ISSN: 1524-4539
Copyright ? 2005 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online
72514
Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX
DOI: 10.1161/CIRCULATIONAHA.105.166559
2005;112;78-83; originally published online Nov 28, 2005; Circulation
Part 7.4: Monitoring and Medications
http://circ.ahajournals.org/cgi/content/full/112/24_suppl/IV-78
located on the World Wide Web at:
The online version of this article, along with updated information and services, is
http://www.lww.com/static/html/reprints.html
Reprints: Information about reprints can be found online at
journalpermissions@lww.com
Street, Baltimore, MD 21202-2436. Phone 410-5280-4050. Fax: 410-528-8550. Email:
Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, 351 West Camden
http://circ.ahajournals.org/subsriptions/
Subscriptions: Information about subscribing to Circulation is online at
by on February 21, 2006 circ.ahajournals.orgDownloaded from
Part 7.4: Monitoring and Medications
T
his section provides an overview of monitoring techniques
and medications that may be useful during CPR and in the
immediate prearrest and postarrest settings.
Monitoring Immediately Before, During, and
After Arrest
Assessment During CPR
At present there are no reliable clinical criteria that clinicians
can use to assess the efficacy of CPR. Although end-tidal CO
2
serves as an indicator of cardiac output produced by chest
compressions and may indicate return of spontaneous circu-
lation (ROSC),
1,2
there is little other technology available to
provide real-time feedback on the effectiveness of CPR.
Assessment of Hemodynamics
Coronary Perfusion Pressure
Coronary perfusion pressure (CPPH11005aortic relaxation [diastolic]
pressure minus right atrial relaxation phase blood pressure)
during CPR correlates with both myocardial blood flow and
ROSC (LOE 3).
3,4
A CPP of H1135015 mm Hg is predictive of
ROSC. Increased CPP correlates with improved 24-hour sur-
vival rates in animal studies (LOE 6)
5
and is associated with
improved myocardial blood flow and ROSC in animal studies of
epinephrine, vasopressin, and angiotensin II (LOE 6).
5–7
When intra-arterial monitoring is in place during the
resuscitative effort (eg, in an intensive care setting), the
clinician should try to maximize arterial diastolic pressures to
achieve an optimal CPP. Assuming a right atrial diastolic
pressure of 10 mm Hg means that the aortic diastolic pressure
should ideally be at least 30 mm Hg to maintain a CPP of
H1135020 mm Hg during CPR. Unfortunately such monitoring is
rarely available outside the intensive care environment.
Pulses
Clinicians frequently try to palpate arterial pulses during
chest compressions to assess the effectiveness of compres-
sions. No studies have shown the validity or clinical utility of
checking pulses during ongoing CPR. Because there are no
valves in the inferior vena cava, retrograde blood flow into
the venous system may produce femoral vein pulsations.
8
Thus palpation of a pulse in the femoral triangle may indicate
venous rather than arterial blood flow. Carotid pulsations
during CPR do not indicate the efficacy of coronary blood
flow or myocardial or cerebral perfusion during CPR.
Assessment of Respiratory Gases
Arterial Blood Gases
Arterial blood gas monitoring during cardiac arrest is not a
reliable indicator of the severity of tissue hypoxemia, hyper-
carbia (and therefore the adequacy of ventilation during
CPR), or tissue acidosis. This conclusion is supported by 1
case series (LOE 5)
9
and 10 case reports
10–19
that showed that
arterial blood gas values are an inaccurate indicator of the
magnitude of tissue acidosis during cardiac arrest and CPR
both in and out of hospital.
Oximetry
During cardiac arrest, pulse oximetry will not function
because pulsatile blood flow is inadequate in peripheral tissue
beds. But pulse oximetry is commonly used in emergency
departments and critical care units for monitoring patients
who are not in arrest because it provides a simple, continuous
method of tracking oxyhemoglobin saturation. Normal pulse
oximetry saturation, however, does not ensure adequate
systemic oxygen delivery because it does not calculate the
total oxygen content (O
2
bound to hemoglobin H11001 dissolved
O
2
) and adequacy of blood flow (cardiac output).
Tissue oxygen tension is not commonly evaluated during
CPR, but it may provide a mechanism to assess tissue
perfusion because transconjunctival oxygen tension falls
rapidly with cardiac arrest and returns to baseline when
spontaneous circulation is restored.
20,21
End-Tidal CO
2
Monitoring
End-tidal CO
2
monitoring is a safe and effective noninvasive
indicator of cardiac output during CPR and may be an early
indicator of ROSC in intubated patients. During cardiac arrest
CO
2
continues to be generated throughout the body. The
major determinant of CO
2
excretion is its rate of delivery
from the peripheral production sites to the lungs. In the
low-flow state during CPR, ventilation is relatively high
compared with blood flow, so that the end-tidal CO
2
concen-
tration is low. If ventilation is reasonably constant, then
changes in end-tidal CO
2
concentration reflect changes in
cardiac output.
Eight case series have shown that patients who were
successfully resuscitated from cardiac arrest had significantly
higher end-tidal CO
2
levels than patients who could not be
resuscitated (LOE 5).
2,22–28
Capnometry can also be used as
an early indicator of ROSC (LOE 5
29,30
; LOE 6
31
).
In case series totaling 744 intubated adults in cardiac arrest
receiving CPR who had a maximum end-tidal CO
2
of
H1102110 mm Hg, the prognosis was poor even if CPR was
optimized (LOE 5).
