ADVISORY:

Notes from the 2010 FLCC Critical Care Transport Paramedic class as was recorded solely by Marcus LaBarbera- NYS
Paramedic. I do not apologize for any spelling or grammar errors, lack of completeness, or recording errors. These are
primarily personal notes but I am offering them to the community as an additional study resource. I will take no
responsibility for persons who fail any quiz or test as a result of this document. Always consult the text books
recommended specifically by UMBC for this course.

Day 2 CCEMTP
Class
TT airway in burns- now controversial from provider to provider

Cormack-Lehane scale

5.5-6.5 TT in a trach, 7.0 is LARGE

DOPE nmumonic for troubleshooting airway problems

Beware mediastinal pneumonia (though prevalence seems to be low?)

Treacheal/ esophageal-arterial-pharangeal…. Fistula (from long term treach application..)

LMA contraindicated in upper GI pathology/ GERD, …

With King LT-D, suction well before insertion to decrease problems later
Passing bouge to transfer King to TT, may not work as well as company reports

Eschmann introducer (bougie)

Bougie as a stylette may facilitate faster intubation if it’s a known or potentially difficult airway

Retrograde intubation- 110mm j wire

Know medication classes for final test

 RSI
“Facilitated” intubation (only atomodate or versed) to assist with intubation which is a poor
experience for the patient. Atomadate given too quickly can cause trismus.

SLAM – street level airway management

7- P’s:

Preoxygenate- if there maintaining oxygenation with spontaneous respers…

Preperation
Premedicate
Paralysis with sedation
Pass the TT
Placement conformation
Post intubation care

Remember to avoid BVM use if it’s not necessary

Remember the basics and provide Oxygen
Remember suction THAT WORKS particularly with portables.

Lidocaine is thought to decrease ICP but no good studies to prove either way

Peds: (up to 10yoa) dose 0.01mg/kg, if you give below 0.1mg/kg it may cause reflex
bradycardia because of enhanced vagal tone

Defaciculating dose of NMBA is nice but not used in general

Remember sedatives DO NOT provide analgesia

Midazolam probably the best for sedation

Depolarizing gents:
Siccinocholine- beware previous history of muscular pathology (Guilian-baret, MS) malignant
Hyperthermia
 30-5 min onset for paralysis

1-2mg/kg, (2 mg for peds because of higher metabolism)

Caution in hyperKalemia states (crushing, burns,..)

Remember to perform the sellic’s maneuver

Wait for flaccidity before starting the procedure (test there jaw for relaxation)

People do better on a vent than on a manual BVM, rate is more consistent and volumes are
uniform.

Sedation:
Etomidate- singal dose for induction
Propofal- good for pt with steady or high B/P
Versed-
Fentanyl- analgesia and sedation and wares off fast

Remember… if you reparalyse resedate

LAB VALUES
Make flash cards with lab data!

Normal values are based on averages

Helps to confirm or validate what your thought was

The body doesn’t do well with abrupt value changes (don’t drop a bg of 1200 to 90)

Sample quality Is dependent on the collection process.

Blood samples that stay stagnant too long before analysis may self-metabolize and show high K
and low bg…

CBC
WBC- Leukocytosis:
Infection
Dehydration (hemo-concentration)
Trauma
Leukemia
Steroid
Inflammatory process
MI
Leukopenia:
Viral infections
Radiation
Immunosupression
Bonemaro depression

Neutrophils-60-70%- bacterial infection

(segs., segmented, usually 3-5 segments)

Bands are immature neutrophils- (a “shift left” is seen in appendicitis)

Basoplils- 0.5-1%- allergic reactions

(on staining they show dark granules)

Eosinophils-

Lymphocytes 20-40%-

Monocyte- 2-6% (like macrophages) ground glass appearance

May have small holes (vacuals)

Usually more neutrophils, when we see more bands it indicates an infection

Vacutainer tubes:
Purple- EDTA
Green- Na Heparin
Blue- ??
“tiger top”- surum separator (with a “clot enhancer”)
Gray top- (ETOH test)
Yellow- cultures
Dark blue- heavy mettles

Red cell:
4.5-6.0 x10⁶
Hgb/ Hct

RULE OF 3’s: to check for lab accuracy

RBC x3~ Hgb
Hgb x3~Hct

Platelets- the smallest blood components

Microcytes- hypochromic cells (red cells with little hemoglobin (anemia)

Thrombocytosis, high red cells, slower flowing

“target cell” a type of thalacemia

Anemia:
Blood loss
Liver disese
Malneutrition/ malabsorption
Menstration
Pregnancy
Hemolytic reaction

Polycythemia:
Seveer dehydration
Pulmonary disese
Altitude compensation
Renal malignancy

Platlet:
150-400 x103
 \_HGB_/PLT

WBC/ HTC \

CPK- createnan phosphokynase (CKMB- for heart but also in other muscles)

LDH- Lactate dehydroginice (MI indicator along with CKMB)

Liver enzymes- TP, Alb, AST, ALT, GGTP, ALP, T –bil. D-bil

Pancreas- Amylase, Lipase (high suggests pancreatitis) ** may be on UMBC exam on what
organ system this

Know chem. 7 for UMBC test

Know testing about what part of the body tests

New tests:
BNP:CHF/ abnormal ventricular function

D-Dimer: DVT, PE, DIC

Troponin L: detects MI earlier

Glucose:
70-110
Power source, important for cellular respiration

Hyperglycemia:
DM
Pituitarry
Trauma
Hyperthyroidism
 Acute stress
Brain trauma
K⁺ deficiency

Hypoglycemia:
Islet cell cancer

BUN:
8-20 mg/dl
A break down in bybroducts
Azothemia
Impaired renal function
Shock/ dehydration
GIB
Excessive protine intake/ catabolism

Creatinine:
0.5-1.2 mg/.dl
A good indicator of kidney function
(BUN/Creat, 24Hr creat. Clearance)

Electrolytes:
Must be in balance…

Sodium
135-145 mEq/L

Hyponat.
Usually results from too much water in the body
Malnutrition
Severe burns
Severe vomiting
Severe diarrhea
edema

HyperNa.
Dehydration
Diabetes insipidus (lack of ADH from the pituitary) where we can’t concentrate urine
 Cussing’s disease
Treachobronchitis

Potassium:
3.5-5 mEq/L

Hypo K:
Loop diuretics
IV fluids without supliments
Malnutrition/ malabsorbtion

Hyper K:
Renal failure
Tissue damage

Chloride:
91-110 mmol/L

Hypo Chlo.
Vomit/ diarrhea
Ulcerative colitius
Burns
Acute infections
Fever

Hyper Chlo.

Na I Cl BUN/ GLU
K I CO2 I Creat\

Anion gap:
8-16 mEq
(Na +K)-(Cl+HCO3)
Inc. gap =metabolic acidosis

Urinalysis:
Spec gravity: 1.005-1.020 SG
pH 4.5-8.0
all other values should be neg. or trace
casts usually indicate some amount of kidney failure

Culture and sensitivity:

(CS)

COAG. Studies:
PT, PTT (heparin therapy)
INR

Guiac:

**UMBC usually focuses on Pressure monitoring (ICP), balloon pumps?... peds?...

ABG:
pH is normal- (if you have acid/ base balance)
tells us about metabolic and respiratory status

PO₂:
80-100 mm/Hg
Measures effency of Oxygen thearpt

pCO₂:
35-45 mm/Hg
An acid, a waste product
A/A gradiant (usually the same as ETCO₂ but if there is a descrepance use ABG values)
36 ATP (Creb cycle)

Glucose+0₂=H₂O, …

HCO₃
19/25 mEq/L

pH:
7.35-7.45 (mean in 7.4
Acid Base system:
The big 3-
Buffer system: (many buffer but we wil stay on the Bicarb pair)
Respiratory: fast, works in minute
Renal: slow
--all 3 are required to maintain balance—

Metabolic acidosis:
(bicarb is less, CO₂ is normal)

Diarrhea
Renal failure

Metabolic alkalosis:

Uncompensated- haven’t fixed the problem and haven’t tried yet

Partially compensated-
 Day 3
Breathing management
C₆ H₁₂ O₆ + 6O₂  6H₂O + 6 CO₂ + ~36ATP (Glucose met.)

1 mol sugar add Oxygen= water and co2 and ATP

Know landmarks (mid auxiliary, nipple, …)

Larynx usually resides bet C4-C6

Trachea begins at C5-C6 and runs about 11cm

Lamina propria- important respiratory structure

Alveolar epithelial membrane

3 types of alveolar cells:

Type 1- allows gas exchange
Type 2- produce surfactant
Type 3- produce macrophages

Know Hilus structure- point of entry for airway, blood vessels, and lymph pathways

2 separate blood supplies to lungs, 1 for gas exchange, 1 for lung tissue perfusion

PO2 of gas at sea level is ~160 torr

As long as there is a pressure gradient in the lungs respiration will continue to occurs- i.e.: hyper
ventilate … then stop and gas exchange will continue to occurs for a period of time.

O2 is relatively unsoulable in water, CO2 is very solulable in water

 Assessing the respiratory system

Remember percussion and fremitus assessment

Fever- 4 breaths per min for every 1°F increase in temp

Listen to each lobe: 2nd, 5th, 7th ICS

Sputum:
Rusty- pneumococcal p.

Mucopurulent- other pneumonia

Mucoid- clear, grey, white

Resp failure are represented in 2 broad categories:

Hypoxic:
Hypercapnic:

VQ mismatch- the most common cause of hypoxia.

(normal VQ ratio is 1:1)

VQ mismatches are either dead space or shunting

As the blood becomes more acidic the hemoglobin has less affinity to hold Oxygen, (a shift of the curve
to the right of the scale).

ETCO2 is ~3mm less than that of a ABG sample taken at the same time

ETCO2 for a patient is a shock state may be inaccurate because of poor blood perfusion in relation to
ventilation (VQ)

Mechanical Vent
Inc in PEEP is also inc. FRC

Total lung capacity:

TLC=6000ml
Tv= 600ml
Forced inhilation~4000ml (Insp reserve cap.)
Forced exhilation~(total 600) (exp reserve vol~100)
 Vital cap.= ~4600ml
Funct. Residual capacity= (1400cc) what is left over, doesn’t leave airway (this can me
augmented through PEEP during mechanical ventilation).

Shouldn’t normally let the I:E get below 1:2 to 1:3 (inverse ratio therapy is sometimes used though)

PIP= Vt/C + (R*Q)

(C= comlpliance)
(R= resistance)
(V*= flow)

 PIP=Vt/C + (R x V*)

A TT ID reduction of 1mm = a resistance increase of 4 (i.e.: place the largest tube possible)

PIP x Vt= directly proportional (inc one the other follows)

PIP x I/C= (compliance) (change compliance by augmenting the chest position and movement)

PIP x R= (resistance) (directly proportional)- hydrate to decrease secretions, bronchodilators

PIP x V= (flow) increase Insp time, decrease Vt,

Plateau pressure (insp hold and read circuit pressure), this will give you the alveolar pressure*

VT= 6-10 cc/Kg Ideal body weight (no longer 10-15cc/kg)

RR(Vf)= 8-20/min
Min Vol (Ve)= 8-10L/min
PIP= <40 cm/H2O
I:E ratio= 1:2-1:3
PEEP= 3-5 cm/H2O (physiologic)

Modes of ventilation:

4 basic modes:
CMV- (controlled mand. Vent
(Ve=Vt x RR)

AC- (will allow patient to initiate a set ventilation)

(may encounter breath stacking ..i.e.: auto PEEP and results in baro trama) (also seen most
times in CPR with BVM ventilation) (give patient a 10-15 sec exhalation phase to correct)
 SIMV- (as the patient is more responsive toward taking over breathing the rate can be turned
down)

PC- (pressure control)- gives you set PIP

Vt= flow rate x insp in seconds

Inverse ratio vent is now commonly used in ARDS

ETT AND TRACHEAL SUCTIONING
Suctioning a TT use around -100mm/Hg suction

Suction diameter should be about ½ the TT diameter

 Day 4
12 Lead ECG/ Cardiology

SA node region I supplied usually by RCA (59%) but may be supplied by LCA or both (3%)

Remember that K+ is MORE positively charged than Ca+

Different cardiac cells have a variation in Ca+ leakage into the cell which accounts for inherent rates in
different regions of the heart.

Parasympathetic stimulation prolongs efflux of K+

Contractile cells center around Na+ for depolarization (i.e.: sodium channel blockers)

Contraction of myocites centers around actin and myosin, Ca++ attaches to Troponin causing
contraction (i.e.: Calcium channel blockers)

CKMB index (calculation)

Troponin I/ T-

Myoglobin peaks fast (6 hrs)

CK-MB peaks (18-24 hrs)
Troponin peaks (24 hrs)

Ischemia starts subendocardial

Prinsmental’s angina “ghost MI” (commonly seen in smokers = precipitated vasoconstriction)

Retevase pharmicodynamics

Conservative treatment for reperfusions arrhythmias

MCL1 question on final exam… (lead III and move (+) to V1 position)
Don’t use ventricular (or paced) rhythms for MI diagnosis

A QS wave is pathologic (nothing but Q)

Hyper acute phase (usually too early for EMS to see)

In RCA infarcts- common to see AV blocks 1°, 2°, 3° with junctional escape (less serious)

“non-diagnostic” = normal.. ECG

Estes criteria- major voltage changes in RS waves in the chest leads

Ventricular aneurysm- diskenetic wall 2° to dead tissue and may show up on an ECG as persistent ST
elevation (usually in v1-v4)

BER- benign early repolarization, produces tall T waves and some ST elevation (seen in anterior and
lateral in males –esp black-, 20-40 years). (ST segment and J point makes a “fish hook” appearance) and
will gradually dissipate in prominence as you age

Digitalis effect “could I serve soup with that?”

Narrow QRS CANNOT be ventricular or a BBB

Assessment of hemiblocks on final-

LAD o0r RAD may suggest a facicular block, the QRS is still narrow, LAD=anterior hemi block
RAD= poststerior block

** Bifascicular block- start with RBBB (wide and upright in v1) with.. axis deviation (RAD or LAD)

This is important in if this is due to a LARGE infarct (and active MI) affecting both pathways, and may
destroy ALL ventricular pathways and lead to ventricular standstill.

Extreme Right axis often accompanies SVT

PWMI (posterior wall MI)- apply v7, v8, v9 (if you suspect reciprocal changes in v1-v4)

RVI (Right ventricular infarct)- v3, v4, v5, v6.. or v4R (always suspect a right sided MI in the presence of
an inferior wall MI).

Hyper K+ - peaked T waves, (seen also in acidosis)

Hypo K+ - U waves may be present, decreasing T waves.

Hypo Ca++ - prolongs QT, (though prolonged QT has other causes)

Hyper Ca++ - shortens the QT to the point that it may be buried.

Pre-excitation syndrome – accessory pathways.

