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Bacillus anthracis Infection
Anthrax
Bacteremia, Primary of UnknownOrigin
tomatic is based on multiple factors, including history
of the patient, physical examination, body temperature,
peripheral leukocyte count and differential, clinical
outpatients or that are first identified within 48 h of
admission are now generally classified as healthcare-
associated if there is a significant history of healthcare
exposure as evidenced by recent admissions to hospital,
residence in a nursing homes or long-term care facility,
hemodialysis, recent intravenous therapy, or specialized
medical care in the home. Community-acquired bacter-
emias are diagnosed when these factors are not present [2].course, results of cultures from other sites, and percentage
of blood cultures positive [1]. The term bacteremia may
be considered synonymous with bloodstream infection.
An important aspect in defining bacteremia is thatDefinitionWhile many definitions for bacteremia exist, it may be
defined by the growth of a microbe from an aseptically
obtained blood culture specimen associated with symp-
tomatic infection. Determining if an infection is symp-VIKAS P. CHAUBEY, KEVIN B. LAUPLAND
Department of Critical Care Medicine, University
of Calgary and Calgary Health Region, Calgary,
AB, CanadaBacillus anthracis
Biological Terrorism, AnthraxB
B2M
Serum and Urinary Low Molecular Weight ProteinsJean-Louis Vincent & Jesse B. Hall (eds.), Encyclopedia of Intensive Care Med# Springer-Verlag Berlin Heidelberg 2012contamination of blood culture specimens must be ruled
out. Common skin contaminants including diphtheroids,
Bacillus spp., Propionibacterium sp., coagulase-negative
staphylococci, and micrococci generally require isolation
from two different blood cultures drawn from separate
sites to be considered as significant. A positive blood
culture is requisite for bacteremia; if the test is not
performed the diagnosis cannot be made. In addition,
prior administration of systemic antimicrobials may ster-
ilize blood culture specimens and result in the under
recognition of bacteremia.
Bacteremia may be classified as being either primary or
secondary. In the former, the origin of the bacteremia is
either associated with an intravascular catheter or is of
unknown origin. In the latter, the bacteremia is associated
with infection concurrently diagnosed at another body site,
such as with pneumonia, meningitis, or bone and joint
infection. Catheter-related bacteremia is a special case of
primary bacteremia that occurs in a patient with an intra-
vascular catheter. Such bacteremia is still considered primary
even if localized signs of infection are present at the access
site. A primary bacteremia that is not catheter-related is also
referred to as a bacteremia of unknown origin.
Traditionally, bacteremias that were present or incubat-
ing at the time of hospital admission were classified as
community-acquired and those that developed as a compli-
cation of hospitalization as nosocomial (usually first identi-
fied more than 48 h after admission). However, over the
recent years, there has been a shift in delivery of healthcare
with an increasing number of sicker patients with multiple
comorbidities managed in the community setting. When
community onset bacteremia occurs in patients that have
had extensive healthcare exposure, it tends to be associated
with higher rates of antimicrobial resistance and mortality
[2]. Bacteremias that occur in either community-basedicine, DOI 10.1007/978-3-642-00418-6,
282 B Bacteremia, Primary of Unknown Origin
EpidemiologyWhile a number of large observational and surveillance
studies have reported on the epidemiology of bacteremia
among critically ill patients, most have focused on noso-
comial infections and have not separated ICU patients
from the general inpatient population. Furthermore, it
must be emphasized that considerable differences exist at
the national, regional, and local levels with respect to the
epidemiology of bacteremia. In most cases, ICU-acquired
primary bacteremias are similar to nosocomial primary
bacteremias in the hospital population at large, with the
exception of an increased risk for antimicrobial resistance.
Gram-positive organisms including coagulase-negative
staphylococci and Staphylococcus aureus are themost com-
mon etiologies of ICU-acquired bacteremia. Community
onset primary bacteremic disease (including healthcare-
associated and community-acquired disease) is less well
defined among patients admitted to ICU, but Escherichia
coli, S. aureus, and Streptococcus pneumoniae are predom-
inant pathogens inmost studies. While coagulase-negative
staphylococci are regularly listed as a major etiology of
bacteremia in critically ill patients, these bacteremias are
almost exclusively healthcare or nosocomially associated
and are invariably related to intravascular catheters or
other implanted prosthetic materials.
The diagnosis of bacteremia of unknown origin is
made by exclusion of a secondary infected source. There-
fore, its identification will depend in part on the degree of
effort made to localize a source by clinical, laboratory, and
radiological means. As a result, there is considerable var-
iability in reported rates of bacteremia of unknown origin
among critically ill patients and ranges from 10% to 50%
of all bacteremias.
