Test 2: Succinylcholine Flashcards
What type of molecule is Succinylcholine?
-Quaternary Ammonium Compound
-2 joined Acetylcholine molecules
-Hydrophilic (poorly lipid soluble)
-Does NOT cross BB Barrier or placenta
-Small volume of distribution
-Highly protein bound
What is the onset of action of Succinylcholine?
-30 to 90 seconds
-Intubating conditions within 1-1.5 minutes
What type of drug is Succinylcholine?
nAchR AGONIST
-high affinity for nAchR
-Depolarizing Muscle Relaxant
Is Succinylcholine competitive or non-competitive?
Non competitive: More ach won’t help. Has to be hydrolyzed.
T/F: The effects of Succ decrease before an adequately preoxygenated patient becomes hypoxic (Patient returns to spontaneous ventilation before hypoxia).
True
What is the MOA of Succinylcholine?
-Mimics Ach at the nAchR generating an AP
-Not metabolized by AchE. therefore producing a prolonged depolarization of the Motor End Plate
-The Motor End Plate cannot repolarize as long as Sux remains bound to the nAchR
-A depolarized postjunctional membrane cannot respond to a subsequent Ach stimulus
-Sodium channels are in the inactivated state = absolute refractory period
-Non-competitive block
What is the reversal for Succinylcholine?
Trick question; No specific agent exists to reverse a depolarizing block.
What is important to know regarding Succinylcholine and pediatrics?
-Typically C/I due to risk of MH due to possible undiagnosed MD
-Given in case of emergency (Laryngospasm)
-Children have increased water, so typically need a greater dose.
How do you calculate the dose of Succ for obese patients?
Use Total Body Weight (1 mg/kg)
-morbidly obese patients have increased fluid compartments and pseudocholinesterase levels and require higher doses to ensure adequate paralysis.
How is Succinylcholine metabolized?
-Rapidly metabolized by Pseudo-AchE
Does Succinylcholine have metabolites?
Yes; Succinylmonocholine (active metabolite)
What is the duration of action of Succ?
<10 minutes
-Full recovery in 12-15 minutes
What is the ED95 for Succ?
0.3 - 0.5 mg/kg
What is the Adult IV dose of Succ?
0.5 mg/kg - 1.5 mg/kg
What is the Peds dose of Succ?
-IV: 2.0 mg/kg - 2.5 mg/kg
-IM: 4 mg/kg - 5 mg/kg
What are the CNS effects of Succinylcholine?
-Fasciculations (not typically in children < 10 or the elderly)
-Myalgias
-Increased IOP
-Increased ICP
What are the Respiratory effects of Succinylcholine?
-Apnea
-Vocal cord paralysis
-Relaxation of airway musculature
What are the CV effects of Succinylcholine?
-Increase OR decrease in HR (profound bradycardia in children)
-Adults brady with 2nd dose
-Dysrhythmias
-Hyperkalemia
What are the misc effects of Succinylcholine?
-Increased intragastric pressure
-Increased LES tone
-Masseter Muscle rigidity
What is the ONLY muscle relaxant with an ultra rapid onset and ultra short duration of action?
Succinylcholine
How is neuromuscular blockade due to succ terminated?
By its diffusion away from the NMJ.
What is the effect of hypothermia on Succinylcholine?
Decreases its hydrolysis by P-AchE.
-Slows metabolism down
What conditions cause a decreased P-AchE level?
-Pregnancy
-Severe Liver disease
-Acute infections
-PE’s
-Muscular dystrophy
-Active MI
-Renal failure/Uremia
-Elderly males
-Malnutrition
-Burns
-Plasmapheresis
-Drugs (separate flash card).
What drugs decrease the amount of P-AchE?
-Echothiophate (Organophosphate)
-Neostigmine (Cholinesterase Inhibitors)
-Pyridostigmine
-Phenelzine (MAOI)
-Cyclophosphamide (Antineoplastic)
-Metoclopramide
-Esmolol
-Pancuronium
-Oral contraceptives
How does pregnancy affect Succinylcholine metabolism?
-40% decrease in P-AchE at term. Diluted in pregnancy due to increase in plasma volume without increased production of P-AchE. Perceived lower amount.
-May not clinically impact secondary to the increase in the pt’s volume of distribution
What is the effect on succinylcholine if P-AchE levels are increased?
Decreased duration of blockade. Succ is hydrolyzed faster
What conditions cause an INCREASE in the levels of P-AchE?
-Nephrotic syndrome
-Thyrotoxicosis
-Hemochromatosis
-Obese patients with diabetes
-Anxiety disorders
What are the clinical effects of Atypical Pseudocholinesterase?