LGL- short PRI, (no delta wave),
WPW- Short PRI WITH widened QRS and delta wave manifestation

** KNOW FOR THE TEST !

 Day 4
12 Lead ECG/ Cardiology

SA node region I supplied usually by RCA (59%) but may be supplied by LCA or both (3%)

Remember that K+ is MORE positively charged than Ca+

Different cardiac cells have a variation in Ca+ leakage into the cell which accounts for inherent rates in
different regions of the heart.

Parasympathetic stimulation prolongs efflux of K+

Contractile cells center around Na+ for depolarization (i.e.: sodium channel blockers)

Contraction of myocites centers around actin and myosin, Ca++ attaches to Troponin causing
contraction (i.e.: Calcium channel blockers)

CKMB index (calculation)

Troponin I/ T-

Myoglobin peaks fast (6 hrs)

CK-MB peaks (18-24 hrs)
Troponin peaks (24 hrs)

Ischemia starts subendocardial

Prinsmental’s angina “ghost MI” (commonly seen in smokers = precipitated vasoconstriction)

Retevase pharmicodynamics

Conservative treatment for reperfusions arrhythmias

MCL1 question on final exam… (lead III and move (+) to V1 position)

Don’t use ventricular (or paced) rhythms for MI diagnosis

A QS wave is pathologic (nothing but Q)

Hyper acute phase (usually too early for EMS to see)

In RCA infarcts- common to see AV blocks 1°, 2°, 3° with junctional escape (less serious)

“non-diagnostic” = normal.. ECG

Estes criteria- major voltage changes in RS waves in the chest leads

Ventricular aneurysm- diskenetic wall 2° to dead tissue and may show up on an ECG as persistent ST
elevation (usually in v1-v4)

BER- benign early repolarization, produces tall T waves and some ST elevation (seen in anterior and
lateral in males –esp black-, 20-40 years). (ST segment and J point makes a “fish hook” appearance) and
will gradually dissipate in prominence as you age

Digitalis effect “could I serve soup with that?”

Narrow QRS CANNOT be ventricular or a BBB

Assessment of hemiblocks on final-

LAD o0r RAD may suggest a facicular block, the QRS is still narrow, LAD=anterior hemi block
RAD= poststerior block

** Bifascicular block- start with RBBB (wide and upright in v1) with.. axis deviation (RAD or LAD)

This is important in if this is due to a LARGE infarct (and active MI) affecting both pathways, and may
destroy ALL ventricular pathways and lead to ventricular standstill.

Extreme Right axis often accompanies SVT

PWMI (posterior wall MI)- apply v7, v8, v9 (if you suspect reciprocal changes in v1-v4)

RVI (Right ventricular infarct)- v3, v4, v5, v6.. or v4R (always suspect a right sided MI in the presence of
an inferior wall MI).

Hyper K+ - peaked T waves, (seen also in acidosis)

Hypo K+ - U waves may be present, decreasing T waves.

Hypo Ca++ - prolongs QT, (though prolonged QT has other causes)

Hyper Ca++ - shortens the QT to the point that it may be buried.

Pre-excitation syndrome – accessory pathways.

LGL- short PRI, (no delta wave),
WPW- Short PRI WITH widened QRS and delta wave manifestation

** KNOW FOR THE TEST !

 GI/GU
Pica- folds found in the GI tract increasing surface area of the tract.

Submucosa- placement of the vascular beds, glands feeding the mucosa

90% of all nutrients are absorbed in the small intestine, 30 cm is minimum for survival. “Short gut
syndrome” is a consequence of shortened bowel.

The flora of the GI tract produces vitamin K for the body

Liver fractures occur along the 2 ligaments that transverse the organ

Hepato-jugular reflex test

The liver is the only organ that we cannot live without but it is also the only organ that has some
regenerative ability.

Morphine causes spasm of the sphincter of Odi (do not give in the presence of a gall bladder attack)

Pancreas- digestive juice contains amylase, lipase and bicarb

Choli-angitis- pain from blockage of the bile duct (gall stones)

Normal BS- 5-35/min

Absent BS is no BS in all 4 quadrants, 5 min in each quadrant (document as hypoactive if a full exam is
not done)

Autonomic disreflexia- seen in high spinal legions

C. Diff- prominent today because of concomitant use of antibiotics and PPI for upper GI maintenance
Paracentesis isn’t done a lot, it’s better to get the fluid back where it came from.

Deep peritoneal lavage- (DPL) now replaced by “fast exam”= ultrasound exam, though it may still be
used in the presence of no ultrasound available.

Nisen Fundoplication- surgery to support cardiac sphincter

Roux-en Y- gastric bypass procedure developed by Dr. Roux

Endocsopic Retrograde Cholangiopancreatography (ERCO) diagnostic x-ray with dye for gall bladder but
may also exacerbate pancreatitis.

Ligament of treits- separating line between upper and lower GI tract

Stress-related erosive syndrome (SRES)- neurologic/ CNS disease responsible for GI “stress” ulcer

The portal vein supplies 1,500 mL/ min, which is important when considering acute vericeal bleed.

Usually acute bleeding doesn’t change the hematocrit since Hct is a percent of the volume.

Glucose may be elevated due to stress induced glucose release

A BUN >40 with a normal Creatatin suggests a significant GIB

Vaopressin drip- used for treating GIB temporarily

Use caution when considering placement of a NG/OG tube when veracies are present
(UMBC- Contraindication to NG/OG tube)

The pancreas can release myocardial depressant factor (MCF)

ARDS is a consideration when pancreatitis is present

Amylase- elevates early and returns to normal 3-4 days post

Lipase- remains elevated several days after Amylase returns to normal

TPN- glucose rich nutrient (10-20%), when changing TPN the pancreas needs time to correct its self.
Switch to D10 solution for transport if TPN is DC’d

Asterexis (liver flap)- patients with liver failure, a test- bring the hand back at the wrist and when you let
the wrist go the hand “flaps” (due to high ammonia levels).

Bilirubin- unconjigated (indirect bilirubin) insoluable in is what is seen in jaundice/ icteris

Bilirubin- conjigated (direct bilirubin)- when it’s changed by the liver to a water soluable form
NYS law- NG/OG tube may be used for tube feeding for up to 24 hours only

Nasointestinal tubes- bypass the stomach (post pyloric sphincter) for prolonged feedings

During transport slow or stop tube feed so you reduce tube feed back-up and aspiration.

T-Tube- common bile duct drain

Normal –ostomy color is “beefy red”

Indiana pouch- Illium/ scecum are turned into a urinary bladder and a tube is placed through the ostomy
for drainage.

Renal
Kidneys receive about 25% of cardiac output (1,200 mL/min)

Nephron units almost always run hypoxic/ ischemic and aly insult will push them over the edge.

Passive reabsorbtion- “solvent drag”

Normal urinary output- normal >500 mL/Day

(20-30 mL/Hr or ½ mL/kg/Hour)~UMBC Standard

Renal failure split into 3 classes-

Pre renal- secondary to: hypovolemia, Cardiac failure
Intra renal- caused by direct damage to the kidney, death oh tubular cells
(-mycin antibiotics are nephrotoxic .. and ototoxic) (mouse drawing)
Post renal-

Acute Tubular Necrosis (ACN)- death of tubulals, though they usually regenerate and recovery is possible
(the most common cause of renal failure-25%)

Common infection by Group A Beta hemolytic strep, pharengitis that isn’t treated properly

Renal failure may be caused secondary to urinary occlusion.

BUN and Creatinine- in renal failure:

**BUN, normal 8-20
**Creatinine, 0.6-1.2 mg/dl- the best indicator of renal function

BUN Creatinine ratio usually 20:1 (normal) (ratio >30:1 indicates pre renal failure)

Protine indicates Intra renal or Post renal failure

Spec. Grav= 1.003-1.030 (normal)(UMBC)

Some glucometers will not work if patients are on a achodextran base PD solution (unusually high
readings) though patient’s are well aware of this.

Continuous veno-venous hemofiltartion (CVVHD)- very slow rate of clearance used for patients sensitive
to hemodialysis (becoming more popular inside a facility)

CFR patients tend to be anemic because of the lack of erythropoietin from the kidneys

Ca⁺⁺ is used to stabilize myocardial membrane

Treatment for hyper-K lemia:

Insulin/ glucose along with insulin to stabilize the glucose level

(K⁺ follows glucose)

Albuterol acts on cAMP to change K⁺ shift)

Bicarb

Kay-exalate treatment.

Diabetes insipidus (DI)- lacking ADH, water is removed redial but all electrolytes are retained, spec. grav
is close to 1 in these patients
Treatment: DDAVP (vasopressin) self admin via nasal spray

SIADH- syndrome of inappropriate ADH-

CBI- continuous bladder irrigation (Murphy drip)

 Neurologic Emergencies
** when was they last time they have been: (sedated, medicated,…)

90-60-30 rule (ABG)

** head injury prevention

Remember to stop the bleeding head injury, esp. in the elderly. An uncontrolled head would may need
transfusion

SCALP mnemonic

The middle meningeal art. Lies behind the temporal bone

Cribaform plate is thin, rough on the inside, the 1 st CN passes through it

The subdural spanning vessels shear as the brain sloshes (more so in patients that have atrophied
brains .. elderly, alcohol abuse…

Brain only runs on glucose, receives 15% of blood, 20% of cardiac output

The story of finius gage (railroad worker)

CN III (ocular mvmnt/ pupilary response) lies just below the tentorium and is pressed and results in
measurable changes.

After changes in the CN III there wil be pressure on the hypothalamus which regulates temp, vomiting

** reticular activating system KEEPS YOU CONCIOUS, maintains the sleep/ wake cycle

Pons- important with sleeping

Medulla- respiratory, cardiac, vasomotor

Understand where they are as compared to what affects them

The “homunculus” (both sensory and motor)

3 major artery sets feed the brain, a stroke to one of these will that particular area

The “pyramidal” tract

Central cord symptoms

Middle cerebral art (MCA) is the most common site of a stroke, usually “embolic” because of the path of
least resistant.

Basal art. Supplies blood to the cerebellum

The blood brain barrier- doe not allow flow of interstitial protines

Arachnoid granulations allow CSF to exit to outside the arachnoids layer, RBC’s in the fluid can block
these and cause increased ICP, (also common in meningitis)

ICP is usually less than 10 mm/Hg

**CPP= MAP-ICP

** monro-killie doctrine brain vol- 80% blood 10%, CSF 10%

CO₂ increases= cerebral vasodilatation

The term “concussion” has fallen out of favor and now use “injury”

Indirect injury (edema, blood, pressure) are worse than the direct injury many times

Epidural- LOC with lucid period and then back to LOC

Subdural- steadily decreasing LOC

New blood on CT is white

Subarachnoid hemorrhage (SAH)- thunderclap “worst headache” occurring communally in circle of Willis

Diffuse brain injury- stretching forces stretch and break axons causing diffuse axional injury
(“concussion”) usually due to rapid deceleration Sx- repeated questions, a little off)

Hippocampus is most sensitive to hypoxia (the brains RAM) no short term memory

Posturing is a result of pressure pushing on the nerve tracts that exit the pons and medulla (medulla-
decorticate, Pons- decerabrate)
Keep head at 20° to 30° to keep ICP lower and still maintain perfusion

A single episode of hypoxia doubles their mortality ! (1 episode of a SPO₂ less than 90%)

Mannitol- 1 Gm/Kg, use filter

Lasix- may decrease ICP (in theory)
D50-

D5W- hypotonic and promotes free water shifting into the tissue

topical anesthetic spray- to minimize noxious stimuli which will reduce a rise in ICP

Lidocaine controversy currently during RSI (it may blunt a rise in ICP by decreasing the cough reflex)

Propofol- be ware hypotension, may want to check for bleeding else ware before starting propofol.
(urine will change green due to dilluant if your on long term or high dose but is otherwise …)

Succx- increasing eye pressure, MS, Myatetmia gravis, any diseases that affect ACH receptors, which
shift K⁺ out and with the increasing ACH receptors causes enough K⁺ to be at a dangerous level.
This is a relative contraindication, depending on the level of function; there is more of a problem as the
patient’s inactivity increases.

Phenytone is slowly being replaced with phos-phenytone because it uses a different dilluant and doesn’t
cause arrhythmias.

Steroids in head injuries are out of favor, though decadron is used for in the setting of brain tumors.

Nimotopine- Ca channel blocker and is sometimes used in subarachnoid hemorrhages

CN VII palsy, (facial nerve) may mimic CVA unable to wrinkle forehead=CN VII, able to winkle- central
(CVA)

Think Aortic dissection if there are unusual CVA type Sx, usually in younger patients

Blowout fractures causing trapping of the inferior rectus muscle (no upward gaze)

Transverse process spine injury can impinge corroded art. And needs to be evaluated

Spinal cord injury without radiographic abnormality (SCIWORA) usually kids <9 who have incre4ased
stretch in spinal cord so.. spinal injury .. good outcome usually
Remember older patients with osteoporosis in low speed MVC’s

Rectal nerves are centrally located and their for are usually last to loose tone

NEXUS study (NYS has taken the field clearing of C-spine from this study)

Remember to pad splints and backboards, pad in void spaces (small of back)

Dopamine in spinal cord injury for better perfusion in the spinal cord (to increase MAP)

Neuro Assessment

GCS- use best response

Motor response (strength)- 0-5, lateralization and pronator drift

DTR- 0- +4 (+2 is normal) one of the first senses to be diminished in spinal cord trauma

ICP

Cerebral edema swelling peaks 3-5 days

Post traumatic hydrocephalis- arachnoid granulation is congested due to white or red blood cells,
correction by placing shunt

3 types of brain herniation:

Uncal-
Central, Transtentorial-
Cingulate-

** CPP = MAP – ICP

When CPP falls below 50 mm/Hg ischemia occurs

If GCS <8 with CT abnormalities are indications for ICP monitoring

Codman external drainage system for measuring and maintaining CSF canula
(when moving or any time the device is not leveled close the stop cock)

Richmond screw or Becker bolt are the 2 common devices in use

C-Waves – 4-8 x/min (abnormal but not so bad)

B-Waves- sharp rhythmic waves (bad) (bad but manageable)

A-Waves- sustained elevations in waveform (bad) (just a bad sign)

SjO₂- Jugular-Venous Oxygen

Remember when setting up management MAP of 65 mm/Hg (SBP >90 mm/Hg)

Burn Management

Burn size tends to be over estimated by up to 50%

Rule of 9’s-
Lund and Brawer chart-
(if using palm size to determine burn % use patient’s hand)

Parkland formula- 4cc LR x TBSA x DRY Weight (Kg)…

SMH decreases rate 10% every hour they meet there fluid requirement (titration gradually)

Quick calc: 1/4cc x TBSA x Kg = IVF/Hour

Pediatrics get D5LR maintenance in accompaniment with Parkland formula

 Pediatrics
70% of all CCT require respiratory therapy

Make sure you know who has rights to make medical decisions. Have guardianship documented in
writing if there are unusual custody situations.

