
Composed of ventral rami (roots), trunks, divisions, cords and their branches.

(Randy Travis drinks cold beers)

(click image to enlarge)

Supraclavicular portion: 5 ventral rami, 3 trunks, 6 divisions  (lies in posterior triangle of neck)

Infraclavicular portion: 3 cords, 4 branches (lies in axilla)

(click image to enlarge)

BP passes between anterior and middle scalene muscles, through posterior triangle of the neck and into the axilla, where they end in the 4 branches that supply upper extremity

RAMI/ROOTS

• -Originate from C5-T1; small % of individuals arise from C4 or T2

TRUNKS

• The 3 nerve trunks (superior, middle, inferior) are enveloped by a fascial “sheath” – arises from fascia of anterior and middle scalene muscles à forms the interscalene space

DIVISIONS

• 6 divisions can be divided further into 3 ventral divisions and 3 dorsal divisions
• Ventral divisions: supply ventral (flexor) portion of upper extremity
• Dorsal divisions: supply dorsal (extensor) portions of upper extremity

CORDS

• 3 cords: posterior, lateral, medial – named according to their position in relation to the axillary artery
• Lateral à divides into muscularcutaneous nerve and portion of median nerve
• Medial à ulnar nerve and portion of median nerve
• Posterior à axillary nerve and radial nerve

NERVE BRANCHES

Branches of lateral and medial cords (median, ulnar, musculocutaneous) predominately supply ventral portion of upper extremity

Posterior cord (radial, axillary) supply dorsal portion of upper extremity

Posterior portion of fingers and hand, considerable cutaneous representation of the “predominantly ventral” median and ulnar nerves

• Radial nerve (C5-C8, T1) is major nerve supply to dorsal extensor muscles (triceps) of upper limb below shoulder, sensory innervation to extensor region of arm, forearm, and hand.
• Musculocutaneous (C5-C7) supplies flexor muscles (biceps, brachialis, coracobrachialis) of ventral portion of arm; supplies sensory to lateral aspect of forearm btwn wrist and elbow as the lateral antebrachial cutaneous nerve.
• Median and ulnar nerves pass through arm and provide sensory and motor innervation to forearm and hand
• Median (C6-T1) supplies flexor and pronator muscles; sensory to ventral portion of thumb, first and second fingers, lateral ½ of third finger, palm of hand
• Ulnar (C8 and T1) supplies motor to most of small flexor muscles.  No sensory innervation of forearm; sensory to medial part of third finger, entire 4^th finger and remaining portion of palm of hand

APPROACHES TO BRACHIAL PLEXUS BLOCK:

Choice of approach should be based on patient considerations, location of planned surgical intervention and skill and experience of the practitioner.

AXILLARY APPROACH (Nysora link)

For surgery at or below elbow (hand, forearm)

Limited rang of motion of extremity (fracture – pain) can limit access to axilla and use of this block

(click image to enlarge)

Clockwise from musculocutaneous --> Median --> Ulnar --> Radial

Mc-M-U-R

(click image to enlarge)

Can use one of 3 techniques:

·        Loss of resistence

·        Penetration of axillary artery

·        Elicitation of paresthesia

INTERSCALENE APPROACH (Nysora link)

Most proximal brachial plexus block; used for surgery involving shoulder and proximal humerus; only technique that can provide anesthesia to shoulder and rest of upper extremity.

(click image to enlarge)

Three trunks of the cervical plexus are revealed lying alongside the subclavian vessels

Catheter is placed at level of trunks

(click image to enlarge)

SUBCLAVIAN APPROACH

Subclavian artery palpated behind midpoint of clavicle (palpate 1-2 cm above clavicle); advance needle here perpendicular to skin

*Must watch for onset of Horner syndrome (triad of miosis, partial ptosis, and loss of hemifacial sweating) as a positive sign of a successful block.

Complication: pneumothorax (pleura of lung is immediately inferior to first rib)

(click image to enlarge)

The needle enters the sheath of the brachial plexus at the farthest possible distance from the SC artery

(click image to enlarge)

The patient is placed in the supine position with the head supported and turned toward the opposite shoulder.

INTERSTERNOCLEIDOMASTOID APPROACH (ISCM)

Newest supraclavicular approach; puncture site situated between heads of SCM muscle

Decreases incidence of Horner syndrome and pneumothorax associated with subclavian approach

Brachial plexus reached at level of trunks; Needle passes between heads of SCM, behind clavicular head, through middle cervical fascia, next to phrenic nerve, through anterior scalene before arriving at brachial plexus

Puncture site is 2 fingerbreadths above sternal notch, btwn heads of SCM, medial to clavicular head.

