Download - Drugs in ICU
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DRUGS IN ICU
Dr Vinay B
Senior Resident
Dept of Anaesthesia And intensive care
PGIMER Chandigarh
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Objectives
Brief knowledge about most commonly
used drugs in ICU care
Proper use
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Sedatives & anxiolytics
Why sedatives & anxiolytics
Distress is common among critically ill
patients
result in untoward physiologic changes
contribute to organ ischemia, fluid and
electrolyte imbalance, and decreasedwound healing
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Important to avoid these deleteriousphysiological consequences
potential etiologies of distress
Pain
Anxiety
Delerium
Dyspnea
Neuromuscular paralysis
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Treatment of distress
Reversible causes of patient discomfort
and distress must be identified and
corrected prior to the prescription of
sedative medications
reassurance, frequent communication
with patient, regular family visits,
establishment of normal sleep cycles, anduse of a variety of cognitive-behavioral
therapies such as music therapy, guided
imagery, and relaxation therapy
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Goals of sedation
Old Obtundation
New sleepy but arousable patient
Almost always a combination ofanxiolytics and analgesics.
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Drugs
Opiods:
alkaloid compounds extracted from
opium, including morphine, codeine, andsemisynthetic derivatives of the poppy
plant.
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classification
Pure agonist
Morphine
Fentanyl Codeine
Meperidine
Methadone DCextropropoxyphene
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Antagonist
Naloxone
Naltrexone
Nalmefene
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Receptor stimulation
Mu ( )
P hysical dependence
M iosis
C onstipation
Analgesia
R espiratory depression
E uphoriaS edation
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Kappa ( k)
S edation
D ysphoriaM iosis
A nalgesia
Diuresis, depression
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Delta ()
analgesia ( spinal & supraspinal)
Release of growth hormone
Sigma ()
Dysphoria
Hallucination
Respiratory and vasomotor stimulation Mydriasis
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Pharmacokinetics of opioids
Absorption
Readily absorbed from GI tract, nasal
mucosa, lung. Also through subcutaneous,
intramuscular, and intravenous route
Distribution
Bound/free morphine accumulates in
kidney , lung, liver, and spleen
CNS is primary site of action ( analgesia/
sedation)
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Metabolism/excretion
Metabolic transformation occurs in liver
It conjugates with glucuronic acid
Excretion by kidneys by glomerularfiltration
Half life is 2.5 to 3 hours
Morphine 3 glucuronide is the mainexcretion product
90 % excreted in 24 hours
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Morphine administration
Not given orally due to erratic
bioavailibility
Significant variable first pass effect from
person to person and have intaspecies
effect ( same dose will vary in person day
to day )
IV morphine acts promptly and its main
effect is at CNS
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Respiratory effects
There is a primary and continous
depression of respiration related to dose.
CNS becomes less responsive to pCO2
there by causing build up of CO2
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Pupil size
Causes miosis ( pinpoint pupil)
Still responsive to bright light
Atropine partially blocks pupillary effectindicating parasympathetic system
involved
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Cardiovascular effects
Vasodilation, thus a decrease in BP
Release of histamine
Supression of central adrenergic tone Supression of reflex vasoconstriction
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Effect on GI system
It increses tone and decreases g.i. motility,
leads to constipation
Decreases concentration of HCL secretion
Tolerence does not develop to this
constipation effect
Contraction of sphincter of oddi leading to
increased biliary tract pressure
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Other effects
Urinary bladder
Tone of detrusor muscle is increased
Feeling of urinay urgencyUrinary retention
Bronchial Muscle
bronchoconstriction , due to histaminerelease
Nausea and vomiting, stimulation of CTZ.
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TOXICITY OF MORPHINE
Acute overdose lethal dose is 250mg
Respiratory depression
Pinpoint pupil stupor./coma
Convulsions
Pulmonary edema at terminal stages
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Treatment
Establish adequate ventilation by positive
pressure ventilation
Maintanance of BP by iv fluids &
vasoconstrictors
Gastric lavage with pot permanganate ;
even when morphine has been injected
Opioid antagonist ( naloxone)
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Fentanyl
Synthetic drug
80 to 100 times more potent than
morphine
Rapidly acting drug ( onset of action 5
min)
Short acting ( 30 45 min)
Very high potency
Highly abused, known as china whiteas
street name
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Benzodiazepines
Act as sedative, hypnotic, amnestic,
anticonvulsant, anxiolytic
No analgesia
Develop tolerance
Synergistic effect with opiates
Lipid soluble, metabolized in the liver,excreted in the urine
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Mechanism of action
Interact with specific receptor in CNS
Enhances the inhibitory effect of various
neurotransmitters
Facilitates GABA receptor binding.
