Skeletal muscle relaxation can be achieved through deep anesthesia, nerve blocks, or muscle relaxants. Succinylcholine is a depolarizing muscle relaxant that facilitates intubation and ventilation by causing skeletal muscle paralysis. It works by depolarizing the neuromuscular junction and has a rapid onset and short duration of action due to its metabolism by pseudocholinesterase. Potential side effects include fasciculations, increased potassium levels, prolonged paralysis, and being a trigger for malignant hyperthermia.

1. SKELETAL MUSCLE RELAXANT
 Skeletal muscle relaxation can be produced by
deep inhalational anesthesia, regional nerve
block, or neuromuscular blocking agents (i.e
muscle relaxants)

2. USES
In conjugation with general anesthesia:
 Facilitate intubation of trachea
 Facilitate mechanical ventilation
 Optimise surgical working condition

4. Neuromuscular transmission

6. Presynaptic membrane
 As a nerve terminal reaches a neuromuscular junction it
loses its myeline sheath and gets insulated from
surrounding fluid by schwann cell.
 Active zones –Thick patches of presynaptic membrane
zone 1-vesicles containing ach which are ready to release
once action potential reach to nerve terminal.
zone 2-Large sized vesicles are present as reserve pool of
Ach.
Active zones also contain voltage gated calcium channels.
Action potential reaches the nerve terminal open VG Ca+
channels Influx of Ca+ fusion and release of ach
containing vesicles

7.  Ach release can be increase by increasing intracellular
calcium.This is seen during post tetanic stimulation.When
muscle is stimulated at very high frequency ,calcium enters
the pre synaptic terminal during each cycle ,but there is no
time for excretion back into extracellular fluid.This high
concentration of calcium causes strong muscle contraction

8. SYNAPTIC/JUNCTIONAL CLEFT
 20-30 mm in size
 It is composed of thin layer of spongy reticular fibres in
between so Muscles and nerve terminals are held tightly
together by these fibres.
 Enzyme acetylcholine esterase is synthesized in the
muscle terminal and secreted into junctional cleft though
It remains attached to the post synaptic membrane.

9. POST SYNAPTIC MEMBRANE
 It is divided into two parts
1) Junctional area- Membrane of the junctional
area is invaginated to form multiple
folds to increases the surface area .
-shoulders are rich in Ach receptors
while deep areas have both Na+
channels and Ach receptor.
2)Peri junctional area-It is rich in Na+ channels and
AchE enzyme.

11. Ach receptor
1)Mature/junctional/adult
Binding of Ach molecule to 2 identical alpha receptor will
lead to opening of ion channel .It will not open if Ach binds to
only one site.
2)Immature /extrajunctional/fetal
It is in the form initially expressed in fetal muscle.
It is located anywhere in the muscle membrane inside or
outside the NMJ.
Present over large surface area & it is more sensitive to Ach.
It remain open for more prolong duration.

12.  The extra-junctional receptors do not contribute to the
paralysing effect of scoline ,since they are not involved in
transmission between nerve & muscle.
 Condition predisposing for development of extra junctional
receptors are:
Prolonged immobilisation
Burns
Sepsis
Neuromusculae disorder
UMN /LMN lesion
 Patients with high density of extrajunctional receptor
become prone for hyperkalemic response after scoline.

14.  As a nerve’s action potential depolarizes its terminal, an influx of
calcium ions through voltage-gated calcium channels into the nerve
cytoplasm allows storage vesicles to fuse with the terminal plasma
membrane and release their contents(Ach)
 The ACh molecules diffuse across the synaptic cleft to bind with
nicotinic cholinergic receptors on the motor end-plate.
 Cations flow through the open ACh receptor channel (sodium and
calcium in; potassium out), generating an end-plate potential
When enough receptors are occupied by ACh, the end-plate
potential will be sufficiently strong to depolarize the perijunctional
membrane.
 The resulting action potential propagates along the muscle
membrane and T-tubule system, opening sodium channels and
releasing calcium from the sarcoplasmic reticulum. This
intracellular calcium allows the contractile proteins actin and
myosin to interact, bringing about muscle contraction

16. Resting Activation Inactivation
Time gate open open close
Activation gate close open open
 Both gate must be open for ion current to flow.
 When muscle membrane reaches its threshold
voltage,activation gate also open which was close
earlier,this causes initial fasciculation seen with scoline.
 Time gate close within few milliseconds,hence stop ion
flow through channel.
 Time gate cannot open unless activation gate closes.
 Activation gate cannot close down unless depolarisation
current stops.