SELECTIVE BLOCKS AT THE ELBOW:

Primarily sensory blocks; pt can still move

When a tourniquet is used during surgery, the intercostobrachial nerve and brachial cutaneous nerve should be blocked in the axilla à permit patient to tolerate tourniquet  Coracobrachial muscle can also be blocked at level of shoulder to tolerate tourniquet

1. ULNAR NERVE BLOCK AT ELBOW:

Ulnar nerve traverses ulnar sulcus of humerus; < 3 ml to prevent ischemia of nerve

Performed 1-2 cm proximal to sulcus

Identify medial condyle of humerus; insertion point of needle is between medial condyle of humerus and olecranon process of ulna

If paresthesia is elicited on introduction of needle, withdraw needle 1 mm and inject 2-3 ml of LA

(click image to enlarge)

The pts elbow is flexed 90 degrees and the medial condyle of the humerus is identified.

2. MEDIAN NERVE BLOCK AT ELBOW:

Anesthesia of forearm and hand can be done with combination of median and ulnar nerve block

Median nerve block can supplement partially successful brachial plexus block

Should be avoided in pts with carpal tunnel syndrome, neuritis, or perforated artery

Needle inserted slightly medial to brachial artery at depth of 0.5-0.75 cm

(click image to enlarge)

Performance of median nerve block, positioning pts arm on a stable surface with the elbow slightly flexed.  After brachial artery is identified, a short needle is inserted slightly medial to the brachial artery.

3. RADIAL NERVE BLOCK AT THE ELBOW

Radial nerve is located in groove formed by fascial border of brachioradialis muscle on lateral edge and biceps tendon medially

SELECTIVE BLOCKS AT THE WRIST (Nysora link)

Anesthesia for outpatient or supplement to brachial plexus anesthesia; only sensory

1. ULNAR BLOCK AT THE WRIST

(click image to enlarge)

With the pts wrist slightly flexed and stabilized on a firm surface, the ulnar flexor muscle of the wrist is identified.  A short needle is inserted perpendicular to the skin on the radial side of the ulnar flexor muscle of the wrist.

2. MEDIAN BLOCK AT THE WRIST

3. RADIAL BLOCK AT THE WRIST

(click image to enlarge)

Anesthesia of radial fibers is achieved by injecting a subcutaenous ring of LA solution at the radial flexor muscle of the wrist, extending to the dorsal surface of the ulnar styloid.

BIER BLOCK: INTRAVENOUS REGIONAL ANESTHESIA (Nysora link)

Best for upper extremity (hand, wrist) soft-tissue surgery of < 1 hr; can be used for lower extremities

Requires use of a tourniquet

Potential for rapid transfer of large volume of LA from extremity to central circulation – have emergency equipment available

1. Apply tourniquet but keep deflated
2. elevate extremity and exsanguinate by wrapping Esmarch bandage from fingers to tourniquet
3. inflate tourniquet to 100 mmHg above SBP (or 250 mmHg); remove bandage
4. inject 50 ml of 0.5% lidocaine via IV – preservative free, no epi
5. can use additional tourniquet (Penrose drain) for faster onset and denser block
6. can add 15 – 30 mg of ketorolac to LA soln

Indications for lower extremity IV regional anesthesia include orthopedic surgery of short duration on foot, removal of fixation plates and screws from bones below the knee, foreign body removal from foot.

INTERCOSTAL NERVE BLOCKS (Nysora link)

Anatomic landmarks easily identified; no extremely painful, high success rate, low complications

Most common complications: pneumothorax and toxicity from LA

Pt who has pain with respiratory effort is able to cough and breathe deeply with reduced pain.

High vascularity of area and large intercostal veins contribute to high plasma level of LA

Pt position can be prone, lateral or sitting

(click image to enlarge)

Intercostal nerve emerges from intervertebral foramen and follows rib in the costal groove.  This groove is located in anteroinferior aspect of rib.  The intercostal artery and vein accompany nerve in this groove.

Catheter can be inserted.

Tachyphylaxis can develop; use a different class of LA (ester or amide)

LOWER EXTREMITY BLOCKS

Anatomy of Lumbar Plexus

Formed from L1-L4; contributions from T12.  Formed in front of quadratus lumborum muscle and behind psoas major muscle.

The lateral femoral cutaneous nerve is formed from L2-L3 and is first to leave compartment.  It emerges from lateral border of psoas major at its midpoint.  Then traverses iliac muscle obliquely toward anterior iliac spine.  Passes under lateral border of inguinal ligament and provides sensory innervation to the lateral aspect of the thigh.

The obturator nerve arises from L2-L4 as an extension of the lumbar plexus.  Emerges from medial border of psoas major at level of sacroiliac joint and is covered by external iliac artery and vein.  Passes into pelvis minor and runs anteroinferiorly to obturator canal which it traverses near obturator vessels.  *Because of the proximity of the nerve to the external iliac artery, it can be injured during surgical procedures.  Frequently injured during pelvic surgery.  Obturator nerve is primarily a motor nerve that has some mixed sensory fibers to hip, medial aspect of femur, and skin and soft tissue of lower portion of thigh.

