For short revision people working in icu anesthesia critical care pulmonology medicine

1. Every 1 french unit is equal to .33 mm increase in diameter
○
French sized catheter
•
16 gauge needle flow rate is 220 mL/min, while a 20 gauge needle flows at only 60 mL/min
•
Limit use of anything more than 20 cm
○
16 cm central venous cath used for rt sided insertions vs a 20 or 30 cm one used for left sided
•
It is called the seldinger technique to thread the catheter over a wire
•
One has chlorhexidine/silver sulfadiazine, the other one has minocycline/rifampin
○
Use these when the duration of central line is expected to be > 5 days
○
Antimicrobial coatings to catheters
•
Basilic or cephalic vein in the arm and advanced into the SVC
○
50 and 70 cm long --> decreased flow capacity
○
PICC lines
•
Flow rate of hemodialysis is 200-300 mL/min
•
Chap 1
Chap 2
If you cath the artery instead of the vein during a central line placement, leave it in place and call vascular surgery
•
There is an UNPROVEN claim that volume depletion does not collapse the subclavian vein
•
You can take a supra or infraclavicular approach to the subclavian vein
•
Pneumo (5%)
○
Brachial plexus injury (3%) - inferior to the vein
○
Phrenic nerve injury (1.5%)
○
Complications of subclavian central line
•
Locate the femoral artery pulse
○
Then go 1-2 cm medial to the pulse and go down 2-4 cm
○
Angle to the opposite shoulder
○
Blind femoral line
•
Most common complication of PICC insertion is catheter induced thrombosis
•
Pressure gradient created when negative intrathoracic pressure during breathing
○
Air entry into the cath at 200-300 mL total over a few seconds can be fatal
○
Prevent with positive pressure ventilation
○
Trendelenburg position also helps prevent
○
Look for sudden onset of dyspnea
○
Left lateral recumbent

Pure O2

Try to aspirate from cath

Really not great management options
○
Venous air embolism
•
Decreases the amount of air in the lungs, pneumo doesn’t change size so it is more apparent
○
Why would doing a forced expiration help see a pneumo on XRAY?
•
Just above the carina
○
You always want the central line cath tip 1-2 cm above RA junction
•
Chap 3
Antimicrobial gel application doesn’t reduce infections of catheters (maybe dialysis)
•
Major complication with peripheral vein catheters is phlebitis --> begins day 3-4
•
One study showed 7% complication rate
○
Also don’t replace if there is just erythema
○
Replacing central lines can actually promote complications
•
Flushing not in use catheters with a heparinized saline flush, then capping it
Heparin lock
•
The ICU Book
Wednesday, September 9, 2020 10:19 PM
Book Notes Page 1

2. Flushing not in use catheters with a heparinized saline flush, then capping it
○
Ideal to prevent thrombosis
○
Non-heparin flushing (with normal saline) is just effective for venous caths (but NOT ARTERIAL)
•
Arterial catheters are flushed at a rate of 3 mL/hr continuously
•
Drugs can precipitate (TMPSMX, digoxin, diazepam, and phenytoin are examples)

Catheter occlusion
○
25% of central venous catheters

Still going, wait another 90 min

2 mL alteplase (2mg) --> then wait 30 min and attempt to draw blood
□
Repeat alteplase 2 mg
□
Can do 0.1 N HCl or 70% ethanol to try and break up drug precipitant
□
Restore patency?

Only take it out when there is arm swelling is severe and painful

Thrombotic occlusion
○
Consider SVC rupture if new pleural effusion

Perforation of the SVC or RA
○
Noninfectious complications
•
Positive compressive US for clot has sensitivity 97%, specificity 96% for DVT
•
Contaminated infusions

Break points in the infusion system or hub

Skin microbes migrate and colonize the catheter

Circulating blood pathogens can seed it

Sources
○
Most common staph epidermidis
○
MICU = 1.8 per 1000 cath days

SICU = 1. 4 per 1000 cath days

Express in number of catheter days
○
Catheter infections
•
Neutropenia
○
Prosthetic valve
○
Indwelling pacemakers
○
Severe sepsis/septic shock
○
Purulent drainage from catheter
○
When do you pull the catheter out if you suspect an infection?
•
Remove cath
○
Snip off distal 2 inches and put in culture tube
○
Draw 10 mL blood for a blood culture
○
How to culture cath tip
•
Ideally there will be greater amounts of microbes in the blood drawn from the cath vs blood drawn from blood
○
How to diagnose a catheter infection when it is left in?
•
Start and end with vanco typically for gram + (can use daptomycin if worried about vanc resistance)
○
Gram negative can get carbapenem, cefipime, or pip/taz
○
Antibiotics for catheter infection?
•
Femoral catheter
○
TPN
○
Hematologic malignancy
○
Prolonged antibiotic rx
○
Recent transplant
○
Other candidia infection
○
When do you cover for candidemia? (use caspofungin)
•
Recommended for all catheters left in place during systemic antibiotic therapy
○
Antibiotic mixed with heparinized saline --> inject this and let sit for 24 hrs
○
Antibiotic lock therapy
•
Coag negative staph --> continue antibiotics for 5-7 days if cath removed, 10-14 days if cath stayed in
○
Staph aureus gets 14 days is cath is removed (but longer (up to 4-6 weeks) if pt sicker)
○
Enterococci or gram negative bacilli get 7-14 days whether or not catheter is removed
○
Candida infections --> 14 days of antibiotics AFTER first negative culture
Duration of treatment?
•
Book Notes Page 2

3. Candida infections --> 14 days of antibiotics AFTER first negative culture
○
Requires thrombosis evidence

Suppurative thrombophlebitis
○
Pretty rare to get nosocominal endocarditis (2-3 episodes per year in most large hospitals)

Don’t rely on new murmur --> can be absent in 66% of pts

Antibiotic therapy for 4-6 weeks is standard

30% mortality rate

Endocarditis
○
Persistent sepsis for 72 hours after antibiotics should lead you to consider:
•
Chap 4
Hep B can remain viable in dried blood at room temperature for up to 1 week
•
Principal pathogen transmitter via the airborne route is TB
•
Chap 5
Mechanical ventilation
○
Platelet < 50k

INR > 1.5

PTT > 2x normal

Coagulopathy
○
Burns > 30% BSA
○
Circulatory shock
○
Severe sepsis
○
Multisystem trauma
○
TBI
○
Renal failure
○
Steroid therapy
○
Risk factors for stress ulcer bleeding --> caused by disrupted gastric mucosal blood flow (top 3 are the highest)
•
Famotidine (20 mg BID) or pantoprazole

Famotidine lasts 10-15 hours single dose

Avoid PPI's with clopidigrel --> PPI can inhibit the activation of clopidigrel

H2 blocker or PPI (H2 blocker most popular)
○
Binds to damaged areas only through bonding to exposed proteins

Dosing at 6 hour intervals

Ex: ciprofloxacin, digoxin, phenytoin, tetracycline, warfarin, etc
□
Avoid by giving 2 hours after administration of other meds
□
Has issues as it binds other drugs in the lumen of the bowel

Fewer adverse effects, but more bleeding with this vs PPI/H2

Only 12% of physicians report using this though

Sucralfate -> cytoprotective agent
○
Preventitive measures for stress ulcers (90% of ICU pts get something)
•
If the mouth gets colonized with gram negative bacilli --> it is a precursor to pneumonia with aspiration
○
6 hours of effect

But only 4 out of 7 trials showed it was effective

Do this before cardiac surgery --> that’s about it

Primarily works against gram + organisms

Clorhexidine
○
Ora base gel (2% gentamycin, 2% colistin, and 2% vanco)

Known as selective oral decontamination

57% decline in tracheal colonization and 67% reduction of VAP

But no evidence for this
□
But IGNORED in the united states because of worry about antibiotic resistance

Nonabsorbable antibiotics
○
Decontaminate the mouth
•
Basically a continuation of oral decon
Selective digestive decontamination
•
Book Notes Page 3

4. Basically a continuation of oral decon
○
Shown to work on decreasing gram negative bacteremia by 70%
○
Intended for ICU pts who stay longer than 72 hours
○
Clinical trials have shown mortality benefit --> but still ignored
○
Chap 6
PE is the most common preventable cause of death in hospitalized pts
•
VTE is considered a universal risk in ICU patients, they all have some risk factors for VTW
•
VTE after surgery likely due to thromboplastin release during the procedure, producing a hypercoagulable state
•
Particularly high risk after a cancer surgery
•
Must bind to a cofactor (antithrombin III) to produce its effect

Strongest inhibition of Iia (thrombin) and Xa

Unfractionated heparin
○
Low doses without producing systemic anticoag

Standard dose is 5000 u BID or TID

50-60% reduction in DVT's in ICU pts

Risk of major bleeding is < 1%

Dose TID in obese patients

Cant do heparin after hip or knee surgery

Low dose unfractionated heparin
○
Must still bind to antithrombin III but the molecules are more standard in size

More potent than unfractionated heparin, but also more predictable dose response

Longer duration of action than unfractionated heparin

Lower risk of HIT

Cleared by kidneys, dose adjust in renal failure pts
□
Drawback?

But wait until 12 hours post procedure for the first dose
□
Superior to unfractionated heparin after orthopedic procedures involving hip/knee

40 mg subcutaneous injection once daily

Renal failure gets 30 mg

Morbid obesity is 0.5 mg/kg

Lovenox (enoxaparin)
□
Once daily even in high risk patients

No dose reduction in kidney failure

Dalteparin
□
Preparations

Low molecular weight heparin
○
Replacement for anticoag drugs in pts who are bleeding or are high risk for bleeds

Can use as an adjunct

Designed to create a pressure gradient to push blood out of the venous leg system

More effective than graded compression stockings

Mechanical
○
Thromboprophylaxis
•
D-Dimer is trash in ICU patients, it will always be high (80% of ICU pts in one study in the absence of VTE)
•
Start with a DVT ultrasound
•
Presence of lung disease produces abnormal scans in 90% of cases
○
Low probability scan doesn’t exclude PE, but just watch them
○
V/Q scans are trash --> secure diagnosis in 25-30% of cases
•
Target PTT is 46-70s

Continuous infusion of unfractionated heparin
○
Use adjusted body weight in obese pts
○
1 mg protamine IV withh neutralize 100u heparin within 5 min

Be ready for HIT
○
Start warfarin --> 5-10 mg daily for the first 2 days, then dose based on INR
○
Treat actual DE/DVT
•
10-12% risk of bleeding, 1-2% risk of ICH
Thrombolytic therapy with PE and hypotension?
•
Book Notes Page 4

5. 10-12% risk of bleeding, 1-2% risk of ICH
○
One of their benefits is that they never seem to get infected
○
IVC filter can fill to 75% of its capacity without compromising the cross sectional area of the IVC
•
MAP estimation using 1/3rd systolic and 2/3rd diastolic is only true when the HR is 60 bpm, which is especially rare
in ICU pts

Chap 7
Then it is in the main pulmonary artery when there is a sudden rise in diastolic pressure without a SBP rise

PAWP is when there is a nonpulsatile pressure typically at the same level of the diastolic pressure of the
pulsatile waveform

