Week 4 (February 1& 3)
Lab/Discussion - Quiz #2

ELM is a 60 YO 110 kg F with c/o (complaint of) bilateral pain in knees with decreased range of motion. The patient is scheduled for a right total knee arthroplasty (surgery where joint surface is replaced with artificial materials, usually metal or high-density plastic) today. The patient has consented to regional anesthesia.

PMH (Past Medical History):

PVD (Peripheral Vascular Disease)
Arthritis
CHF (Congestive Heart Failure)
Leg cramps
Degenerative joint disease

MEDS:

Enalapril 20 mg po BID
Ibuprofen 800 mg po TID
Furosemide 40 mg po BID
KCl 20 mEq po BID
FeSO4 300 mg po TID

ALLERGIES: Sulfa, Chloroprocaine

ADMITTING VITALS: BP 176/86, P 84, RR 14, T 36.7 degrees C

LOCAL ANESTHETIC: Ropivacaine 1%

ANESTHESIA RECORD:

Time (PM)	BP	P	OR Course
230	200/100	115	Pt. brought to OR – monitors applied. Pt. given 2 mg midazolam.
240	190/100	110	Under sterile conditions, with pt. sitting, inserted L3-4 (lumbar 3-4) interspace with 17 gauge needle advanced to LOR (loss of resistance). No blood/CSF. 2 cc NS injected. Catheter advanced to 3 cm w/o difficulty. 3 cc 1.5% lidocaine given w/o Sx. Catheter secured.
250	190/85	105	15 cc 1% ropivacaine given
252	140/67	90	Pt restless, responsive with slurred speech, develops tonic-clonic seizure.
253	130/75	110	Diazepam 10 mg given. Pt. stops seizing. IVF (IV Fluid) increased.
255	140/75	110	Pt. stabilized, surgeon notified.
257	140/78	110
258	138/75	108
300	140/65	100	50 mcg fentanyl given
315	108/55	80
330	110/55	80	2 mg midazolam given, propofol 25 mcg/kg/min started
400	110/60	77
430	108/58	80
500	110/60	75
530	110/60	80	Tourniquet time up to 350, surgeon notified; propofol stopped
600	120/70	80

Day: __________ Room Number: ______________ Group Number: _______________

Member Names: ___________________________ _____________________________

___________________________ _____________________________

___________________________ _____________________________

1. Describe the effect of ropivacaine in this patient from the time of 255 to 600. How long would you expect the effect to last?

Ropivacaine dropped the systolic blood pressure by 20-30 mmHg and provided analgesia for the duration of the case. Expected duration: 5-7 hours. 

• Which nerve fibers are more susceptible to the action of local anesthetics? Explain why.

Peripheral nerve functions are not affected equally by local anestethics. Loss of sympathetic function usually occurs first, followed by loss of pin-prick sensation, tough, and temperature, and lastly, motor function. This phenomenon is called differential blockade. Differential blockade may be due to the size of the nerve, the presence or absence of myelin, and firing frequency. 

Size of nerve. Local anesthetics preferentially block small fibers because the distance over which such fibers can passively propagate an electrical impulse (related to space constant) is shorter. During the onset of local anesthesia, when short sections of nerve are blocked, the small-diameter fibers are the first to fail to conduct. 

Presence or absence of myelin. For myelinated nerves, three successive nodes must by blocked to halt impulse propagation. The thicker the nerve fiber, the farther apart the nodes tend to be-which explains, in part, the greater resistance to block of large fibers (e.g., motor fibers to skeletal muscle). Myelinated fibers tend to become blocked before unmyelinated fibers of the same diameter. For this reason, the PREGANGLIONIC B FIBERS may be blocked (i.e., sympathetic fiber block leading to vasadilation and hypotension) before the smaller unmyelinated C fibers (carrying pain sensation). 

Firing frequency. Another important reason for preferential blockade of sensory fibers follows directly from the state-dependent mechanism of action of the local anesthetics. Block by these drugs is more marked at higher frequencies of depolarization and with longer depolarizations. Sensory fibers, especially pain fibers, have a high firing rate and a relatively long action potential duration (up to 5 msec). Motor fibers fire at a slower rate and have shorter action potential duration (< 0.5 msec). A delta and C fibers are small diameter fibers that participate in high-frequency pain transmission. Therefore, they are blocked sooner with lower concentrations of local anesthetics than are A alpha (motor) fibers to skeletal muscle. 

2. The patient is allergic to chloroprocaine. Explain whether you would have expected to see any problems with ropivacaine.

No, because ropivacaine is an amide, while tetracaine is an ester. Cross-sensitivity does not exist between classes of local anesthetics. Therefore patients allergic to ester local anesthetics can receive amide local anesthetics. This assumes that the local anesthetic and not preservatives, which may be common to both classes of anesthetics, is responsible for the allergic reaction.

• Classify the local anesthetics.

Esters – procaine, chloroprocaine, tetracaine

Amides – lidocaine, mepivacaine, bupivacaine, etidocaine, prilocaine, ropivacaine

• Is one class of agents more likely than another class to cause allergic reactions? Explain. What other factor can lead to allergic reaction?

Ester local anesthetics that produce metabolites related to para-aminobenzoic acid are more likely to evoke allergic reactions than are amide local anesthetics, which are not metabolized to para-aminobenzoic acid.