1,2,24,25,32,33
But this prognostic indicator
was unreliable immediately after starting CPR in 4 studies
(LOE 5)
1,2,32,33
that showed no difference in rates of ROSC
and survival in those with an initial end-tidal CO
2
of
H1102110 mm Hg compared with higher end-tidal CO
2
. Five
patients achieved ROSC (one survived to discharge) despite
an initial end-tidal CO
2
of H1102110 mm Hg.
In summary, end-tidal CO
2
monitoring during cardiac
arrest can be useful as a noninvasive indicator of cardiac
output generated during CPR (Class IIa). Further research is
needed to define the capability of end-tidal CO
2
monitoring to
(Circulation. 2005;112:IV-78-IV-83.)
? 2005 American Heart Association.
This special supplement to Circulation is freely available at
http://www.circulationaha.org
DOI: 10.1161/CIRCULATIONAHA.105.166559
IV-78
guide more aggressive interventions or a decision to abandon
resuscitative efforts.
In the patient with ROSC, continuous or intermittent
monitoring of end-tidal CO
2
provides assurance that the
endotracheal tube is maintained in the trachea. End-tidal CO
2
can guide ventilation, especially when correlated with the
PaCO
2
from an arterial blood gas measurement.
Medications for Cardiovascular Support
Vasoactive drugs may be administered immediately before,
during, and after an arrest to support cardiac output, espe-
cially blood flow to the heart and brain. Drugs may be
selected to improve heart rate (chronotropic effects), myocar-
dial contractility (inotropic effects), or arterial pressure (va-
soconstrictive effects), or to reduce afterload (vasodilator
effects). Unfortunately many adrenergic drugs are not selec-
tive and may increase or decrease heart rate and afterload,
increase cardiac arrhythmias, and increase myocardial ische-
mia by creating a mismatch between myocardial oxygen
demand and delivery. Myocardial ischemia, in turn, may
decrease heart function. Moreover, some agents may also
have metabolic effects that increase blood glucose, lactate,
and metabolic rate.
Specific drug infusion rates cannot be recommended be-
cause of variations in pharmacokinetics (relation between
drug dose and concentration) and pharmacodynamics (rela-
tion between drug concentration and effect) in critically ill
patients,
34,35
so initial dose ranges are listed below. Vasoac-
tive drugs must be titrated at the bedside to secure the
intended effect while limiting side effects. Providers must
also be aware of the concentrations delivered and compati-
bilities with previously and concurrently administered drugs.
In general, adrenergic drugs should not be mixed with
sodium bicarbonate or other alkaline solutions in the intrave-
nous (IV) line because there is evidence that adrenergic
agents are inactivated in alkaline solutions.
36,37
Norepineph-
rine (levarterenol) and other catecholamines that activate
H9251-adrenergic receptors may produce tissue necrosis if extrav-
asation occurs. If extravasation develops, infiltrate 5 to 10 mg
of phentolamine diluted in 10 to 15 mL of saline into the site
of extravasation as soon as possible to prevent tissue death
and sloughing.
Epinephrine
The use of epinephrine in cardiac arrest is discussed in Part
7.2: “Management of Cardiac Arrest.” Epinephrine can also
be used in patients who are not in cardiac arrest but who
require inotropic or vasopressor support. For example, epi-
nephrine is considered Class IIb for symptomatic bradycardia
if atropine and transcutaneous pacing fail or pacing is not
available (eg, in the out-of-hospital setting). It may also be
used in cases of anaphylaxis associated with hemodynamic
instability or respiratory distress.
38
To create a continuous infusion of epinephrine hydrochlo-
ride for treatment of bradycardia or hypotension, add 1 mg (1
mL of a 1:1000 solution) to 500 mL of normal saline or D
5
W.
The initial dose for adults is 1 H9262g/min titrated to the desired
hemodynamic response, which is typically achieved in doses
of2to10H9262g/min. Note that this is the nonarrest infusion
preparation and dose (ie, for bradycardia or hypotension).
Vasopressin
The use of vasopressin in cardiac arrest is discussed in Part
7.2. Like epinephrine, vasopressin may be used in prearrest
and postarrest conditions. Vasopressin has been used for
management of vasodilatory shock, such as septic shock and
sepsis syndrome.
39,40
Standard therapy for vasodilatory septic
shock includes antimicrobial agents, intravascular volume
expansion, vasopressors, and inotropic agents that increase
myocardial contractility. Inotropic agents and vasoconstrictor
drugs that are commonly used in this setting, however, may
have a diminished vasopressor action.
41
If conventional
adrenergic vasopressor drugs are ineffective, a continuous
infusion of vasopressin may be beneficial (Class IIb).
42
Norepinephrine
Norepinephrine (levarterenol) is a naturally occurring potent
vasoconstrictor and inotropic agent. Cardiac output may
increase or decrease in response to norepinephrine, depending
on vascular resistance, the functional state of the left ventri-
cle, and reflex responses (eg, those mediated by carotid and
aortic baroreceptors). Norepinephrine usually induces renal
and mesenteric vasoconstriction; in sepsis, however, norepi-
nephrine improves renal blood flow and urine output.
43,44
It
may be effective for management of patients with severe
hypotension (eg, systolic blood pressure H1102170 mm Hg) and a
low total peripheral resistance who fail to respond to less
potent adrenergic drugs such as dopamine, phenylephrine, or
methoxamine.