You know the swan ganz cath is in the RV when a pulsatile waveform appears

Very popular crit care value

High in cardiogenic shock, low in hypovolemic and vasogenic shock

CVP equals RAP equals RVEDP

CO/BSA

Normally 60% of the CO

Cardiac index → adjusted CO for body surface area

DO2 (oxygen delivery) = CO X 1.3 X Hb X SaO2

Chap 8
Showed to not be true

Picc lines typically not used to measure CVP because there were concerns that the length would attenuate the
pressure signal

Need to set the baseline for measuring CVP at the same level of the RA

CVP and wedge pressure should be measured at the end of expiration

Disconnect pt from ventilator to measure CVP --> PEEP can artificially inflate the cardiac filling pressures at end
expiration

Larger the heart chamber size, the greater the wall stress, but the greater the ventricular hypertrophy the less the
wall stress

As the patients hct drops, the CO increases because the viscocity decreases

Chap 9
Variability of the VO2 is +/- 18%, meaning that the VO2 has to change at least 18% for it to be considered a
significant change

Can make up to 20% of the whole body VO2 when there is inflammation in the lungs → common in ICU pts

VO2 via the modified Fick equation is not whole body VO2 because it doesnt include the lungs

To measure whole body VO2 you basically need the pt to be intubated

6 hour gap between first evidence of a low VO2 to an increase in the blood lactate levels

SaO2 measured with pulse ox

SvO2 measured with pulm cath or central line

Normal is 20-30%

> 50% means threatened or inadequate tissue perfusion

< 20% means defect in O2 utilization by the tissues --> usually cell injury in septic shock

You can monitor the O2 extraction using SaO2 - SvO2 (as long as SaO2> 90%)

When measuring SvO2, a change must be greater than 5% and last longer than 10 min to be considered real

Kind of --> called ScvO2 and it is higher by an average of 7 +/- 4 in critically ill pts

But the changes mirror each other

ScvO2 > 70% can be used as an early goal management in sepsis

Can you use a central line to measure SvO2?

Can track lactate --> probability of survival is related to initial lactate prior to treatment, and the time required
for the lactate to return to normal

> 4 gives a significant risk of fatal outcome during an icu stay

Good prognosis when lactate clears within 24 hrs, bad if > 48 hours

Accumulation in sepsis due to accumulation of pyruvate due to inhibition of pyruvate dehydrogenase by
endotoxin and bacterial cell wall components

Lactate

Chap 10
Book Notes Page 5

6. endotoxin and bacterial cell wall components
Evidence that the heart uses it as fuel in pts with septic shock

Actually possible lactate can help in severe sepsis

More specific marker of metabolic acidosis than the serum bicarb

Defined as the amount of base that must be added to 1L of blood to raise the pH to 7.4

Normal is < 2

Severe is > 15

Sexy in trauma --> normalize this with resus, good outcomes

Lactate better to determine outcomes in the ICU

Base deficit

Chap 11
Interstitial fluid moves into the blood (can add up to 1 L)

Activation of RAAS

Blood loss triggers compensation

But if not resuscitated it drops by RAAS dilution

8-12 hrs after blood loss

Hct changes show poor correlation with blood volume deficits in acute hemorrhage

Central venous pressure should never be used to make fluid resus decisions

Only about 50% of critically ill pts are fluid responsive when given 500 cc

RL is only 25% as effective

Colloid fluid is better → large molecules that dont escape into the extravascular space

All comes down to cost

Reason why colloid fluid not used?

Colloid fluid (dextran-40) is best fluid for augmenting CO

Believed to originate with reperfusion of the splanchnic circulation

No therapy, but reverse ischemia

Postresus injury

Chap 12
But no survival benefit when given to people who need a lot of volume but cant get a lot of fluid in

250 mL of 7.5% hypertonic NS results in a 1235 mL increase in ECF

Addition of D5 to IV fluids increases osmolality (50g dextrose adds 278 mOsm/L to IVF)

Glucose utilization of critically ill pts can be decreased, so addition of D5 can cause cellular dehydration

Association between hyperglycemia and increased M/M

Dont let blood glocose levels stay > 180 mg/dL in ICU pts

Safe to use in volume resus except in TBI

5% given in boluses of 250 mL

Does not replace fluid → dont use in volume resus

25% given in boluses of 50-100 mL

Either 5% (50g/L) or 25% (250g/L) mixed with 0.9% NaCl

Volume effect dissipates at 6 hours, and is lost at 12 hours

Albumin solutions

6% solution in NS

Very similar to 5% albumin for volume resus

Effects dissipate within 1 hour

But clinically significant coagulopathies are uncommon unless large volumes

Can impair hemostasis by inhibiting Factor VII and vWF

Mechanism unclear

Can cause renal injury in severely ill patients

Hydroxyethyl starch

Glucose polymers incubated in a sucrose medium → not popular in the US due to perceived risk of adverse
reactions

Dose related bleeding tendency

Can affect ability to crossmatch blood → coat RBC

Can cause renal injury (but rare)

Dextrans

Book Notes Page 6

7. Can cause renal injury (but rare)

The key was initially to replete the lost interstitial volume, which saline/LR is good for

But has not yet reached the US

But recently we know that CO and O2 delivery are the primary focus, which colloid fluids do better than
crystalloid

Can cause edema + positive fluid balance, not great for critically ill pts

Issue with crystalloid is that 3x more volume is needed to resus

Overall there is much debate over which to use

Chap 13
Earliest sign of ventricular dysfunction is increased cardiac filling pressure (ie: PCPW)

Promote sodium excretion in the urine to decrease preload

Dilates systemic blood vessels

Stimulate lipolysis

Natriuretic peptides

Baroreceptors sense decreases in stroke volume

Positive inotropic/chronotropic effects

SNS

Renin released due to renal hypoperfusion

Not activated until late in HF, and its effects are counter-productive

RAAS

HF responses

Increased wall tension releases it

Clearance through kidneys

Falsely lower in obese pts → BNP can be cleared by peptide receptors in adipose tissue

Uncertain if between 100-500

Likelihood of HF with BNP levels → likely if > 500 in any age

Not evaluated for a marker of response to therapy

Most useful in the ED → not as much in the ICU

BNP

Hallmark is the decrease in ventricular distensibility with impaired ventricular filling during diastole

Diastolic HF can be up to 60% of all cases

In the ICU, PEEP and positive pressure ventilation can cause diastolic HF

Systolic is < 45%

Diastolic > 50%

Normal is > 55%

Classically utilize a transthoracic echo

EF

Most cases caused by pulm HTN and inferior wall MI

This delayed rise can result in undetected

Increase in RVEDV, but the CVP doesnt rise until the increase in RVEDV is restricted by the pericardium

Equalization of rt and left ventricular filling pressures is also characteristic of cardiac tamponade

CVP > 10 and CVP = PAWP or CVP within 5 mm of PAWP

Rt sided HF can produce diastolic dysfunction in the LV via “interventricular interdependence”

LV chamber size reduced as the septum is pushed into the LV

Right heart failure

Give lasix to a pt in acute HF exacerbation if volume overloaded or if PAWP remains > 20 despite nitro therapy

Start infusion at 5 ug/min, and increase by 5 every 5 min

Dont go above 200 ug/min

Major drawback is tachyphlaxis (rapidly diminishing response to a successive doses of a drug)

Nitroglycerin

Nitroprusside releases cyanide ions, which are cleared by the liver/kidneys

Sodium thiosulfate can be added as a preventative measure

Potent B1, weak B2 agonist

Dobutamine

PDE inhibitor

Milrinone

Inodilators are used after nitro with normal BP pts in HF

Book Notes Page 7

8. PDE inhibitor

Similar to dobutamine but more likely to cause hypotension

Needs to be renally dosed

Sensitizes cardiac myofilaments to calcium

Appealing in pts with CAD, no increase in myocardial O2 consumption

Only one associated with improved survival

Levosimendan

IV furosemide can cause a decrease in CO in acute HF

Pulmonary edema in acute HF is not evidence of excess ECV, and could be caused by increase in PAWP from
diastolic dysfunction

Excess ECV is going to be weight gain or peripheral edema, or with a PAWP > 20 mmHg

Diuretic management (reasons to be cautious)

Diuresis begins within 15 min, peaks at 1 hour, lasts 2 hours

Double dose to 80 mg after 2 hours if at least 1L doesnt come out

Initial dose 40 mg IV (if normal renal function)

Renal insufficiency dose of 100 mg IV

If normal Cr clearance load with 100 mg IV, then 10 mg/hr

Continuous infusion?

Furosemide is a sulfonamide → but can be used safely in pts with sulfa drug allergy

Goal of diuresis is a min weight loss of 5-10% of body weight

Can do metolazone (thiazide diuretic) if there is furosemide resistance (give it with furosemide)

End point of RHF treatment is Increase in PAWP or CVP

Chap 14
Key to identify infection → only 25-50% of pts with SIRS have an infectious cause
○
Lots of people fit the SIRS criteria → one study showed 93% of pts in a surgical ICU were SIRS positive
•
40% of pts with severe sepsis have ARDS (that seems high)
•
There is a direct relationship between number of organs affected in shock and the mortality rate
•
This is because mortality rate is not related to sit of infection of causative organism
○
Seems that inflammation, not infection, is the principal determinant of outcome in septic shock
•
Systemic vasodilation
○
Oxidation injury to vascular endothelium leads to fluid extravasation and hypovolemia
○
Cytokines promote cardiac dysfunction, but CO usually increased
○
Splanchnic blood flow is reduced
○
Low CVP
○
Hemodynamic alterations in septic shock
•
A declining cardiac output in septic shock indicates poor prognosis
•
Tissue oxygenation was found to be more than adequate in severe sepsis and septic shock
•
CVP should not be utilized to guide fluid management, not an accurate reflection of circulating blood volume
•
Norepi first → dose is 0.1 per kg/min
○
Utilize vasopressors to achieve MAP of 65 or more
•
Corticosteroids → unfortunately even with their antiinflammatory properties they have never been shown to
provide benefit, but continue to be used
•
One dose of abx can sterilize blood cultures within 1 hour
•
Given to relieve the itching
○
Both diphenhydramine and ranitidine (H2 blocker) given together
○
H1 blockers for anaphylaxis
•
Chap 15
Book Notes Page 8

9. •
Little noticeable effect when cardiac function is normal
○
Very pronounced at rapid HR
○
Atrial contraction is responsible for 25% of the ventricular EDV
•
Ca blocker that helps rate reduce in 90% of uncomplicated A fib cases

Better sustained response than amiodarone or digoxin

Negative inotropic effects --> but used safely in pts with mod-severe HF

Side effects --> hypotension and cardiac depression

In the ED I personally have seen 10 mg bolus and then 5 mg drip

Dose is 0.25 mg/kg IV over 2 min, then infuse 5-15 mg/hr

Peaks at 5-7 min

Diltiazem (cardizem)
○
Preferred agent when A-fib is associated with hyperadrenergic states (ie: MI, postcardiac surg)

Esmolol and metoprolol

Esmolol half life is 9 min

500 micrograms/kg IV bolus, then infuse at 50 micrograms/kg/min

Max rate is 200 mcg/kg/min

Esmolol dosing

2.5-5 mg IV over 2 min

Can repeat every 5-10 min for 3 doses

No drip

Metoprolol dosing

Beta blockers
○
Favored by some people for A fib in pts with HF, less cardiac depression