Talk with receiving facility for orders

Under 4 years/ 40 Lbs, a car seat should be used

MAP should be about the gestational age (weeks)

Sinus arrhythmias in teens are normal (it should correlate with respirations)

Normal:
90+(2x the child’s age (in years)

Hypo
70+(2x the child’s age (in years)

*Do not draw off more than 5% of normal circulating blood volume in 24 hours

Hemolysis is more likely in children due to smaller needles

Towel support under shoulders to maintain airway position (up to 8-9 sometimes)

Infants are prone to bradying down during suctioning and airway maintenance

Ketamine is suggested for children esp. for airway instructions

(dissociative sedative, teenagers have more fearful after effects )
(may increase ICP)
When kids have vocal cords in spasm holding crycoid pressure may relieve it.

Remember propofol is in a soy base and may cross react with soy/ peanut

Push fentynal slowly (potential of “ridged chest” which will sustain for several minutes)

Atroping for under 8 years (40 kg)

ETT depth is 3x diameter of mouth at the teeth

Murmur is not uncommon in peds because of a more lateral position of the heart with blood flow
towards the chest wall.

Look for Hepatomegaly

Diaper count may not be accurate with the high absorbent diapers and relatively high cost of diapers

Blood can be pushed through a 24GA catheter

Greater risk of extravagation if IO is used continuously for more than 30 min

10-20cc/kg for fluid replacement

Fluid challenge is given over 1 hour

*Rule of 6 – in administering vasoactive drugs (usually proves disastrous in real life)

6mg drug x childs weight in 100cc of fluid
1cc/hr – 1gtt/min=1mcg/kg/min

After every 2 units of blood, give FFP

Fencing reflex- turn the head toward one side and that side arm will extend

Hemangeoma seen in the beard section of the face you should consider additional hemangeomas in the
airway and be careful with intubation

Rewarming times from hypothermia should occur slower

Pain scales: Wong Baker faces, number 1-5, objective scoring.. overall it is difficult to get a good results

Always give fentynal slow, start at 5mcg/kg and titrate up

Spinal bifita patients tend to have latex sensitivity (usually because they have extensive exposure to
latex during treatment

Obstetrical

CO increases 25-30%
HR increases 10-15% SV increases 10%
Plasma volume increases 50% (probably to prepare for the blood loss during delivery)
Art. pH increases
Pregnancy produces a hypercoagulable state

Nagel’s rule: First day of the last menses, subtract 3 months and add 7 days

McDonalds rule: 1cm for each week of pregnancy

20 weeks the top of the fundus should be at the umbilicus (<20 weeks the fetus is not likely to be viable)

Ectopic pregnancy occurs in 1 in 200 pregnancies

15-20% of ectopic pregnancies experience referred shoulder pain

3% of all deliveries are breach

Flight Physiology

Physiologic zone- 10,000 Ft., normally not a problem living in this zone

Physiologic deficient zone- 10,000-50,000 ft PO₂ decreases

Sea level: 1 Atm.= 760 Tor, 14.7 psi

Boyle’s Law- as atmospheric pressure goes down gas expands (Balloon)

Charle’s Law- as temperature goes up volume goes up (CAKE)

Dalton’s Law- all the parts equal the sum (Dalton Gang)

Henry’s Law- when you pop the top the CO2 comes out (Heiniken)
Hypoxia:
4 forms-
Hypoxic
Anemic
Stagnant
Hystotoxic

Above 5,000 ft we loose 28% of our night vision

10,000-15,000 ft vitals increase, though we may not be aware of the changes

15,000-20,000 ft CNS disturbances start to occur

Transport Start to Finish

 Pharmacology
Review: “manipulative physiology”
2 types of receptors, stim/ inhib.

Cl follows Na (from outside to inside when there’s a shift)

PO4 intracellular but sticks to everything
HCO3 intracellular because its made there from – and water
Ca is the trigger for almost everything that happens inside the cell
Mg whatever Ca turns on Mg turns off. If ATP is in use usually Mg is there also to release the reaction

Anything that makes the cell more positive (or less neg.) stimulates a reaction

Cells like to stay at rest, maybe leak a little K..

99.99% of all enzymes are proteins which stimulates or inhibits

Any change in shape changes the way enzymes react (temp, pH, …)

The more negative a cell is the more stimulation it takes to make the cell react

Antiarrhythmics:
Na= depolarization
K= repolarization

Na/K ATP-ase pump works to reset the cell to it’s original state

Phase 4 is rest (how close we are to threshold)

As cells are used they become more accustom to reaction (i.e.: tachycardia)

The longer the cell is at rest the more K can leak and the more stimulation is needed to cause a new
reaction
**Vaughn- Williams Classification

Amiodarone (class III) blocks everything!

(a high percentage of amiodarone is Iodine, caution in hypothyroidism which may precipitate a thyroid
storm)

GABA.. puts people to sleep

Lidocaine- rapid 1st pass metabolism, (shortens QT)

Esmolol (Brevibloc) is an excellent drug for management of acute severe hypertension

Amiodarone- beware in thyroid disease, pulmon fibrosis in long term use, …

Ca Channel blockers- works best on pacemaker cells but also enhances conduction through the
accessory pathway responsible for WPW

Antimicrobials

What are you trying to kill?

PCN- bacterialcidal (punch holes in the bacterial cell wall), though now the cells start to make
penicilinase that changes the receptor sites making it less effective.

** Rocephin (skull-cilin)- open skull Fx gets 1Gm rocephin

** Ancef (bung-cilin)-

Carbapenams- broad spectrum/ kill everything used for nosocomal infections

Bactariaostatic antibiotics- stop the bacteria cells from dividing to allow the patient’s own immune
system a chance to work (if the patient has one)

-Cyclines bind with calcium, may cause sleep

Macrolides (Z-pak)

Clindamycin- foams VERY easy

Sulfa drugs- good for GI infections, poorly absorbed, stay in systems a long time, good for UTI
Has a tendency to cause Stevens Johnsons.
Quinalones/ Cipro- headache/ dizzy/ ataxia. Will stop cell division in children therefore not for use in
children.

NMB
It takes 2 acetylcholine into 2 receptors to open 1 channel

2 type of NMB processes:

Depolarization- Succx.
Non-depolorizing- rest and stay at rest (longer to work and last longer)

Succinylcholine- causes fasciculation during depolarization,

Short acting (30 sec-90 sec onset, 5-10 min duration of action)

** dose for Succinylcholine 1.5-2mg/kg (kids always get 2mg/kg because of faster metabolism)

0.5-1mg increase in K⁺ during a normal administration.

Degenerative neuro diseases (due to increasing nicotinic receptors resulting in a prolonged uptake),
renal pt’s, burn patients

May cause Bradicardia/ tachycardia, always have atropine at hand pre-treat children and pt’s on Ca
Channel blockers

Non depolarizing agents

Longer lasting, used to “synchronize ventilation”

Decreases ICP and metabolic demands

** vech/ Norcuron- a defasciculating (0.01mg dose) (1/10 th dose for pre treating)
Onset 3-5 min duration 15 min, doe not cause histamine release (no vasodilation)

Stage 1 decube. Can begin in a soon as 5 min (on a backboard)

“my job is to make my job easier” ~RP Breese

Etomidate- short acting non-barditurate IV anesthetic with hypnotic effects (hypnotics put people to
sleep). Used for facilitation of intubation

Low hemodynamic profile

Fast acting (30 sec)
Myoclonus is common
Patient awake from induction within 3-5 min
1.1 mg/kg bolus will produce 100s of sleep (0.2mg=200s sleep)

**always give sedative first and paralytic second … except:: patients already in a rapid downward
decline give succx first and sedative right after so both onset at the same time.

acts on MDA receptors

GABA- chief inhibitory ..
Many of the sedatives used enhance GABA, keep GABA around

Volume Expanders

Body is 60% water, 2/3 intracellular, 1/3 extracellular (25% intravascular,…)

Crystaloid:
NaCl/ LR

Colloids:
Protines- PPF/ Albumin
Or
Carbsp Hespan

Colloids exerts a low hydrostatic pressure (high oncottic pull) so it pulls extracellular fluid back in.
Altered permeability- colloids may leak and the other fluids go with them

Usual treatment.. start with a couple liters of crystalloid then colloid or blood

Albumin (plasma protine), ha a negative charge and redially binds with many drugs.

Considered salt-poor (vs old time “salt rich” which was used to preserve fluid in WW I)

5% albumin- treatment in acute blood loss

25% albumin-
Though…

It doers bind calcium

Volume overload is a problem
Hemo-reactions are possible

Hetastarch:
(large glucose mol. And makes clotting increase, then after clotting factors are used up, DIC)
Increases serum amalase

Thrombolytics
ST elevation that is greater in aVR than in v1 = Left main disease

Reocclusion of legion is higher after thrombolytics than when compared to angioplasty

ASA acetalates the COX enzyme for the life of the thrombocite

Heparin- binds antithrombin III (AT III) and makes it 1,000x more potent and halts further thrombus
formation.

Heparin MUST be used any time a –lytic is used

60 units/ kg bolus followed by 16 units/kg/hr

**Heparin reversal- Protomine (Heparin antagonist)

Coumadin inhabitation works on K dependant factors (VII, IX, X, II)

INR goal is 2-3

EVERYTHING interacts with Coumadin

Glycoprotine IIb IIIa is the point that the glycoprotine attaches to via vonwillobrans factor
(Integrlin) … must do a creatatin clearance

Beta blockers are given to MI patient’s unless there is a contraindication

** review cases in handouts

(Bob says paste is useless)

Fentynal is just as effective as morphine without vasoactive sideeffects

Vasopressors

In shock,
treat by fix the rate
fill the bucket (look at their neck veins for distension)
Squeeze the bucket (pressors)
Fix the pump

** dose range is meaningless.. there is no max dose (of dopamine) (is it doing what it’s supposed to?).
the common side effect is tachycardia

Always pigiback dopamine

Over 10 mcg it should go through a central line

Epi:
1mg-250/ 2mg 500

Levophed- (doesn’t have the effect on the lungs and increases SVR), good as a secondary agent in shock.

“the more you squeeze the less urine you make”

Anatdote for extravisation of pressors is- fentolamine

Phenylepherine- causes bradycardia, have atropine on hand

Dobutamine, increased contractility without peripheral vasoconstriction (good in Cardiogenic shock)

As a rule look at the first pressor the patient was on (usually dopamine) start there at cutting it back

Vasopressin 40Units in 250ml (if all else fails)

What was the last pressor applied?.. start titrating that

Mess with norepi last (it’s a good drug)

Consider giving fluid

MAP of 65 (60) is minimum

 Antihypertensives

Hydralyzine- drug of choice for pregnancy induced hypertension

Na Nitropruside- if given too fast it may drop the blood pressure so fast it will “suck the blood”
(coronary steel) out of the coronary art.
Metabolized to cyanide
Very UV reactive

If you do treat hypertension decrease by no more than 10%/ hr unless they have brain herniation

In treating HTN, treat pain first and see what it does to reduce the overall BP

Anyone with Cerebrial edema gets manitol (usually given with lasix)

Sedatives

Prevent harm to patient and staff

Whatever they were on in the ICU is ¼ of what they will need in route

Benzoes tend to accumulate esp. in older people

Versed if they’re on more than 24 hours the drug lasts up to a week.. unless they’re an alcoholic then no
dose is high enough

Examples:
Haloperidol
Great for hepatic encephalitis, (dopamine antagonist)
Benzos
Midazolam- longer onset, longer duration less side effects than valium
(plan to redoes q-15 min for continued sedation)
Diprivan
Versed
Fentynal
Ativan
Long acting (1-2mg)
Mixed in propylene glycol, kidneys die w glycol metabolism
Demerol lowers the seizure threshold, DO NOT USE IN CCT

Antianginals

Nitro IV:
Lo-sorb sets are not required but you will have to increase the dose and retitrate when the IV line is
changed again.

Cardio selective beta blockers aren’t cardioselective at doses normally seen in the ICU, they become
general beta blockers

Bronchodilators

Bata Agonists:
Also stimulate the heart

** albuterol is more potent than trebutaline

Theophyline:
Has a narrow therputic window, patient’s have been known to become toxic while in fever

Everything reacts to it

Mg:
Start at 2gms and titrate up

** defaciculating dose is 10% of full dose

**Clonadine dose: 0.1-0.2mg

** ketamine is the sedative of choice for asthmatics

 CHAPTER 6
AIRWAY
CN: IV (Glossopharyngeal) Innervates the post. Tongue, valleculae, and parts of the epiglottis.

CN: X (Vagus) (a branch of the superior laryngeal) provides strong sensory innervations to the
larynx which may produce sympathetic stimulation.

The trachea is approximately 9-15 mm in diameter and approximately 12-15 cm long, not quite
cylindrical and contains 12-15 cartilaginous “C” shaped rings to maintain it’s structure

The trachea divides at the carina into the right and left mainstem bronchi and continue for 23
divisions and terminate at the alveolar ducts where gas exchange occurs.

There are 300 million alveoli that each make contact with a pulmonary capillary (the junction is
referred to as the alveolar capillary membrane (AC).

Alveoli are made of type I and type II squamous cells,

Type I cells- gas exchange
Type II cells- manufacture surfactant

Normal pulmonary artery pressure is 25/10 (normal systemic pressure being 120/80)

VQ ratio is the ratio between blood flow and gas exchange, normal VQ ratio is 0.8 for the entire
lung. For every 4 L of gas (V), there must be 5 L of blood (Q).

Changes in the VQ ratio are the most common cause of hypoxia.

Pediatric patients should have a towel placed under their shoulders to compensate for their
proportionally large Occiput. They are obligate nose breathers and their tongue is
proportionally larger.
The glottic opening is more cephalad and anterior and the epiglottis is larger and lies at a 45°
angle. Large adenoidal tissue especially in infants.

Pediatric Oxygen demands are about double that of an adult.

In the AC membrane
(in the capillary) the partial pressure of Oxygen (PO₂) is 40 mm/Hg and the partial pressure of
Carbon dioxide (PCO₂) is 45 mm/Hg
(in the alveolus) the (PO₂) is 100 mm/Hg and the (PCO₂) is 40 mm/Hg

Normal blood returning via the pulmonary vein contains a 100 mm/Hg of Oxygen and 40
mm/Hg of CO₂ (these are normal ABG values).

CO₂ diffuses 20 times faster than Oxygen

Low VQ ratio= examples: pneumonia, atelectasis, mucus plug

High VQ ratio= examples: PE, Pulmon. Infarct, Cardiogenic shock
Silent Unit= examples: Pneumothorax, ARDS

Oxyhemoglobin Dissociation Curve

The patient can experience hypoxia even if PaO₂ and Oxygen saturations are normal.

Carbon monoxide has 240 times the affinity for hemoglobin as Oxygen does.