17.  Continuous end-plate depolarization causes
muscle relaxation because opening of
perijunctional sodium channels is time limited
After the initial excitation and opening these
sodium channels inactivate and cannot reopen
until the end-plate repolarizes. The end-plate
cannot repolarize as long as the depolarizing
muscle relaxant continues to bind to ACh
receptors.

18. DEPOLARISING MUSCLE
RELAXANT

19. SUCCINYLCHOLINE/
SUXAMETHONIUM
 Short acting depolarising muscle relaxant.
 Structure:Dicholine ester of succinic acid
(2 acetylcholine molecule linked by acetate methyl group)
 Physical properties: It is clear ,colourless.
It should be stored under refrigeration (2–8°C)
and should generally be used within 14 days after
removal from refrigeration and exposure to
room temperature.
Pharmachokinetics:
DISTRIBUTION-It has very low Volume of distribution because
of its low lipid solubility,This underlies to rapid
onset of action(30-60sec).
 Infants and neonates have a larger extracellular space per kg of TBW
than adults. Therefore, dosage requirements for pediatric patients are
often greater than for adults.

20.  Vd of is increase in pregnant however due to decrease in
pseudocholinesterase level(apx 25%) dose remain same as
that with adult.
 METABOLISM:scoline metabolise by
pseudocholinesterase(serum)into succinylmonocholine.
Rapid metabolism occurs as it enters into circulation
hence small fraction of the injected dose even reaches
the NMJ. As drug level fall in blood it diffuse away
from NMJ .this limiting the duration of action .

21. PSEUDOCHOLINESTERASE :
It is lipoprotein in nature and synthesised in liver .
 MIVACURIUM ,COCAIN also metabolise by this
enzyme.
 It it not present in NMJ hence drug has to go back into circulation
to terminate the action
 Prolonged Paralysis after scoline can occurs due to
1)Reduce level of psudocholine esterase enzyme i.e pregnancy,renal
failure,heart disease ,hypoproteinemia,thyrotoxicosis .
2)Depress activity of enzyme when use with other drugs
OCP,cytotoxic agents,lignocaine
3)Atypical pseudocholine esterase because it has reduce capacity to
metabolise
 To check adequacy of enzyme function dibucaine number.is used

22.  DIBUCAINE Number:
% of activity of pseudocholinesterase is termed
as dibucaine number
Dibucaine no duration of paralysis
 Typical pseudochE 70-80 <10min
 atypical pseudochE
(Heterozygous) 50-60 20-30min
 atypical pseudochE
(Homozygous) 20-30 4-8 hours
Prolong paralysis can be treated with continuous mechanical
ventilation + sedation until muscle function returns to normal
by clinical signs.

23.  DOSES:
 IV DOSE:
1)Adult dose for intubation 1-1.5 mg/kg
(ED95 is 0.51-0.63mg/kg )
ED95-dose that causes 95% suppression of neuromuscular
response
2)Obese 1 mg/kg
3)Paediatrics 2-5mg/kg

24. SIDE EFFECTS AND CLINICAL CONDITIONS
1)CVS:
 Low doses of succinylcholine can produce negative
chronotropic and inotropic effects, but higher doses usually
increase heart rate and contractility and elevate circulating
catecholamine level.
 Children are particularly susceptible to profound bradycardia
following administration of succinylcholine. In adults when
a second bolus of succinylcholine is administered
approximately 3–8 min after the first dose because
succinylmonocholine sensitizes muscarinic cholinergic
receptors in the sinoatrial node to the second dose of
succinylcholine, resulting in bradycardia.

25.  Intravenous atropine (0.02 mg/kg in children, 0.4 mg in
adults) is normally given prophylactically to children
prior to the first and subsequent doses, and usually
before a second dose of succinylcholine is given to
adults.