Can be a downside though because if not anticoagulated can throw a clot

Also an antiarrhythmic, can convert to normal sinus rhythm

Dosing is 150 mg IV over 10 min, then infusion at 1 mg/min for 6 hours (then 0.5 mg/min for 18 hours)

Hypotension

Infusion phlebitis

Bradycardia

Elevated liver enzymes

Interactions with other drugs

Adverse effects

Amiodarone
○
Response is slow to develop --> can take 1 hour, and peak at 6 hours

Digoxin
○
A fib rate control meds
•
Book Notes Page 9

10. Response is slow to develop --> can take 1 hour, and peak at 6 hours

May have a role of treating Afib in HF pts, but should be used alone

More than 50% of afib episodes will spon convert back to sinus within 72 hours
•
1-7% chance of stroke
○
Cardiovert biphasic shock with 200J starting
•
150 mg BID
○
Make sure to renally reduce dose by 50%
○
Dabigatran suggested as the antithrombic therapy for Afib pts who meet criteria
•
Anything that blocks conduction in the AV Node
○
Ca blockers
○
Beta blockers
○
Digoxin
○
WPW drogs NOT to use
•
Cardiac arrests have been noted
○
Recommended to halve the dose to 3 mg (and then 6mg)
○
Adenosine through a central line
•
Treat torsades with 2 grams of magnesium sulfate (MgSO4)
•
Chap 16
Oxygen is a vasoconstrictor in all organs except for lungs
•
Good for reduction of mortality and re-infarction
○
Aspirin in MI --> survival benefit absolute decrease of 2-3%
•
Thrombolytic therapy survival benefit is time dependent --> lost if > 12 hrs have elapsed from CP onset
•
Active bleeding
○
Malignant intracranial neoplasm
○
Cardiovascular anomaly
○
Suspected aortic dissection
○
Ischemic stroke within 3 months
○
Prior history of ICH
○
Significant closed head/facial trauma in past 3 months
○
Absolute contraindications to thrombolytic therapy (we do PCI now)
•
Convert plasminogen to plasmin, which breaks fibrin
○
How do thrombolytic agents work?
•
Should be performed within 90 min
○
PCI --> time improves mortality, increased mortality if wait longer than 2 hours
•
Advantageous after thrombolytic therapy to counteract the prothrombin actions of thrombin released by clot
breakdown
○
Dosing is 100 u/kg --> max 500 u
○
Why is heparin given in an MI?
•
Class of drugs that blocks surface receptors involved in ADP-induced platelet aggregation
○
Clopidogrel, ticlodipine, tigrecalor, prasugrel
○
Oral loading dose of 600 mg prior to PCI

Standard dose of 75 mg daily

d/c 5 days prior to surgery

Clopidogrel (plavix) is the most popular one
○
Thienopyridines
•
Abciximab, eptifibatide, tirofiban
○
Managed by the interventional cardiologist
○
We don’t really use glycoprotein receptor antagonists (Iib/IIIa inhibitors)
•
Acute mitral regurg after an MI can kill --> 70% mortality without surgery, 40% mortality even with surgery
•
Mortality is 90% without surgery if the ventricular septum ruptures (20-50% with surgery)
•
MI that causes immediate HF (because of its size) has a mortality of about 80%, that is only reduced 10% by timely
PCI intervention
•
Aortic dissection can happen from a disease like Marfan's, or from prolonged hypertension
•
And of course 5% of pts have 0 pain at all
○
Chest pain of dissection can actually subside spontaneously for hours to days
•
Dissection common findings?
•
Book Notes Page 10

11. HTN (50%)
○
Aortic insufficiency (50%)
○
Only 15% of pts have unequal pulses
○
EKG can be normal in 30% of pts
○
Normal CXR in up to 20% of cases
○
Dissection common findings?
•
Surgical repair makes it 10% at 24 hrs and 12% at 48 hours
○
Dissection mortality?
•
Chap 17
You have 4 min after cardiac arrest before anoxic cell death can be expected
○
O2 in the circulating blood is about 800 mL, and the body consumes about 250 mL/min
•
Compress at a rate of 30:2 until you have an advanced airway in place
•
Chest compressions deliver CO that are 25-30% normal
•
Outcomes in cardiac arrest are most favorable when initial rhythm is Vtach or Vfib
•
Epi is associated with increased ROSC but overall no survival benefit
○
There are no documented survival benefit to using resus drugs
•
30% increase in coronary perfusion following IV epi, lasts 3 min
•
End tital pCO2 which suggested death was anything below 10-15 after 20 min of CPR
•
Inflammatory response triggered by cardiac arrest
○
Dysfunction in one or more major organs (most often brain/heart)
○
Brain injury is most common --> 23-68% of deaths following cardiac arrest
○
Cardiac wise, it can be a combo of systolic and diastolic dysfunction
○
SIRS is almost universal --> basically whole body reperfusion therapy
○
Post cardiac arrest syndrome
•
Monitor temperature with catheter
○
Infuse 30 ml/kg of ice cold saline/LR
○
Control shivering with propofol, midazolam, or fentanyl
○
Temp then kept low by automated cooling systems for 24 hrs
○
Hypothermic cooling is considered for anyone who doesn’t wake up after ROSC
•
The mechanism is the K+ goes into the cells
○
Hypokalemia is common during cooling, but don’t treat aggressively or you will have rebound hyperkalemia once pt
is rewarmed
•
Fever and hyperglycemia following a cardiac arrest are associated with unfavorable neuro outcomes
•
Hypothermia has not been proven to delay time to awaken
○
Most pts (80-95%) who ever regain consciousness after ROSC are awake within 72 hrs
•
When pupillary light reflexes or corneal reflexes are absent 3 days after ROSC, 0% of pts have a good neuro outcome
•
Poor motor responses within 72 hours is a bad sign for pts unless they underwent hypothermia, after which 25% of
pts may have delayed motor response after 72 hrs
•
Myoclonic status epilepticus often appear within the first 24 hours after a cardiac arrest, and it is a poor prognostic
sign for any patient
•
Less than 10% of pts who receive CPR survive to discharge from the hospital
•
Chap 18
Interestingly there was a study that showed just standing up can increase the plasma volume by 400 mL via
interstitial fluid moving into the blood
•
Increased plasma volume is common in critically ill pts
•
Inhibits EPO release from the kidneys

Reduces marrow responsiveness to EPO

Iron sequestered in macrophages

Inflammation (chronic disease)
○
40-70 mL of blood on average is drawn daily from ICU pts

This can reach one unit (500 mL) of blood in a week

Phlebotomy
○
ICU related anemia
•
Physiologically, anemia leads to an increase in CO and an increase in O2 extraction from capillary blood
•
Book Notes Page 11

12. It actually leads to enhanced tissue oxygenation if the flow augmentation in response to anemia is greater
than the decrease in hematocrit
○
Physiologically, anemia leads to an increase in CO and an increase in O2 extraction from capillary blood
•
The maximum O2 extraction is about 50%, this could be used as a trigger point for RBC transfusion
•
Animal studies show that with maintenance of intravascular volume, a Hb of 1.5-3 can be tolerated
•
Guidelines right now suggest transfusion below 7, and below 9 if ACS
•
No info about the adequacy of tissue oxygenation
○
Decreases in Hb can be dilutional
○
Why is Hb as a transfusion trigger flawed?
•
Oxygen extraction of 50% can be a trigger
○
Can be monitored via pulse ox and a central venous oximetry catheter (SaO2 - SvO2)
○
An ScvO2 < 70% can be a trigger
○
What can we do instead?
•
Takes about 2 hours per unit (at 5 mL/min)
○
Each pRBC has a volume of 250 mL and a hct of 60%
•
But studies have shown a lack of effect on VO2 (O2 uptake), which again suggests that tissue oxygenation isnt
enhanced
○
1 u pRBC can raise Hb by 1 and Hct by 3%
•
Defined as a temp increase of > 1 degree celcius

Leukocyte reduced RBC decreases this risk

Nonhemolytic fever = 1 in 200
○
Urticaria = 1 in 100

Anaphlaxis = 1 in 1000

Hypersensitivity rxn
○
Acute hemolytic reaction = 1 in 35k
○
Fatal reaction = 1 in 1 million
○
Transfusion reactions
•
Hep B = 1 in 220k
○
Hep C = 1 in 1.6 mil
○
HIV = 1 in 1.6 mil
○
Transfusion errors are wayyyy more common at 1 in 30k
○
Infection risk
•
The organism most frequently isolated in stored RBC is yersinia enterocolitica
•
Basically ARDS caused by transfusion
○
1 in 12k transfusions
○
Mortality rate of 6%
○
Theory that it is caused by antileukocyte antibodies in donor blood that bind to antigens on circulating
neutrophils in the recipient
○
TRALI
•
In 42 of 45 studies, the benefits of transfusion were outweighed by adverse events (only 1 showed benefit to
transfusion)
○
17 of the 18 studies that looked at survival showed that RBC transfusions were related to death
○
A review of 45 clinical studies of RBC transfusions in critically ill patients showed BAD RESULTS
•
Blood doesn’t save lives, blood VOLUME saves lives
•
Chap 19
Thrombocytopenia is the most common hemostatic disorder in critically ill patients (can be up to 60%)
•
Platelet count < 100k is most appropriate for identifying clinically significant thrombocytopenia
•
The biggest risk of platelet count < 10k is spontaneous ICH, which is rare
•
Where antibodies to EDTA (anticoag in blood collection tubes) produces clumbing of platelets
○
Seen in 2% of hospitalized pts
○
Pseudothrombocytopenia?
•
Most common cause of thrombocytopenia in the ICU is systemic sepsis
•
HIT is NOT dose dependent and can happen from heparin based flushes of catheters
•
Argatroban cleared by the liver
○
Lepirudin is cleared by kidneys
Difference between argatroban and lepirudin?
•
Book Notes Page 12

13. Lepirudin is cleared by kidneys
○
But not until platelet count is back over 150k
○
Also cannot use more than 5 mg
○
After HIT, then use warfarin
•
Fewer febrile rxs
○
Fewer CMV transmissions
○
Lower incidence of platelet alloimmunization
○
Leukocyte reduction is becoming standard for all platelet transfusions
•
One unit of platelets should increase 35-40k at one hour, but 40% lower at 24 hours
•
Platelets can only be stored for 5 days
•
Active bleeding maintain above 50k
○
Active ICH maintain above 100k
○
No active bleeding, usually transfuse at 10k or below
○
> 40k for laparotomy, craniotomy, tracheotomy, percutaneous liver biopsy, and bronchoscopy

> 20k for LP

> 10k for central line

Procedures
○
Platelet counts for things
•
Required culture all concentrates

Bacteria transmission, more likely in platelet concentrates because of room temperature storage
○
Can be seen in 30% of pts