In terms of lung compliance:

Compliance can be defined as the change in the volume per unit of pressure(∆V/∆P)

Resistance is the amount of force needed to move a gas or fluid through a tube
(Poiseuille’s Law: Viscosity, length of the tube, driving pressure and radius contribute to the
work required to move the fluid through the tube).

The normal drive to breath comes from the need to remove CO₂ from the blood.
CO₂ combines with water to produce carbonic acid which is then broken down to H⁺ and HCO₃.
As CO₂ increases so does H⁺ which causes the pH to fall. This change is transmitted through the
blood brain barrier and simulation of the respiratory centers occurs.

As a back-up there are chemoreceptors located in the Aortic arch and carotid arteries that
activate when they sense a PaO₂ less than 60 mm/Hg and stimulate increased breath rates.

The respiratory center is located in the brain stem which comprises the Medulla and Pons.

Medulla- The dorsal respiratory group regulates impulses to the diaphragm.

- The ventral respiratory group controls expiratory impulses, the upper airway
muscles, and the intrinsic pattern of breathing.
- The Pontine respiratory group and the Pneumotaxic center fine tune the respiratory
pattern.

The diaphragm is innervated by the Phrenic nerve which exits the spinal column at the level of
C3 to C5.

Lung Volumes and Capacities:

Minute volume- the amount of air breathed in 1 minute (Respiratory rate x average V T)
Normal minute volume is 5-10 L/min.

Normal Vital capacity (Vc)= 60-70 mL/Kg of ideal body weight.

A decrease in vital capacity to less than 10-15 mL/Kg indicates
poor pulmonary reserve and the inability to cough effectively.
 These patients almost always require mechanical ventilation
assistance.

Dead space (VD) is air not exchanged in the upper airway and is approximately 2mL/Kg

Shunt effect (Qt)- a condition where the airway is not able to participate in gas exchange
(i.e.: pneumonia). Normal Qt ranges are 3% to 5%, a range above 20% is critical.

Anemic hypoxia (Hypemic hypoxia)- reduction or dysfunction of hemoglobin.

Examples: anemia, hemorrhage, sulfa drugs, CO.

Stagnant hypoxia- reduced cardiac output resulting in tissue hypoxia due to lack of circulation.
Examples: heart failure, shock, CPAP, increased G forces, PE

Hystotoxic hypoxia- when cells are unable to use Oxygen due to inactivation or destruction of
key enzymes.
Examples: Cyanide, Strychnine, and later stages of CO poisoning.

I:E ratio- normal is 1:2, 1:5 is seen in airway obstruction, 1:1 is seen in Tachypnea

LEMON pneumonic:
L- Look externally
E- Evaluate 3-3-2
3- Fingers Mouth Opening
3- Fingers Hypomental Distance between the tip of the jaw and the beginning of the neck
(under the chin)
2- Fingers between the thyroid notch and the floor of the mandible (top of the neck)
M- Mallampati classification
O- Obstruction
N- Neck mobility

Mallampati Classification:

(Measurement is made with the patient in the upright seated position)

Normal VT is calculated as 7-10 mL/Kg of ideal body weight
   

  

Chapter 20:  Neuromuscular Blockers

Table of Contents
 Skeletal muscle relaxants
 Spasticity
 Anti-spasmolytic drugs
o Other clinical uses
 Drugs for acute local spasm
 Neuromuscular-blocking agents
 Pharmacokinetics:
Neuromuscular-blocking drugs
 Introductory comments about
specific nondepolarizing agents
 Depolarizing neuromuscular-
blocking drugs
 Pharmacodynamics
 Clinical Uses
 Depolarization Neuromuscular-
blockade
 Succinylcholine (Anectine)--
adverse effects
 Nondepolarizing blockers
 Clinical Pharmacology
 Some neuromuscular-blocking
drugs

Neuromuscular Blocking Drugs

Skeletal Muscle Relaxants

Spasmolytic agents

 Spasticity-characteristics
o Increased in tonic stretch reflexes
o Increased flexor muscle spasm
o Muscle weakness
 Clinical conditions associated with spasticity:  Cerebral palsy, Multiple sclerosis,
Stroke
  Clinical spasticity -- mechanisms:
o Reflex arc involvement
o Higher center involvement ("upper motor neuron disease") affects descending
pathways leading to alpha motoneurons hyperexcitability
 Mechanisms of drug action {diminishing spasticity}
o Alteration in stretch reflex arc
 o Attenuation of excitation-contraction coupling

Anti--Spasmolytic Drugs
 botulinu
 carisoprod
 baclofen m toxin
ol (Soma,
(Lioresal) type A
Rela)
(Botox)

 chlorzoxa
 chlorphen  cyclobenza
zone
esin prine
(Paraflex,
(Maolate) (Flexeril)
generic)

 dantrolene
 diazepam  metaxalone
(Dantrium
(Valium) (Skelaxin)
)

 methocarb  orphenad  tizanidine

amol rine (Zanaflex)
(Robaxin) (Norflex)
 

 Diazepam (Valium)
o  Enhances CNS GABA inhibitory activity; active at most (all) GABAA synapses.
o  Anti-spasmolytic effect in part due to action in the spinal cord {effective in
patients with cord transection}
o  Tends to be sedating
 Baclofen (Lioresal)
o Mechanism: GABA agonist at GABAB receptors
 Receptor activation causes increased K+ conductance (hyperpolarization)
in the brain and spinal cord
 Spinal cord effects probably occur following increased presynaptic
inhibition which reduces transmitter released by reducing calcium influx.
o Similar anti-spasticity compared to diazepam (Valium) but with less sedation
o Pharmacokinetics:
 Orally active;well absorbed
 half-life: 3-4 hours
o  Adverse Effects:
 drowsiness; increased seizure activity in patients with epilepsy
o Intrathecal Baclofen (Lioresal) use:
 Management of severe spasticity/pain when nonresponsive to
medication by other routes of administration.
  Few peripheral symptoms; higher concentrations may be used
   Partial tolerance may develop
  Major disadvantage: maintaining the integrity of the delivery
catheter.
  Advantage: significant improvement of quality of life in some
patients
 Tizanidine (Zanaflex)
o Overview
 Tizanidine (Zanaflex) is related to clonidine (Catapres)
 Enhances both pre-& postsynaptic inhibition in the spinal cord

 Also inhibits nociceptive transmission (dorsal horn)

o Clinical Use
 Probably a significant benefit for patients with spasticity (several types)
 Comparable efficacy compared to: diazepam (Valium), baclofen
(Lioresal), and dantrolene (Dantrium)
 Dosage must be carefully titrated for each patient
o . Adverse Effects:
 drowsiness, dry mouth, asthenia, hypotension
 Dantrolene (Dantrium)
o Overview
  Unique mechanism -- acts outside the CNS
  Interferes with muscle fiber excitation-contraction coupling
o  Mechanism of action
 Blockade of sarcoplasmic reticulum calcium channel {ryanodine channel}
 Reduced calcium concentration diminishes actin-myosin interaction
 Motor units contracting more rapidly are more sensitive to dantrolene
(Dantrium)
 Cardiac muscle & smooth muscle are only slightly affected
{different calcium release mechanism}
o Pharmacokinetics
 bioavailability: about 33% of oral dose absorbed
o  Adverse Effects:
 Muscle weakness
 Sedation
 Hepatitis (occasional)
o Other Clinical Use
  Malignant hyperthermia, is associated with hereditary abnormality in
sarcoplasmic reticulum calcium sequestration affecting probably, in some
cases affecting the ryanodine receptor (calcium channel in the SR) is
triggered by:

o  General anesthesia
 o  Neuromuscular blocking drugs
 Clinical Presentations:

 Significant muscle contractions

 Sudden and prolonged calcium release
 Increased lactic acid production
 Increased body temperature
 Dantrolene (Dantrium) reduces calcium release
  Other interventions are required to reduce body temperature and
manage acidosis

 "The open and closed states of the Ca2+-release channel are shown side by side
in three different views: top, side and bottom. Important details are marked: the
clamp-shaped domain (C), the handle (H) which connects the clamp shaped
domain to the central part of the cytoplasmic side (CY) of the tetramer. The
putative transmembrane (TM) part of the assembly resembles the stem of the
mushroom-shaped protein. In the open-state reconstruction the transmembrane
region of the channel appears open towards the SR, whereas in the closed state
a central opening is not seen in this region. As is clearly visible in these images,
the clamp-shaped domains (C) are open in the open-state reconstruction
whereas the fingers of the clamps touch in the closed state
 reconstruction." From Orlova, E. et al. Nature Structural Biology v3(6) 547-52.
1996. 
 Drugs for Acute Local Spasm
o Sedatives acting at the brain stem or spinal cord level include:
1.  Carisoprodol (Soma, Rela)
2.  Chlorphenesin (Maolate)
3.  Chlorzoxazone (Paraflex,generic)
4.  Cyclobenzaprine (Flexeril)-- not useful for muscle spasms secondary to
spinal cord injury or cerebral palsy; strong antimuscarinic and sedative
effects
5.  Metaxalone (Skelaxin)
6.  Methocarbamol (Robaxin)
7.  Orphenadrine (Norflex)

Katzung, B.G.., Skeletal Muscle Relaxants, in Basic and Clinical Pharmacology, (Katzung, B.
G., ed) Appleton-Lange, 1998, pp 434-449;White, P. F. "Anesthesia Drug Manual", W.B.
Saunders Company, 1996

.return to Table of Contents

Neuromuscular Blocking Agents

Overview-Neuromuscular Blocking Drugs

 Chemistry/Structure
o NMJ blockers: Structural similarity to acetylcholine
  Succinylcholine (Anectine) {depolarizing blocker, SCh} -- two linked
acetylcholine molecules
  Nondepolarizing agents also contain a "double-acetylcholine" form;
however this form is hidden by ring systems-- e.g. pancuronium
(Pavulon)
  Contains 1-2 quaternary nitrogens which result  in limited lipid-solubility
{limited CNS penetration}
 Major classes of nondepolarizing blocking drugs:

Isoquinoline 
   Isoquinoline derivatives 
o  Tubocurarine
o  Atracurium (Tracrium)
o  Doxacurium (Nuromax)
o  Mivacurium (Mivacron)
  Steroid derivatives -- e.g.
o  Pancuronium (Pavulon)
o  Vecuronium (Norcuron)
o  Pipecuronium (Arduan)
o  Rocuronium (Zemuron)

NMJ blockers: Isoquinoline derivatives

NMJ blockers: Isoquinoline NMJ blockers: Isoquinoline

derivatives, Atracurium (Tracrium) derivatives,  Mivacurium (Mivacron)

Other NMJ blockers

 NMJ blockers: Steroid NMJ blockers: Depolarizing
derivatives,  Pancuronium (Pavulon) blocker  Succinylcholine (Anectine) 

Pharmacokinetics: Neuromuscular Blocking Drugs

Nondepolarizing agents --Elimination characteristics

 Fast initial distribution; slower elimination

 Limited volume of distribution {expected for highly ionized agents -- tending not
to cross readily biological membranes}
 Route of elimination-- important determinant of duration of action
o  Renal elimination:
  Long half lives; long durations of action (> 35 min)
o  Hepatic elimination:
  Shorter half lives: (< 30 min)

Isoquinoline derivatives
Duration of action
Drug Elimination mechanism
(minutes)
ester hydrolysis (enzymatic
Atracurium (Tracrium) 20-35
& nonenzymatic)
spontaneous (Hoffmann
Cisatracurium (Nimbex) 25-44
elimination)
Doxacurium (Nuromax) renal > 35
 Metocurine (Metubine
renal (40%) > 35
Iodide)
plasma
Mivacurium (Mivacron) 10-20
pseudocholinesterase
Tubocurarine renal (40%) > 35

Steroid Derivatives
Drug Elimination mechanism Duration of action (minutes)
Pancuronium (Pavulon) renal (80%) > 35
Pipecuronium (Arduan) renal (60%) & hepatic > 35
Rocuronium (Zemuron) hepatic (75-90%) & renal 20-35
Cecuronium (Norcuron) hepatic (75-90%) & renal 20-35

Other Drugs of Interest

Drug Elimination mechanism Duration of action (minutes)
gallamine (Flaxedil) renal (100%) > 35
plasma
succinylcholine (Anectine) <8
pseudocholinesterase

*-- adapted from Table 27-1: Miller, R.D., Skeletal Muscle Relaxants, in Basic and Clinical
Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p. 438

Introductory comments about specific Nondepolarizing agents

 Overview: Intermediate-duration agents (e.g. vecuronium (Norcuron) & rocuronium

(Zemuron)) --mainly dependent on hepatic metabolism and biliary excretion for
elimination:
o  Intermediate-duration drugs are most commonly used clinically {compared to
longer acting renal-excreted drugs}
 Vecuronium (Norcuron) vs. pancuronium (Pavulon):
o  Similar steroid nucleus -- one contains a tertiary rather than quaternary nitrogen
o  Vecuronium (Norcuron) -- shorter duration of action; minimal cardiovascular
effects; 85% hepatic metabolism/elimination
 NMJ blockers: Steroid NMJ blockers: Steroid
derivatives,  Vecuronium (Norcuron) derivatives,  Pancuronium (Pavulon)

 Rocuronium (Zemuron)
o  Most rapid onset among nondepolarizing blockers
o  A drug of choice for rapid-sequence anesthesia induction and intubation (when
succinylcholine is contraindicated or clinical circumstances suggest that it not be
used)
 Atracurium (Tracrium) (isoquinoline derivative) -- similar characteristics as
vecuronium (Norcuron)
o  Hoffman elimination inactivation {spontaneous breakdown}
o  Atracurium (Tracrium) breakdown product --laudanosine may accumulate due
to very slow hepatic metabolism and upon crossing into the brain may
cause seizures
  Seizures occur at laudanosine concentrations above that obtained
during surgical procedures; however long-term use of atracurium
(Tracrium) within the intensive care setting may result in concentration
sufficient to induce seizures
 Cisatracurium (Nimbex) {atracurium (Tracrium) stereoisomer}
o   Similar to atracurium (Tracrium), but less laudanosine formed and less
histamine released
 Mivacurium (Mivacron): shortest duration of action among nondepolarizing agents
o   Rapid clearance of isomer mixture by plasma cholinesterase
(pseudocholinesterase, i.e. butrylcholinesterase) activity
 Prolonged duration of mivacurium (Mivacron) action in patients with
renal failure {renal failure is associated with reduced plasma
cholinesterase activity}
 Depolarizing Neuromuscular Blocking Agents

 Overview -- succinylcholine (Anectine)

o Very brief duration of action (5-10 minutes)
o Brief duration of action due to: rapid hydrolysis by plasma cholinesterase
(butrylcholinesterase/pseudocholinesterase)
  Extended duration of action would occur with reduced plasma
cholinesterase activity.
o Initial metabolite of succinylcholine (Anectine): succinylmonocholine (very weak
neuromuscular blocking effect)
o Termination of pharmacological effect--diffusion away from postsynaptic
receptors (note the absence of pseudocholinesterase at post-junctional sites
  Genetic variation: effects on duration of action of succinylcholine (Anectine)
blockade
o Abnormal plasma cholinesterase may prolong succinylcholine (Anectine) effects
o "Dibucaine (Nupercainal, generic)-number" test identifies patients with abnormal
plasma cholinesterase {dibucaine (Nupercainal, generic) inhibits the "normal"
enzyme by 80% & the abnormal enzyme by only 20%}
  dibucaine (Nupercainal, generic)-variants are the most common plasma
cholinesterase genetic variants.