The femoral nerve is formed from L2-L4 is at junction of middle and lower 1/3 of psoas major muscle.  Remains within the groove of the psoas major and iliac muscles and runs deep under the inguinal ligament where it comes anterior to iliopasoas muscle and lateral to femoral artery.  Forms 2 branches: anterior and posterior bundles.
Anterior branch provides innervation to anterior surface of thigh and sartorius muscle.
Posterior branch provides innervation to quadriceps muscles, knee joint, and its medial ligament and is the origin of the saphenous nerve.
*Femoral nerve is encased in a sheath anatomically similar to brachial plexus - same techniques used in upper extremities can apply here.

(click image to enlarge)

PSOAS COMPARTMENT BLOCK (Nysora link)
Blockade of the lumbar plexus as a unit can be accomplished by injecting LA into the fascial sheath surrounding the plexus.  This can be done at the level of the psoas compartment.
This approach attempts to block the plexus as it lies in the fascial plane bordered medially by the vertebral column, dorsally by the quadratus lumborum muscle, and ventrally by the psoas major muscle.

(click image to enlarge)

INGUINAL PERIVASCULAR TECHNIQUE AND FEMORAL NERVE BLOCK (Nysora link)
This is also known as the three-in-one block, or Winnie's block.
The lumbar plexus is "sandwiched" among the psoas major, quadratus lumborum, and iliacus muscles and is enclosed by the fascia of these three muscles.

Complication: infection of deeper tissues

(click image to enlarge)

Site of injection is 1 cm lateral to femoral artery and 1 cm inferior to inguinal ligament.  Volume 30 ml

CONTINUOUS FEMORAL NERVE BLOCK

Similar to previous block but catheter is inserted 5-10 cm beyond tip of needle.  Continuous infusion of LA is initiated after 15-20 ml bolus injection at a rate of 8-10 ml/her.
0.2% ropivacaine or 0.25% bupivicaine

FASCIA ILIACA COMPARTMENT BLOCK

An anterior lumbar plexus approach with a punture point distant from neurovascular sheath.  Used widely for postop analgesia after lower limb surgery in children and adults after hip, femoral shaft, or knee surgery.
*Compared to 3-in-1 block, it provides fater and more consistent simultaneous blockade of lateral femoral cutaneous and femoral nerves

SCIATIC NERVE BLOCK
Sciatic nerve, in combination with lumbar plexus, femoral and saphenous nerve blocks, provides complete anesthesia and postop analgesia for lower-extremity surgery.

*Posterior and lateral popliteal approaches most commonly for ankle and foot surgery
*Higher approaches to sciatic nerve are more commonly for surgery below, above and at the knee.

Anatomy: Sciatic nerve is the continuation of the upper division of the sacral plexus and is the largest nerve trunk in the body.  Supplies the muscles of the back of thigh, skin of the leg, and muscles of lower leg and foot.  Passes out of the pelvis through the great sacrosciatic foramen below the piriform muscle.  Descends between the major trochanter and tuberosity of the ischium to the lower 1/3 of the thigh, where it divides into the internal and external popliteal nerves.

(click image to enlarge)

A line is drawn from posterior superior iliac spine to greater trochanter of femur.  2nd line is drawn from sacral hiatus to greater trochanter, and 3rd line is drawn perpendicular to and bisecting the first line.  Intersection of 2nd and 3rd line is point of needle entry.

POPLITEAL FOSSA BLOCK (Nysora link)
Use of 3 anatomic landmarks that define the posterior popliteal fossa: popliteal crease, medial border of femoris biceps muscle laterally, and tendon of semitendinous muscle medially.

(click image to enlarge)

Popliteal nerve block

A line is drawn joining the medial border of the femoris biceps muscle laterally and the lateral border of the semiteninous muscle medially at the level of the popliteal crease.  From the middle of this line, a perpendicular line is extended 15 cm cephalad.  This site of insertion of the needle is 1 cm laterally.

ANKLE BLOCKS (Nysora link)
For patients requiring surgery of the foot, not ankle. (i.e. gangrene or diabetic foot ulcer)
Done by blocking 5 nerves at level of the ankle: tibial, sural, superficial peroneal, deep peroneal, saphenous.

(click image to enlarge)

Direction and redirection of needle in ankle block technique

Tibial Nerve
Arises from nerve roots of L4-L5 & S1-S3
Path lies on medial side of Achilles tendon.  Passes into ankle with the posterior tibial artery.  Nerve lies behind artery and between the tendons of the long flexor muscles of the toes and the long flexor muscles of the great toe.  Several branches leave the neural bundle at the level of the medial malleolus.  Has 2 braches: medial and lateral plantar nerves.  Provides sensory innervation to foot.

(click image to enlarge)

Path of the posterior tibial nerve, with the posterior tibial artery past the Achilles tendon

Sural Nerve
Formed from the union of a branch of the tibial nerve and the common peroneal nerve.  Travels superficially with the short saphenous nerve behind the lateral malleolus into the ankle, where it provides sensory innervation to the posterior portion of the sole of the foot, and posterior portion of heel, and portion of Achilles tendon immediately above the ankle.