Probably due to multiple donors per bag

Fever
○
Hypersensitivity reactions
○
Acute lung injury (TRALI)
○
Adverse effects
•
Volume of 230mL
○
Stored for a year while frozen, thawed can be stored for 5 days
○
FFP
•
Can normalize the INR in less than 30 min (vs hours for FFP)
○
PCC
•
Concentrated factor VIII --> now replaced
○
Contains 200 mg fibrinogen, can be used to correct variceal bleeding
○
Cryoprecipitate
•
Dose of 0.3 mcg/kg by injection or 30 mcg/kg intranasal
○
Effect lasts 6-8 hours
○
Desmopression can elevate the levels of wvF
•
Chap 20
When the alveolar-capillary interface is destroyed
○
When blood flow is reduced
○
When alveoli are overdistended
○
When does dead space increase?
•
An increase in dead space results in hypoxemia and hypercapnia
•
When the small airways are occluded
○
When the alveoli are filled with fluid
○
When the alveoli collapse
○
When capillary flow is excessive
○
When does a shunt occur?
•
Varies with age and concentration of inspired O2
○
Normal level Rises steadily with age
○
Normal A-a gradient rises 5-7 mmHg for each 10% FiO2 increase
○
The A-a gradient is an indirect measurement of V/Q abnormalities
•
Cant really rely on routine monitoring of these numbers
○
The PO2 and PCO2 varied widely in a study over 1 hour of stable trauma pts
•
Defined as an arterial PO2 below what is expected for the patient's age
Hypoxemia
•
Book Notes Page 13

14. Defined as an arterial PO2 below what is expected for the patient's age
○
Doesn’t raise red flags until PO2 < 60 mmHg
○
No V/Q imbalance, so normal A-a gradient

Usually in the ICU these are caused by drug induced respiratory syndrome or neuromuscular weakness

Can be caused by obesity (if BMI > 35)

For neuromuscular weakness look at the max inspiratory pressure to be > 80 mmHg (if it cant get higher
than 25 very suggestive of neuromuscular issue)

Hypoventilation
○
Most cases of hypoxemia

Virtually any lung disease

A-a gradient is almost always elevated

v/q mismatch
○
Decrease in delivery of O2 is usually accompanied by an increase in O2 uptake into the tissues

Can have increased A-a gradient but not always

If venous PO2 < 40, its DO2/VO2 mismatch

Mixed venous PO2 helps separate from V/Q mismatch

DO2/VO2 imbalance
○
Three categories of hypoxemia
•
Seems to only occur in pts with hematologic malignancies who have marked leukocytosis
○
No method to prevent this
○
Spurious hypoxemia is hypoxemia in an arterial blood sample without corresponding hypoxemia in circulating blood
(measured by pulse ox)
•
Can be caused by overfeeding pts with lung disease/resp failure

Measure VCO2 with special carts with infrared devices

Increased CO2 production (VCO2)
○
Hypoventilation
○
Usually rises when dead space is > 50% (normal is 30%ish)

Increased dead space ventilation
○
Hypercapnea causes
•
Chap 21
Pulse oxygenation measures only the arterial oxygenation by focusing only on the pulsating phasic changes in
arterial blood
•
Then it calculated the ratio of HbO2 to total Hb (oxy plus deoxy)
○
The pulse oxygenation is then a percentage
○
Pulse ox wavelengths are 660 nm (measures deoxygenated hb) and 940 nm (measures oxygenated Hb)
•
SaO2 differs from the pulse ox at less than 3% (when at a pulse ox of > 70%)
•
There is a product called the Rainbow Pulse Cooximeter that measures all forms
○
For methemoglobin or carboxyhb, the oxygen saturation decreases because HbO2 is a lower fraction of the total Hb
pool, but the pulse ox is not influenced (and thus overestimates actual O2 saturation)
•
Dark skin can cause a variation in O2 sats when it is between 70-80% (but at this point we would already have
oxygen on)
•
Dark fingernail polish produces a small (2%) discrepancy between the saturations
•
But the major limitation is LOW oxygen sat when there is localized venous congestion which can come from
positive pressure mechanical ventilation (gives enhanced venous pulsations, tricking the device)
○
Forehead pulse ox is the preferred second site, less prone to vasoconstriction than the distal finger arteries
•
Changes in oxygen saturation that are clinically relevant (> 10%) actually are associated with minor changes in the
O2 content of arterial blood
•
The lowest O2 sat needed to support aerobic metabolism has never been Ided
•
But we use capnography now
○
The only time (theoretically) when you cant trust the colorimetric CO2 detector is during cardiac arrest when the
intubation may not change the color
•
Shape of the normal capnogram = "the outline of a snake that has swallowed an elephant"
•
VERY GOOD in cardiac arrest ROSC
○
Overdistension of alveoli from high TV or PEEP

Sudden decrease in end tidal
○
End tidal PCO2 monitoring is being looked at as a noninvastive detection of CO changes
•
Book Notes Page 14

15. Overdistension of alveoli from high TV or PEEP

Migration of the ET tube into the mainstem

Acute PE

Acute pulmonary edema

Pneumonia

Chap 22
There is only about 13 mL of O2 dissolved in all the tissues of the human body
•
No evidence that hypoxemia impairs tissue oxygenation, regardless of severity
•
Oxygen therapy produces systemic vasoconstriction (not pulm vasoconstriction)
•
The FIO2 max of nonrebreather O2 delivery is 80% (theoretically can be 100% but due to leaks it is 80%)
•
The hydroxyl radical is the most reactive molecule known in biochemistry, very destructive
•
Hydrogen peroxide is not a free radical, can move through the body and cause widespread damage though
•
NAC can serve as a glutathione surrogate
○
Only used sparingly as an antioxidant though
○
Only 3-5% of oxygen metabolism generates free radicals, but depletion of antioxidants like glutathione will change
this proportion
•
Vitamin E can become a free radical when it serves as a chain breaking antioxidant to halt the progression of lipid
oxygenation, but it is NOT DANGEROUS
•
Chap 23
Lung consolidation in ARDS is believed to originate with the activation of circulating neutrophils
•
The source of fibrin accumulation is a procoagulant state triggered by release of tissue factor from the lungs
•
Acute onset
○
Severe hypoxemia
○
But CT imaging shows the lung infiltration is confined to dependent lung regions

Bilateral pulm infiltrate without evidence of LHF or volume overload
○
Principle features of ARDS?
•
Also need a pulm wedge pressure < 18 to prove its not LHF (but we don’t do this any more)
○
PaO2/FiO2 of <200 is ARDS, but <300 for acute lung injury (conduct at PEEP of 5)
•
Not enough to ID ARDS with CXR alone
•
Low neutrophil count can be used to exclude ARDS
○
Not commonly done
○
ARDS pulmonary lavage shows as many as 80% neutrophils
•
The principle cause of death in ARDS is multiorgan failure (70%)
•
Low tidal volumes (6 mL/kg)
○
Higher PEEP (ie: 15 vs 5) have been shown to reduce mechanical ventilation time, and survival increase
when the PaO2/FiO2 ratio is < 200

But we don’t PEEP above 10 unless oxygenation issue

Increases in PEEP can reduce cardiac output

PEEP helps limit atelectrauma (cyclic opening and closing of small airways that can cause trauma)
○
Goal plateau pressure of < 30 cm H20
○
Arterial PCO2 levels of 60-70 and pH of 7.2-7.25 are safe, but the target pH is 7.3-7.45

Permissive hypercapnia
○
Lung protective ventilation for ARDS
•
Treat the inciting condition if possible
○
Inflammatory exudate in the lungs should NOT be influenced by fluid balance

But avoiding a positive fluid balance will prevent unwanted accumulation in the lungs, and this can
reduce the time on ventilation

But avoid fluid deficits too

Fluid management
○
No consistent survival benefit, but OTHER benefits

Improved gas exchange

Benefits

Corticosteroids
○
Nonventilatory management of ARDS
•
Book Notes Page 15

16. Improved gas exchange

Reducer in inflammatory markers

Shorter ventilation duration

Shorter ICU stay

Methylprednisone IV loading dose of 1 mg/kg of ideal body weight, then influse 1 mg/kg/day for 14
days, then taper over the next 14 days

5 days after pt is able to ingest oral meds, you can orally dose once daily

Loading of 2 mg/kg ideal weight

Infusion 2mg/kg for 14 days

Infusion 1 mg/kg for 7 days

Taper

You need to do a DIFFERENT DOSE if the pt is at risk for pulmonary fibrosis

Seen in 10-15% of pts
○
Very worrisome, the measures to treat often provide little/no survival benefit
○
Delivers small tidal volumes of 1-2 mL/kg using rapid pressure oscillations

Limits risk of volutrauma

May not be found in all hospitals

High frequency oscillatory ventilation

5-10 ppm NO is a pulmonary vasodilator that can improve arterial oxygenation by increasing flow
to areas of high dead space ventilation

Increase in arterial oxygenation is temporary (1-4 days)

Adverse effects include methemoglobinemia (usually mild) and renal dysfunction

Inhaled nitric oxide

Diverts blood away from the poorly aerated lung regions in the posterior thorax and increases
blood flow to the anterior thorax

Little impact on mortality

Labor intensive and problems with nursing care, but with a hospital that has limited resources may
be the only possible treatment

Prone position

Variable success, only used when all else has failed

ECMO

Possible treatments
○
Refractory hypoxemia in ARDS
•
Chap 24
For asthma/COPD, the two key lung measurements to get are FEV1 and PEFR (peak flow)
•
FEV1 is less variable and more likely to detect obstruction in the smaller airways
•
When a nebulizer is used, only 12% of the intended dose reaches the lung
•
When used without a spacer 80% of the meds go to the oropharynx
○
Spacer doubles the dose getting to the lungs (from 9% to 20%)
○
Yet bronchodilator responses are equivalent (due to difference in doses)

Nebulizer delivers less than inhaler with spacer (12% vs 20%)
○
Metered dose inhaler can shoot out at 60 mph, most goes to the back of the throat
•
Aerosol delivery more effective than oral or IV (with fewer side effects)

Albuterol can be dosed every 20 min for 3 doses

Rapid onset of action (less than 5 min)

Levalbuterol is the R-enantiomer of albuterol that is equally effective at half the dose, but no
clinical difference

Albuterol

Tachycardia

Tremors

Hyperglycemia

Decrease in K+, Mg, and phosphate levels

Side effects

Beta 2 receptor agonists
○
Only offer marginal benefits in acute asthma

Anticholinergics
○
Asthma exacerbation treatment
•
Book Notes Page 16

17. Only offer marginal benefits in acute asthma

Restricted to combo therapy

Ipatropium bromide 0.5 mg mixed with albuterol, every 20 min for 3 doses

Small risk of anticholinergic effects

Side effects

No benefits after the initial few house in acute asthma exacerbation

Accelerate the rate of resolution and reduce the risk of relapses

No difference in efficacy in IV vs oral

Beneficial effects not seen until 12 hours after therapy (will not change things in ED)

No dose response curve

No evidence doses above 100 mg of prednisone daily help

A 10 day steroid course can be stopped without taper

Recommended dosing is 40-80 mg daily of prednisone (oral) or methylprednisone (IV) in one or two
doses

Corticosteroids
○
Often triggered by viral infection, but don’t treat with antibiotics unless proven bacterial infection

IV magnesium (2g over 20 min) has mild bronchodilator effects --> but NO EFFECT on clinical course of
acute asthma

Consider ketamine when intubating these patients

Arterial blood gas recommended for someone who doesn’t respond well to albuterol treatment --> a
normal PCO2 warrants ICU admission

Considerations
○
Duonebs

Even though COPD is supposed to be bronchodilator non-responsive, you use it in COPD exacerbations
○
7-10 days of steroids helps decrease ventilation and makes treatment shorter

But NNT is 10

Dosing is lower than asthma --> 30-40 mg prednisone

Corticosteroids
○
Airway infections are responsible for 50% of acute exacerbations of COPD
○
Because COPD exacerbations that get admitted should get antibiotics