Inhibits normal neuronal function
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Propofol
Sedative, anesthetic, amnestic,anticonvulsant
Respiratory and CV depression
Highly lipid soluble Rapid onset, short duration
Onset
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Propofol- Side effects
Unpredictable respiratory depression
Hypotension
Increased triglycerides
Bradycardia
Prolonged infusion > 48 hrs at >4mg/kg/hr is associated with severe
bradycardia, metabolic acidosis,rhabdomyolysis & hepertriglyceridemia (propofol infusion syndrome)
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Butyrophenones
Haldol
Anti-psychotic tranquilizer
Slow onset (20 min)
Not approved for IV use, but is probablysafe
No respiratory depression or
hypotension.Useful in agitated, delirious, psychotic
patients
Side effects- QT prolongation, NMS,EPS
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Initiation Of sedation
Selection
Etiology of patient's distress, desired
depth of sedation, and expected duration
of therapy must be considered
Combination therapy appropriate for
more than one cause of distress (anxiety
and pain, delirium and pain).
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short-acting drug with rapid recovery time,
such as midazolam or propofol, used if
brief duration of sedation (24 hours) sedation ispredicted
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short-acting drug with rapid recovery time,
such as midazolam or propofol, used if
brief duration of sedation (24 hours) sedation ispredicted
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Monitoring sedation
Many scoring systems, none are validated
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Vasopressors and inotropes
Vasopressors are powerful class of
drugs that induce vasoconstriction elevate
MAP
differ from inotropes, which increase
cardiac contractility.
however, many drugs have both
vasopressor and inotropic effects
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Receptor physiology
adrenergic receptors relevant to
vasopressor activity are alpha-1, beta-1,
and beta-2 adrenergic receptors, as well
as dopamine receptors
b1myocardium- contractility
b2arterioles- vasodilation
b1SA node- chronotropy
b2lungs- bronchodilation
aperipheral- vasoconstriction
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Inotropes
Adrenergic
Eg;epinephrine,norepinephrine,dopami
ne
Nonadrenergic
Eg;vasopressin,milrin
one,amrinone
1 2(periphe
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(peripher
al)
1
(cardiac)
2(periphe
ral)
Norepinephri
ne++++ ++++ 0
Epinephrin
e
++++ ++++ ++
Dopamine ++++ ++++ ++
Isoproterin
ol
0 ++++ ++++
Dobutamin
e
+/0 ++++ ++++
Phenylephr ++++ 0 0
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Dopamine (Intropin)
Renal (2-4 mcg/kg/min)- increase in
mesenteric blood flow
b(5-10 mcg/kg/min)- modest positiveionotrope
a(10-20 mcg/kg/min) vasoconstriction
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Dobutamine
Primarily b1, mild b2. Dose dependent increase in stroke
volume, accompanied by decreased filling
pressures. SVR may decrease, baroreceptor
mediated in response to SV.
BP may or may not change, depending ondisease state.
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Useful in right and left heart failure.
May be useful in septic shock.
Dose- 5-15 mcg/kg/min.
Adverse effects- tachyarrhythmias.
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Isoproteraline
Mainly a positive chronotrope.
Increases heart rate and myocardial
oxygen consumption.
May worse ischemia.
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Epinephrine
bat very low doses, aat higher doses. Very potent agent.
Some effects on metabolic rate,
inflammation. Useful in anaphylaxis.
AE- Arrhythmogenic, coronary ischemia,
renal vasoconstriction, metabolic rate. 0.1mcg/kg/min 0.3mcg/kg/min
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Norepinephrine
Potent aagent, some b Vasoconstriction (that tends to spare the
brain and heart).
Good agent to SVR in high output shock.
Dose 1-12 mcg/min
Can cause reflex bradycardia (vagal).
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Phenylephrine
Strong, pure aagent.
Vasoconstriction with minimal in heartrate or contractility.
Does not spare the heart or brain.
BP at the expense of perfusion.
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indication
Hypotension
Hypovolemia(haemorrhage)
Pump failure ( MI)Pathologicalmaldistribution of
blood flow (sepsia,anaphylaxis)
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COMPLICATIONS
Hypoperfusion
Arrythmias
Myocardial ischemia
Local effects
hyperglycemia
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Practical issues
1. Volume resuscitation
2. Selection and titration
3. Route of administration
4. Subcutaneous delivery of medications
5. Frequent reevaluation
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Paralytics
Paralyze skeletal muscle at the
neuromuscular junction.
They do not provide any analgesia or
sedation.
Prevent examination of the CNS
Increase risks of DVT, pressure ulcers,
nerve compression syndromes.
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Use of paralytics
Intubation
Facilitation of mechanical ventilation
Preventing increases in ICP
Decreasing metabolic demands
(shivering)
Decreasing lactic acidosis in tetanus,NMS.