(click image to enlarge)

Path of the sural nerve behind the lateral malleolus in the ankle

Superficial Peroneal Nerve
Arises from L4-L5 & S1-S2
Nerve becomes superficial in middle 2/3 of the lower leg and remains subcutaneous as multiple braches proceed into the dorsum of the foot.  Just above the ankle the nerve begins to branch - for this reason, a single injection site does not provide sufficient anesthesia

(click image to enlarge)

The superficial peroneal nerve proceeds to the dorsum of the foot subcutaenously through multiple branches

Deep Peroneal Nerve

Arises from same nerve roots at superficial peroneal nerve.
Remain inside anterior tibial muscle and long extensor muscle of great toe as it traverses leg into ankle.  Provides innervation to short extensors of toes and sensory to skin on lateral side of hallux and on medial side of second digit.  Nerve and artery cross each other so the nerve lies lateral to the anterior tibial artery and medial to long extensor muscle of the great toe that is in the ankle. 

*This nerve if frequently missed when regional is administered to the ankle.

Saphenous Nerve

This is the terminal branch of the femoral nerve and travels subcutaneously from lateral side of knee joint.  Follows the greater saphenous vein to the medial malleolus and provides sensory innervation to medial side of malleolus and skin of the medial aspect of the lower leg
*If the block of this nerve is inadequate, pt is unable to tolerate a tourniquet above the ankle.


ANSWER 1: (A) The stellate ganglion is a fusion of the inferior cervical and firsth thoracic ganglia and lies at the level of the 7th cervical vertebra.  The ganglion is a sympathetic ganglion and receives fibers whose cell bodies are located at T1-T8 levels of the spinal cord.  Stellate ganglion block has many potential complications, including pneumothorax, intravascular injection, and subarachnoid injection

ANSWER 2: (D) The most superior approach to the brachial plexus is the interscalene block in which the needle is inserted between the anterior and middle scalene muscles

ANSWER 3: (B) The obturator nerve supplies motor innervation to the adductor muscles of the hip and sensory innervation to the medial aspect of the knee

REFERENCES:
McGraw-Hill Specialty Board Review

Nagelhout, Plaus. Nurse Anesthesia
NYSORA.com

CLOTTING CASCADE & PLATELETS

QUESTION 1: A 66 y/o male with a history of DM, HTN and CAD is to undergo urgent surgery for an expanding 6.4 cm infrarenal abdominal aortic aneurysm.  He had a MI 2 months ago at which time he underwent percutaneous coronary angioplasty with placement of drug-eluting stents to the LAD and RCA.  Current medications include clopidogrel and aspirin, which were started after the stent placement.  With respect to the combonation of these two drugs and the intraoperative risk of bleeding it is true that:
A. both drugs exert their antiplatelet effect through the same mechanism
B. clopidogrel does not add significantly to the risk of bleeding posed by aspirin
C. if these drugs were stopped one day prior to surgery, the risk of bleeding would be minimized
D. both drugs can be antagonized
E. clopidogrel should be discontinued 7 days prior to surgery in elective cases where surgical hemostasis is needed

QUESTION 2: A 62 y/o male with history of DM, HTN and CAD is admitted tot he hospital for unstable angina.  He was recently diagnosed with heparin-induced thrombocytopenia type II and is now scheduled to undergo off-pump CABG for severe three-vessel coronary artery disease.  A suitable agent for intraoperative anticoagulation would be:
A. heparin
B. warfarin
C. argatroban
D. danaparoid
E. clopidogrel

(answers at bottom of post)

HEMOSTASIS AND BLOOD COAGULATION

When a vessel is damaged/ruptured, hemostasis is achieved by 4 mechanisms:
1. vascular constriction
2. formation of platelet plug
3. formation of blood clot from blood coagulation
4. growth of fibrous tissue into blood clot to close hole in vessel permanently (fibrin mesh)

1. VASCULAR CONSTRICTION

• Local myogenic spasm
• Platelets release a vasoconstrictor substance called thromboxane A2

2. PLATELET PLUG

• Platelets = thrombocytes; 150,000-300,000 per microliter
• Surface of cell membrane of platelets contain glycoproteins that adhere to injured areas of vessel (repulses adherence to normal endothelium) - especially exposed collagen from deep within vessel wall
• Platelet membrane contains large amt of phospholipids that activate blood-clotting process
• 1/2 life in blood of 8-12 days; eliminated by tissue macrophage system (spleen)
• Platelets that come in contact with collagen fibers in damaged vascular wall immediately change and become "sticky" - adhere to a protein called von Willebrand factor in tissue wall.
• ADP and thromboxane A2 secreted by plts act on nearby plts to activate them as well which adhere to original activated platelets --> platelet plug
• This is initially loose but just enough to stop bleeding until stronger fibrin threads/mesh forms

3. FORMATION OF BLOOD CLOT

• Activator substances from traumatized vascular wall, from plts and from blood proteins adhere to traumatized vascular wall to initiate clotting process.  Within 3-6 min entire opening is filled with clot
• After 20 min to an hr clot retracts