26. 2)HYPERKALEMIA:
 Normal muscle releases enough potassium during
succinylcholine induced depolarization to increase serum
potassium by 0.5 Meq /L.
 This is clinically insignificant in patient with normal basline k+
level.
 it can be life threatening in patients with preexisting
hyperkalemia. (conditions with development of extrajunctional
receptors)
Burn injury Massive trauma
Severe intraabdominal infection Spinal cord injury Encephalitis
Stroke Severe Parkinson’s disease
Tetanus Ruptured cerebral aneurysm
Polyneuropathy Closed head injury
Hemorrhagic shock with metabolic acidosis Myopathies

27. Treatment of scoline induce hyperkalemia:
 1)Antagonising cardiac toxicity
10ml of 10% of calcium gluconate over 2-3 min.
 2)BY shifting k+ intracellularly
G-I drip(10U of insuline+50ml of 50%glucose)
neb with beta2 agonist (salbutamol)
hyperventilation
NaHCO3
 3)By increasing renal clearance
Furosemide 20-40 mg IV
Volume expander with isotonic saline
fludrocortisone
Hemodialysis

28. 3)Fasciculation:
 visible motor unit contractions .
 Indicate onset of paralysis by succinylcholine.
 These can be prevented by pretreatment with a small dose of
nondepolarizing relaxant.
 Fasciculations are typically not observed in young children and
elderly patients.

29. 4)MUSCLE PAIN/MYALGIA
 It is due to the initial unsynchronized contraction of muscle
groups(fasciculation); associated with myoglobinemia and increases
in serum creatine kinase.
 Administration of rocuronium (0.06–0.1 mg/kg) prior to
succinylcholine has been reported to be effective in preventing
fasciculations and reducing postoperative myalgias.
 Perioperative NSAID and BZD may reduce the incidence and
severity of myalgia.

30. 5)Intragastric pressure:
Abdominal wall muscle fasciculations increase intragastric pressure.
There is increase in lower esophageal sphincter tone therefore no risk
of gastric reflux or pulmonary aspiration .
6)IOP:
Prolonged contraction of extraocular muscles following administration
of succinylcholine transiently raise intraocular pressure and It could
compromise an injured eye.

31. 7)Masseter muscle rigidity:
Succinylcholine transiently increases muscle tone in the masseter
muscles. Some difficulty may initially be encountered in opening the
mouth because of incomplete relaxation of the jaw. A marked increase
in tone preventing laryngoscopy is abnormal and can be a premonitory
sign of malignant hyperthermia.
8)MALIGNANT HYPERTHERMIA:
Succinylcholine is a potent triggering agent in patients susceptible to
malignant hyperthermia, a hypermetabolic disorder of skeletal muscle
although some of the signs and symptoms of neuroleptic malignant
syndrome (NMS) resemble those of malignant hyperthermia.

32. 9)ICP:
Slight increases in cerebral blood flow and intracranial pressure in some
patients.
Muscle fasciculations stimulate muscle stretch receptors, which
subsequently increase cerebral activity.
The increase in intracranial pressure can be attenuated by maintaining
good airway control and instituting hyperventilation.
It can also be prevented by pretreating with a nondepolarizing muscle
relaxant and administering intravenous lidocaine (1.5–2.0 mg/kg) 2–3
min prior to intubation.

33. 10)Generalised muscle contraction
11)Prolonged paralysis
12)Histamine release

34.  MALIGNANT HYPERTHERMIA
genetic hypermetabolic muscle disease, most commonly
appear with exposure to inhaled halogenated general
anesthetics or succinylcholine , which is charecterised by any
two or more of this signs i.e
muscle rigidity,tachycardia,unexplained hypercarbia and
increase temperature.
MH may occasionally present more than an hour after
emergence from an anesthetic, rarely may occur without
exposure to known triggering agents.
Most cases have been reported in young males
50% of patients who experience an episode of MH have had at
least one previous uneventful exposure to anesthesia during
which they received a recognized triggering agent.

36. PATHOPHYSIOLOGY
 Ryanodine channel responsible for calcium release from the
sarcoplasmic reticulum and it plays an important role in
muscle depolarization. Mutation in gene for the ryanodine
(Ryr 1 ) receptor, located on chromosome 19.
 The sudden release of calcium from sarcoplasmic reticulum
removes the inhibition of troponin, resulting in sustained
muscle contraction.
 Increased ATP activity results in an uncontrolled increase in
aerobic and anaerobic metabolism. The hypermetabolic state
markedly increases oxygen consumption and CO2
production, producing severe lactic acidosis and
hyperthermia.

