drugs in icu

8/11/2019 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

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