4. FORMATION OF FIBRIN MESH

• Blood clot invaded by fibroblasts within few hours after clot is formed and continues for 1-2 weeks

BLOOD COAGULATION:

1. Net result of activating coagulation cascade is formation of a complex of activated substances collectively called prothrombin activator
2. Prothrombin activator converts prothrombin ---> thrombin
3. Thrombin acts as an enzyme to convert fibrinogen ---> fibrin that create fibrin mesh which stabilizes platelet plug
4. Thrombin also activates fibrin-stabilizing factor that strengthens fibrin mesh

Summary: prothrombin activator --> prothrombin --> thrombin --> fibrinogen --> fibrin mesh

FORMATION OF PROTHROMBIN ACTIVATOR:
Formed in 2 ways:
1. Extrinsic Pathway (begins with trauma to vascular wall and surrounding tissues)
2. Intrinsic Pathway (begins with trauma to blood or exposure to collagen)
*Both converge into the Common Pathway

(Click to view larger image)



*Most of the clotting factors (proteins) circulate in the inactive forms.  When converted to active forms, their enzymatic actions cause the cascade reactions of the clotting process.  This active form is designated as "a".  Eg. Factor VIIIa  or Factor 8a = activated factor 8

Extrinsic Pathway:

• Release of tissue factor from damaged vessel
• Tissue factor activates Factor 7 (thromboplastin)
• Factor 7a activates Factor 10 (start of Common Pathway)
• Factor 10a complexes with Factor 5 to make the prothrombin activator

Summary: Tissue factor --> Factor 7a --> Factor 10a + 5 = prothrombin activator --> prothrombin --> thrombin --> fibrinogen --> fibrin (mesh)

Intrinsic Pathway:

• Blood trauma causes activation of Factor 12
• Factor 12a activates Factor 11
• Factor 11a activates Factor 9
• Factor 9a + Factor 8 activates Factor 10 (start of Common Pathway)
• Factor 10a complexes with Factor 5 to make prothrombin activator

Summary: Factor 12 --> 12a --> Factor 11a --> Factor 9a + 8 --> Factor 10 + 5 = prothrombin activator

*Hemophilia lacks Factor 8

ANTICOAGULANTS:
The blood has natural anticoagulants:
1. the fibrin fibers that are formed during the process of clotting
2. an alpha-globulin called antithrombin III or (antithrombin-heparin cofactor)
3. heparin is also found naturally in blood but in low concentrations
4. Plasminogen, when activated by endogenous t-PA, becomes plasmin, which digests fibrin fibers and other coagulants (fibrinogen, F 5, F 8, prothrombin, F 12)
*t-PA = tissue plasminogen activator (released by injured tissues)

HEPARIN:
negatively charged conjugated polysaccharide
Mechanism: when it combines with antithrombin III, the effectiveness of antithrombin III for removing thrombin increases by 100-1000 fold.  In the presence of heparin, removal of free thrombin from the circulating blood by antithrombin III is almost instantaneous.
The heparin-antithrombin III complex also removes several other coagulation factors: 12a, 11a, 10a, and 9a. (Intrinsic pathway)

Check PTT
Antagonized by positively charged PROTAMINE

WARFARIN (Coumadin):
Mechanism: Inhibiting the enzyme that activates Vitamin K (vitamin K epoxide reductase complex 1 - VKOR c1).  By inhibiting VKOR c1, warfarin decreases available active form of Vitamin K

Vitamin K dependent factors: 2, 7, 9, 10, protein C & S
Check PT and INR

• Prothrombin Time (PT) gives an indication of the [ ] of prothrombin in the blood.  Tissue factor is mixed with a sample of blood which activates the prothrombin-to-thrombin reaction by the extrinsic pathway.  The time required for coagulation to take place is known as the prothrombin time.  Normal is 12 seconds.  However, results may vary greatly from sample to sample from the same individual.
• International Normalized Ratio (INR) was devised as a way to standardize measurements of PT.  INR is the ratio of the person's prothrombin time to a normal control sample raised to the power of the ISI (international sensitivity index).  Normal is 0.9 to 1.3.  Patients on warfarin should have an INR of 2.0 to 3.0

ASPARIN:
Mechanism: Arachidonic acid is converted by an enzyme, cyclooxegenase 1 (COX), to thromboxane A2 - which activates platelets.  ASA irreversibly blocks COX enzymes.

CLOPIDOGREL (plavix):
Mechanism: prevents platelets from releasing the 2b/3a receptor during an activated state which is responsible for platelets connecting (sticking) to one another to form platelet plugs.