Norepinephrine is relatively contraindicated in patients
with hypovolemia. It may increase myocardial oxygen re-
quirements, mandating cautious use in patients with ischemic
heart disease. As noted above, extravasation may cause
ischemic necrosis and sloughing of superficial tissues and
must be treated promptly.
Norepinephrine is administered by adding 4 mg of norepi-
nephrine or 8 mg of norepinephrine bitartrate (1 mg of norepi-
nephrine is equivalent to 2 mg of norepinephrine bitartrate) to
250 mL of D
5
W or 5% dextrose in normal saline (but not in
normal saline alone), resulting in a concentration of 16 H9262g/mL of
norepinephrine or 32 H9262g/mL of norepinephrine bitartrate. The
initial dose of norepinephrine is 0.5 to 1 H9262g/min titrated to effect.
It should not be administered in the same IV line as alkaline
solutions, which may inactivate it.
Dopamine
Dopamine hydrochloride is a catecholamine-like agent and a
chemical precursor of norepinephrine that stimulates both H9251-
and H9252-adrenergic receptors. In addition, there are receptors
specific for this compound (DA
1
,DA
2
dopaminergic recep-
tors). Physiologically dopamine stimulates the heart through
both H9251- and H9252-receptors. Pharmacologically dopamine is both
a potent adrenergic receptor agonist and a strong peripheral
dopamine receptor agonist. These effects are dose dependent.
During resuscitation dopamine is often used to treat hypo-
tension, especially if it is associated with symptomatic
bradycardia or after ROSC. Dopamine in combination with
other agents, including dobutamine, remains an option for
Part 7.4: Monitoring and Medications IV-79
management of postresuscitation hypotension. If hypotension
persists after filling pressure (ie, intravascular volume) is
optimized, drugs with combined inotropic and vasopressor
actions like epinephrine or norepinephrine may be used.
Positive effects include increases in both cardiac output and
arterial perfusion pressure. Although low-dose dopamine
infusion has been frequently recommended to maintain renal
blood flow or improve renal function, more recent data has
failed to show a beneficial effect from such therapy.
45,46
The usual dose of dopamine ranges from 2 to 20 H9262g/kg per
minute. DosesH1102210 to 20 H9262g/kg per minute may be associated
with systemic and splanchnic vasoconstriction. Higher doses
of dopamine, like all adrenergic vasoconstrictor drugs, can be
associated with adverse effects on splanchnic perfusion in
some patients.
Dobutamine
Dobutamine hydrochloride is a synthetic catecholamine and
potent inotropic agent useful for treatment of severe systolic
heart failure. Dobutamine has complex pharmacology be-
cause of the effects of the different racemic components. The
(H11001) isomer is a potent H9252-adrenergic agonist, whereas the (H11002)
isomer is a potent H9251
1
-agonist.
47
The vasodilating H9252
2
-
adrenergic effects of the (H11001) isomer counterbalance the
vasoconstricting H9251-adrenergic effects, often leading to little
change or a reduction in systemic vascular resistance. The
beneficial effects of dobutamine may be associated with
decreased left ventricular filling pressure. In addition to its
direct inotropic effects, dobutamine may further increase
stroke volume through reflex peripheral vasodilation (barore-
ceptor mediated), reducing ventricular afterload, so that
arterial pressure is unchanged or may fall even though cardiac
output increases. Hemodynamic end points rather than a
specific dose should be used to optimize treatment with
dobutamine.
The usual dose of dobutamine ranges from 2 to 20 H9262g/kg
per minute; however, there is a wide variation in individual
response to the drug in critically ill patients. Elderly patients
may have a significantly decreased response to dobutamine.
At doses H1102220 H9262g/kg per minute, increases in heart rate of
H1102210% may induce or exacerbate myocardial ischemia. Doses
of dobutamine as high as 40 H9262g/kg per minute have been
used, but such doses may greatly increase adverse effects,
especially tachycardia and hypotension.
Inodilators (Inamrinone and Milrinone)
Inamrinone (formerly amrinone) and milrinone are phospho-
diesterase III inhibitors that have inotropic and vasodilatory
properties. Phosphodiesterase inhibitors are often used in
conjunction with catecholamines for severe heart failure,
cardiogenic shock, and other forms of shock unresponsive to
catecholamine therapy alone. Optimal use requires hemody-
namic monitoring. These drugs are contraindicated in patients
with heart valve stenosis that limits cardiac output.
Inamrinone is administered as a loading dose of 0.75
mg/kg over 10 to 15 minutes (may give over 2 to 3 minutes
if no left ventricular dysfunction) followed by an infusion of
5to15H9262g/kg per minute, titrated to clinical effect. An
additional bolus may be given in 30 minutes.
Milrinone is more often used today because it has a shorter
half-life than inamrinone and is less likely to cause thrombo-
cytopenia.
48,49
Milrinone is renally excreted with a half-life of
around 1
1
?2 to 2 hours, so it requires 4
1
?2 to 6 hours to achieve
near–steady state concentrations if given without a loading
dose. A slow milrinone IV loading dose (50 H9262g/kg over 10
minutes) is followed by an IV infusion at a rate of 0.375 to
0.75 H9262g/kg per minute (375 to 750 ng/kg per minute) for 2 to
3 days. In renal failure the dose should be reduced. Adverse
effects include nausea, vomiting, and hypotension.