All ICU pts with COPD exacerbation are candidates for antibiotics
○
Levofloxacin

Pip/taz

Antibiotics used
○
Give antibiotics for 5-7 days
○
COPD Exacerbation management
•
Over 50% of pts admitted to the ICU with asthma or COPD exacerbation are intubated
•
Creates auto-PEEP (due to trapped gas in distal airways)

Increased work of breathing is required

Dynamic hyperinflation
○
Low tidal volumes (6 mL/kg)

Maximize expiration time by preventing rapid RR, and maintaining an inspiratory:expiratory ratio of 1:2
or higher

Ventilator strategies
○
Considerations of ventilation in these pts
•
Chap 25
Tidal volume is preselected, and the ventilator automatically adjusts the inflation pressure to give the
volume

Rate of lung inflation can be constant or decelerating

Volume controlled ventilation
○
Inflation pressure is selected along with the duration of inflation, then the tidal volume to match that is
delivered

Pressure controlled ventilation
○
Two general methods of positive pressure ventilation
•
The peak pressure at the end of each lung inflation
○
Overcomes both resistive and elastic forces in the lungs and chest wall
End inspiratory pressure
•
Book Notes Page 17

18. Overcomes both resistive and elastic forces in the lungs and chest wall
○
Minimum pressure in the alveoli during a ventilatory cycle
○
ZEEP --> zero end expiratory pressure, "zero point" for breathing
○
Applied PEEP prevents the collapse of distal airspaces at the end of expiration

Occult PEEP is also known as AUTO-PEEP

Applied vs occult PEEP
○
End expiratory pressure
•
Average pressure in the airway during the ventilatory cycle, influenced by several variables
○
Area under the airway pressure waveform
○
Linked to the hemodynamic effects of positive pressure ventilation
○
MAP 5-10 for normal lungs, 10-20 for airflow obstruction, and 20-30 for still lungs (noncompliant)
○
Mean airway pressure
•
Expresses distensibility
○
Measurements are difficult --> you need no inspiratory flow at the end of inspiration, and the TV changes
○
Thoracic compliance
•
Can only be determined if inspiratory flow rate is constant (volume controlled ventilation)

Most of the inspiratory resistance in pts with normal lungs who are intubated is caused by the
endotracheal tube

Inspiratory
○
Tries to detect the tendency for small airways to collapse during mechanical ventilation

Expiratory
○
Airway resistance
•
Caused by large tidal volumes

Can rupture alveoli and produce air leaks

It was found to be caused by the volume, not the pressure

Effects more of an issue in infiltrative lung diseases like penumonia and ARDS

Volutrauma
○
Repetitive opening and closing of small airways during positive pressure ventilation can damage the
airway epithelium

Mitigate this by using PEEP to keep those airways open

Atelectrauma
○
Proinflammatory cytokine release from the lungs, can trigger SIRS

Biotrauma
○
Rupture of the airways and distal airspaces

Barotrauma
○
Ventilator induced lung injury
•
TV of 8 mL/kg
○
Plateau pressure not allowed to go above 30 (above 30 means too much alveolar volume)
○
Minimum PEEP of 5
○
Rise in PCO2 is allowed during low volume ventilation as long as pH is not below 7.3
○
Lung protective ventilation protocol
•
PPV can reduce preload

Increased vascular resistance, decreased venous return, decreased distensibility

Preload
○
Decreases LV afterload due to decrease in transmural wall pressure during systole

Afterload
○
Overall depends on preload vs afterload balance, which depends on cardiac function, intravascular
volume, and intrathoracic pressure

Decrease in preload hurts more if pt has a normal heart (which is weird)

Increase in intraabdominal pressure increased though which can augment preload

Known as the "ventricular assist" in advanced HF

In pts with heart failure, the decrease in afterload helps more, and thus you get an INCREASE IN
CO

Cardiac function

Preload decreasing predominates in both normal and failing heart, CO declines

Low intravascular volume

Cardiac output
○
Cardiac performance in PPV
•
Book Notes Page 18

19. Preload decreasing predominates in both normal and failing heart, CO declines

Need to maintain volume when on the ventilator

Chap 26
When resistance or compliance changes, the ventilatory changes to maintain the desired TV and
thus minute ventilation

Constant TV

Advantages
○
This is assumed to be a risk for lung injury, BUT the rate of lung injury is related to peak
alveolar pressures, and this is the same in both kinds of ventilation

At any TV, the pressures at the end of inspiration are higher in volume control than pressure
control

Airway pressure

Duration of inspiration is short, can lead to uneven alveolar filling

Max inspiratory flow is limited when flow is constant

Inspiratory flow

Disadvantages
○
Volume control (constant volume delivered)
•
Control the peak alveolar pressure, which is the pressure most closely related to risk of lung injury

Negligible risk of lung injury if peak alveolar pressure in < 30

Alveolar pressure

Attributed to high initial flow rate and longer duration of inspiration

Patient comfort

Advantages
○
Decrease in alveolar volume if there is an increase in airway resistance or a decrease in compliance

Particularly of concern in respiratory failure

Alveolar volume

Disadvantages
○
Pressure control (inflation pressure is selected)
•
Hybrid that produces a constant TV, but limits the end-inspiratory airway pressure
○
"intelligent" volume control
○
No documented clinical advantage, but gaining in popularity
○
Pressure regulated, volume controlled
•
Patient can initiate a ventilator breath, but if this isnt possible then the ventilator breath is delivered at a
preselected rate
○
Can be volume or pressure controlled
○
Will dip below line --> vs a ventilator generated one starts from 0 line

Negative pressure of 2-3 cm H2O

Double the negative pressure generated during quiet breathing, this is why 1/3rd of inspiratory
efforts fail to trigger a ventilator breath when negative pressure is the trigger signal

Rates of 1-10 L/min are usually required

An issue with this is auto-triggering if the system is leaky

INSTEAD, you can use flow triggering --> involves less mechanical work --> now the STANDARD

Patient

Triggers
○
Increasing inspiratory flow rate

Reducing the TV

Decreasing the inspiratory time

Can increase this ratio by

General rule is I:E ratio of at least 1:2
○
Rapid breathing can curtail the time for exhalation, and increases risk of Auto-PEEP
○
Assist control ventilation
•
Designed to allow spontaneous breathing between ventilator breaths
○
Places a spontaneous breathing circuit in parallel with the ventilator
○
Called SIMV --> synchronized IMV
○
Can pressure or volume control SIMV
Intermittent mandatory ventilation
•
Book Notes Page 19

20. Can pressure or volume control SIMV
○
Increased due to resistance in the ventilator circuit

Pressure support overcomes this and helps reduce the work of breathing, now used during
spontaneous breathing periods in IMV

Work of breathing

Increases LV afterload during the spontaneous breathing periods, which can decrease CO in HF pts

Cardiac output

Adverse effects
○
Allows the patient to terminate the lung inflation during patient triggered PCV
○
Patient can control the inspiratory time and TV
○
Decelerating inspiratory flow rate
○
Pressure augmented breath is terminated when the inspiratory flow rate falls to 25% of the peak level
○
Can be used for weaning from the ventilator
○
Ideally it reduces the work of breathing without augmenting the TV
○
Pressure support ventilation
•
Called alveolar recruitment

Low levels of PEEP help keep the airways open, while high PEEP (20-30) can reopen distal airspaces that are
collapsed
○
PEEP
•
May need to do SIMV if pt is breathing too rapidly in assist control mode

Select assist control as the initial mode
○
Can also do PRVC --> hybrid

Volume vs pressure control is a personal preference --> pts tend to prefer pressure control
○
Then reduce to 6 mL/kg over the next 2 hours

In volume control this is plateau pressure

In pressure control this is end-inspiratory pressure

Keep peak alveolar pressure < 30

TV of 8 mL/kg (of ideal body weight)
○
60 L/min if pt is breathing quietly or has no spon respirations

Higher (like 80 L/min) if pt has respiratory distress or a high minute ventilation

Flow rate
○
Greater than 1:2

I:E ratio
○
Try to match patient's minute ventilation prior to intubation

Do not go above 35 (unless pt needs this to blow off CO2)

If the pt is triggering every breath, set RR just below spontaneous RR

After 30 min check an ABG and adjust based on PCO2

RR
○
5

Increase it only if hypoxemia or FIO2 > 60% is required to maintain oxygenation

If there is auto-PEEP, prolong the expiration time by increasing the I:E ratio

PEEP
○
What are the "best" ventilator settings if you get asked
•
Chap 27
Continuous positive airway pressure
○
Increases the FRC --> volume in the lungs at the end of expiration
○
Limited because it does not augment the tidal volume, limiting its use in respiratory failure
○
Cardiogenic pulmonary edema treatment
○
CPAP
•
High pressure level with inspiration, and low pressure with expiration

Bilevel positive airway pressure
○
Results in higher mean airway pressures than CPAP
○
No direct augmentation of TV, but can increase lung compliance which increases TV
○
IPAP = 10 (duration 3 s), EPAP = 5 are good initial settings
○
BIPAP
•
Patients who are candidates for non-invasive ventilation
•
Book Notes Page 20

21. Acute respiratory failure is not an immediate threat to life
○
There is no life threatening circulatory disorder (like shock)
○
Patient is awake or arousable and cooperative
○
Airway protective measures are intact
○
No hematemesis or recurrent vomiting
○
No facial anomaly or trauma
○
No obstruction that prevents a face mask from delivering O2
○
Patients who are candidates for non-invasive ventilation
•
COPD
○
Obesity hypoventilation syndrome
○
Asthma exacerbation
○
Cardiogenic pulmonary edema
○
ARDS (but limited success)
○
What diseases typically get this?
•
You fail non-invasive ventilation if after one hour there is a failure to improve gas exchange
•
Not a huge problem

NG tubes often placed, but not necessary

Gastric insufflation
○
Incidence was 8-10%, but this is less than the 19-22% seen with intubation

Nosocomial pneumonia
○
Adverse effects?
•
Chap 28
Smaller endotracheal tubes in adults (at least 7, preferably 8) impede the clearance of secretions and create
increased resistance when weaning from vent
•
If not visible, carina should be T4-T5
○
Tip of ET tube should be 3-5 cm above carina
•
For intubations don’t push the tube past 21 cm for women and 23 cm for men
•
One of the big reasons for trach after 2 weeks of intubation is laryngeal damage
•
It does reduce sedative requirements and promotes early mobilization
○
Early tracheostomy does not reduce incidence of ventilator acquired penumonia, and no reduction in mortality rate
•
If a trach tube is dislodged before the stoma tract matures (1 week), it closes very quick and false passages can be
had
•
Most cases are asymptomatic
○
Most feared complication of tracheostomy is tracheal stenosis, appears in the first 6 months after the tube is
removed
•
Usually detected by audible sounds during lung inflation
○
Rarely caused by the cuff, usually the result of nonuniform contact between the cuff and the wall of the
trachea, or dysfunction of the valve on the pilot balloon (where you blow up the ET cuff)
○
Take off vent and do BVM

Check tube position

Never blindly add air to the cuff (except for trach tube)

