SUXAMETHONIUM---A NECESSARY EVIL

Suxamethonium (sch) still enjoys popularity, despite a long list of side effects, because it is the only ULTRA RAPID onset, ULTRA SHORT duration NMBA (neur0 muscular blocking agent) available.
NEUROMUSCULAR EFFECTS:
1. The drug depolarizes pre-synaptic, post-synaptic and extra junctional. however, when the receptor is in contact with agonist for a long time, it ceases to respond to the agonist. Normally, this DESENSITIZATION process does not take place because of rapid breakdown of Ach (acetylcholine) (< 1 m sec). However, Sch remains at the end plate for much longer time and desensitization develops.
Another possible mechanism is the inactivation of sodium channels in junctional and pre-junctional areas, which occur when the membrane remains depolarized. This inactivation prevents the propagation of action potential
2. Within 1 min after sch injection and before the paralysis manifest, "FASCICULATIONS", as a result of depolarization of nerve terminal produced by activation of pre-synaptic receptors are observed.
3. In masseter muscle, a sustained increase in tension that may last for several minutes can be observed. This increase in masseteric tone, may lead to imperfect intubation conditions. Masseter spasm may be an exaggerated form of this response.
CHARACTERISTICS OF DEPOLARIZING BLOCKADE:
1. Sch blockade is potentiated by inhibitors of acetylcholinesterase, such as neostigmine.
2. After administration of 7-10 mg/kg or 30-60 minutes exposure of sch, train of four and tetanic fade becomes apparent. Neostigmine can antagonize this block which is termed a PHASE-11 BLOCK.
PHARMACOLOGY:
1.Sch is rapidly hydrolyzed by plasma cholinesterase
2.Subparalyzing dose upto 0.3-0.5 mg/kg reach their maximal effect within 1.5-2 minutes at adductor pollicis muscle and within 1 minute at more central muscles, such as masseter and laryngeal muscles. With larger doses (1-2 mg/kg), abolition of twitch response can be reached even more rapidly.
SIDE EFFECTS:
1. CARDIOVASCULAR:

• Bradycardia is more common in children
• Even ASYSTOLE, after a 2nd dose of sch especially in pediatric and elderly patients can occur
  
• The parasympathetic effects can be attenuated with atropine or glycopyrrolate
  
• Sch increases catecholamine release.
  

2.FASCICULATIONS:

• These are more common especially in muscular adults after the rapid injection of sch. These can be prevented by:

1. a small dose of non-depolarizing muscle relaxants (ndmr) given 3-5 minutes before sch is effective. Rocuronium (0.03mg/kg, that is 10%of ED95), atracurium (0.02 mg/kg) are effective in decreasing the incidence of fasciculations. After these ndmr, the dose of sch must be increased from 1 mg/kg to 1.5 or even 2 mg/kg because of the antagonism between depolarizing and non-depolarizing muscle relaxants.
2. Other drugs such as diazepam, lidocaine, fentanyl, magnesium etc.have also been used to prevent fasciculations
3. "SELF- TAMING", that is the administration of small (10 mg) dose of sch one minute before the intubating dose, does not appear to be effective and has largely been abandoned.
   

3. MUSCLE PAINS:

• Generalized aches and pains, similar to the myalgesia that follow violent exercise, are common 24-48 hours after sch administration
• They are more common in young and ambulatory patients.
• Pre-curarization dose of ndmr and lidocaine(1-1.5 mg/kg) are effective in preventing pain.

4. INTRA-GASTRIC AND INTRA CRANIAL PRESSURE are increased by the administration of sch.
5. INTRA-OCULAR PRESSURE:

• IOP increases by 5-15 mm Hg after injection of sch has lead to the widespread recommendation to avoid sch in open eye injuries.
• Inadequate anesthesia, elevated systemic blood pressure and insufficient neuro muscular blockade during laryngoscopy and tracheal intubation might also increase IOP

7. HYPERKALEMIA:

• Serum potassium increases by 0.5 to 1 mEq/L after the injection of sch.
• Severe hyperkalemia, occasionally leading to cardiac arrest has been described in patients after major denervation injuries, spinal cord transactions, peripheral denervation, stroke, trauma extensive burns and prolonged immobilization with disease.
  