Pharmacodynamics

 Neuromuscular blocking drug pharmacodynamic characteristics determined by

measuring:
o  Speed of onset
o  Duration of neuromuscular blockade
 Clinical method of determining neuromuscular-blockade properties --
o  Determine skeletal muscle response evoked by supramaximal electrical
stimulation using a peripheral nerve stimulator
o  Typically: single twitch response to 1Hz {adductor pollicis muscle -- ulnar nerve
stimulation}
 Potency determination comparing neuromuscular-blocking drugs:
o  Dose required to suppress 95% of the single twitch response (ED95}
  Potency determined in the presence of nitrous oxide-barbiturate-
opioid anesthesia
  Volatile anesthetics will significantly decreased ED95.
  Neuromuscular blocking drugs: sequence of muscles affected
o  Small, rapidly moving muscles (fingers, eyes) before diaphragm
o  Recovery in reverse order
o  IV neuromuscular blocker injection (nondepolarizing) to an awake patient:

1.  Initial difficulty in focusing & weakness in mandibular muscles

2.  then ptosis, diplopia and dysphagia
o  Consciousness and sensorium: unaffected, even with complete neuromuscular
block
 Blockade onset:
o  More rapid, less intense effect at laryngeal muscles (vocal cords) then at adductor
pollicis (peripheral muscle example)

  More rapid laryngeal muscle onset is probably due to a more rapid drug
plasma: drug muscle equilibration
  Reduced initial intensity of effect at laryngeal muscle (fast fibers)
follows from the requirement for more complete receptor blockade for
effect then for muscles mainly composed of slow fibers, e.g. adductor
pollicis.
o  Neuromuscular diaphragm blockade:
 Requires 2 times the dose required for adductor pollicis muscle blockade
  Adductor pollicis monitoring: poor indicator of cricothyroid muscle
(laryngeal) relaxation
 Facial nerve stimulation with orbicularis oculi muscle response monitoring
is a better reflection of neuromuscular diaphragm blockade onset
 Orbicularis oculi muscle monitoring is preferable to monitoring adductor
pollicis as indicator of laryngeal muscle blockade

"The orbicularis oculi is the thin sphincter muscle of the eyelids. It is

innervated by temporal and zygomatic branches of the facial nerve.", Image courtesy
 of Vesalius, used with permission
(http://www.vesalius.com/graphics/cf_storyboards/orbit/cfsb_orb7.asp)

Adductor Pollicis

Image courtesy of EatonHand (http://www.eatonhand.com/mus/mus005.htm)

Cricothyroid Muscle
 Cricothyroid Muscle: Vesalius Site, used with permission
(http://www.vesalius.com/graphics/archive/archtn_lar.asp)

Clinical Uses

 Primary uses of neuromuscular-blocking drugs:

1. Skeletal muscle relaxation facilitating tracheal intubation
2. Skeletal muscle relaxation to improve intraoperative surgical conditions
 Dose guidelines:

o  Facilitation of tracheal intubation -- 2 x ED95 dose of nondepolarizing muscle

relaxant
 Laryngospasm: effectively treated with succinylcholine (Anectine)
o  Optimal intraoperative conditions -- 95% single twitch response suppression
 Neuromuscular-blocking drugs: -- no CNS depression; no analgesia therefore they
do not substitute for anesthetic agents
 Other clinical uses:
o In managing patients requiring mechanical ventilation (intensive care
environment)
  Adult respiratory distress syndrome
  Tetanus
  Suppression of spontaneous respiration

Miller, R.D., Skeletal Muscle Relaxants, in Basic and Clinical Pharmacology, (Katzung, B. G.,
ed) Appleton-Lange, 1998, pp 434-449. Stoelting, R.K., "Neuromuscular-Blocking Drugs", in
Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp
182-219. White, P. F. "Anesthesia Drug Manual", W.B. Saunders Company, 1996.

 Rationale for Monitoring Neuromuscular Blockade:

1. NMJ blocking drugs are dangerous in that they interfere with respiration.
2. Depression of ventilation is a significant cause of anesthesia-related
morbidity/mortality--an important factor is the extent of residual
neuromuscular blockade.
3. Narrow drug safety margin (corresponds to a narrow range of receptor
occupancy)
4. Significant patient-to-patient response variabilty to the same dosage
5. Interactions between NMJ blocking drugs with other agents

Depolarization Neuromuscular Blockade

Succinylcholine (Anectine)

 Time course:
o rapid onset (30-60 seconds) -- IV
o short duration of action: 3-5 minutes
 Applications
o Skeletal muscle relaxation, facilitating intubation
  Mechanism of Action:
o Succinylcholine (Anectine) binds to nicotinic cholinergic receptors
 Promotes post synaptic membrane depolarization causing a relatively
long-term depolarization (compared acetylcholine) due to reduced
synaptic breakdown.
  Blockade occurs because depolarized membrane is unresponsive to
subsequent acetylcholine-receptor interaction
  Phases -- Phase I
o  Depolarization component is the phase I blockade
o  Prolonged phase I blockade may be associated with potassium transport (from
inside cell out): which may increase serum potassium by 0.5 mEq/L.
o  Properties of phase I blockade:
 Reduced amplitude; sustained response to continuous electrical
stimulation
 Reduced contractile-response to single twitch stimulus
 Enhanced neuromuscular-blockade following anticholinesterase drug
administration
  Train-of-four (TOF) ratio of > 0.7 (the height of the 4th twitch to that of
the 1st twitch); a measure of presynaptic membrane effects. When the
single twitch height has recovered to about 100%, the train-of-four ratio is
about 70%.
 No post-tetanic facilitation
 Skeletal muscle fasciculations are associated with initial (onset)
succinylcholine (Anectine) action.
 Phases -- Phase II
o Continued succinylcholine (Anectine) administration results in a transition
from endplate depolarization to endplate repolarization.
o However, this repolarization state is not susceptible to acetylcholine
depolarization provided succinylcholine (Anectine) remains present
 Blockade, even following repolarization, has led to the description of
phase II block as "a desensitization blockade".
o Transition from a phase I to a phase II blockade may be rapid (following a
succinylcholine (Anectine) dose of 2-4 mg/kg IV)
 Phase II onset: initial manifestation -- tachyphylaxis with need to increase
succinylcholine (Anectine) infusion rate or to administer larger doses
 Various degrees of phase I & phase II blockade may coexist
 Mainly phase I: -- anticholinesterases enhance neuromuscular-
blockade
 Mainly phase II: --anticholinesterases antagonize phase II blockade
 Small doses of edrophonium (Tensilon) (0.1-0.2 mg/kg, IV) may
be useful in discriminating phase I vs. phase II block
 Time course/Duration of Action -- Succinylcholine (Anectine)
o  Duration of action determined by plasma cholinesterase-mediated
succinylcholine (Anectine) hydrolysis
  Plasma cholinesterase: hepatic enzyme
  Initial succinylcholine (Anectine) metabolite: succinylmonocholine (very
weak neuromuscular-blocking)
o Plasma cholinesterase activity determines the amount of succinylcholine
(Anectine) reaching the endplate {most succinylcholine (Anectine) is
hydrolyzed by plasma enzyme}
o  Factors influencing plasma cholinesterase (pseudocholinesterase) activity
 Reduced hepatic enzyme synthesis
 The presence of atypical (genetic) plasma cholinesterase which exhibits
reduced succinylcholine (Anectine) hydrolytic capacity
 Liver disease (severe)
 Drug effects, e.g. neostigmine (Prostigmin) -- a carbamylating
cholinesterase inhibitor
 Drugs which may prolong succinylcholine (Anectine) action due to effects on
pseudocholinesterase:
 o Insecticides
o Nitrogen mustard, cyclophosphamide (Cytoxan) -- plasma cholinesterase
inhibition
o Metoclopramide (Reglan) (10 mg IV)
o High estrogen levels (parturients)
  Resistance to succinylcholine (Anectine)

  Genetic: increased plasma cholinesterase activity

  Obesity -- more plasma cholinesterase activity
  Pharmacodynamic effects, e.g. myasthenia gravis
  In myasthenia gravis: reduced number of nicotinic, neuromuscular
junctional receptors -- the target for the drug succinylcholine (Anectine)
  Atypical Pseudocholinesterase (plasma cholinesterase)
  Consequence: prolonged neuromuscular-blockade (1-3 hours) following normal
succinylcholine (Anectine) dosage
  Dibucaine (Nupercainal, generic)-related cholinesterase variant: most
important
 Dibucaine is an amide local anesthetic that inhibits wild type plasma
cholinesterase by 80%; however, it inhibits atypical enzyme by only 20%.
 If dibucaine (Nupercainal, generic) number equals 80: normal
cholinesterase
 If dibucaine (Nupercainal, generic) number equals 20: homozygous for
atypical cholinesterase -- frequency = 1/3200
 Clinical consequences of atypical cholinesterase on neuromuscular-blockade
duration
  1 mg/kg IV succinylcholine (Anectine): > three hours duration
 25% recovery of single twitch response following 0.03 mg/kg IV {small dose}
mivacurium (Mivacron): 80minutes
 For heterozygous atypical plasma cholinesterase patients (frequency: 1/480) --
dibucaine (Nupercainal, generic) number equals 40-60
 Moderately prolonged duration-- as long as 30 minutes following
succinylcholine (Anectine)
 Dibucaine (Nupercainal, generic) analysis only measures enzyme capability for
succinylcholine (Anectine) hydrolysis--
  reduced active enzyme {due to affects the liver disease [reduced
synthesis] or enzyme inhibition due to anticholinesterases} will affect
succinylcholine (Anectine) duration, but not be detected by dibucaine
(Nupercainal, generic) analysis

Miller, R.D., Skeletal Muscle Relaxants, in Basic and Clinical Pharmacology, (Katzung, B. G.,
ed) Appleton-Lange, 1998, pp 434-449. Stoelting, R.K., "Neuromuscular-Blocking Drugs", in
Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp
182-219 White, P. F. "Anesthesia Drug Manual", W.B. Saunders Company, 1996.

 Succinylcholine (Anectine) side effects

Succinylcholine (Anectine): major side effect categories

 increased
 hyperkalemia  arrhythmias  myalgia intraocular
pressure
 increased ICP  increased
 skeletal muscle
(intracranial myoglobinuria intragastric
contractions
pressure) pressure

o note: Many succinylcholine (Anectine) side effects may be reduced by prior

administration of non-paralyzing doses of nondepolarizing neuromuscular-
blocking agents
 This pre-treatment does not reduce the extent of potassium release
caused by succinylcholine (Anectine)
   Small children are extremely sensitive to succinylcholine given that
the parasympathetic system develops in advance of the sympathetic
system.  Should intubation not be successful following a single
succinylcholine dose, the tendency to give a second dose should be
resisted since the second dose may precipitate cardiac arrest.  
o Cardiac arrhythmias:
 Classification:
 sinus bradycardia
 Junctional rhythm
 Sinus arrest
 Mechanism:
  Direct activation by succinylcholine (Anectine) of muscarinic,
cardiac cholinergic receptors
 Cardiac Effects: most likely following a second succinylcholine
(Anectine) dose, administered about five minutes following the
initial dosage.
   Atropine pre-treatment does not prevent bradycardia following a
second succinylcholine (Anectine) dose

Other autonomic effects:

  Succinylcholine (Anectine) activates ganglionic cholinergic

receptors producing:
 Increased heart rate
 Increased systemic blood-pressure
 Hyperkalemia -- following succinylcholine (Anectine)
   Risk factors:
  Muscular dystrophy (clinically unrecognized)
  Severe skeletal muscle trauma
  Skeletal muscle atrophy following denervation
  Unhealed third degree burns
 Other factors/considerations:
  Succinylcholine (Anectine)-mediated potassium
release secondary to severe abdominal infection
 Potassium release following denervation (begins
within four days, may last six months or more)
 Pre-treatment with subparalyzing doses of
nondepolarizing blockers is not effective in
preventing or affecting the extent of potassium
release following succinylcholine (Anectine)
 Male children with undiagnosed myopathy --
predisposed to succinylcholine (Anectine)-induced:
  Hyperkalemia
  Rhabdomyolysis
  Cardiac arrest
 Muscular dystrophies:
  Most common form of muscular dystrophy
(frequency 1/3300 male births): Duchenne's
muscular dystrophy
 Diagnosis not possible until 2-6 years of age
 Becker muscular dystrophy (X-linked; (frequency:
1/33,000 male births), less common then
Duchenne's)
 Clinical Implications:
 Probable small percentage of pediatric
patients present with undiagnosed
myopathy -- alternative to succinylcholine
(Anectine) use -- a nondepolarizing
neuromuscular-blocking agent
  Myalgia-- postoperative succinylcholine (Anectine) skeletal
muscle effect
 Most common localization
 Neck (pharyngitis)
 Back
 Abdominal muscles
 Possibly due to succinylcholine (Anectine)-induced skeletal
muscle fiber contractions {affect reduced by prior treatment with
non-paralyzing doses of tubocurarine} -- vecuronium (Norcuron)
 when used in place of succinylcholine (Anectine) does not prevent
myalgia following laproscopy.
 Increased Intragastric Pressure
 Succinylcholine (Anectine): frequently increases intragastric
pressure
 Thought to be related to intensity of succinylcholine
(Anectine)-induced muscle fasciculation {intragastric
pressure increases prevented by previous administration of
nondepolarizing agent}
 Associated risk:

 Possible gastric fluid passage into esophagus,

pharynx, and long

o gastroesophageal sphincter more likely to

open at pressures > 28 cm H2O
 Rarely seen in children {probably due to limited
muscle fasciculation associated with
succinylcholine (Anectine)}
 Increased Intraocular Pressure
 Succinylcholine (Anectine): transient increase beginning 2-4
minutes after administration and lasting about 5-10 minutes
 Possible risk: in open eye injury (unsubstantiated by research};
however, this concern may limit use of succinylcholine (Anectine)
in this patient population

Masseter Jaw Anatomy

 images obtain from: http://www.teaching-
biomed.man.ac.uk/student_projects/1999/surtees/tester/mm.htm; Site concerned with
"The Structural and Functional Anatomy of Mastication" by Paul Surtees, B.Sc; The
Victoria University of Manchester (1999). permission requested

   Excessively-long skeletal muscle contraction -- masseter jaw rigidity

o Halothane (Fluothane)-succinylcholine (Anectine) sequence associated
with masseter jaw rigidity/incomplete jaw relaxation in children
 Considered normal; frequency -- about 4%
 Clinical Challenge:
 Normal response vs. masseter jaw rigidity prodromal for
malignant hyperthermia

Miller, R.D., Skeletal Muscle Relaxants, in Basic and Clinical Pharmacology, (Katzung, B. G.,
ed) Appleton-Lange, 1998, pp 434-449; .Stoelting, R.K., "Neuromuscular-Blocking Drugs", in
Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp
182-219; White, P. F. "Anesthesia Drug Manual", W.B. Saunders Company, 1996.