37. Clinical Manifestations:
 Earliest signs of MH during anesthesia are succinylcholine-
induced masseter muscle rigidity or other muscle rigidity,
tachycardia, and hypercarbia (due to increased CO2
production)
 Unanticipated doubling or tripling of end-tidal CO2 in the
absence of a ventilatory change is one of the earliest and
most sensitive indicators of MH.
 If the patient survives the first few minutes then develop
organ failure.
AKI
DIC
cerebral edema
seizures
hepatic failure.
Most MH deaths are due to DIC and organ failure due to delayed
or no treatment with dantrolene.

39.  Laboratory testing:
mixed metabolic and respiratory acidosis with a marked base
deficit,
Electrolyte imbalance(hyper K+,hyper Mg+,Serum ionized ca+
concentration is variable it may initially increase before a later
decrease).
Increase serum myoglobin,
Increase serum CK(When peak serum CK levels ,usually 12–18 h
after anesthesia exceed 20,000 IU/L the diagnosis is strongly
suspected)

41.  Dantrolene Therapy:
Class:hydantoin derivative,
MOA:Directly interferes with muscle contraction by
binding the Ryr 1 receptor channel and inhibiting calcium
ion release from the sarcoplasmic reticulum. Dose: 2.5 mg/kg
intravenously every 5 min until the episode is terminated
(upper limit, 10 mg/kg).
After initial control of symptoms, 1 mg/kg of
dantrolene intravenously is recommended every 6h for 24–48h.
 used :
Mainstay of treatment in MH
Decrease temperature in patients with thyroid “storm” and NMS.
 SIDE EFFECTS :
1. hepatic dysfunction, the most serious complication
2. generalized muscle weakness that may result in respiratory
insufficiency or aspiration pneumonia
3. Dantrolene can cause phlebitis in small peripheral veins

43.  POSTOPERATIVE CONSIDERATIONS:
1) halothane–caffeine contracture test:
fresh biopsy specimen of living skeletal muscle is obtained and exposed to
a caffeine, halothane, or combination caffeine–halothane bath If the
halothane–caffeine contracture test is positive, genetic counseling and
testing of family members should done.
2)Differential diagnosis:
THYROID STORM: hypokalemia is very common.
thyroid storm generally develops postoperatively
PHEOCHROMOCYTOMA:No increase in ETCO2, co2
production,temperature.
SEROTONIN SYNDROME: MAOIs and SSRIs
MAOIs and meperidine

44. NEUROLEPTIC MALIGNANT SYNDROME (NMS) :
 It appears to involve abnormal central dopaminergic activity,
as opposed to the altered peripheral calcium release seen in
MH.
 characterized by hyperthermia, muscle rigidity with
extrapyramidal signs (dyskinesia), altered consciousness, and
autonomic lability in patients receiving antidopaminergic
agents.(phenothiazines, butyrophenones, thioxanthenes, or
metoclopramide)
 nondepolarizing relaxants reverse the rigidity of NMS, but
not the rigidity associated with MH.
 develop within 2 weeks of a dose adjustment.
 Hyperthermia generally tends to be mild, and appears to be
proportional to the amount of rigidity.

46.  NDMR
DURATION STRUCTURE
Short acting steroidal
1)mivacurium 1)Pancuronium
Intermediate acting 2)vecuronium
1)Atracurium 3)rocuronium
2)Cisatracurium
3)Vecuronium Benzylisoquinolinium
4)Rocuronium 1)atracurium
Long acting 2)cisatracurium
1)Pancuronium 3)mivacurium
2)dTC 4)doxacurium
3)Doxacurium 5)dTC
4)gallamine

47.  Competitive antagonist of Ach receptor.
 Quaternary ammonium compounds with two positive charges separated by
bridging structure which is lipophilic .
 ABSORPTION:NDMRs are not absorbed orally hence given via IV route.
 DISTRIBUTION:poorly lipid soluble compound ,unable to cross blood brain
barrier,placenta,renal tubular epithelium.
Vd resembles ECF volume.