(click to view larger image)

Inactivated fibrinogen also serves to connect platelets to one another via 2b/3a receptor.  Integralin serves as an antagonist to the 2b/3a receptor (sits on receptor and renders it inactive)



Clotting Factors and their Synonyms :

• Fibrinogen = Factor 1   (normal level is 100-700 mg/dl)
• Prothrombin = Factor 2
• Tissue factor = Factor 3 or tissue thromboplastin
• Calcium = Factor 4
• Factor 5 = Proaccelerin; labile factor; Ac-globulin (Ac-G)
• Factor 7 = thromboplastin; serum prothrombin conversion accelerator (SPCA)
• Factor 8 = antihemophilic factor A
• Factor 9 = antihemophilic factor B; plasma thromboplastin component (PTC)
• Factor 10 = Stuart factor
• Factor 11 = antihemophlic factor C; plasma thromboplastin antecedent (PTA)
• Factor 12 = Hageman factor
• Factor 13 = fibrin-stabilizing factor
• Prekallikrein = Fletcher factor
• high-moleculare weight kininogen = Fitzgerald factor

*von Willabran Factor is usually complexed with Factor 8

ANSWER 1: (E) Aspirin irreversibly blocks the production of thromboxane A2 in platelets, whereas clopidogrel exerts its antiplatelet effect by blocking the platelet ADP receptor.  Because of their discrete mechanisms, the effect of these drugs is additive or even synergistic, which results in a higher risk for excessive bleeding during surgical procedures.  There are no antagonists available for these medications.  Because of their long duration of action, stopping the drugs one day prior to surgery would not decrease the risk of bleeding.  Current recommendations are to stop clopidogrel 7 days prior to surgery in elective cases where surgical hemostasis is needed.

ANSWER 2: (C) Use of heparin in a patient with heparin-induced thrombocytopenia type II can lead to life-threatening thrombotic complications and is therefore not indicated.  Warfarin is an oral anticoagulant.  Danaparoid is a mixture of nonheparin glycosaminoglycans and is approved for prophylaxis of deep vein thrombosis.  It can be administered SC or IV, however, it has a long half-life of about 24 hrs.  Clopidogrel is an antiplatelet agent for the secondary prevention of stroke and the reduction of cardiac events after percutaneous coronary intervention.  Argatroban is a direct thrombin inhibitor with a relatively short half-life of 1 to 2 hours that can be continously infused during CABG surgery.

References:
McGraw-Hill Specialty Board Review
Guyton, Hall. Medical Physiology. Ch. 36: Hemostasis and Blood Coagulation

NDMRs: ROCURONIUM & VECURONIUM

QUESTION 1: Factors that will potentiate nondepolarizing neuromuscular blockade include all of the following EXCEPT:
A. Respiratory acidosis
B. Large body surface area burn
C. Administration of a volatile anesthetic
D. Hypothermia
E. Hypermagnesemia

QUESTION 2: Vecuronium:
A. Has a longer duration in children as compared to adults
B. Has an onset time independent of dose
C. Is totally eliminated by the kidneys
D. Activity is not prolonged by hepatic disease
E. inhibits histamine catabolism

(answers at bottom of post)

HIGHLIGHTS OF NONDEPOLARIZING NEUROMUSCULAR BLOCKING DRUGS:
Categorized in 2 ways:
1) long-, intermediate- and short-acting drugs
2) benzylisoquinoline (-curium) or aminosteroid compounds (-curonium)

Overview:

• Quarternary ammonium group (4 carbon atoms attached to 1 nitrogen atom)--> highly ionized and water-soluble (cannot easily cross lipid membrane barriers such as BBB, renal tubular epithelium, GI epithelium, placenta)
• Lack CNS depressant and analgesic effects
• Competitive antagonists
• NDMR have one positively charged nitrogen atom that binds to one alpha subunit of the postsynaptic cholinergic receptor (which is negatively charged)
• Vec and Roc are monoquarternary
• Aminosteroids lack hormonal activity
• specificity of a drug for autonomic ganglia nicotinic receptors versus the NMJ depends on length of carbon chain separating the 2 positively charged ammonium groups.

 Nicotinic nAChR (ion channel) contains 5 subunits.  2 ACh molecules need to bind to alpha units simultaneously to activate receptor.  1 Succs molecule needed which binds to both alpha units to activate receptor.

Pharmacokinetics/dynamics:

-Not highly bound to plasma protein

Causes of Altered Responses:
Certain drugs can enhance NDMR:

• Volatile Anesthetics: produce dose-dependent enhancement of magnitude and duration of neuromuscular blockade from NDMR.  Anesthetic induced depression of CNS decreases tone of skeletal muscles
• Aminoglycoside antibiotics: decrease release of ACh & stabilize post junctional membranes.  PCNs and cephalosporins do not have this effect.
• Local anesthetics: interfere with prejunctional release of ACh, stabilize membranes and directly depress skeletal muscle fibers.  Ester LA compete for PC (prolonged SCh)
• Cardiac antidysrhythmic drugs: primarily Lidocaine & Quinidine
• Diuretics: Furosemide, decrease release of ACh (inhibition of cAMP), & Azathioprine.  Osmotic diuretics (mannitol) does not influence NDMR
• Magnesium: more with Vec; more important in OB (Mg gtts)
• Lithium
• Cyclosporine

Resistance to NDMR:

• Anticonvulsants: phenytoin and carbamazepine result in resistance to NDMR - higher dose needed; faster recovery

Changes can also occur d/t:

• Hypothermia: prolongs duration d/t decreased clearance and slowed rate of effect site equilibration; also decr degradation by ester hydrolysis and Hofmann elimination
• Acid-base alterations
• Changes in serum potassium concentrations: decr in extracellular K+ increases transmembrane potential, causing hyperpolarization of cell membranes; hypokalemia enhances NDMR
• Adrenocortical dysfunction
• Thermal/burn injury: causes resistance to NDMR; NOT associated with extrajunctional receptors; mechanism is altered affinity of nAChRs for NDMR
• Paresis or Hemiplegia: causes resistance to NDMR d/t proliferation of extrajunctional receptors.  **Place twitch monitor on unaffected side for accurate assessment of twitches**
• Gender: women are more sensitive and require lower dose than men

ROCURONIUM (Zemuron):
Intermediate-acting, monoquaternary aminosteroid

Dose: 0.6-1.2 mg/kg (intubating dose)
Not given as an infusion
Onset: 1-2 min
Duration: 20-35 min

*rapid onset of action is more likely to be achieved with a less potent drug (roc compared to vec) bc of a greater number of molecules being available to diffuse into the NMJ --> may serve as an alternative to SCh in RSI (if SCh is contraindicated)

*laryngeal adductor muscles and diaphragm are more resistant to rocuronium than the adductor pollicis muscles

Metabolism/Excretion: largely excreted unchanged in bile (50%); 30% renal excretion
hepatic deacetylation does not occur
Characteristics:
Generally no CV effects of histamine release; cases of slight vagolytic effects
Prolonged by renal and hepatic dysfunction

VECURONIUM (Norcuron):
Intermediate-acting, monoquaternary aminosteroid

Dose: 0.08-0.15 mg/kg (intubating dose)
Infusion: 1 mcg/kg/min
Onset: 3-5 min
Duration: 20-40 min
Metabolism: hepatic deacetylation
Excretion: 30% unchanged in urine & 40% unchanged in bile
Characteristics:
Prolonged duration in renal dysfunction and hepatic cirrhosis
Devoid of CV effects; no histamine release - vagolytic effect is controversial
large volume of distribution

ANSWER 1:  (B) Patients with burns over a large portion of their body surface area are resistant to nondepolarizing neuromuscular blockade.  The other factors all potentiate such blockade.

ANSWER 2: (E) Vecuronium inhibits hitsmine-N-methyltransferase, the enzyme responsible for degrading histamine.  It has a shorter duration of action in children.  The onset time will be faster if the dose is increased.  About 10% is eliminated through the kidneys and the activity is prolonged by hepatic disease.

dTc inservice.  I wonder who's - I mean - what's for lunch?

NITROUS OXIDE (N2O)

QUESTION: If a nitrous oxide tank is contaminated with water vapor, ice will form on the cylinder valve as a result of the:
a. latent heat of vaporization
b. specific heat
c. vapor pressure
d. low pressure of the nitrous oxide
e. ambient temperature

HIGHLIGHTS ON N2O:
Inorganic anesthetic gas; nonexplosive and nonflammable (but can combust like O2)
Gas at room temperature and ambient pressure; can be kept as liquid under pressure bc critical temperature lies above room temperature.  Inexpensive.
*analgesic, anxiolysis and anesthetic properties

System Effects/SE:
CNS: increases CBF and cerebral blood volume --> incr ICP
incr CMRO2

CV: no significant net effects/changes in ABP, CO and HR

Pulm: increases RR, decreases tidal volume (Vt) --> minimal change in minute ventilation and ETCO2
hypoxic drive (mediated by peripheral chemoreceptors in carotid bodies) is markedly depressed by N2O

Neuromuscular: unlike VAAs, does not provide muscle relaxation; not a triggering agent for MH

Renal: increase renal vascular resistance, decr renal blood flow
decr GFR and UOP

Hepatic/GI:
minimal decrease in hepatic blood flow
PONV (controversial) d/t activation of CTZ & vomiting center in medulla

Heme:
Bone marrow depression (megaloblastic anemia)
alters immune response to infection
pernicious anemia; peripheral neuropathy

Other:
Inhibits enzymes (cobalt atom) that are Vitamin B12 dependent --> methionine synthetase (myelin formation), thymidylate synthetase (DNA synthesis)
Teratogenic effects

Diffusion into closed air spaces:
N2O is insoluble compared to other VAAs, but it is 35 times more soluble than nitrogen in blood.  Thus, it tends to diffuse into air-containing cavities more rapidly than nitrogen is absorbed by the bloodstream.  Example - pneumothorax: the N2O will diffuse into the cavity more rapidly than the air (nitrogen) diffuses out.  If the walls surrounding the cavity are rigid, pressure rises instead of volume.
**Examples of conditions in which N2O may be hazardous:
air embolism, pneumothorax, acute intestional obstruction, intracranial air, tympanic membrane grafting (tympanoplasty) in middle ear, tracheal tube cuffs, pulm HTN, pulm blebs