Don’t metabolize Succ normally. Prolonged block.
What is heterozygous Atypical Pseudocholinesterase?
-one normal and one abnormal pseudocholinesterase gene
-Prolonged block of 20-30 minutes
What is homozygous Atypical Pseudocholinesterase?
-two abnormal pseudocholinesterase genes
-Produce P-AchE that has little or no affinity for Sux
-Prolonged block of 3-8 hrs
-Pts require extended mechanical ventilation (and will also need some sedation)
What does the Dibucaine # test tell you?
-Qualitative test
-A blood test that determines the presence of Normal P-AchE, NOT normal levels (u/L) of circulating P-AchE.
What is Dibucaine?
A local anesthetic that inhibits NORMAL P-AchE
-Normal P-AchE = 80% inhibition by Dibucaine
What are the results of the Dibucaine test with Heterozygous Atypical Pseudocholinesterase?
40-60% inhibition
What are the results of the Dibucaine test with Homozygous Atypical Pseudocholinesterase?
20% inhibition
What are the adverse effects associated with Succinylcholine?
-Dysrhythmias/ Bradycardia (linked to K+ flow)
-Fasciculations
-Hyperkalemia (avoid in hyperkalemic patients)
-Muscle Pain/Myalgia
-⬆ Intragastric Pressure & ⬆ Lower Esophageal Sphincter Tone
-⬆ Intraocular Pressure (concern with open globe injuries due to extrusion of intraocular contents)
-⬆ Intracranial Pressure
-Masseter Muscle Rigidity (Also called Trismus)
-Histamine Release
-Malignant Hyperthermia
Which adverse effects of Succ can be diminished with a pre-treatment dose of a NDMR?
-Fasciculations
-Muscle pain/myalgia
-⬆ Intragastric Pressure & ⬆ Lower Esophageal Sphincter Tone
-⬆ Intracranial Pressure
What do you need to know regarding Masseter Muscle rigidity and succ?
Could be a SE of the Succ, or could be an early sign of MH.
-Has to go away after 90 sec or risk of MH. If it releases within 90 sec or relaxes with anesthetic, it’s probably just a SE of succinylcholine administration.
What are the CV effects of Succ at low vs high doses?
-Low Doses = low HR/BP
-High Doses = higher HR/BP & catecholamines
nAchR of the SNS and the PNS (esp Muscarinic receptors) in the SA Node can increase or decrease HR and BP.
What are the CV effects of Succ in children and how do you prevent it?
-Profound bradycardia
-Pretreat with IV Atropine 0.02 mg/kg
When do adults typically experience bradycardia with succ?
Typically do not brady unless a second dose of succ is given.
-Prevent with Atropine or pre-treat with small dose of Roc
How does Succ cause Dysrhythmias?
-Associated with Succ Drips
-Succ goes to other Nicotinic receptors, like at the Autonomic ganglia.
-Blocks PNS, allowing for SNS override
-Can cause various dysrhythmias: Sinus Arrest, PVCs, AV nodal blockade with junctional rhythm, peaked T-waves associated with inc K+ (treat with CaCl).
What are Fasciculations?
-Visible muscle contractions
-Disorganized muscle activity resulting from the depolarization of the nerve terminal
-Produced by the presynaptic receptors
-Typically not observed in young children < 10 or elderly
-Potential to cause pathologic fractures in patients with osteoporosis
-May worsen a pre-existing fracture
-Can lead to serious myalgias
How can you prevent fasciculations with Succ?
Use a pre-treatment dose of NDMR given 3-5 minutes before Succ.
-Usually results in an increase dose of Sux (1.5 - 2.0mg/kg) for depolarizing block
-Ex. Rocuronium 0.06-0.1 mg/kg
What is a “Self-Taming” Dose of Succ?
-The administration of small doses of Sux 1 min prior to the intubating dose to prevent fasciculations
-Ineffective and abandoned
How much does Succ depolarization increase K+ levels?
0.5 - 1.0 mEq/L
-Within 3 min of admin lasting less than 10-15 minutes
Why are patients who have upregulation of receptors at risk for hyperkalemia?
-Still have ion flow at these extrajunctional receptors even though they don’t affect paralysis of skeletal muscle.
What conditions cause susceptibility to Succ induced Hyperkalemia? (Blue Box!)