48. GENERAL CONSIDERATION:
1) Temperature:
Hypothermia prolongs blockade by decreasing metabolism (eg
atracurium and cisatracurium) and delaying excretion (eg
pancuronium and vecuronium).
2) Acid–Base Balance:
Respiratory acidosis potentiates the blockade of most
nondepolarizing relaxants and antagonizes its reversal. This could
prevent complete neuromuscular recovery in a hypoventilating
postoperative patient.
3) Electrolyte Abnormalities:
Hypokalemia and hypocalcemia augment a nondepolarizing block.
Hypermagnesemia, potentiates a nondepolarizing blockade by
competing with calcium at the motor end-plate.
Hypermagnesemia seen in pre eclamptic patient being manages with
mgso4 .

49. 4)Age:
Neonates have an increased sensitivity to nondepolarizing relaxants
because of their immature NMJ , it does not necessarily decrease
dosage requirements, as the neonate’s greater extracellular space
provides a larger volume of distribution.

50. 5) Drug interaction:
A)Volatile agents-Potentiation of neuromuscular block via
increase delivery of MR to skeletal muscle.
Makes post junctional membrane refractory to repolarization.
NMJ # depends upon
Type of volatile agent :DESFLURANE>SEVOFLURANE
Type of muscle relaxant : dTC,Pancuronium
>vecuronium,atracurium
Dose of volatile agents
IF volatile agent and NDMR using simultaneously dose of MR
reduce to 15-20% to avoid difficulty in extubation.

51. B)Local anaesthetics:
clinically significant mainly when used iv as antiarrythmic .
C)Magnesium:
It will compete with calcium and reduce release of Ach from nerve
terminal.
It should be carefully used in pre eclamptic and eclamptic patient who
is in Mgso4 therapy.
Mg potentiate block of depolarising and non depolarising agent.
D)Antibiotics:
Aminiglycoside,polymyxine,clindamycin can prolong NMJ block
Treatment –Continuous mechanical ventilation till spontaneous
respiration returns.

52. 6)AGE:
A)INFANTS-
Onset - high cardiac output in infants leads to fast onset of action.
Dose requirement –will not change much as Infants having more
sensitive NMJ receptors so low dose is required but Vd in infants is
more because of more TBW (60-70%) which increase dose
requirement.
Duration- increase ,because immature liver and kidney so clearance
of drug is delayed.
B)GERIATRIC-
Dose requirements-Reduced TBW and increase total body fat will
reduce Vd of drug hence dose requirement will be less in geriatric.
Duration- increase,because reduce hepatic and renal blood flow and
reduce metabolising capacity of liver.

53. 7)RENAL DYSFUNCTION:
NDMR depends on kidney for elimination are
Major
Gallamine
This group of
drug should not
be use
Partial
Pancuronium
Vecuronium
Rocuronium
Can be use with
titration
Loading dose of
drug remain
same
Maintenance
dose increase
depending upon
TBW
Non
dependent
Atracurium
Cisatracurium
Laudonosine –
metabolite of
atracurium will
accumulate in
renal failure.
It is significant in
icu patient which
is on infusion of
atracurium.

54. 8)HEPATIC DYSFUNCTION:
Drug major dependent
on liver:
ROCURONIUM
Hence should not be use
in hepatic obstruction
Partial dependent on liver:
PANCURONIUM
VECURONIUM
Hence should be avoided if
repeated doses require for
prolong surgery.

56. ATRACURIUM:
Class: Benzylisoquinoline structure ,quaternary Ammonium group,
intermediate acting.
uses: intubation
maintainance
 Physical properties:
Atracurium is available as a solution of 10 mg/ mL.
It must be stored at 2–8°C.
 Metabolism & Excretion
1) Hofmann Elimination- A spontaneous nonenzymatic chemical
breakdown occurs at physiological pH and temperature.
2)Ester Hydrolysis -This action is catalyzed by nonspecific esterases, by
acetylcholinesterase or pseudocholinesterase

57.  Doses:
intubation dose-0.5-0.6 mg/kg IV
Maintanance dose-0.15-0.25 mg/kg
Infusion dose-5-10mcg/kg/min
.

58.  Side Effects & Clinical Considerations:
A. Hypotension and Tachycardia
Cardiovascular side effects are seen when doses in excess of 0.5
mg/kg are administered.
it is due to transient drop in systemic vascular resistance .
B. Bronchospasm
Severe bronchospasm is occasionally seen in patients without a history of
asthma.
C. Laudanosine Toxicity
it is tertiary amine, Laudanosine is metabolized by the liver and excreted in
urine ,it has been associated with central nervous system excitation, resulting
in elevation of the minimum alveolar concentration and even precipitation of
seizures. Concerns about laudanosine are probably irrelevant unless a patient
has received an extremely large total dose or has hepatic failure.
D. Temperature and pH Sensitivity
atracurium’s duration of action can be markedly prolonged by hypothermia
and to a lesser extent by acidosis.