Non-depolarizing Blocking Drugs

Table of Contents
  Mechanism of action  Diuretics
 Cardiovascular effects  Magnesium
 Myopathy associated with critical  Phenytoin (Dilantin)
illness  Lithium
 Factors altering patient responses  Cyclosporine (Sandimmune,
to nondepolarizing drugs Neoral)
 Interaction of nondepolarizing  Ganglionic blocking drugs
neuromuscular agents with  Hypothermia
anesthetics  Burns
 Differential effects based on
duration of action
 Antibiotic effect on
neuromuscular-blockade
 Local anesthetics:enhancement of
block by nondepolarizing agents
 Antiarrhythmic drugs:
interaction with nondepolarizing
blockers

 Mechanism of Action: Nondepolarizing neuromuscular-blocking drugs

o  Combination with nicotinic, cholinergic receptors
o  Greater than 80%-90% receptor blockade required for neuromuscular
transmission failure
  Reflects wide safety margin as well as basis for neuromuscular
blockade clinical monitoring
 Cardiovascular Effects: nondepolarizing neuromuscular blockers
o Secondary to:
  Histamine/other vasoactive substance release
  Effects mediated by cardiac muscarinic cholinergic receptors
  Effects mediated by autonomic nicotinic cholinergic receptors
o Factors responsible for cardiovascular effect variation between patients:
  Basal autonomic state
  Preoperative medications
  Choice of agent for anesthesia maintenance
  Other drugs' presence
o Clinical Significance: cardiovascular effects of nondepolarizing agents are usually
not significant
o "Autonomic Margin of Safety": difference between dosage producing
neuromuscular-blockade and dosage producing circulatory effects
   Relatively low autonomic safety margin --
   pancuronium (Pavulon): e.g. ED95 pancuronium (Pavulon) dosage
which produces neuromuscular-blockade highly likely to produce
cardiovascular effects (particularly chronotropic changes)
  Relatively high autonomic safety margin --
  vecuronium (Norcuron), rocuronium (Zemuron), cisatracurium
(Nimbex): wide safety margins, i.e. neuromuscular-blocking doses
are much less than doses required to influence cardiovascular
status
o Myopathy associated with Critical Illness
  Definition: patients on nondepolarizing neuromuscular blockers to
facilitate mechanical ventilation during prolonged illness may show
skeletal muscle weakness following recovery
  Critical illness may be associated with acute injury (multi-organ
failure), or asthma
  Moderate to severe quadriparesis (+/- areflexia) may be exhibited
  Weakness time-course: unpredictable
  Duration: weeks/months following discontinuation of
nondepolarizing agent
   Probably more common with aminosteroid agent (e.g.
pancuronium (Pavulon) or vecuronium (Norcuron)); has also
been observed with atracurium (Tracrium)
  Possible increased risk: pre-treatment with glucocorticoids

Factors which alter patient responses to nondepolarizing agents

Drugs
ganglionic blocking aminoglycoside
diuretics magnesium
agents antibiotics
antiarrhythmic
local anesthetics volatile anesthetics lithium
agents

Other Factors Influencing Responses to Nondepolarizing Agents

hypotension altered serum potassium adrenocortical abnormality
abnormal acid-base
burned injury allergic reactions
balance

Gender may also influence duration of action;  combinations of nondepolarizing neuromuscular-

blocking agents may result in different effects than agents used separately

 Volatile Anesthetics: interactions with neuromuscular, nondepolarizing agents

 o Dose-dependent increases in magnitude + duration of neuromuscular-blockade
{nondepolarizing agents}-- decreasing neuromuscular blocker dose requirement
o  Most prominent with:
 Isoflurane (Forane)
 Desflurane (Suprane)
 Sevoflurane (Sevorane, Ultane)
o  Intermediate effects with:
 halothane (Fluothane)
o  Least effect with:
 nitrous oxide-opioid combinations
o Differential effects based on duration of action of neuromuscular blocking
drug:
 Less reduction in blocker dosage as a result of volatile anesthetic use
with intermediate-duration agents:
 Atracurium (Tracrium)
 Vecuronium (Norcuron)
 Rocuronium (Zemuron)
 Cisatracurium (Nimbex)
 Greater reduction in blocker dosage as a result of volatile anesthetic
use are required with long acting agents:
 Pancuronium (Pavulon)
 Doxacurium (Nuromax)
 Pipecuronium (Arduan)
  Advantage of using intermediate-duration neuromuscular-blocking
agents:
 Reduced effects on dosage by volatile anesthetics allows "more
predictable degree" of skeletal muscle block {in the Absence of
and exact information about brain anesthetic partial pressures}
  Mechanism of volatile anesthetic effect on nondepolarizing
neuromuscular-blocking drugs:possible causes --

1.  Anesthetic-induced CNS depression -- with secondary decrease

in skeletal muscle tone
2.  Decreased postjunctional synaptic membrane sensitivity to
depolarization
o Volatile anesthetics decreased twitch response (50%
reduction) at higher MAC values, i.e. {1.25-1.75 MAC
enflurane (Ethrane); 2.8-3.7 MAC halothane (Fluothane)}

 Antibiotic effects on neuromuscular-blockade {nondepolarizing agents}

o Some antibiotics increase the effect of nondepolarizing neuromuscular blockers
o Aminoglycoside antibiotics are most likely to produce this increased blocking
effect
 Some aminoglycosides
  Streptomycin   Amikacin (Amikin)
  Gentamicin (Garamycin)   Kanamycin (Kantrex)& Neomycin
  Tobramycin (Nebcin)   Spectinomycin (Trobicin)

 Local Anesthetics (low-dose): enhancement of blockade by nondepolarizing agents

o Higher local anesthetic doses: complete neuromuscular blockade
o Local anesthetics may:
 Inhibit acetylcholine release
 "Stabilize" postsynaptic membrane {making depolarization more difficult}
 Direct muscle fiber depression
 Cardiac antiarrhythmic agents/nondepolarizing neuromuscular blocker
interactions
o Lidocaine (Xylocaine) (IV): may increase preexisting blockade
 Clinical context: lidocaine (Xylocaine) administration during general
anesthesia {protocol includes neuromuscular-blockade} recovery.
o Quinidine gluconate (Quinaglute, Quinalan)
 Increased blockade {for both nondepolarizing & depolarizing drugs}
 Probable mechanism: attenuation of acetylcholine release
 Clinical Context: quinidine gluconate (Quinaglute, Quinalan)
administration during recovery from general anesthesia
{protocol includes neuromuscular blockers}
 Diuretics -- furosemide (Lasix)
o Increases neuromuscular-blocking by nondepolarizing agents
o Probably due to reduced acetylcholine release
o Related issues:
 Hypokalemia associated with chronic diuretic use:
 Decreases pancuronium (Pavulon) dose requirements
 Increases neostigmine (Prostigmin) dosage required for
neuromuscular blockade antagonism
 Magnesium:
o Accentuates neuromuscular-blockade by nondepolarizing drugs; to a lesser degree
also accentuates blockade by succinylcholine (Anectine)
o  Interaction may be more pronounced with magnesium & vecuronium (Norcuron)
than with other agents
o Clinical Context:
 Observed as enhancement of neuromuscular blockade {nondepolarizing
agent mediated} when magnesium is administered to patients treated with
magnesium for pregnancy-caused hypertension (toxemia of pregnancy)

 Phenytoin (Dilantin):
 o Patients chronically treated with phenytoin (Dilantin) are resistant to
neuromuscular-blockade produced by nondepolarizing agents
o Mechanism: pharmacodynamic {higher neuromuscular blocker-plasma
concentration are required to produce a given level blockade in patients treated
with phenytoin (Dilantin) than to produce same level of blockade in untreated
patients}
 Lithium: (used to treat bipolar disorder) -- possible enhanced neuromuscular-blockade
by both depolarizing & nondepolarizing drugs
 Cyclosporine (Sandimmune, Neoral) -- possible prolongation of neuromuscular-
blockade by nondepolarizing drugs
 Ganglionic blocking drugs (e.g., mecamylamine (Inversine)) may affect duration of
neuromuscular-blockade by:
o Reduced skeletal muscle blood flow
o Plasma cholinesterase in addition
o Reduced post-junctional, nicotinic cholinergic receptor sensitivity
 Hypothermia:
o Increased neuromuscular-blockade duration (pancuronium (Pavulon) &
vecuronium (Norcuron))
 Mechanism: decreased hepatic inactivating enzyme activity (temperature
dependency); decreased biliary & renal drug clearance
o  Increased neuromuscular junctional sensitivity to pancuronium
o  Increased duration of atracurium (Tracrium) action {also reduces infusion rate
necessary to maintain stable neuromuscular-blockade}
 Atracurium (Tracrium) effect: probably caused by decreased rate of
Hoffmann elimination & reduced ester hydrolysis
 Burns:
o  Prolonged resistance to nondepolarizing neuromuscular blockers
 Starts about 10 days following injury
 Peaks about 40 days later
 Declines after about two months {may last considerably longer > one-
year}
o Mechanism: -- probably pharmacodynamic {higher plasma drug
concentration required to cause a given extent of twitch suppression
compared to similar extent in non--burn patients}

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219; White, P. F. "Anesthesia
Drug Manual", W.B. Saunders Company, 1996; Miller, R.D., Skeletal Muscle Relaxants, in
Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 434-449.

return to Table of Contents

Clinical Pharmacology
 Role of neuromuscular blockade in anesthesia.

 Primary uses of neuromuscular-blocking drugs:

1. Skeletal muscle relaxation facilitating tracheal intubation
2. Skeletal muscle relaxation to improve intraoperative surgical conditions

o Dose guidelines:
  Facilitation of tracheal intubation -- 2 x ED95 dose of nondepolarizing
muscle relaxant
 Laryngospasm: effectively treated with succinylcholine (Anectine)
  Optimal intraoperative conditions -- 95% single twitch response
suppression
o Neuromuscular-blocking drugs: -- no CNS depression; no analgesia therefore they
do not substitute for anesthetic agents
o Other clinical uses:
 in managing patients requiring mechanical ventilation (intensive care
environment)
  Adult respiratory distress syndrome
  Tetanus
  Suppression of spontaneous respiration

Miller, R.D., Skeletal Muscle Relaxants, in Basic and Clinical Pharmacology,

(Katzung, B. G., ed) Appleton-Lange, 1998, pp 434-449.Stoelting, R.K.,
"Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in Anesthetic
Practice, Lippincott-Raven Publishers, 1999, pp 182-219. White, P. F.
"Anesthesia Drug Manual", W.B. Saunders Company, 1996.

Reversal of non-depolarizing blockers: Antagonist-assisted reversal of neuromuscular

blockade produced by nondepolarizing neuromuscular-blocking agents

 Antagonist-assisted neuromuscular-blockade reversal:

o Edrophonium (Tensilon), neostigmine (Prostigmin), or pyridostigmine
(Mestinon)-- effective by increasing acetylcholine availability of neuromuscular
junction {secondary to acetylcholinesterase inhibition}
 Physostigmine (Antilirium): not used because dosage requirement is
excessive
o Anticholinesterase agents are usually administered during spontaneous
neuromuscular-blockade recovery
  Recovery rate is the sum of (1) spontaneous recovery from the blocking
drug and (2) the activity of the pharmacologic antagonist
(anticholinesterase drugs)
  Therefore: pharmacologic antagonism is more effective for short-or
intermediate-acting neuromuscular-blocking drugs (undergoing plasma
 hydrolysis or Hofmann elimination) compared to long-acting
nondepolarizing neuromuscular-blocking agents
o Special Considerations: use of muscarinic antagonists with
anticholinesterases in Reversal of Neuromuscular Blockade
 Reversal of nondepolarizing neuromuscular-blockade: necessitates only
nicotinic cholinergic effects of anticholinesterases agents
 Minimizing muscarinic receptor-mediated effects of
anticholinesterase drugs is beneficial an accomplished by a
concurrent administration of atropine or glycopyrrolate (Robinul)
(antimuscarinics)
 The antimuscarinic agent should have a more rapid onset than the
anticholinesterase drugs -- reducing drug-induced bradycardia

  if edrophonium (Tensilon) (0.5 mg/kg) is used; atropine 7 ug/kg is

appropriate
  a higher dose atropine (10-15 ug/kg) has been recommended,
particularly if opioid-based maintenance anesthetic has been used
  if neostigmine is used (slower onset of action compared
edrophonium (Tensilon)), then atropine or glycopyrrolate
(Robinul) and may be administered as the antimuscarinic agent;
 Concurrent administration of these drugs results in an
initial tachycardia because of atropine's more rapid onset
o Factors influencing the speed and extent of neuromuscular blockade reversal
by anticholinesterase agents
  Intensity neuromuscular-blockade when reversal is initiated (train-of-four
visible twitches)
  Which nondepolarizing neuromuscular-blocking drug is being reversed is
a factor
 Edrophonium (Tensilon): less effective than neostigmine in
reversing deep neuromuscular blockade (twitch height < 10% of
control) produced by continuous atracurium (Tracrium),
vecuronium (Norcuron), or pancuronium (Pavulon) infusions.
 Edrophonium (Tensilon), probably better than neostigmine
(Prostigmine for reversing atracurium (Tracrium) blockade
 Neostigmine (Prostigmin), probably better than edrophonium
(Tensilon) for reversing vecuronium (Norcuron) blockade
   Prevention/inhibition of anticholinesterase-mediated antagonism of
neuromuscular-blockade -- Possible factors
 Certain antibiotics
 Hypothermia
 Respiratory acidosis (PaCO2 >50 mm Hg
 Hypokalemia/metabolic acidosis
  Reversal of phase II block (following prolonged/repeated
succinylcholine (Anectine)): may be reversed with edrophonium
(Tensilon) or neostigmine (Prostigmin) in patients with normal
plasma cholinesterase
  In patients with atypical plasma cholinesterase, phase II block
reversal may not be reliable, requiring mechanical ventilation until
blockade subsides.

Stoelting, R.K., "Anticholinesterase Drugs and Cholinergic Agonists", in Pharmacology and

Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, 224-237.