Calcium
Although calcium ions play a critical role in myocardial
contractile performance and impulse formation, retrospective
and prospective studies in the cardiac arrest setting have
shown no benefit from calcium administration.
50,51
Further-
more, high serum calcium levels induced by calcium admin-
istration may be detrimental. For this reason, calcium should
not be used routinely to support circulation in the setting of
cardiac arrest. When hyperkalemia, ionized hypocalcemia
(eg, after multiple blood transfusions), or calcium channel
blocker toxicity is present, use of calcium is probably
helpful.
52
Ideally, ionized calcium concentration should be
measured because total calcium concentration does not cor-
relate well with ionized concentration in critically ill
patients.
53,54
When necessary, a 10% solution (100 mg/mL) of calcium
chloride can be given in a dose of 8 to 16 mg/kg of the salt
(usually 5 to 10 mL) and repeated as necessary. (The 10%
solution contains 1.36 mEq of calcium or 27.2 mg elemental
calcium per milliliter.)
Digitalis
Digitalis preparations have limited use as inotropic agents in
emergency cardiovascular care. Digitalis decreases the ven-
tricular rate in some patients with atrial flutter or fibrillation
by slowing atrioventricular nodal conduction. The toxic to
therapeutic ratio is narrow, especially when potassium deple-
tion is present. Digitalis toxicity may cause serious ventric-
ular arrhythmias and precipitate cardiac arrest. Digoxin-
specific antibody is available for the treatment of serious
toxicity (Digibind, Digitalis Antidote BM).
Nitroglycerin
Nitrates are used for their ability to relax vascular smooth
muscle. Nitroglycerin is the initial treatment of choice for
suspected ischemic-type pain or discomfort (see Part 8:
“Stabilization of the Patient With Acute Coronary
Syndromes”).
IV nitroglycerin is also an effective adjunct in the treat-
ment of congestive heart failure from any cause,
55
and it may
be useful in hypertensive emergencies, particularly if related
to volume overload. The action of nitroglycerin is mediated
through local endothelial production of nitric oxide, particu-
larly in the venous capacitance system. Nitroglycerin is most
effective in patients with increased intravascular volume.
Hypovolemia blunts the beneficial hemodynamic effects of
nitroglycerin and increases the risk of hypotension; nitrate-
induced hypotension typically responds well to fluid replace-
ment therapy. Other potential complications of use of IV
IV-80 Circulation December 13, 2005
nitroglycerin are tachycardia, paradoxical bradycardia, hy-
poxemia caused by increased pulmonary ventilation-
perfusion mismatch, and headache. Nitroglycerin should be
avoided with bradycardia and extreme tachycardia or within
24 to 48 hours of the use of phosphodiesterase inhibitors to
treat erectile dysfunction.
Nitroglycerin is administered by continuous infusion (ni-
troglycerin 50 or 100 mg in 250 mL of D
5
W or 0.9% sodium
chloride) at 10 to 20 H9262g/min and increased by 5 to 10 H9262g/min
every 5 to 10 minutes until the desired hemodynamic or
clinical response occurs. Low doses (30 to 40 H9262g/min)
predominantly produce venodilatation; high doses (H11350150
H9262g/min) provide arteriolar dilatation. Uninterrupted adminis-
tration of nitroglycerin (H1102224 hours) produces tolerance.
56
Sodium Nitroprusside
Sodium nitroprusside is a potent, rapid-acting, direct periph-
eral vasodilator useful in the treatment of severe heart failure
and hypertensive emergencies.
57
Its direct venodilatory ef-
fects decrease right and left ventricular filling pressure by
increasing venous compliance. The net effect on venous
return (preload) depends on the intravascular volume. In
many patients cardiac output improves secondary to the
afterload-reducing effects of nitroprusside, meaning that ve-
nous return must also increase, but the latter occurs at a lower
end-diastolic pressure, resulting in relief of pulmonary con-
gestion and reduced left ventricular volume and pressure.
Arteriolar relaxation causes decreases in peripheral arterial
resistance (afterload), resulting in enhanced systolic emptying
with reduced left ventricular volume and wall stress and
reduced myocardial oxygen consumption. In the presence of
hypovolemia, nitroprusside can cause hypotension with reflex
tachycardia. Invasive hemodynamic monitoring is useful
during nitroprusside therapy.
Although nitroprusside may be useful for the treatment of
pulmonary artery hypertension, it reverses hypoxic pulmo-
nary vasoconstriction in patients with pulmonary disease (eg,
pneumonia, adult respiratory distress syndrome). The latter
effect may exacerbate intrapulmonary shunting, resulting in
worse hypoxemia. The major complication of nitroprusside is
hypotension. Patients may also complain of headaches, nau-
sea, vomiting, and abdominal cramps.
Nitroprusside is rapidly metabolized by nonenzymatic
means to cyanide, which is then detoxified in the liver and
kidney to thiocyanate. Cyanide is also metabolized by form-
ing a complex with vitamin B
12
.
58
Thiocyanate undergoes
renal elimination. Patients with hepatic or renal insufficiency
and patients requiring H110223 H9262g/kg per minute for more than 72
hours may accumulate cyanide or thiocyanate, and they
should be monitored for signs of cyanide or thiocyanate
intoxication, such as metabolic acidosis.