Pharmacokinetics/dynamics
Almost all N2O eliminated by exhalation.  Small amount diffuses out through skin
0.004% undergoes reductive metabolism in GI tract by anaerobic bacteria

MAC 105% (low potency)
BG Coefficient: 0.47
OG Coefficient: 225

Clinical Use:
65% N2O decreases MAC of other VAAs by 50%
concentration of N2O flowing through vaporizer can influence concentration of VAA delievered

2nd gas effect: incr vapor pressure and insoluble nature of N2O will enable it to be absorbed from alveolus first resulting in incr alveolar concentration of O2 and VAA

Diffusion Hypoxia: elimination of N2O is so rapid that alveolar oxygen and CO2 are diluted; prevented by admin of 100% during emergence

1845 - Horace Wells disgraces himself with unsuccessful demonstration of N2O in surgery



ANSWER: (a) The nitrous oxide tank contains a liquid, and in order for it to become vaporized, heat must be supplied.  As the cylinder is opened, heat is removed from the cylinder and from the air in the immediate vicinity.  The temperature falls, causing condensation.

REFERENCES:
Morgan, Mikhail. Clinical Anesthesiology (4th ed). pg. 164-166
Dershwitz. McGraw-Hill specialty board review: anesthesiology examination & board review (6th ed)

KETAMINE

QUESTION: A patient has been given an injection of ketamine in a dose calculated to be sufficient for anesthesia.  His eyes remain open, and there is slight nystagmus and occassional purposeless movements.  This is an indication that:
a. the dose is inadequate
b. more ketamine should be given to stop the movements
c. the dose is excessive
d. the dose is adequate for anesthesia
e. the patient is having a seizure

HIGHLIGHTS ON KETAMINE:
Dose: 1-2 mg/kg IV (induction) 4-8 mg/kg IM
0.2-0.5 mg/kg IV (analgesia)
15-30 mcg/kg/min (infusion)

Overview:
Phencyclidine derivative that produces "dissociative anesthesia" - dissociation between the thalamocortical and limbic system.  Resembles a cataleptic state in which the eyes remain open with a slow nystagmic gaze.  Pt is noncommunicative; wakefulness may appear to be present.  Varying degrees of hypertonus and purposeful skeletal muscle movements occur independent of surgical stimulation. 
*Has amnestic and analgesic properties.  (however, no retrograde amnesia)

Structure Activity Relationships:
Two optical isomers (racemic mixture):
left-handed = S(+) --> more intense analgesia, rapid metabolism and recovery, less emergence rxn
right-handed = R (-)

Mechanism:
Binds noncompetitively (allosteric site) to N-methyl-D-aspartate (NMDA) receptors.  (Also exerts effects on several other receptors, including opioid and GABA receptors)
NMDA receptors are ligand-gated ion channels.  Endogenous ligands to NMDA are glutamate and glycine.  Presynaptic release of glutamate is also decreased by ketamine.

Pharmacokinetics/dynamics:
Onset: 1 min
Duration: 5-15 min
water-soluble
Metabolism: by hepatic microsomal enzymes; demethylation of ketamine by CYP450  enzymes to form norketamine - an active metabolite (1/5-1/3 as potent as ketamine)

Clinical Use:
*ketamine increases salivary secretions - administer antisialagogue (0.2 mg glyco) preop
*has been mixed with propofol to decrease occurance of hypotension
*No pain on injection

System Effects/SE:
CNS: Increases CBF & CMRO2 but not ICP (potent cerebral vasodilator)
Neuroprotective role (although not strongly supported by research)
Does not induce seizures (controversial)

CV: direct central SNS stimulation, incr catecholamine [ ], but negative cardiac inotropic effect
Increase in ABP, HR, CO and myocardial O2 requirements

Pulm: *maintains intact airway muscle tone and reflexes, and ventilation
Breathing frequency may decrease for several minutes after admin; apnea can occur if given too quickly or admin with opioid
bronchodilatory activity - has been used to treat bronchospasm and status asthmaticus

Heme: Inhibits platelet aggregation (impt in bleeding disorder)
Inhibits plasma cholinesterase activity (may see prolonged duration of succs)

Psych: Emergence delirium (5-30%; misinterpretation of auditory and visual stimuli) - typically in young and middle aged adults; decreased incidence with preop Versed; usually only given to very young and very old patients.
hallucinations can occur 24 hr post admin

Other: does not affect hepatic/renal systems; does not cause histamine release so rarely causes allergic rxns

ANSWER: (d) Traditional signs of the anesthetic state are not seen with ketamine administration. Purposeless movements are seen, and these do not indicate the need for more anesthetic.

REFERENCES:
Stoelting, Hillier. Pharmacology & Physiology in Anesthetic Practice (4th ed). pg. 167-174
Dershwitz. McGraw-Hill Specialty Board Review: Anesthesiology Examination & Board Review (6th ed)