 Neuromuscular blockade: depolarizing agent followed by nondepolarizing agent

(Succinylcholine (Anectine), then nondepolarizing agent)
o Clinical Context
1. Initial administration of succinylcholine (Anectine){1 mg/kg, IV}--
supporting tracheal intubation
2. Subsequent administration nondepolarizing agent

 Greater neuromuscular-blockade in this case (even if evidence of

succinylcholine (Anectine) effect has significantly diminished)
 Counterintuitive effect: since the drug effects should be
antagonistic
 Duration of action of nondepolarizing agents (atracurium (Tracrium) or
vecuronium (Norcuron))is not affected -- just the initial increased response
 At lower succinylcholine (Anectine) doses (0.5 mg/kg)-- no initial
enhancement of vecuronium (Norcuron) mediated neuromuscular-
blockade.

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219

 Combinations of Neuromuscular-blocking agents

o Neuromuscular-blockade enhancement due to drug combinations:
  Example-- Different major site of action {postsynaptic vs. presynaptic}
  Pancuronium (Pavulon) + metocurine (Metubine Iodide) or
tubocurarine
 shorter duration than with pancuronium (Pavulon) alone
  Vecuronium (Norcuron) + tubocurarine
  Combinations of nondepolarizing agents -- same degree of blockade with
smaller dose of each drug
 Benefit: fewer dose-related side effects
  Example: BP/heart rate effects of pancuronium (Pavulon)
+ metocurine (Metubine Iodide) < with pancuronium
(Pavulon) monotherapy
 Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in
Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219

 Gender and neuromuscular-blockade

o Differential drug sensitivity due to gender:
  Pancuronium (Pavulon)
  Vecuronium (Norcuron)
  Rocuronium (Zemuron)
o Women:
  require 22% less vecuronium (Norcuron) than men to obtain the same
degree of neuromuscular junctional blockade
  30% more sensitive to rocuronium (Zemuron) than men.
o Clinical significance:
 Normal rocuronium (Zemuron) dose should be reduced in women
compared to men
o Possible mechanism: men have a greater skeletal muscle mass percentage--
requiring a higher neuromuscular-blocking dosage

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219

return to Table of Contents

Some Neuromuscular blocking drugs

 Doxacurium (Nuromax)
 Pancuronium (Pavulon)
 Pipecuronium (Arduan)
 Intermediate Acting Agents
o Atracurium (Tracrium)
o Cisatracurium (Nimbex)
o Vecuronium (Norcuron)
o Rocuronium (Zemuron)  
 Metocurine (Metubine Iodide)
 Gallamine (Flaxedil)
 Succinylcholine (Anectine)
 Tubocurarine (generic)
 Short-acting nondepolarizing
agent: Mivacurium (Mivacron)

 Doxacurium (Nuromax)
o Overview: Doxacurium (Nuromax)
  Nondepolarizing agents; ED95 -- 30 ug/kg
  Time to onset: 4-6 minutes
  Duration of action: about 60-90 minutes
  Renal clearance (similar to pancuronium (Pavulon))
  Extended duration in elderly patients
  No histamine release; no cardiovascular effects
 o Drug interactions:
  Volatile anesthetics
 Reduce doxacurium (Nuromax) dose requirements by 20%-40%
compared to blocking doses for nitrous oxide-fentanyl (Sublimaze)
anesthesia

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219

 Pancuronium (Pavulon)
o Overview: pancuronium (Pavulon)
 Commonly used long-acting nondepolarizing agent
 Low-cost advantage
 Cardiovascular side effects {doxacurium (Nuromax) & pipecuronium
(Arduan) -- similar to pancuronium (Pavulon) but without cardiovascular
side effects}
 Pancuronium (Pavulon) and related agents have replaced older, long-
acting nondepolarizing drugs such as:
 tubocurarine
 metocurine (Metubine Iodide)
 gallamine (Flaxedil)
 No enhancement of histamine release
 No autonomic ganglia blockade
o General properties: pancuronium (Pavulon)
 nondepolarizing agent: ED95 = 70 ug/kg
 onset: 3-5 minutes
 duration: 60-90 minutes
 Pancuronium (Pavulon) block enhanced by respiratory acidosis which
opposes neostigmine (Prostigmin) antagonism
o Pharmacokinetics: pancuronium (Pavulon)
 Renal excretion: 80% of dose excreted unchanged
  Renal dysfunction: pancuronium (Pavulon) clearance may decrease by
33%-50%
 Hepatic metabolism (10%-40%)-with at least one potent metabolite
  Pancuronium (Pavulon) elimination halftime: affected by hepatic
cirrhosis/total biliary obstruction
 Aging: decreased pancuronium (Pavulon) plasma clearance
 Mechanism: -- probably reduced renal function
o Cardiovascular Effects: pancuronium (Pavulon)
 Slight increase (10%-15%):
 Heart rate
 Mean arterial pressure
 Cardiac output
  Mechanism:
 Atropine-like effect on cardiac, muscarinic cholinergic receptors
 Sympathetic, autonomic nervous system activation
  Adverse Effects:
 Increased incidence of cardiac arrhythmias following pancuronium
(Pavulon) (but not succinylcholine (Anectine)) in patients treated
chronically with digitalis glycosides
 Increased cardiac arrhythmias may occur due to enhanced
sympathetic nervous system activity

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219;  White, P. F. "Anesthesia
Drug Manual", W.B. Saunders Company, 1996.

 Pipecuronium (Arduan)
o Overview: pipecuronium (Arduan)
  nondepolarizing neuromuscular for; ED95 -- 50-60 ug/kg
  time to onset: 3-5 minutes
  duration of action: 60-90 minutes
  Enhanced potency increased/duration of action shortened in infants
{relative to adults or children}
  No histamine release; no cardiovascular changes associate with
pipecuronium (Arduan) administration
o Pharmacokinetics:
  similar to pancuronium (Pavulon) in terms of renal clearance
  Hepatic cirrhosis -- no effect on pipecuronium (Arduan)
pharmacodynamics/ pharmacokinetics

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219; White, P. F. "Anesthesia
Drug Manual", W.B. Saunders Company, 1996.

Introduction: Intermediate-acting Nondepolarizing Blockers

 Overview: Intermediate-acting Nondepolarizing Blockers

o Atracurium (Tracrium), vecuronium (Norcuron), rocuronium (Zemuron),
cisatracurium (Nimbex)
o Efficient clearance mechanisms (reduced likelihood of significant accumulation
following repeated administration)
 Useful; but more expensive alternatives to succinylcholine (Anectine) &
pancuronium (Pavulon)
 Particularly useful for tracheal intubation/skeletal muscle relaxation for
short procedures (e.g. outpatient)
 Properties:
 o Intermediate-acting agents (compared to long-acting agents):
  Similar time to onset {exception: roncuronium (Zemuron) -- rapid onset,
similar to succinylcholine (Anectine)}
  Duration of action -- about one-third of long-acting agents
  30%-50% more rapid recovery rate
  Minimal/absent cardiovascular effects
o Intermediate duration -- due to rapid/efficient plasma clearance
 Special considerations:
o Rocuronium (Zemuron)-- rapid onset (similar to succinylcholine (Anectine))
 Rapid onset -- within one-minute; good choice for tracheal intubation
facilitation
o Method for accelerating onset for other "intermediate acting" agents
  Use a small, subparalyzing dose (about 10% of ED95); followed about
four minutes by the larger dose (2-3 X ED95)
  Divided dose technique = priming principal (neuromuscular-
blockade:two-step process)
1. Initial binding of spare receptors (no clinical effect)-- but reduces
safety factor for neuromuscular transmission.
2. Deeper blockade
o Priming dose technique may be less valid now with the availability of single,
large IV roncuronium (Zemuron) dose -- providing rapid onset -- no risk of drug-
induced weakness in awake patients
 Antagonism of blockade cause by intermediate-acting nondepolarizing drugs:
o anticholinesterase agents -- effective (within 20 minutes of administration of the
paralyzing intermediate-acting nondepolarizing drug dose)
 Pharmacologic antagonism (administration of anticholinesterase drugs)
coupled with rapid clearance of the blocker results in enhanced, recovery
rates

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219; White, P. F. "Anesthesia
Drug Manual", W.B. Saunders Company, 1996.

 Atricurium (Tracrium)
o Overview:atracurium (Tracrium)
  Nondepolarizing, neuromuscular blocker (multiple isomers)
  ED95: 0.2 mg/kg
  Time to onset: 3-5 minutes
  Duration of action: about 20-35 minutes
  Site of action:
 Presynaptic & postsynaptic membrane nicotinic receptors
  Degradation: spontaneous, in vivo (Hofmann elimination)
 More stable in acid pH (storage --pH 3.25-3.65)
  Should not mix atracurium (Tracrium) with alkaline drugs
(e.g. barbiturates) or expose to solutions of more alkaline
pH
 alkaline pH: accelerated breakdown
o Clearance-- two mechanisms
 Hofmann elimination -- nonenzymatic; accounts for one-third of the
degradation
 Hydrolysis catalyzed by plasma esterases (nonspecific, i.e. not plasma
cholinesterase); accounts for about two-thirds of degraded atracurium
(Tracrium)
 Clearance not dependent on hepatic or renal function
 Clearance not affected in patients with atypical cholinesterase
o Laudanosine -- major metabolite of both catabolic atracurium (Tracrium)
pathways
 CNS stimulant --even with long, continues atracurium (Tracrium)
infusions in the surgical setting--laudanosine concentrations remain below
those apparently required for cardiovascular/CNS action; in the ICU
setting with longer durations seizure potential becomes much more likely
o Cumulative effects
 No significant cumulative effect due to rapid clearance from plasma
(hydrolysis + Hofmann elimination)
o Cardiovascular Effects:
 With these background anesthetics: nitrous oxide, fentanyl (Sublimaze),
halothane (Fluothane), isoflurane (Forane)
 no BP/heart rate change associated with rapid IV atracurium
(Tracrium) up to (2 X ED95)
 With nitrous oxide-fentanyl (Sublimaze) anesthesia, IV atracurium
(Tracrium) (3 X ED95): slight increase in heart rate (8%); decreased in
mean arterial pressure (20%)
 Cardiovascular effects: transitory (< 5 minutes)
 Facial/truncal flushing may be due to histamine release (no
circulatory effects if patients are pretreated with H1/H2 receptor
blockers)
 H1/H2 receptors may be activated by prostacyclin (not histamine)
o Special Patient Populations
 Pediatric patients
 Similar atracurium (Tracrium) doses in adults and children (2-16
years old) when doses are calculated using mg/m2 rather than on a
mg/kg basis.
 Infants -- 1-6 months: require about 50% of the atracurium
(Tracrium) dose given to older children
 continuous infusion rate (to maintain steady-state
blockade): 25% less during the first month of life
 Elderly patients
  Increasing age: no effect on atracurium (Tracrium) continuous
infusion rate required for constant degree of neuromuscular-
blockade
 Mechanism -- age independence of Hofmann elimination &
plasma ester hydrolysis inactivation processes
{renal/hepatic state independent}

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219; White, P. F. "Anesthesia
Drug Manual", W.B. Saunders Company, 1996.

 Cisatracurium (Nimbex)
o Overview: cisatracurium (Nimbex)
  nondepolarizing neuromuscular blocker
  ED95: 50 ug/kg
 Time to onset: 3-5 minutes
  Duration of action: 25-30 minutes
  Similar pharmacological profile to atracurium (Tracrium) compared
atracurium (Tracrium)
  Cisatracurium (Nimbex)(Tracrium) onset slightly slower
  Cisatracurium (Nimbex) much less likely to cause histamine
release, compared atracurium (Tracrium)
  Spontaneous neuromuscular blockade recovery not affected by
prolonged infusion (80 hr) to patients requiring ventilation in the
intensive care environment-- by contrast to vecuronium (Norcuron)
 Recovery: accelerated by the use of anticholinesterase agents
o  Clearance: cisatracurium (Nimbex)
  Hofmann elimination (77% cisatracurium (Nimbex) clearance)
 16%: renal
 Neuromuscular-blockade characteristics not affected by hepatic or renal
dysfunction
 Cisatracurium (Nimbex) pharmacokinetics: not appreciably affected by
advanced age (slight delay in time to onset)
o Cardiovascular Effects: cisatracurium (Nimbex)
 No histamine-releasing effects (by contrast yo atracurium (Tracrium))
 Large doses (8 X ED95, IV) do not typically induce cardiovascular changes
 Less change in cerebral hemodynamics compared to equal potent
atracurium (Tracrium) dosage

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219; White, P. F. "Anesthesia
Drug Manual", W.B. Saunders Company, 1996.

 Vecuronium (Norcuron)
o Overview: vecuronium (Norcuron)
  Nondepolarizing neuromuscular blocker
  ED95: 50 ug/kg
  Time to onset: 3-5 minutes
  Duration of action: 20-35 minutes
  Structurally resembles pancuronium (Pavulon) -- vecuronium (Norcuron)
reduced anti-vagal properties compared to pancuronium (Pavulon)
  Unstable in solution; supplied as lyophilized powder
o  Clearance
 Overview
 hepatic metabolism & renal excretion
 metabolites generally much less active than vecuronium
(Norcuron)
  More lipid-soluble compared pancuronium (Pavulon) -- promotes
biliary excretion & significant hepatic uptake
  Rapid hepatic uptake may be responsible for short duration of
action
   Reduced renal function
 Vecuronium (Norcuron) action prolonged in patients with renal
failure -- increased concentration of metabolites also contribute to
prolonged skeletal muscle paralysis following long-term
vecuronium (Norcuron) infusion
   Reduced liver function
 When used in patients with hepatic cirrhosis, vecuronium
(Norcuron) at 0.2 mg/kg IV, longer duration of action (longer
elimination halftime); not observed that the 0.1 mg/kg IV dose
level
  In patients with cholestasis, undergoing biliary surgical
procedures: vecuronium (Norcuron) duration of action is increased
(at the 0.2 mg/kg IV dosage)
o Cardiovascular Effects
 Minimal even at 3 X ED95, with rapid IV administration
 No vagolytic action
 apparently no/minimal histamine release
 possible vagotonic vecuronium (Norcuron) effect if administered nearly
concurrently with potent opioids (e.g. sufentanil (Sufenta))
  vagotonic action may be serious -- promoting sinus nodal exit
block & cardiac arrest
o Use in pediatric patients
 Vecuronium (Norcuron) potency {during nitrous oxide-halothane
(Fluothane) anesthesia}: similar in --
 infants (7-45 weeks)
 children (1-8 years)
 adults (18-38 years)
  Onset of action: more rapid in infants compared to adults; (infants have
high cardiac output -- promoting rapid onset)
 Duration of action: longest in infants; shortest in children-- (infants have
less/immature enzyme systems -- increased volume of distribution)
o Use in Elderly patients
 With increased age: decreased continuous infusion rate required to
maintain a given level of block
  Mechanism:
  Age-related hepatic blood flow decrease;
  Age-related decreased renal blood flow;
  Age-related reduced hepatic microsomal enzyme system
activity (possibly)
 With increased age: prolonged recovery time if vecuronium (Norcuron)
was administered by continuous infusion (recovery from individual IV
doses of vecuronium (Norcuron): not age sensitive)
o Use in Obstetric patients
 Clinically significant fetal effects not observed with nondepolarizing
neuromuscular-blocking drugs.
  Vecuronium (Norcuron) clearance: increased during late pregnancy;
possibly due to enhance microsomal enzyme activity {by progesterone}
  Vecuronium (Norcuron)-induced neuromuscular blockade: prolonged
immediately postpartum
o Obesity:
 Vecuronium (Norcuron) duration of action (but not atracurium
(Tracrium)) prolonged in obese (> 130% of ideal body weight) compared
with nonobese adults
o Malignant Hyperthermia
 Not associated with vecuronium (Norcuron) or atracurium (Tracrium)
administration in animal models
 In a patient susceptible to malignant hyperthermia and therefore
pretreated with dantrolene (Dantrium): duration of vecuronium
(Norcuron) action prolonged
  Mechanism:  Dantrolene (Dantrium) may prolonged action of
neuromuscular-blocking agents secondary to dantrolene
(Dantrium)-mediated impairment of presynaptic calcium release

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219;  White, P. F. "Anesthesia
Drug Manual", W.B. Saunders Company, 1996.