• This hyperkalemia may be related to the potassium loss via a proliferation of extra junctional receptors.

ABNORMAL PLASMA CHOLINESTERASE:
1. Plasme cholinesterase activity is reduced in;

• Pregnancy
• Liver disease
• Uremia
• Malnutrition
• Burns
• Oral contrceptives

These conditions usually lead to a slightly clinically unimportant increase in duration of action of sch
2. Plasma cholinesterase activity is reduced by neostigmine so that the duration of sch given after neostigmine, but not after edrophonium is increased.
3. In some patients plama cholinesterase is absent or an abnormal form of enzyme is present. Only patients with HOMOZYGOUS for the condition have prolonged paralysis (3-6 hours) after usual dose of sch(1-1.5mg/kg)
In heterozygous group patients, the duration of action is only slightly prolonged compared with normal individuals
4. Whole blood or fresh frozen plasma can be given to accelerate sch metabolism in patients with low or absent plasma cholinesterase. The best course of action is probably MECHANICAL VENTILATION OF LUNGS until full recovery of neuromuscular function can be demonstrated. Neostigmine is unpredictable in reversal of abnormally prolonged sch blockade and is best avoided.
CLINICAL USES:

• To facilitate tracheal intubation.
• It is especially indicated for the rapid sequence induction when the patient presentw with a full stomach and there is possibility of aspiration of gastric contents
  

PHARMACOLOGICAL CHARACTERISTICS OF NEUROMUSCULAR AGENTS

INTRODUCTION:
Neuromuscular drugs interact with acetylcholine (Ach) receptor either by depolarizing the endplate or by competing with Ach for binding sites. The former mechanism is characteristic of depolarizing drugs and the latter of non depolarizing agents. The only depolarizing agent still in use is SUCCINYLCHOLINE. All others are of the nondepolarizing type.
PHARMACOLOGICAL CHARACTERISTICS
1. POTENCY:
Potency of each drug is determined by constructing dose-response curves which describe the relationship between twitch depression and dose
2. ONSET TIME:
It is the time to the maximum blockade, can be shortened if the dose is increased.
3. DURATION OF ACTION:
It is the time from injection of neuromuscular blocking drug to the return of 25% of twitch height compared with control. The 25% twitch height is chosen because rapid reversal can normally be achieved at this level.
4. RECOVERY INDEX
It is the time interval between 25% and 75% twitch height. It provides information about the speed of recovery once return of twitch is manifest.
5. ASSESSMENT OF INTUBATING CONDITIONS:
The pharmacological characteristics of NMBA are completed by an assessment of intubating conditions. Intubating conditions depend on paralysis of centrally located muscles, but also on type and quantity of narcotic and hypnotic drug given for induction of anesthesia.Criteria to grade intubating conditions as EXCELLENT, GOOD, POOR, or IMPOSSIBLE in a scoring system is adopted

NEUROMUSCULAR BLOCKING AGENTS-Clinical Pearls

1. NMBA (Neuro muscular Blocking Agents) are used to improve conditions for TRACHEAL INTUBATION, to provide IMMOBILITY during surgery and to facilitate MECHANICAL VENTILATION.
2. The introduction of NMBA in 1942 was one of the most important MILESTONES in the history of Anesthesia. However, in1954, in a paper on anesthetic mortality, Beecher and Todd claimed that mortality increased by six folds when NMBA were used. This situation was probably because of suboptimal use of mechanical ventilation and reversal drugs
3. Incidence of awareness is greater when NMBA are used. However, anesthetics act at spinal cord level to produce immobility, and movement in response to a noxious stimulus indicates INADEQUATE ANALGESIA and not insufficient unconsciousness. THEREFORE, AWARENESS DOES NOT OCCUR BECAUSE TOO MUCH NMBA HAS BEEN GIVEN, BUT BECAUSE TOO LITTLE ANESTHETIC IS ADMINISTERED.
4. NMBA make a difference in lower abdominal surgery and surgical conditions are better in patients receiving these agents
5. By providing optimal intubating conditions, NMBA decrease the incidence of voice hoarseness and vocal cord damage
6. It is very essential to make sure that the effects of NMBA have worn off or are reversed before the patient regains consciousness