Troubleshoot
○
Cuff leaks
•
Chap 29
Lung infection is the most common nosocomial infection in the ICU patient (65%)
•
Over 90% of ICU-acquired pneumonias occur during mechanical ventilation, with 50% of those happening within 4
days of intubation
•
VAP may not be life threatening, but will prolong ventilation and ICU stay
•
Oral decontamination is not standard in all ventilator dependent pts
•
Fever or hypothermia
○
Leukocytosis or leukopenia
○
Increase in respiratory secretions or a change in character of the secretions
○
But only about 40% of pts with all these features have VAP
Clinical features of VAP
•
Book Notes Page 21

22. But only about 40% of pts with all these features have VAP
○
Tracheal aspirate with more than 10 squamous epithelial cells per low power field indicates there is contamination
with mouth secretions
•
Presence of macrophages (regardless of number) is evidence the specimen is from the lower respiratory tract
•
Bronchoalveolar lavage cultures have the highest overall accuracy for the diagnosis of pneumonia
•
The effusion is large or increasing in size
○
There is an air-fluid level in the effusion or a hydropneumothorax (indicating a bronchopleural fistula or
possible empyema)
○
The patient develops severe sepsis or septic shock
○
The pt is not responding to antimicrobial therapy
○
When do pleural effusions associated with pneumonia need intervention?
•
Pop/taz, carbepenem, or ceftaz or cefipime
○
Duration of therapy is 1 week of antibiotics (documented that 8 days is as good as 15 days)
○
Empiric VAP antibiotics
•
Chap 30
Patients who trigger ventilation breaths are more likely to preserve the strength of the diaphragm
•
Deep sedation and benzos for sedation are associated with delays in weaning from the vent
•
Adequate gas exchange (normal PCO2) at FIO2 of < 50%
○
Low levels of PEEP
○
No evidence of cardiac ischemia
○
No severe tachycardia (> 140)
○
No circulatory shock
○
No ongoing sepsis/fever
○
When is a pt ready for a wean?
•
d/c vent to obtain TV, RR, RR/TV ratio, and max inspiratory pressure
○
To help overcome resistance of tube, give low pressure levels

Pressure support

Uses a T-piece to decrease work of breathing

Theoretically advantage because it is better for pts with increased ventilatory demands, closer
approximation of normal conditions of breathing

Disconnect ventilator, and give high flow O2

Spontaneous breathing trial
○
How to wean?
•
But make sure rapid breathing not due to anxiety (try a sedative drug)

Signs of respiratory distress
○
Signs of respiratory weakness
○
What is failure of wean
•
Adequacy of gas exchange in the lungs
○
Adequacy of systemic oxygenation
○
What is success
•
Especially when pts are not triggering breaths

Mechanical ventilation
○
Critical illness neuromyopathy
○
Mag and phos specifically

Electrolyte depletion
○
Potential causes of respiratory muscle weakness
•
Max inspiratory pressure used to measure respiratory muscles
•
Thickness of diaphragm
○
Length of excursion of diaphragm during inspiration
○
Reliability of these measurements is unknown
○
Ultrasound is emerging as potential way to measure diaphragm strength
•
Work of breathing typically increases after extubation
•
Absence of air leak suggests a higher risk of upper airway obstruction

Cuff leak test measures the volume of inhaled gas that escapes through the larynx when the cuff is deflated
○
Can pretreat with steroids
Upper airway obstruction from laryngeal edema is a major cause of failed extubations
•
Book Notes Page 22

23. IV steroids for 12-24 hours --> 20-40 mg prednisolone q4-q6

Don’t do it right before, no evidence that single dose right before extubation helps

Can pretreat with steroids
○
80% get stridor within 30 min, but can be delayed up to 2 hours

Can treat with inhaled epi, but not proven for adults (proven for kids)

First sign of this is stridorous breathing after extubation
○
Chap 31
Skipped due to acid-base
•
Chap 32
Lactate in critically ill pts is increased uptake into the myocardium
•
Shock, lactate elevated correlates with increased mortality
○
Normalization of elevated lactate within 24 hours is a good marker for recovery
○
Lactate as a biomarker
•
Clinical shock syndrome
○
SIRS
○
High output HF

Wernicke encephalopathy

Peripheral neuropathy

Caused by a deficiency in thiamine pyrophosphate, serving as a cofactor for pyruvate
dehydrogrenase

Lactic acidosis

Thiamine deficiency
○
Metformin, antiretroviral meds, eoi, nitroprusside, and linezolid

Medications
○
Propylene glycol (can also be seen in drugs like lorazepam, diazepam, esmolol, nitro, and phenytoin)

Cyanide

CO

Toxidromes
○
Seizures
○
Hepatic insufficiency
○
Causes of hyperlactemia
•
Bicarb is NOT an effective buffer --> standard one used for lactic acidosis though
○
Bicarb can be harmful, can increase CO2 --> really just an acid load
○
Carbicarb --> less bicarb than standard bicarb, can help
○
Alkali therapy has no role except when deteriorating rapidly
○
Correcting lactic acidosis
•
If the K+ is < 3.3, do not give insulin until you replete K+
○
DKA K+
•
Chap 33
The most common acid base disturbance in hospitalized pts is metabolic alkalosis
•
Loss of H+ ions from ECF
○
Gain in bicarb in the ECF
○
Decrease in ECV
○
What can cause an alkalosis?
•
Most of bicarb in the kidney is reabsorbed in the proximal tubule
•
If chloride is depleted, bicarb gets reabsorbed and secretion of bicarb is inhibited; same with hypokalemia
•
Chloride depletion
○
Hypokalemia
○
Mineralocorticoid excess
○
Three principal causes of sustained metabolic acidosis are:
•
Chloride responsive
Chloride responsive vs chloride nonresponsive (determined by urinary chloride concentration)
•
Book Notes Page 23

24. Low urinary chloride

Loss of gastric secretions

Therapy with diuretics that promote urinary chloride excretion

Volume depletion

Laxative abuse

Causes

Improves with normal saline

Chloride responsive
○
Mineralocorticoid excess

Corrected with K+ repletion

Chloride resistant
○
Chap 34
Pts with AKI who require hemodialysis have a mortality of 50-70%
•
50% increase in serum creatinine and a decrease in urine output to 0.5 ml/kg/hr
○
That’s because it doesn’t, revised criteria shows a 0.3 mg/dL rise in creatinine over 48 hours

I feel like this doesn’t hold up now, its usually a 30% increase in creatinine
○
What defines an AKI?
•
Decrease in renal blood flow

30-40% of AKI cases

Prerenal
○
50% of AKI

Inflammatory (oxidative) injury to the epithelial cell lining of tubules

Damaged cells are sloughed into the lumen where they cause an obstruction

This obstruction creates a back pressure and decreases the GFR

Result of sepsis, radiocontrast dye, medications, or rhabdo

ATN

Inflammatory injury, but located in the renal interstitium

AIN

Renal
○
Obstruction

Only 10% of cases

Can be to the ureters or the urethra

Stones don’t cause this unless they block both ureters

Postrenal
○
categories
•
Sepsis
○
Major surgery
○
Hypovolemia
○
Low CO
○
Nephrotoxic agents
○
Most common causes overall
•
If it is < 20, evidence of prerenal
○
Unless diuretic therapy or CKD

If it is > 40, it is intrinsic
○
Urine sodium (spot)
•
In normal renal function this is 1%
○
If it is < 1%, prerenal
○
If it is > 2%, intrinsic (increase in Na excretion)
○
FeNa
•
Low <35% in prerenal
○
High > 50% in intrinsic
○
One big benefit is this is not affected by diuretics
○
FeUrea
•
Don’t use diuretics until prerenal cause is eliminated

Volume infusion to promote renal blood flow
○
Manage generally?
•
Book Notes Page 24

25. Don’t use diuretics until prerenal cause is eliminated

Stop any nephrotoxic meds
○
Treat any conditions that predispose to AKI
○
It can increase urine output and can be trialed to relieve fluid accumulation

IV furosemide does not improve renal function
○
BAD MEDICINE

Can have bad effects on hemodynamics (decrease splanchnic blood flow), AND immune function
(inhibits T cells), AND endocrine (inhibits TSH release)

Low dose dopamine (around 2 mcg/kg/min) can renally vasodilate
○
Stop nephrotoxic drugs
○
Manage intrarenal generally?
•
Incidence is 8-9%, appearing within 72 hours of scan

In the ED --> give 300-500 mL saline just before procedure

Prevent with IV hydration --> 100-150 mL/hr started 3-12 hours prior to procedure and continued for
6-24 hrs after

NAC has shown a 50% risk reduction --> but oral NAC which SUCKS

Contrast induced renal injury
○
Most are the result of a hypersensitivity drug reaction (antibiotics most common offender)

Infections can cause this too

Sterile pyuria and EOSINOPHILURIA

Recovery can take months, no specific treatment besides stopping the medication

Acute interstitial nephritis
○
Myoglobin can damage the renal tubular epithelial cells --> iron moiety in heme can cause oxidative cell
injury

Aggressive volume resuscitation

About 30% of pts need dialysis

Monitor K+ and phosphate levels, these are released by injured skeletal muscle

Myoglobinuric renal failure
○
ACS occurs when intraabdominal pressure rises above 20 mmHg and there is evidence of new organ
dysfunction

Traditionally associated with abdominal trauma, can be caused by large volume resus, gastric distension,
bowel obstruction, ileus, ascites, hepatomegaly, positive pressure breathing, and obesity

Kidney is the most frequently affected organ

MAP - IAP is the driving force of renal perfusion --> need to maintain this calc above 60

Measure IAP through a bladder cath

Sedation

Avoid elevating head more than 20 degrees

Avoid a positive fluid balange

Can surgically decompress --> but more of a last resort

Reducing IAP

Abdominal compartment syndrome
○
Specific conditions
•
Chap 35
Calculated plasma osmolality includes Na, glucose, and BUN
•
Effective osmolality does not include BUN, because an increase in BUN doesn’t increase the osmolality --> it will just
go right into cells
•
Plasma sodium accounts for 98% of the effective osmotic activity of the extracellular fluid
•
Loss of Na and H2O, with water loss > Na loss
○
Free water loss
○
Gain of sodium and free water, with Na gain > free water gain
○
Hypernatremia can be caused by 3 things
•
Low ECV = fluid management, isotonic saline
○
Normal ECV = replace H2O deficit slowly
○
High ECV = diuresis
○
Treat hypernatremia
•
Principal consequence of hypernatremia is an increase in the effective osmolality, drawing water out of the cells
•
Book Notes Page 25

26. This can result in hypernatremic encephalopathy, ranging from agitation and lethargy to coma and seizures
○
Principal consequence of hypernatremia is an increase in the effective osmolality, drawing water out of the cells
•
Excessive diuresis
○
Excessive sweat loss (in heat related illnesses)
○
Normal or accentuated fluid losses in elderly, debilitated patients
○
Common sources of hypotonic fluid losses
•
Current TBW = Normal TBW (60% of body weight in kg) X (140/current Pna)
○
H2O deficit = Normal TBW - Current TBW
○
Calculate the free water deficit
•
Volume = H2O deficit X (140/[Na] in IVF)
○
0.45% NaCl = 77 mEq/L of Na
○
You can replace about half of the free water deficit in the first 12-24 hrs
○
Correct the deficit
•
Printed 11/8
In central DI --> vasopression is given at 2-5 units q4-6 h
•
Chap 36
98% of total body potassium is in the cells
•
Most of the K+ that is filtered by the glomerulus is passively reabsorbed in the PCT
○
Controlled by aldosterone and plasma K+