59
When thiocyanate
concentrations exceed 12 mg/dL, toxicity is manifested as
confusion, hyperreflexia, and ultimately convulsions. Treat-
ment of elevated cyanide or thiocyanate levels includes
immediate discontinuation of the infusion. If the patient is
experiencing signs and symptoms of cyanide toxicity, sodium
nitrite and sodium thiosulfate should be administered.
Sodium nitroprusside is prepared by adding 50 or 100 mg
to 250 mL of D
5
W. The solution and tubing should be
wrapped in opaque material because nitroprusside deterio-
rates when exposed to light. The recommended dosing range
for sodium nitroprusside is 0.1 to 5 H9262g/kg per minute, but
higher doses (up to 10 H9262g/kg per minute) may be needed.
IV Fluid Administration
Limited evidence is available to guide therapy. Volume
loading during cardiac arrest causes an increase in right atrial
pressure relative to aortic pressure,
60
which can have the
detrimental effect of decreasing CPP. The increase in CPP
produced by epinephrine during CPR is not augmented by
either an IV or intra-aortic fluid bolus in experimental CPR in
dogs.
61
If cardiac arrest is associated with extreme volume losses,
hypovolemic arrest should be suspected. These patients
present with signs of circulatory shock advancing to pulseless
electrical activity (PEA). In these settings intravascular vol-
ume should be promptly restored. In the absence of human
studies the treatment of PEA arrest with volume repletion is
based on evidence from animal studies.
60–63
Current evidence
in patients presenting with ventricular fibrillation (VF) nei-
ther supports nor refutes the use of routine IV fluids (Class
Indeterminate).
Animal studies suggest that hypertonic saline may improve
survival from VF when compared with normal saline.
64,65
Human studies are needed, however, before the use of
hypertonic saline can be recommended. If fluids are admin-
istered during an arrest, solutions containing dextrose should
be avoided unless there is evidence of hypoglycemia.
Sodium Bicarbonate
Tissue acidosis and resulting acidemia during cardiac arrest
and resuscitation are dynamic processes resulting from no
blood flow during arrest and low blood flow during CPR.
These processes are affected by the duration of cardiac arrest,
the level of blood flow, and the arterial oxygen content during
CPR. Restoration of oxygen content with appropriate venti-
lation with oxygen, support of some tissue perfusion and
some cardiac output with good chest compressions, then rapid
ROSC are the mainstays of restoring acid-base balance
during cardiac arrest.
Little data supports therapy with buffers during cardiac
arrest. There is no evidence that bicarbonate improves like-
lihood of defibrillation or survival rates in animals with VF
cardiac arrest. A wide variety of adverse effects have been
linked to bicarbonate administration during cardiac arrest.
Bicarbonate compromises CPP by reducing systemic vascular
resistance.
66
It can create extracellular alkalosis that will shift
the oxyhemoglobin saturation curve and inhibits oxygen
release. It can produce hypernatremia and therefore hyperos-
molarity. It produces excess carbon dioxide, which freely
diffuses into myocardial and cerebral cells and may paradox-
ically contribute to intracellular acidosis.
67
It can exacerbate
central venous acidosis and may inactivate simultaneously
administered catecholamines.
In some special resuscitation situations, such as preexisting
metabolic acidosis, hyperkalemia, or tricyclic antidepressant
overdose, bicarbonate can be beneficial (see Part 10: “Special
Resuscitation Situations”).
Part 7.4: Monitoring and Medications IV-81
Sodium bicarbonate is not considered a first-line agent for
the patient in cardiac arrest. When bicarbonate is used for
special situations, an initial dose of 1 mEq/kg is typical.
Whenever possible, bicarbonate therapy should be guided by
the bicarbonate concentration or calculated base deficit ob-
tained from blood gas analysis or laboratory measurement. To
minimize the risk of iatrogenically induced alkalosis, provid-
ers should not attempt complete correction of the calculated
base deficit. Other non–CO
2
-generating buffers such as Car-
bicarb, Tham, or Tribonat have shown potential for minimiz-
ing some adverse effects of sodium bicarbonate, including
CO
2
generation, hyperosmolarity, hypernatremia, hypoglyce-
mia, intracellular acidosis, myocardial acidosis, and “over-
shoot” alkalosis.
68–70
But clinical experience is greatly lim-
ited and outcome studies are lacking.
Diuretics
Furosemide is a potent diuretic agent that inhibits reabsorp-
tion of sodium in the proximal and distal renal tubule and the
loop of Henle. Furosemide has little or no direct vascular
effect, but it reduces venous and pulmonary vascular resis-
tance through stimulation of local prostaglandin production
71
and therefore may be very useful in the treatment of pulmo-
nary edema. The vascular effects occur within 5 minutes,
whereas diuresis is delayed. Although often used in acute
renal failure to stimulate increased urine output, there is no
data to support this indication, and some data suggests an
association with increased mortality.
72
The initial dose of
furosemide is 0.5 to 1 mg/kg IV injected slowly.
Newer “loop” diuretics that have an action similar to that
of furosemide and a similar profile of side effects include
torsemide and bumetanide. In patients who do not respond to
high doses of loop diuretics alone, a combination of such
agents together with the administration of “proximal tubule”–
acting thiazide diuretics (such as chlorothiazide or metola-
zone) may be effective. Such combinations require close
observation with serial measurement of serum electrolytes to
avoid profound potassium depletion from their use.