 Rocuronium (Zemuron)
o Overview: rocuronium (Zemuron)
 Nondepolarizing agent; ED95 -- 0.3 mg/kg
 Time to onset: 1-2 minutes
  Duration of action: 20-35 minutes
 reduced potency (relative to vecuronium (Norcuron)) probably responsible
for relatively rapid onset [lower potency requires higher dose {more
molecules administered} -- more molecules increased the likelihood of
initial blockade]
o Time to onset: Clinical implications --
  Time to onset of maximal single twitch depression (following 3-4 X
ED95): similar to time to onset for succinylcholine (Anectine) (when
mg/kg, IV)
  Rocuronium (Zemuron): only nondepolarizing agent which may
substitute for succinylcholine (Anectine) when:
  Succinylcholine (Anectine) is contradicted
  Rapid onset is required to promote tracheal intubation
  Differences between rocuronium (Zemuron) & succinylcholine
(Anectine)
  Laryngeal muscles more resistant to rocuronium
(Zemuron) than adductor pollicis: large dose rocuronium
(Zemuron) effects resemble succinylcholine (Anectine) at
adductor pollicis but will be delayed relative to
succinylcholine (Anectine) effects at laryngeal adductors.
o Duration of action:
  Similar to other intermediate-acting agents-- at normal doses
  With large dose rocuronium (Zemuron) --3-4 X ED95-- to achieve onset
rates similar to succinylcholine (Anectine)-- duration is prolonged (more
similar to long-acting nondepolarizing drugs, e.g. pancuronium (Pavulon))
 Large IM doses (rocuronium (Zemuron)) -- 1-8 mg/kg given to
infants/children to support rapid tracheal intubation results in relatively
long durations (sixty minutes) -- This long duration may limit clinical
utility.
o Effects on muscle groups
  Laryngeal adductor muscles and diaphragm: more resistant to rocuronium
(Zemuron) than adductor pollicis muscles
  Therefore, complete single twitch response suppression of adductor
pollicis is not sufficient to ensure paralysis of laryngeal muscles and
diaphragm.
 Maximal paralysis of laryngeal muscles may not be recognized if
suppression of adductor pollicis single twitch response is being
monitored as the clinical sign for optimal conditions supporting
intubation.
 Direct laryngoscopy for intubation performed at peak laryngeal
muscle paralysis may result in abdominal muscle/diaphragmatic
motion when the tracheal tube is positioned -- because the
diaphragm and abdominal muscles are not yet fully paralyzed:
   This condition is undesirable especially in those cases
when pulmonary aspiration gastric contents is considered a
risk.
o  Pharmacokinetics -- Clearance:
 Rocuronium (Zemuron)
 -- up to 50% excreted in the bile {animal studies}
 -- > 30% renal excretion (in 24 hours)
  Liver disease: possible increased drug effect duration due to increased
volume of distribution
  Elderly patients:
 similar time to onset (compared to young adults)
 prolonged duration (compared to young adults)
o Cardiovascular Effects --
 No histamine released (as with other non-polarizing agents)
 Small anti-vagal effect -- may be useful in certain surgical procedures
which cause vagal stimulation (e.g. opthalmological, laproscopic
procedures)
 Bradycardia (reflex) may occur with atracurium (Tracrium) or
vecuronium (Norcuron) in patients undergoing these procedures

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219; White, P. F. "Anesthesia
Drug Manual", W.B. Saunders Company, 1996.

Short-acting nondepolarizing neuromuscular blocker: Mivacurium (Mivacron)

 Overview: mivacurium (Mivacron)

o Only clinically useful nondepolarizing agent classified as short acting
o ED95: 80 ug/kg
o Time to onset: 2-3 minutes
o Duration of action: 12-20 minutes (about 2 X longer than succinylcholine
(Anectine); about 30%-40% that of intermediate-acting neuromuscular-blocking
agents)
o mivacurium (Mivacron): no malignant hyperthermia likely (based on swine
model)
o Pancuronium (Pavulon), then mivacurium (Mivacron) leads to prolonged
mivacurium (Mivacron) duration of action
 Muscle effects: mivacurium (Mivacron)
o Mivacurium (Mivacron) (2 X ED95):
 Maximal depression (single twitch) of orbicularis oculi prior to maximal
depression at adductor pollicis {different from succinylcholine (Anectine)
which produces maximal depression at the sites concurrently}
 Loss of orbicularis oculi function (but not adductor pollicis) correlates
with maximal laryngeal adductor muscle and diaphragm paralysis
  Clearance: mivacurium (Mivacron)
o Short duration of action due to: plasma cholinesterase-mediated hydrolysis
 Hydrolytic rate for mivacurium (Mivacron) about 90% that observed for
succinylcholine (Anectine)
o  Mivacurium (Mivacron) hydrolysis decreased with increased duration of
action in the presence of atypical plasma cholinesterase
 In patients with atypical plasma cholinesterase: mivacurium
(Mivacron) blockade is intense in prolonged
 Effective antidote: administration of human plasma
cholinesterase {anticholinesterase agents appear ineffective}
o  Renal status: renal excretion -- minor pathway for mivacurium (Mivacron)
clearance
o  Hepatic status:
 Patients with liver cirrhosis may experience prolonged mivacurium
(Mivacron) blockade if the liver disease is associated with reduced plasma
cholinesterase activity
 Increase volume of distribution associate with liver disease because
reduced neuromuscular-blockade
o  Pharmacological Antagonism:
  May not be needed given rapid spontaneous recovery from mivacurium
(Mivacron) blockade
  Anticholinesterase agents (e.g. neostigmine (Prostigmin)) because
they inhibit plasma cholinesterase may interfere with normal recovery
mechanism
  Moderate mivacurium (Mivacron)-mediated blockade may
respond to neostigmine (Prostigmin)
  Deep mivacurium (Mivacron)-mediated blockade maybe
antagonized by edrophonium (Tensilon)
  Cardiovascular Effects: mivacurium (Mivacron)
o minor at doses up to 2 x ED95
o rapid IV administration of 3 x ED95 may provoked a decrease in BP (10%-20%),
secondary to histamine release

Stoelting, R.K., "Neuromuscular-Blocking Drugs", in Pharmacology and Physiology in

Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 182-219; White, P. F. "Anesthesia
Drug Manual", W.B. Saunders Company, 1996.

Review Class
[ - will be on the test]
Propofol will be on test

Ketamine will be on the test

Timing and waveforms in IABP:

Inflate at the dicrotic notch and deflate just prior to the next systole (the end of the R wave)

Not Bad: Late inflation and early deflation (may be used safely if you have an eratic
rhythm)

Bad: Early inflation and late deflation

CO= SV x HR (rate, preload, afterload, contractility)

 normal CO = 4-6

CI= 2.4 (<2.2 is treatable)

Think of right heart and left heart as 2 separate organs

 CO preload, afterload, contractility

complication of PCWP measurement (embolism, infection, rupture)

Invasive lines:
Components: transducer, flush system (300mmHg), stop cock, central line

Zero the system (open to atmosphere)

Level- (phlebostatic axis, RA- 4 ICS, mid clavicular)

Dampening (over and under dampening)

 Common overdamping caused by a near empty flush bag

PACING:
V-O-O (pacing without sensing or inhibiting)
V-V-I (vent. Paced, vent sensed, a spike inhibits the next pace)

Not enough energy= failure to pace

Sensitivity- lower= more sensitive, high less sensitive
Absolute and relative refractory periods

universal donor- Type O

Universal recipient- Type AB

AB- has all usual antigens

O- has no antigens

IABP:
Rupture
Platelet damage
Misplacement (high=CVA Sx – occludes Left breachial cephalic, Left..)
(Low, decreased renal output, decreased GI motility, abdominal pain)

right atrial pressure questions

Remember to keep the arterial lines safe and patent, don’t forget patient safety

From the board:

RA- 2-6
PAP- 20-30 / 10-15
SBP- 120 / 60
SVR- 800-1200 / 71 (600)

a child cannot be rewarmed more than 1degree an hour

When pregnant females get dehydrated they release ADH (but it pitosin is also released along with it out
of default)

Pediatric maintenance fluid replacement:

4cc- 1st 10kg
2cc- 2nd 10kg
1cc- remaining weight

20mg/kg is a pediatric fluid bolus (trauma, vomiting, etc.) kids can usually handle excess fluids well

double fluids for dehydration

Magnesium given IV causes decreased DTR (Mg toxicity may hinder diaphragm movement)

Calcium Gluconate is given for Mg Toxicity

Normal urine output for:

Child= 1cc/kg/hr
Infant= 2cc/kg/hr (kidneys aren’t as developed and are more at risk for dehydration)

CVP= Preload

ABG questions on last test (a lot of them)

 10-15 cc/kg for Vt (UMBC standard)

Goal of CCT- to maintain the same care between facilities

Ground- <50 miles

Helo- 10-150 miles
Fixed wing- >150 miles

Staffing: RN, FP-C

And poss. RRT, MD, …

what patients DO NOT meet criteria for a CCT

EMTALA- facility must do a screening and stabilization prior to transport

lab data- CBC, Chem7,

Treatment of hyper K:
Pretreat with calcium (to stabilize cardiac membraine)
Bicarb
Insulin R/ Glucose
Albuterol
Dialysis
Kay-exelate (potassium binder that acts in the gut)= GI will become mobile!
ABG values:

Bilirubin- byproduct of RBC degradation

Amylase/ Lipase- Pancreases

CPK/ CK- (CKMB is fractionated for myocardial distress)

CBC
Na, K, Cl, Creat.
ABG

Shock:
Distributive (septic, anaphylactic, Neurogenic)
Obstructive
Cardiogenic

Management- fix the cause

Septic- surgery is a treatment for septic shock

Neurogenic shock- lack of sympathetic tone, fix with a pressor (epi, neo, dopamine, levophed)

Colloids- large particles, used to draw fluid into vascular space (albumin, blood) (is manitol???)

Breathing management:

CMV- controlled mandatory ventilation, (total control)

AC- assist control, (set RR but able to breathe over at a set Vt)
SIMV- Sync Intermittent Mandatory Vent (may breath over with regard to rate and Vt) (will insure a
minimum rate and volume)
Pressure control- gas delivered to a set pressure (at the PIP) (PIP is usally less than 40)

Minute Vol- regulates CO₂ (low Minute Vol >CO₂

PEEP- alveolar recruitmenmt, more gas exchange
Flow rate- I:E ratio (PEEP and expiratory time have no direct corolation)

High PEEP may decrease preload via compressing the venicava, correct this by increasing fluid if you cant
lower PEEP

Wean PEEP slowly, don’t be afraid to increase PEEP

Vt= 10-15 cc/kg (UMBC standards) (6-10cc/kg is currently used in clinical setting)

Chest tubes:

Decrease air in the plural space, drain fluid

Water seal unit: 3 sections, collection, water seal, suction (water column/ 20 mm, H₂O) (add water to
increase suction... in older units)

If chest tube is pulled out, seal the site, monitor for Pneumothorax

clamp the chest tube IS THE WRONG ASNWER!!!!

If water seal is broken during transport, place the tube in a bottle of saline

Suctioning:
Is a sterile technique

RSI:
Prepare- (meds drawn up, 2 ETT, back-up tube, 10cc syringe on the tube), make sure the suction works
Airway assessment
Preoxygenate- NRB 1-2 min, BVM with Oxygen (cautiously)
Premedicate- atropine, lidocaine, sedative (ketamine, atomadate, propofol, fentynal)
Paralytic- succinicoline 1-2mg/kg, (2mg in kids) (the only depolorizing paralytic, onset 30 sec,
duration 5 min). (increases free Potassium, patient with neuromuscular diseases may have a
lower uptake in the neurons, may have paralysis up to days), contraindication burns and crush
injuries, malignant hyperthermia (Dantraline is a treatment for..), increased interoccular
pressure
Pass the tube and confirm
Post intubation care- analgesia and sedation

Ketamine- cuses hypotension, (My Cousin Caity Has Asthmia)

study the big medications, study the classes (classs I Na Channel blockers, II Beta, III Potassiun, IV Ca, V
nucleoside- Adenocard) (the periodic table- Na, Boron, K, Ca, …)
Trebutuline, Ketamine (ketamine is only listed in the pediatric section)

ICP monitoring:
0-15 is normal range
MAP-ICP=CPP (CPP should be >70)
Monro-Kellei doctrine- if the patient has a inter-ventricular catheter you can decrease the 10% of fluid,
but there is a high risk of infection
Axis to level the cranial catheter is the tragus of the ear
ICP Waves: (remember this is seen in trending over time, hours)
A waves- high with a plateu, sustaining with >60 mm/Hg, seen in brain herniation
B waves- sharp pulsations,up to 50mm/Hg high pressure increases, poor compensation
B waves need to be treated before this point optimally.
C waves- rhythmic, small amplitude, 4-8/min, clinically insignificant

Neuro assessment- the key is to continuously recheck, DTR (graded 0-4, 2 is normal)

Pupilary assessment-

Vital signs-

Inline position of the neck may decrease drainage and flow of CSF (C-Collar)

To manage ICP:

Oxygen
Sedation (will lower ICP)
Manitol (crystallizes very easy, use filtered needle)

levophed for sepsis, dopamine is never the first answer for CC transports

TEST:

Final exam is 110 questions

Passing is 70%
Avg. score is 75-80%
BRING #2 Penile
May write on the exam sheet
May leave for bathroom one at a time
Standard calculators may be used
No time limit
Retest may be taken twice
Usually testing is done by 11am
Missing 1 cert, may take exam but cannot see results, missing 2 certs, may NOT take the exam

© 2010 M.N. LaBarbera