K+ is secreted in the DCT and collecting ducts
○
Excreting K+
•
Beta-2 receptors are stimulated which helps move K+ into cells
○
But albuterol has a mild effects, drops serum K+ by 0.5
○
Moving K+
•
We have K+-sparing diuretics to avoid this
○
Remember this when trying to get rid of K+ long term
○
Leading cause of renal K+ loss is diuretics
•
Concentration of K+ in diarrhea is 15-40 mEq/L
○
Major cause of extrarenal K+ loss is diarrhea
•
U wave is the classic
○
Flipped T waves
○
Prolonged QT
○
None of these are specific
○
EKG changes in hypokalemia
•
Eliminate or treat anything that is promoting K+ shift into the cells
○
If you don’t have any of those, then replete with KCl
○
KCl is super osmotic, and needs to be diluted
○
Apparently safe to do up to 100 mEq/hour but you need a central line

Also don’t do something super fast into the SVC or it goes right into the heart

Add 20 mEq K+ to 100 mL of NS and then infuse over 1 hour
○
Manage HYPOkalemia
•
Blood sample clotting caused by blood going "too fast" into the tube, lysing, and then releasing the K+
○
Hyperkalemia in digitalis occurs only with acute toxicity, not chronic
○
Renal failure can cause it, but the GFR has to drop below 10 mL/min
○
Hyperkalemia
•
ACEi
○
ARB
○
K+ sparing diuretics
○
NSAIDs
○
Heparin
○
TMP-SMX
○
Drugs that impaire renal K+ excretion? (all inhibit RAAS)
•
Not a thing
Calcium is "theoretically" contraindicated in digitalis toxicity for "stone heart"
•
Book Notes Page 26

27. Not a thing
○
Temporary 30-60 min effect
○
10u insulin + 1 amp of D50 = 0.6 drop in K+
•
Albuterol dose to drop the K+ 0.5-1 mEq is 4x normal dose, DON’T USE
•
Short term infusions (even over 4 hours) don’t have an effect of K+
○
Bicarb can form complexes with calcium which can then destabilize the heart
○
Avoid bicarb for hyperkalemia
•
Kayexalate works by binding K+, and 6 hours is needed for maximum effect
•
Chap 37
Magnesium depletion can be caused by a whole bunch of things, seen in as many as 65% of ICU pts
•
Seen in 30% of pts

Aminoglycosides block mag reabsorption in the ascending LOH
○
Antibiotics that deplete mag are aminoglycosides, amphotericin B, and pentamidine
•
Malnutrition
○
Chronic diarrhea
○
Magnesium depletion in alcoholics
•
Can try magnesium in dixogin toxicity
○
Magnesium deficiency magnifies digoxins effect on the membrane pump, which will magnify the digitalis effect
•
Daily Mag maintenance therapy is 5 mg/kg
•
Start to replace mag when below 1.5
•
1st degree AV block --> complete heart block --> cardiac arrest
○
Mag is "natures physiologic calcium blocker"
○
Hemodialysis ideally, but in the moment Ca gluconate (1g over 2-3 min) can temporarily help
○
Hypermagnesemia EKG
•
Chap 38
Aminoglycosides and heparin are the most common ICU meds that can bind Ca and cause hypocalcemia
•
Most cases of hypocalcemia have no apparent adverse consequences
•
Isotonic saline recommended
○
But saline doesn’t correct hypercalcemia 70% of the time
○
40-80 mg IV lasix every 2 hours (in cases of volume overload)
○
Hypercalcemia can be treated with saline or furosemide
•
Impaired myocardiac contractility
○
Reduced CO
○
Reduced deformability of RBC
○
Depleted 2,3-DPG and thus shifted oxy-hb curve to the left
○
Reduces ATP availability
○
Hypophosphatemia effects
•
Chap 39
40% gallstones
○
30% alcohol
○
20% idiopathic
○
Drugs
○
Hypertriglyceridemia
○
Infections
○
Abdominal trauma
○
Causes of pancreatitis
•
If the pt is in the ICU its likely necrotizing pancreatitis
•
Antibiotic prophylaxis does not reduce the incidence or influence mortality
○
33% of pts with necrotizing pancreatitis develop infections, almost always gram negative
•
Abdominal compartment syndrome has been reported in as many as 55% of pts with severe pancreatitis
•
1/3rd of pts with SBP are asymptomatic
•
Preferred antibiotic for SBP is cefotaxime (2 g IV every 8 hours)
•
Book Notes Page 27

28. Or another 3rd gen cephalosporin
○
Preferred antibiotic for SBP is cefotaxime (2 g IV every 8 hours)
•
30% of pts with SBP develop hepatorenal syndrome
•
Use LR for fluid in pts with cirrhosis, limits Na and limits ascites
•
8.5 mg/kg for each L of fluid removed
○
Albumin dosing, start once > 5 L
•
Renal failure in pts with advanced cirrhosis
○
Result of hemodynamic alterations in the splanchnic and renal circulations
○
Renal failure DOESN’T respond to albumin infusions
○
Splanchnic vasoconstrictor (terlipressin)

Volume expander (albumin)

TIPS can improve renal function, but reserved for transplant candidates

Manage?
○
Hepatorenal syndrome
•
Cerebral edema, disordered thinking, and AMS
○
Usually in acute on chronic liver failure, some insult to the body causes it
○
Glutamine accumulation draws water into the astrocytes

Ammonia crosses the blood brain barrier and is taken up by astrocytes, which use ammonia to convert
glutamate to glutamine, and more
○
Should not have focal neuro deficits
○
Acidifies the bowel and reduces the ammonia burden

Lactulose

Less toxicity than neomycin

Rifamaxin

Treat?
○
Hepatic encephalopathy
•
Chap 40
1/3rd of pts are missing RUQ pain
○
Most common symptoms are fever, elevated bilirubin, hypotension, and sepsis
○
Hepatobiliary scan is the gold standard
○
Should start antibiotics and get surgery on board ASAP due to high mortality
○
90% of acalculous cholecystitis cases have positive blood cultures
•
Half as much using fidoxamycin as oral vanc
○
75% of relapses clear using the same therapy
○
C diff recurrences
•
Chap 41
Just having a urethral cath has a 3-8% incidence of bacteriuria per day
•
Cleaning catheter insertion sites can actually increase the risk of bacteriuria
•
Over 90% of pts in the ICU with a foley who have > 10^5 CFU have no symptoms
•
Fever/leukocytosis (often have another infection)
○
Cloudy urine
○
Pyuria
○
What are not reliable for diagnosis of CA-UTI?
•
Pip/taz
○
Carbapenem
○
Levofloxacin is 2nd line
○
Treat CA-UTI?
•
Chap 42
Antipyretic agents are useles in hyperthermia
•
Thermal sweating can achieve rates of 1-2 L/hr of loss
•
Cyproheptadine is oral only, but can crush and put down NG tube
•
Osborn waves on EKG are not specific for hypothermia, and can also occur with hypercalcemia, SAH, cerebral
•
Book Notes Page 28

29. Osborn waves on EKG are not specific for hypothermia, and can also occur with hypercalcemia, SAH, cerebral
injuries, and MI
•
Chap 43
98.6 degrees was derived from a study of axillary temperatures in 25k healthy adults in the 19th century
•
Elderly subjects have a mean body temp of 0.5 degrees celcius (1 degree F) lower than younger adults
•
Apparently an ICU fever is defines as > 101 unless neutropenic, then its 100.4
•
Fever can be a sign of inflammation and not infection
•
SIRS
○
Not actually caused by atelectasis, 75% of pts with post-op day 1 atelectasis have no fever

Early postop fever
○
PE
○
Platelet transfusion
○
Blood transfusion
○
Drug fever
○
Adrenal failure
○
Acalculous cholecystitis
○
Iatrogenic fever
○
Noninfectious causes of ICU-acquired fevers
•
Pneumonia
○
UTI
○
Bloodstream infection
○
Surgical site infections
○
4 infections account for 75% of ICU-acquired infections
•
Antipyretic therapy in sepsis was associated with higher mortality rates
○
Fever is important in sepsis, pts who are hypOthermic instead of hyperthermic have at least 2x the mortality
•
Likely that the inflammatory response to sepsis is causing the tachycardia, not the fever
•
1000 mg every 6 hours

Tylenol
○
600 mg q6h

Ibuprofen
○
0.5 mg/kg

Toradol
○
Fever suppression meds
•
Think twice about automatically suppressing a fever
•
Chap 44
Over 40% of hospitalized pts with delirium have psychotic symptoms
○
Hyperactive delirium is really rare besides alcohol withdrawal
○
Delirium is an acute confusional state with attention deficits, disordered thinking, and a fluctuating course
•
The CAM-ICU (confusion assessment method) is the most reliable tool for the detection of delirium
•
Load with 1 mcg/kg over 10 min, then drip at 0.2 - 0.7 mcg/kg/hr
○
Can cause bradycardia and hypotension
○
Sedation with dexmedetomidine (precedex) is associated with fewer episodes of delirium
•
Mortality is 5-15%
○
Initial control of DT's is ativan 2-4 mg IV every 5-10 min, then give 2-4 mg every few hours to keep pt calm
○
About 5% of pts who experience alcohol withdrawal get DT's
•
Give apneic oxygenation, but wait 6-7 min for PaCO2 levels to raise to 20 mmHg over baseline
○
If there is no spon breathing, pt is brain dead
○
Apnea test
•
Chap 45
Lorazepam 4 mg IV over 2 min (effect lasts for 12-24 hours)
○
Midazolam 10 mg IM
Treat seizures
•
Book Notes Page 29

30. Midazolam 10 mg IM
○
Phenytoin 20 mg/kg IV

Fosphenytoin 150 mg/min infusion

Stage 2 drugs
○
Valproic acid 20-40 mg/kg

Alternative drugs
○
Phenobarbital 5-15 mg/kg IV over 1 hour, then infuse 0.5-1 mg/kg/hr (max rate infusion of 3)
○
Midazolam 0.2 mg/kg load, infuse at 4-10 mg/kg/hr
○
Propofol 2-3 mg/kg load, bolus at 1-2 mg/kg as needed until seizure stops, then infuse at 3-10 mg/kg/hr for 24
hours
○
Treat refractory status epilepticus?
•
Chap 46
A stroke is unlikely if the NIHSS is < 10
•
TPA studies have shown improved neuro recovery but no improvement in survival
•
6% of pts who get TPA suffer from a brain bleed
•
After TPA, maintain BP < 180/105 for multiple days later to keep that risk low for hemorrhagic conversion
•
Deteriorating neuro status
○
Sudden rise in BP
○
Headache complaint
○
When do you stop TPA?
•
Chap 47
The main point is that malnutrition in critically ill pts is caused by metabolic derangements, so providing nutrients
alone will not correct the malnutrition until the metabolic derangements resolve
•
Chap 48
Tube feeds
•
Chap 49
Parennteral nutrition
•
Chap 50
Leading causes are severe sepsis and septic shock
○
Abrupt discontinuation of chronic steroid therapy

Adrenal hemorrhage from DIC

Drugs that inhibit the synthesis of cortisol or accelerate its metabolism

Noninfectious causes
○
Primary symptom is hypotension refractory to volume resusitation
○
Increase < 10 is the best predictor of adrenal suppression