Summary
Maintenance of adequate CPP is linked with survival follow-
ing CPR. Rescuers can support adequate CPP by providing
compressions of adequate rate and depth, allowing full chest
recoil after each compression, avoiding overventilation, and
minimizing interruptions in chest compressions (see Part 4:
“Adult Basic Life Support”). Exhaled CO
2
can be a useful
indicator of cardiac output produced by chest compressions.
Pulse oximetry is not helpful during arrest, but it should be
monitored in high-risk patients to ensure adequate oxygena-
tion. No medications have been shown to improve neurolog-
ically intact survival from cardiac arrest. Better tools are
needed to monitor effectiveness of CPR.
References
1. Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and
outcome of out-of-hospital cardiac arrest. N Engl J Med. 1997;337:
301–306.
2. Wayne MA, Levine RL, Miller CC. Use of end-tidal carbon dioxide to
predict outcome in prehospital cardiac arrest. Ann Emerg Med. 1995;25:
762–767.
3. Paradis NA, Martin GB, Rivers EP, Goetting MG, Appleton TJ, Feingold
M, Nowak RM. Coronary perfusion pressure and the return of spon-
taneous circulation in human cardiopulmonary resuscitation. JAMA.
1990;263:1106–1113.
4. Halperin HR, Tsitlik JE, Gelfand M, Weisfeldt ML, Gruben KG, Levin
HR, Rayburn BK, Chandra NC, Scott CJ, Kreps BJ, et al. A preliminary
study of cardiopulmonary resuscitation by circumferential compression of
the chest with use of a pneumatic vest. N Engl J Med. 1993;329:762–768.
5. Kern KB, Ewy GA, Voorhees WD, Babbs CF, Tacker WA. Myocardial
perfusion pressure: a predictor of 24-hour survival during prolonged
cardiac arrest in dogs. Resuscitation. 1988;16:241–250.
6. Lindner KH, Prengel AW, Pfenninger EG, Lindner IM, Strohmenger HU,
Georgieff M, Lurie KG. Vasopressin improves vital organ blood flow
during closed-chest cardiopulmonary resuscitation in pigs. Circulation.
1995;91:215–221.
7. Little CM, Angelos MG, Paradis NA. Compared to angiotensin II, epi-
nephrine is associated with high myocardial blood flow following return
of spontaneous circulation after cardiac arrest. Resuscitation. 2003;59:
353–359.
8. Connick M, Berg RA. Femoral venous pulsations during open-chest
cardiac massage. Ann Emerg Med. 1994;24:1176–1179.
9. Weil MH, Rackow EC, Trevino R, Grundler W, Falk JL, Griffel MI.
Difference in acid-base state between venous and arterial blood during
cardiopulmonary resuscitation. N Engl J Med. 1986;315:153–156.
10. Kette F, Weil MH, Gazmuri RJ, Bisera J, Rackow EC. Intramyocardial
hypercarbic acidosis during cardiac arrest and resuscitation. Crit Care
Med. 1993;21:901–906.
11. Adrogue HJ, Rashad MN, Gorin AB, Yacoub J, Madias NE. Arterio-
venous acid-base disparity in circulatory failure: studies on mechanism.
Am J Physiol. 1989;257:F1087–F1093.
12. Tucker KJ, Idris AH, Wenzel V, Orban DJ. Changes in arterial and mixed
venous blood gases during untreated ventricular fibrillation and cardio-
pulmonary resuscitation. Resuscitation. 1994;28:137–141.
13. Tang W, Weil MH, Sun S, Kette D, Gazmuri RJ, O’Connell F, Bisera
J. Cardiopulmonary resuscitation by precordial compression but without
mechanical ventilation. Am J Respir Crit Care Med. 1994;150:
1709–1713.
14. Gudipati CV, Weil MH, Gazmuri RJ, Deshmukh HG, Bisera J, Rackow
EC. Increases in coronary vein CO2 during cardiac resuscitation. J Appl
Physiol. 1990;68:1405–1408.
15. Capparelli EV, Chow MS, Kluger J, Fieldman A. Differences in systemic
and myocardial blood acid-base status during cardiopulmonary resusci-
tation. Crit Care Med. 1989;17:442–446.
16. von Planta M, Weil MH, Gazmuri RJ, Bisera J, Rackow EC. Myocardial
acidosis associated with CO2 production during cardiac arrest and resus-
citation. Circulation. 1989;80:684–692.
17. Grundler W, Weil MH, Rackow EC. Arteriovenous carbon dioxide and
pH gradients during cardiac arrest. Circulation. 1986;74:1071–1074.
18. Sanders AB, Ewy GA, Taft TV. Resuscitation and arterial blood gas
abnormalities during prolonged cardiopulmonary resuscitation. Ann
Emerg Med. 1984;13:676–679.
19. Nowak RM, Martin GB, Carden DL, Tomlanovich MC. Selective venous
hypercarbia during human CPR: implications regarding blood flow. Ann
Emerg Med. 1987;16:527–530.
20. American Heart Association in collaboration with International Liaison
Committee on Resuscitation. Guidelines 2000 for Cardiopulmonary
Resuscitation and Emergency Cardiovascular Care: International Con-
sensus on Science, Part 6: Advanced Cardiovascular Life Support:
Section 4: Devices to Assist Circulation. Circulation. 2000;102(suppl
I):I105–I111.
21. Abraham E, Fink S. Conjunctival oxygen tension monitoring in
emergency department patients. Am J Emerg Med. 1988;6:549–554.