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Classification
Depolarizing agents
Succinylcholine
Non-depolarizing agents
Pancuronium
Vecuronium
Atracurium
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Complications
Persistent neuromuscular blockade
Drug accumulation in critically ill patients
Renal failure and >48 hr infusions raise
risk
In patients given neuromuscular blockers
for >24 hours, there is a 5-10% incidence
of prolonged muscle weakness (post-
paralytic syndrome).
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Post-paralytic syndrome
Acute myopathy that persists after NMB is
gone
Flaccid paralysis, decreased DTRs,
normal sensation, increased CPKs.
May happen with any of the paralytics
Combining NMB with high dose steroids
may raise the risk.
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Drugs for acid prophylaxis
H2 receptor blockers
Ranitidine, famotidine, cimetidine etc
Impede acid production in stomach by
blocking the action of histamines
Ranitidine most commonly used
Devoid of major side effects
Dose: P.O 150mg bd, IV 50 mg bd
Onset 30 45 min, duration 8 10 hrs
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Proton pump inhibitors
Reduce production of acid by blocking
enzyme in the wall of stomach that
produces acid
Pantoprazole,omiprazole,esomeprazole,rabeprazole
Long acting, so once a day dose is
sufficient
Devoid of major side effects
P O Pantoprazole 40 mg od, P O
ome razole 20m od
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Diuretics
Loop Diuretics
Act on ascending loop of Henle to inhibit
sodium & chloride transport
Effective at lower GFR ( as occurs in
CRF), where other diuretics are ineffective
Increases potassium, calcium and
magnesium excretion
Decrease urate excretion
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Rapid GI absorption. Also given i.m. and
i.v.
Short half lives in general
Elimination: unchanged in kidney or by
conjugation in liver and secretion in bile
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Clinical uses
Edema due to CHF, nephrotic syndrome
or cirrhosis
Brain edema
Hypercalcemia
CRF
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Mannitol
Osmotic diuretic
Used clinically to reduce acutely raised
intracranial pressure
Administered intravenously in a dose of
0.25 gm/kg to 1 gm/kg body wt
Contraindicated in patients with anuria
and congestive heart failure
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Potassium chloride
Indicated in patients requiring parenteral
administration
Usually indicated when K+ is < 3.5 meq/l
Treatment of digitalis intoxication
GREAT CARE SHOULD BE TAKEN IN
ADMINISTERING KCL BY IV ROUTE
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Dilute before administering
Dose and rate depends on the patient
condition
In patients whose serum K+ is > 2.5
meq/l, rate of infusion not to exceed
10meq/hr, in a conc of < 30 meq/l. Total
dose should not exceed 200 meq/24 hrs
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If urgent treatment is required ( K+ < 2
meq/l with symptoms), infuse Kcl in a
suitable conc at a rate of 40 meq/hr, up to
a maximum of 400 meq/24hr Each ml of sterile concentrated solution
contains potassium 2 meq in water for
injection Preferrably given through central line
C l i l
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Calcium gluconate
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An ampoule contains 10 ml of 10%
calcium gluconate
Calcium chloride vs calcium gluconate
1 gm calcium gluconate 90mg 4.5 meq
1 gm calcium chloride 270mg 13.5 meq
I di ti f l i th
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Indications of calcium therapy
Hypocalcemia
Hyperkalemia
Massive blood transfusion
Magnesium toxicity
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S di Bi b t
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Sodium Bicarbonate
An ampoule contains 25 ml of 7.5% W/V
of sodium carbonate
From 1gm of sodium Bicarbonate we get
12 meq of Na+ and Hco3 respectively
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D d li t
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Drug delivery systems
Basic InfusionSystem
Flow by gravity
Flow controlled by
roller clamp
Difficult to set and
control infusion
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I f i P
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Infusion Pumps
Why are they used? To provide accurate and controllable flow over a
prescribed period or on demand
What are they used for?
Wide range of drugs and therapies including
Chemotherapy
Pain management
Total parental nutrition
Anaesthesia/sedation
Etc. etc.
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S i P
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Syringe Pump
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S ringe P mps
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Syringe Pumps
Generally used for low volume, low flow rateinfusions
Good short term accuracy
Long start up time at low flow rates
Prime and purge line before connecting topatient
Alarms: End/near end of infusion; drive
disengaged, occlusion, battery low Specialised syringe pumps for ambulatory use,
PCA, sedation, insulin etc
Volumetric Pumps
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Volumetric Pumps
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Latch
Cam followers
(fingers)
Pressure sensor
Air in line
detector
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Volumetric Pumps
Preferred for medium and high flow ratesand large volumes
Generally not suitable for rates < 5ml/h
Variable short term accuracyAlarms: Latch/door open, set out, occlusion,
battery low, air-in-line
Specialised volumetric pumps forambulatory use, epidural infusions etc.
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Do not use a model you have not
been trained and are deemedcompetent to use
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THANK YOU