A popular but unnecessary test is the rapid ACTH stim test --> random baseline cortisol level obtained, then pt
is given ACTH (cosyntropin) and then 1 hour later cortisol is drawn
○
Treat with 200-300 mg daily of IV hydrocortisone
○
Adrenal insufficiency is common in critically ill pts --> overall prevalence is 10-20%
•
Most thyroid issues in critically ill pts is not a result of thyroid disease
•
TSH can vary by as much as 40% over the day, highest at night
•
Chap 51
The most painful experiences for ICU pts are endotracheal suctioning and being turned in bed
•
Vitals signs show a poor correlation with patient reports of pain, and they can remain unchanged in the presence of
pain
•
Fentanyl
Opiates most consistently used in the ICU
•
Book Notes Page 30

31. More rapid onset of action (600x more lipid soluble than morphine)

Less risk of hypotension (doesn’t promote histamine release)

No concern in pts with renal failure

Infusion rate is 0.7 - 10 mcg/kg/hr

Fentanyl
○
Reduce maintenance dose by 50% in pts with renal failure

Active metabolites can accumulate in pts with renal failure

Infusion rate is 2 - 30 mg/hr

Morphine
○
No clinical advantage over morphine

Infusion rate is 0.5 - 3 mg/hr

Hydromorphone (Dilaudid)
○
Ultra short acting opioid

Lose analgesic effects 10 min after drip stopped, good for neuro checks

Remifentanil
○
Potential for neurotoxicity makes it a bad ICU choice

Meperidine (demerol)
○
Opiates not used as much
•
PCA meds = patient controlled analgesia
•
NSAID

IV dosing is 15mg

IM dosing is 30 mg (can cause hematomas)

Decrease dosing by 50% in elderly pts (> 65 YO)

Gastric mucosal injury and GI bleed are potential adverse events, avoid in those pts

Only give for up to 5 days

Ketorolac
○
IV 400-800 mg q6h

Can treat infinity days

Ibuprofen
○
1g q6h

No anti-inflammatory activity, downside in the ICU

Acetaminophen
○
Non-opiate pain meds
•
Gabapentin 600mg q8h
○
Carbamazepine 100 mg q6h
○
Neuropathic pain
•
Effects are seen within 1-2 minutes

Rapid clearance, gone within 1-2 hours

Preferred over ativan for continuous IV --> but max duration of 2 days due to drug accumulation

Part of the Cytochrome P450 pathway for degrading

Midazolam (versed)
○
Longer acting drug, lasts up to 6 hours

While commonly used in the ED for sedation of agitated patients, versed is a much better choice

Contains propylene glycol --> continuous infusions cause toxicity

Lorazepam
○
Dose dependent amnestic effect

Anticonvulsant effects

Good for drug/alcohol withdrawal pts

Benzos advantages
○
In one study in ICU pts, time to emerge from sedation was 30.2 hours for midazolam vs 4.4 hours
for lorazepam

Prolonged sedation

Bind GABA receptors which are known to be a part of delirium pathway

Delirium

Propylene glycol toxicity with ativan

Benzos disadvantages
○
Sedation benzos
•
Other sedation meds
•
Book Notes Page 31

32. Produces sedation in 1-2 min, and the effect lasts 5-8 min

Dosing based on IDEAL body weight

No adjustment for renal failure or moderate hepatic insufficiency

Respiratory depression and hypotension are the two downsides

Bradycardic heart failure, lactic acidosis, rhabdo, and acute renal failure

Usually occurs during prolonged, high dose propofol infusions

30% mortality rate

Reduce the risk by keeping dose below 5 mg/kg/hr (if you do go above, limit for < 2 days)

Propofol infusion syndrome

Propofol
○
Alpha 2 receptor agonist

"cooperative sedation"

Arousal is maintained, despite deep sedation levels --> very unique

Lower delirium prevalance vs benzos

Decrease HR, BP, and norepi levels

Dexmedetomidine (precedex)
○
More for agitation and delirium

Sedation evident in 10-20 min, lasting 3-4 hours

Bad side effects though --> EPS, NMS, and QT prolongation

Haldol
○
Same doseage

Known to have more rapid onset than haldol when studied in the ED agitation setting (even when
comparing 5 mg droperidol vs 10 mg haldol)

Onset similar (10 min IM), lasting 2-4 hours

Droperidol (better than haldol)
○
Other sedation meds
•
Chap 52
Bactericidal
○
Very active against gram negatives, including pseudomonas
○
Once daily dose based on ideal body weight and renal function
○
Affects the proximal tubulues

"obligate nephrotoxins" --> will develop renal impairment in all pts if treatment continues
○
Aminoglycosides
•
Plagued by toxic reactions

Used as a backup or for really bad fungal infections

IV only, given over 4 hours typically

Try to premedicate with tylenol and benadryl

70% of pts getting infusion get fever, chills, N, V, and rigors

Cr > 3 develops --> pause for a few days

Can cause renal injury that appears like RTA

Hypokalemia and hypomagnesemia are common

Amphotericin B
○
Fluconazole is largely devoid of serious toxicity

Triazoles (fluconazole, itraconazole, and voriconazole)
○
Very active against candida (more broad than fluconazole)

Caspofungin is a flagship drug, and equivalent to amphotericin for invasive candidiasis

No dose adjustment for renal impairment

Echinocandins (caspofungin, micafungin, and anidulafungin)
○
Antifungals
•
Incredibly broad
○
4 available ones: imipenem, meropenem, doripenem, and ertapenem
○
Ertapenem is the LEAST desirable one since it does not have pseudomonas activity
○
All require renal dose adjustment
○
Imipenem has a seizure risk (1-3% of pts who get the drug, usually in pts with hx of seizure disorder)
○
Do NOT cover MRSA
Carbapenems
•
Book Notes Page 32

33. Do NOT cover MRSA
○
Only available IV
○
4 generations
○
Most popular one if cefazolin (ancef)

First gen covers gram negatives, but not MRSA
○
Most popular is cefoxatin (mefoxin)

Second generation covers gram positive, but adds gram negative coverage
○
Most popular are ceftriaxone and ceftazidime (covers pseudomonas but not much gram + at all)

Third gen is not super good at gram positive, but very good at gram negative, also available ORALLY
○
Only drug in the class is cefepime (also covers pseudomonas)

Fourth gen have gram negative and gram positive
○
Ceftaroline

Fifth gen covers MRSA (in addition to gram +/-)
○
Need to be adjusted for renal failure
○
Cephalosporins
•
Only 3 are used --> ciprofloxacin, levofloxacin, and moxifloxacin (bolded the "newer ones" which cover strep
and atypical infections)
○
Lots of resistance to these, most used for non-ICU treatment
○
Need to renally dose adjust cipro and levo --> moxifloxacin is metabolized in the liver
○
Ciprofloxacin interferes with theophylline and warfarin, and can increase those drug levels
○
Technically can prolong the QT, and I guess rupture tendons
○
Fluoroquinolones
•
Really not a factor in the ICU
○
Extended-spectrum penicillins like ampicillin and amoxicillin, pip/taz are used though
○
Need to renally dose

Pip/Taz contains piperacillin in an 8:1 ratio with tazobactam
○
Penicillins
•
Basically covers all gram positive cocci and MRSA
○
Will increase resistance

As much as 2/3rd of vanco use in the ICU is not goal directed, but more so "empiric coverage"
○
Has to be renally dosed --> let pharmacy handle that
○
Red man syndrome --> just slow the infusion rate down to less than 10 mg/min
○
Vancomycin
•
Covers MRSA and vanco-resistant enterococci (VRE)

Can cause serotonin syndrome

Linezolid
○
MRSA and VRE coverage

Renally dose

Can NOT be used for pneumonias --> inactivated by lung surfactant

Skeletal muscle myopathy is primary toxicity --> keep track of a CK level

Daptomycin
○
Technically can cover VRE, but had a lot of bad side effects like myalgias and arthralgias

Quinupristin-Dalfopristin
○
Random
•
Chap 53
○
Catecholamines
•
Book Notes Page 33

34. ○
Primarily a beta 1 agonist, but has weak B2 action

Thus the HR increases, while there is peripheral vasodilation thanks to beta-2

BP usually unchanged, since even though there is an increased SV, there is a decreased SVR

Can be an issue in HF

Cardiac stimulation increases cardiac work and myocardial O2 consumption

Preferred for cardiogenic shock, but often times needs norepi with it

Usually 5-20 µg/kg/min

Hard cap at 40 µg/kg/min

Started at infusion rate of 3-5 µg/kg/min

Can occasionally cause significant tachycardia

Contraindicated in HCOM pts

Dobutamine
○
IGNORE

Literally the crappiest drug in the world

If your ICU is using this, ignore everything they are doing

The whole "low, medium, high" infusion rate has been shown to not be real

Sinus tach and a-fib are reported in 25% of pts receiving dopamine infusions

Dopamine
○
Stimulates both alpha and beta receptors

Nonuniform vasoconstriction --> mostly in the subcutaneous, renal, and splanchnic circulations

 Initial dosing typically 1-2 µg/min, but get up to 5-15 µg/min fairly quickly
 Max dose 60 µg/min
 Increases serum lactate due to increased glycolysis (not technically an adverse effect)
 Adverse effects --> can cause tachycardia, hyperglycemia, damage to the bowels via splanchnic
hypoperfusion
Epinephrine
○
 Principally a beta-2 receptor mediated effect, but also has some weak B1 activity
 Basically now its first line for everything
 Start at 5-10 µg/min --> titrate to MAP of 60-65
 Cap at 60 µg/min, but be thinking about adding a second pressor at 15-20 µg/min
○ Norepi
 Pure alpha
 Reflex bradycardia, can decrease cardiac output
 Good for spinal shock
 Can be used as a push dose pressor
 Infuse initially at 0.1-0.2 mg/min
○ Phenylephrine
 Vasoconstrictor effects mediated by V1 receptors on smooth muscle
 Really only works in pts with hypotension (normal people don’t have a BP rise if they get it)
 Never do this alone, always pair with something else, usually norepi
 0.01-0.04 u/hr (0.03 u/hr most popular dose)
 Adverse effects are quite rare
○ Vasopressin
Terlipressin
• Adjunctive pressors
Book Notes Page 34

35.  Vasopressin analog that is a selective V1 receptor
 Longer duration of action --> single dose of IV 1-2 mg can raise BP for 4 hours
 Increased risk of ischemic effects, and cant really reverse it
○ Terlipressin
○ Dose dependent dilation of arteries and veins
○ NO produces muscle relaxation by promoting cGMP formation
 Higher infusion rates start to dilate arteries
○ Venodilation predominates at infusion rates < 50 µg/min
○ As much as 80% of the drug can be lost with standard plastic infusion systems --> this is why it is in a glass
bottle
○ Initial infusion rate of 5-10 µg/min, can be increased with max of about 200 µg/min (usually for flash
pulmonary edema)
○ Never give in preload dependent states
○ Tolerance is well described, can appear after 24-48 hours on a drip --> drug free interval of at least 6 hours is
needed
• Nitroglycerin
Treat with 5-10 mg phentolamine in 15 mL of saline
○
Extravasation of pressors?
•
Chap 54+ 55 are on Drug overdoses (skipped because toxicology is a whole separate book to review)
Book Notes Page 35