22. Bhende MS, Thompson AE. Evaluation of an end-tidal CO2 detector
during pediatric cardiopulmonary resuscitation. Pediatrics. 1995;95:
395–399.
23. Callaham M, Barton C. Prediction of outcome of cardiopulmonary resus-
citation from end-tidal carbon dioxide concentration. Crit Care Med.
1990;18:358–362.
24. Grmec S, Klemen P. Does the end-tidal carbon dioxide (EtCO2) concen-
tration have prognostic value during out-of-hospital cardiac arrest? Eur
J Emerg Med. 2001;8:263–269.
25. Grmec S, Kupnik D. Does the Mainz Emergency Evaluation Scoring
(MEES) in combination with capnometry (MEESc) help in the prognosis
of outcome from cardiopulmonary resuscitation in a prehospital setting?
Resuscitation. 2003;58:89–96.
IV-82 Circulation December 13, 2005
26. Grmec S, Lah K, Tusek-Bunc K. Difference in end-tidal CO2 between
asphyxia cardiac arrest and ventricular fibrillation/pulseless ventricular
tachycardia cardiac arrest in the prehospital setting. Crit Care. 2003;7:
R139–R144.
27. Mauer D, Schneider T, Elich D, Dick W. Carbon dioxide levels during
pre-hospital active compression–decompression versus standard cardio-
pulmonary resuscitation. Resuscitation. 1998;39:67–74.
28. Sanders AB, Kern KB, Otto CW, Milander MM, Ewy GA. End-tidal
carbon dioxide monitoring during cardiopulmonary resuscitation: a prog-
nostic indicator for survival. JAMA. 1989;262:1347–1351.
29. Entholzner E, Felber A, Mielke L, Hargasser S, Breinbauer B, Hun-
delshausen VB, Hipp R. Assessment of end-tidal CO2 measurement in
reanimation. Anasthesiol Intensivmed Notfallmed Schmerzther. 1992;27:
473–476.
30. Garnett AR, Ornato JP, Gonzalez ER, Johnson EB. End-tidal carbon
dioxide monitoring during cardiopulmonary resuscitation. JAMA. 1987;
257:512–515.
31. Bhende MS, Karasic DG, Karasic RB. End-tidal carbon dioxide changes
during cardiopulmonary resuscitation after experimental asphyxial
cardiac arrest. Am J Emerg Med. 1996;14:349–350.
32. Ahrens T, Schallom L, Bettorf K, Ellner S, Hurt G, O’Mara V, Ludwig
J, George W, Marino T, Shannon W. End-tidal carbon dioxide mea-
surements as a prognostic indicator of outcome in cardiac arrest. Am J
Crit Care. 2001;10:391–398.
33. Cantineau JP, Lambert Y, Merckx P, Reynaud P, Porte F, Bertrand C,
Duvaldestin P. End-tidal carbon dioxide during cardiopulmonary resus-
citation in humans presenting mostly with asystole: a predictor of
outcome. Crit Care Med. 1996;24:791–796.
34. Kellum JA, Pinsky MR. Use of vasopressor agents in critically ill
patients. Curr Opin Crit Care. 2002;8:236–241.
35. Zaritsky AL. Catecholamines, inotropic medications, and vasopressor
agents. In: Chernow B, ed. The Pharmacologic Approach to the Critically
Ill Patient. 3rd ed. Baltimore, Md: Williams & Wilkins; 1994:387–404.
36. Grillo JA, Gonzalez ER, Ramaiya A, Karnes HT, Wells B. Chemical
compatibility of inotropic and vasoactive agents delivered via a multiple
line infusion system. Crit Care Med. 1995;23:1061–1066.
37. Bonhomme L, Benhamou D, Comoy E, Preaux N. Stability of epineph-
rine in alkalinized solutions. Ann Emerg Med. 1990;19:1242–1244.
38. Ellis AK, Day JH. Diagnosis and management of anaphylaxis. CMAJ.
2003;169:307–311.
39. Dunser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann G, Pajk W,
Friesenecker B, Hasibeder WR. Arginine vasopressin in advanced vaso-
dilatory shock: a prospective, randomized, controlled study. Circulation.
2003;107:2313–2319.
40. Mutlu GM, Factor P. Role of vasopressin in the management of septic
shock. Intensive Care Med. 2004;30:1276–1291.
41. American Heart Association in collaboration with International Liaison
Committee on Resuscitation. Guidelines 2000 for Cardiopulmonary
Resuscitation and Emergency Cardiovascular Care: International Con-
sensus on Science, Part 6: advanced cardiovascular life support: Section
6: pharmacology II. Agents to optimize cardiac output and blood
pressure. Circulation. 2000;102(suppl I):I129–I135.
42. Delmas A, Leone M, Rousseau S, Albanese J, Martin C. Clinical review:
vasopressin and terlipressin in septic shock patients. Crit Care. 2005;9:
212–222.
43. Marin C, Eon B, Saux P, Aknin P, Gouin F. Renal effects of norepineph-
rine used to treat septic shock patients. Crit Care Med. 1990;18:282–285.
44. Bellomo R, Giantomasso DD. Noradrenaline and the kidney: friends or
foes? Crit Care. 2001;5:294–298.
45. Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose
dopamine in patients with early renal dysfunction: a placebo-controlled
randomised trial. Australian and New Zealand Intensive Care Society
(ANZICS) Clinical Trials Group. Lancet. 2000;356:2139–2143.