-Burns
-Massive trauma/peripheral denervation
-Spinal Cord injury/transection
-Stroke
-Guillain-Barre Syndrome
-Prolonged total body immobility
-Closed head injury
-Myopathies
-Severe intra-abdominal infection
-Encephalitis
-Polyneuropathy
-Hemorrhagic shock with metabolic acidosis
-Tetanus
-Ruptured cerebral aneurysm
Why is hyperkalemia r/t succ NOT altered by pre-treatment with a NDMR?
-Even with some ionic receptors being blocked by NDMR, the ones that are open can still lead to increased K+
What is important to know regarding succ-induced hyperkalemia and renal patients?
-Not threatening in normokalemic renal patients
-Dialysis patients are relatively used to a high level of K+
-But, we have other choices, so don’t use it unless risk/benefit outweighs other options (ex: need for true RSI)
-Cisatracurium is better choice for renal dz patient.
Myalgias/Muscle pain due to Succ administration is most common in what populations?
-Females and inactive patients
-Increased severity in young ambulating patients
Where are myalgias/muscle pain due to succ located?
Subcostal region, trunk, neck, upper abs, shoulders
What is important to know regarding succ administration and myalgias/muscle pain?
-May be prevented/decreased by NDMR pre-treatment & NSAIDs
-Onset 24-48 hours after admin but may last 2-7 days
-Decreased fasiculations = decreased myalgias
-Theory: the initial unsynchronized contractions increase myoglobin levels and creatinine kinase
-Indicates muscle damage/muscle injury
-Myoglobinemia is a rare complication after extensive fasciculation or in Malignant Hyperthermia (MH)
What is important to know regarding the ⬆Intragrastic Pressure and ⬆LES Tone associated with Succ administration?
-Secondary to the abdominal wall muscle fasiculations
-⬆ Intragastric pressure increases the risk of aspiration
-Lower esophageal sphincter may open spontaneously at pressures of >28 cmH2O
-Risk of aspiration simultaneously ⬇ by the ⬆ in lower esophageal sphincter (LES) tone
-Both effects diminished/reduced by pre-treatment with NDMR
How does succ administration affect Intraocular pressure (IOP)?
-Increases it by 5-15 mmHg for 10 min (less than the inc in IOP r/t coughing/bucking)
-Theory: Dilation of the choroidal vessels & the contraction of the extraoccular muscles
-Could compromise the already injured eye
-Theory: Extrusion of intraocular contents of an open eye injury
-NOT reduced by pre-treatment with NDMR
What is the effect of Succ administration of increased Intracranial Pressure (ICP)?
-Increases ICP r/t increased cerebral activity and cerebral blood flow (CBF)
-Exact cause unknown, inconsistent observation
-Decreased or prevented with hyperventilation and/or pre-treatment with a NDMR and/or Lidocaine
-Have to counteract elevations in ICP with an at-risk patient
What other things can cause increases in IOP & ICP? (Blue Box!)
Increases in IOP & ICP are also seen with inadequate anesthesia, inadequate relaxation, and the stimulation from intubation.
What is important to know regarding Succ administration and Masseter Muscle rigidity?
-Transient increase in tone
-Potential for difficulty in opening the jaw for direct laryngoscopy (DL)
-Seen more often in children
-Marked increase in tone preventing DL
-May be a sign of MH
-If not MH, can do blind/fiberoptic nasal intubation, deepen anesthetic, or bag them for 10 minutes until it wears off (may need surgical airway if can’t ventilate)
Does Succ cause Histamine release?
Yes, slightly.
-But causes anaphylaxis more than any other anesthetic drug (Barash).
What is the relationship between Succ administration and Malignant Hyperthermia?
-Genetic predisposition
-Mechanism by which Sux triggers MH is unknown.
What are Contraindications for the use of Succ?
-Malignant Hyperthermia
-Hyperkalemia
-Burn pts with burns over 35% TBSA 3rd degree burn
-Severe muscle trauma
-Severe sepsis
-Muscle wasting, prolonged immobilization,
-Extensive muscle denervation (Spinal cord injury)
-Duchenne Muscular Dystrophy
-Atypical P-AchE
-Allergy
-Children and adolescent patients
Why is Succ avoided in children and adolescent patients?
-Especially those under 8 y.o.
Due to the risk of:
-Hyperkalemia
-Rhabdomyolysis
-Cardiac arrest in children with undiagnosed cardio-myopathies or dystrophies
Only used for emergency laryngospasm issues
When and how does Succinylcholine cause bradycardia?
-Repeat dosing in adults
-Any dose in children
Due to:
-ANS ganglia and PNS muscarinic receptor stimulation
-Metabolite stimulates cholinergic receptors in the SA Node