Also, allergic reactions following local anesthetic administration may be due to the use of preservatives in commercial preparations of amide and ester local anesthetics. These preservatives resemble para-aminobenzoic acid. Documentation of local anesthetic allergy is based on clinical history (rash, edema, hypotension, bronchospasm) and perhaps use of intradermal testing with preservative free solutions. Hypotension associated with syncope, tachycardia, or bradycardia when epinephrine-containing solutions are used is more suggestive of an accidental intravascular injection or a psychogenically-mediated reaction than of an allergic reaction.

3. What characteristics of local anesthetics make them ideal agents for anesthesia?

Rapid onset, long duration of action, and reversible and selective blockade of sensory nerves without motor blockade, also minimal systemic toxicity

• What characteristics of ropivacaine make this an ideal agent for this specific case?

Long duration of action, reversible and selective blockade of sensory nerves without motor blockade and minimal systemic toxicity. 

4. Two minutes after the epidural was started, the patent’s blood pressure dropped and she had a tonic-clonic seizure. What happened? How would you explain this?

Systemic toxicity is a rare but significant side effect of local anesthetics. Systemic toxicity can be manifested as CNS (central nervous system) or CV (cardiovascular) changes. Also, neurotoxicity and allergic reactions are rare but significant side effects of local anesthetics.

Systemic toxicity is due to excess plasma concentrations of these drugs, most often as a result of accidental intravascular injection of local anesthetic solutions during performance of nerve blocks. Less often, systemic toxicity can be a result of excess plasma concentrations of local anesthetics from tissue absorption sites.

CNS changes are seen initially as restlessness, vertigo, tinnitus, and slurred speech culminating in tonic-clonic seizures. Seizures can be followed by CNS depression (apnea) and death. The onset of seizures may reflect selective depression of inhibitory cortical neurons by local anesthetics, leaving excitatory pathways unopposed. Treatment of local anesthetic-induced seizures includes administration of drugs to stop seizures and supplemental oxygen.

The CV system is more resistant to toxic effects of local anesthetics than is the CNS. However, high plasma concentrations of local anesthetics can produce profound hypotension due to relaxation of the arteriolar vascular smooth muscle and direct myocardial depression. Part of the cardiac toxicity reflects the ability of local anesthetics to block cardiac sodium channels. As a result, cardiac automaticity and conduction of cardiac impulses are impaired, manifesting on the electrocardiogram as prolongation of the PR interval and widening the QRS complex.

• What factors can alter the severity of these side effects?

The magnitude of this systemic absorption depends on: (1) the dose injected, (2) vascularity of the injection site, and (3) inclusion of a vasoconstrictor in the local anesthetic solutions. Establishing maximal doses of local anesthetics for use during regional anesthesia is an attempt to limit plasma concentrations that result from systemic absorption of these drugs. Systemic absorption of local anesthetics is greatest after injection for intercostals nerve blocks and caudal anesthesia, intermediate following epidural anesthesia, and least after brachial plexus blocks. Systemic toxicity is seen as changes in the CNS and CV system. 

• Describe another possible side effect of local anesthetics.

 Neurotoxicity—local anesthetics are not neurotoxic when administered at recommended concentrations, except for chloroprocaine, which is not recommended for IV regional anesthesia or spinal anesthesia b/c of potential irritant effects. For example, accidental injection of large volumes of chloroprocaine into the subarachnoid space during the intended performance of epidural anesthesia may result in prolonged or permanent neurological damage. These neurotoxic effects may be due to low pH (3.0) of the anesthetic solution and sodium bisulfite, an antioxidant in chloroprocaine, and thus are not a unique effect of the local anesthetic. Newer preparations of chloroprocaine do not contain bisulfite.

Allergic reactions—rare, despite frequent use of these drugs. Fewer than 1% of all adverse reactions to local anesthetics are due to allergic reactions.

Other risks of epidural administration – dural puncture (wet tap), hypotension, and high spinal (which means the local anesthetics moves up the spinal cord and numbs the diaphragm, causing respiratory depression)

 5. The attending physician’s comment after the patient’s seizure was: "I’m glad we weren’t using bupivacaine." Why?

 Local anesthetics differ in their ability to produce cardiotoxicity. Bupivacaine (and etidocaine) is more cardiotoxic than equieffective doses of lidocaine. It can cause the sudden appearance of dangerous arrhythmias (including ventricular fibrillations).

According to Goodman & Gilman, the enhanced cardiotoxicity is probably due to multiple factors. Lidocaine and bupivacaine both block cardiac sodium channels rapidly during systole (block develops during this phase). Bupivacaine, however, dissociates much more SLOWLY (remember high protein binding) than does lidocaine during diastole (block dissipates during this phase), so a significant fraction of sodium channels remain blocked at the end of diastole with bupivacaine. Thus, the block produced by bupivacaine is cumulative and substantially more than would be predicted by its local anesthetic potency.

At least a portion of the cardiac toxicity of bupivacaine may be mediated centrally, as direct injection of small quantities of bupivacaine into the medulla can produce malignant (i.e., does not respond well to treatment) ventricular arrhythmias.

Ropivacaine has less cardiotoxicity than bupivacaine. Ropivacaine is unique among local anesthetics because it is prepared as an isomer (the S-enantiomer of the propyl homologue of bupivacaine) rather than a racemic mixutre. The S-enantiomer has lower toxicity than the R isomer. This is presumably due to lower uptake resulting in lower blood levels for a given dose. Cardiotoxicity is intermediate between that of lidocaine and bupivacaine.