46. Holmes CL, Walley KR. Bad medicine: low-dose dopamine in the ICU.
Chest. 2003;123:1266–1275.
47. Ruffolo RR Jr. The pharmacology of dobutamine. Am J Med Sci. 1987;
294:244–248.
48. Alousi AA, Johnson DC. Pharmacology of the bipyridines: amrinone and
milrinone. Circulation. 1986;73(suppl III):III10–III24.
49. Edelson J, Stroshane R, Benziger DP, Cody R, Benotti J, Hood WB Jr,
Chatterjee K, Luczkowec C, Krebs C, Schwartz R. Pharmacokinetics of
the bipyridines amrinone and milrinone. Circulation. 1986;73(suppl III):
III145–III152.
50. Stueven HA, Thompson B, Aprahamian C, Tonsfeldt DJ, Kastenson EH.
The effectiveness of calcium chloride in refractory electromechanical
dissociation. Ann Emerg Med. 1985;14:626–629.
51. Stueven H, Thompson BM, Aprahamian C, Darin JC. Use of calcium in
prehospital cardiac arrest. Ann Emerg Med. 1983;12:136–139.
52. Ramoska EA, Spiller HA, Winter M, Borys D. A one-year evaluation of
calcium channel blocker overdoses: toxicity and treatment. Ann Emerg
Med. 1993;22:196–200.
53. Urban P, Scheidegger D, Buchmann B, Barth D. Cardiac arrest and blood
ionized calcium levels. Ann Intern Med. 1988;109:110–113.
54. Cardenas-Rivero N, Chernow B, Stoiko MA, Nussbaum SR, Todres ID.
Hypocalcemia in critically ill children. J Pediatr. 1989;114:946–951.
55. DiDomenico RJ, Park HY, Southworth MR, Eyrich HM, Lewis RK,
Finley JM, Schumock GT. Guidelines for acute decompensated heart
failure treatment. Ann Pharmacother. 2004;38:649–660.
56. Kirsten R, Nelson K, Kirsten D, Heintz B. Clinical pharmacokinetics of
vasodilators. Part II. Clin Pharmacokinet. 1998;35:9–36.
57. Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet. 2000;356:
411–417.
58. Zerbe NF, Wagner BK. Use of vitamin B12 in the treatment and pre-
vention of nitroprusside-induced cyanide toxicity. Crit Care Med. 1993;
21:465-467.
59. Rindone JP, Sloane EP. Cyanide toxicity from sodium nitroprusside: risks
and management [published correction appears in Ann Pharmacother.
1992;26:1160]. Ann Pharmacother. 1992;26:515–519.
60. Ditchey RV, Lindenfeld J. Potential adverse effects of volume loading on
perfusion of vital organs during closed-chest resuscitation. Circulation.
1984;69:181–189.
61. Gentile NT, Martin GB, Appleton TJ, Moeggenberg J, Paradis NA,
Nowak RM. Effects of arterial and venous volume infusion on coronary
perfusion pressures during canine CPR. Resuscitation. 1991;22:55–63.
62. Jameson SJ, Mateer JR, DeBehnke DJ. Early volume expansion during
cardiopulmonary resuscitation. Resuscitation. 1993;26:243–250.
63. Voorhees WD, Ralston SH, Kougias C, Schmitz PM. Fluid loading with
whole blood or Ringer’s lactate solution during CPR in dogs. Resusci-
tation. 1987;15:113–123.
64. Fischer M, Dahmen A, Standop J, Hagendorff A, Hoeft A, Krep H.
Effects of hypertonic saline on myocardial blood flow in a porcine model
of prolonged cardiac arrest. Resuscitation. 2002;54:269–280.
65. Breil M, Krep H, Sinn D, Hagendorff A, Dahmen A, Eichelkraut W,
Hoeft A, Fischer M. Hypertonic saline improves myocardial blood flow
during CPR, but is not enhanced further by the addition of hydroxy ethyl
starch. Resuscitation. 2003;56:307–317.
66. Kette F, Weil MH, Gazmuri RJ. Buffer solutions may compromise
cardiac resuscitation by reducing coronary perfusion pressure. JAMA.
1991;266:2121–2126.
67. Graf H, Leach W, Arieff AI. Evidence for a detrimental effect of bicar-
bonate therapy in hypoxic lactic acidosis. Science. 1985;227:754–756.
68. Katz LM, Wang Y, Rockoff S, Bouldin TW. Low-dose Carbicarb
improves cerebral outcome after asphyxial cardiac arrest in rats. Ann
Emerg Med. 2002;39:359–365.
69. Sun S, Weil MH, Tang W, Fukui M. Effects of buffer agents on post-
resuscitation myocardial dysfunction. Crit Care Med. 1996;24:
2035–2041.
70. Blecic S, De Backer D, Deleuze M, Vachiery JL, Vincent JL. Correction
of metabolic acidosis in experimental CPR: a comparative study of
sodium bicarbonate, carbicarb, and dextrose. Ann Emerg Med. 1991;20:
235-238.
71. Pickkers P, Dormans TP, Russel FG, Hughes AD, Thien T, Schaper N,
Smits P. Direct vascular effects of furosemide in humans. Circulation.
1997;96:1847–1852.
72. Mehta RL, Pascual MT, Soroko S, Chertow GM. Diuretics, mortality, and
nonrecovery of renal function in acute renal failure. JAMA. 2002;288:
2547–2553.
Part 7.4: Monitoring and Medications IV-83