59.  E. Chemical Incompatibility Atracurium will precipitate as a free acid if it is
introduced into an intravenous line containing an alkaline solution such as
thiopental.
CISATRACURIUM
 Physical Structure: Cisatracurium is a stereoisomer of atracurium that is four times
more potent. Cisatracurium should be stored under refrigeration (2–8°C) and should
be used within 21 days after removal from refrigeration and exposure to room
temperature.
 Metabolism & Excretion:
Hofmann elimination. The resulting metabolites (a monoquaternary acrylate and
laudanosine) have no neuromuscular blocking effects.
 intubating dose : 0.1–0.15 mg/kg within 2 min and results in muscle blockade of
intermediate duration.
 maintenance infusion 1.0–2.0 mcg/kg/min. Thus, it is more potent than atracurium.
 Side Effects & Clinical Considerations
production of laudanosine,
pH and temperature sensitivity,
chemical incompatibility.

60.  VECURONIUM:
CLASS: steroidal , Monoquaternary ,Intermediate acting NDMR
Pancuronium minus a quaternary methyl group (a monoquaternary relaxant). This
minor structural change beneficially alters side effects without aff ecting potency.
USE: intubation
maintenance
Dose:intubating dose is 0.08–0.12 mg/kg
maintenance dose is 0.01 mg/kg
infusion dose is 1-2mcg/kg/min.
Formation :It is available as dry powder form,re constitution done with normal saline.
Duration:brief duration of action because of short elimination half lift and rapid
clearance.
Long-term administration of vecuronium to patients in intensive care units has resulted
in prolonged neuromuscular blockade (up to several days), possibly from accumulation
of its active 3-hydroxy metabolite, changing drug clearance, and in some patients,
leading to the development of a polyneuropathy.

61. Metabolism: Vecuronium is metabolized to a small extent by
the liver
Elimination: primarily on biliary excretion and secondarily
(25%) on renal excretion.
 Side Effects & Clinical Considerations:
A. Cardiovascular: Even at doses of 0.28 mg/kg, vecuronium
is devoid of significant cardiovascular effects. Potentiation
of opioid-induced bradycardia may be observed in some
patients.
B. Liver Failure:dependent on biliary excretion
duration of action of vecuronium is significantly
prolonged in patients with cirrhosis if dose greater than
0.15 mg/kg given.
effect of Age :age does not affect initial dose
requirements, although subsequent doses are required less
frequently in neonates and infants.

62. ROCURONIUM :
Class-Monoquaternary steroid analogue of vecuronium
Elimination-primarily by the liver and slightly by the kidneys.
Duration of action:prolonged by severe hepatic failure
and pregnancy.
It requires 0.45–0.9 mg/kg intravenously for intubation and
0.15 mg/kg boluses for maintenance. A lower dose of 0.4
mg/kg may allow reversal as soon as 25 min aft er intubation.
Intramuscular rocuronium (1 mg/kg for infants; 2 mg/kg for
children) provides adequate vocal cord and diaphragmatic
paralysis for intubation, but not until aft er 3–6 min (deltoid
injection has a faster onset than quadriceps), and can be
reversed aft er about 1 hr. Th e infusion requirements for
rocuronium range from 5–12 mcg/kg/min

63. uses
1)RSI:0.9-1.2 mg/kg has onset of action that approaches
succinylcholine (60–90 s), making it a suitable alternative
for rapid-sequence inductions.
2)PRECURARIZATION:0.1 mg/kg IV decrease
fasciculations and postoperative myalgias hence use for
precurarization prior to administration of succinylcholine.
3)INFUSION in ICU: Because rocuronium does not have
active metabolites,it may be a better choice than
vecuronium .

64. Thank you