Risk factors specifically for primary bacteremia in criti-
cally ill patients have not been studied extensively. However,
even if not recognized as a focal source, intravascular cathe-
ters likely represent the main risk factor for development of
healthcare-associated, nosocomial, and ICU-acquired bac-
teremias. Factors associated with development of catheter-
related bacteremia include inexperience of the operator, high
patient-to-nurse ratios, catheter insertion with less than
maximal sterile barriers, placement in the internal jugular
or femoral vein rather than subclavian vein, placement in an
old site by guidewire exchange, heavy colonization of the
insertion site or contamination of a catheter hub, and
prolonged duration of use.
It is well documented that ICU-acquired bacteremia
increases cost, length of ICUand hospital stay, andmortality.
However, few studies have looked specifically at the effect of
primary bacteremia on outcomes. Generally speaking,primary bacteremia is associated with a significantly lower
mortality rate than with secondary bacteremia. This may in
part be due to a lower mortality attributable to catheter-
related bacteremias where the infectious source is easily
removed. In one case-control study of 111 episodes of bac-
teremia in 15 French ICUs, the authors found that the excess
mortality was 20% in patients with primary bacteremia and
was 55% for secondary bacteremia. The excess mortality for
those with catheter-related bacteremia was considerably
lower at 12% [3].
DiagnosisAt least two cultures of blood should be taken from separate
blood draws at different sites in patients suspected of having
bacteremia. Increasing the number of culture sets will
improve the detection rate for pathogens. While the sensi-
tivity of two sets of blood cultures has been reported to be
8090%, three and four setsmay be required to detect>95%
and >99% of bacteremias, respectively. At least one culture
should be drawn by peripheral venipuncture. Cultures may
be obtained through intravascular devices but should not be
taken throughmultiple ports of the same intravascular cath-
eter. Another advantage of multiple blood culture draws is
that it can aid in the assessment of the potential significance
of common contaminants. Isolating common contaminants
from multiple samples increased the probability that true
bacteremia is present [4]. Markers such as procalcitonin
may also help distinguish blood culture contaminants
from true positive blood cultures. However, the current
clinical standard involves integration of all available clin-
ical and microbiological data.
In patients where bacteremia is documented,
a thorough evaluation must be undertaken to determine
the source of infection as this can considerably influence
management. Common secondary sources for bacteremia
in critically ill patients include pneumonia, vascular cath-
eters, intra-abdominal and surgical site infections, and to
a much lesser degree sinusitis and urinary tract infections.
Catheter-associated bacteriuria is not commonly symp-
tomatic and rarely causes bacteremia. A detailed clinical
examination should be performed, and basic investiga-
tions should include a chest roentgenogram and cultures
of suspected body sites (i.e., urine, wounds, cerebrospinal
fluid, synovial fluid) as appropriate. Depending on the
suspected clinical source and the pathogen, further spe-
cific radiologic investigations may be indicated [4].
Endocarditis is an important diagnosis to consider in
any patient with bacteremia. While classical clinical signs
such as Janeway lesions, Osler nodes, and splinter hemor-
rhages are important when present, they are insensitive
Bacteremia, Primary of Unknown Origin B 283
Band their absence does not rule out this diagnosis with any
certainty. Other clues that may suggest a diagnosis of
endocarditis include persistently positive blood cultures
(particularly while on adequate therapy), persistent fever
after 72 h of appropriate therapy, and long-term intravas-
cular and hemodialysis catheter use. The specific etiology
of bacteremia is also important. This is especially so with
Staphylococcus aureus as approximately 1020% patients
with bacteremia due to this organism may have occult
endocarditis, with the rate highest in those with commu-
nity acquired disease. All patients with Staphylococcus
aureus bacteremia and those with other organisms and
clinical concern should undergo echocardiography.
Increased sensitivity of transesophageal echocardiography
makes it the diagnostic modality of choice to reliably rule
out endocardial complications of S. aureus bacteremia [5].
Upon suspicion of catheter-related bacteremia, the
catheter should be promptly removed under usual cir-
cumstances. A confirmation of line-sepsis can be done by
one of several methods including sonication, vortexing,
and the semiquantitative Maki roll-plate method.
Although there is concern about the sensitivity of the
Maki-method in detecting endoluminal infection, this
method performs well. Each of these methods has
a sensitivity of 90%. The specificity of both sonicationand the Maki-method are similar at approximately 80%,
while vortexing has a higher specificity of 90%. How-ever, the simplicity of the Maki-method frequently makes
it the procedure of choice in many laboratories. Briefly,
the Maki-method involves rolling the catheter tip across
a blood agar plate and uses a cut-off of 15 colony forming
units (CFUs) to diagnose true infection versus coloniza-
tion [5].
Controversy exists as to whether all central line tips
that are removed should be cultured or only those that are
removed after identifying bacteremia. On one hand, cul-
turing all removed lines may lead to over treatment of
many patients with uncomplicated line colonization. On
the other hand, such an approach may lead to preemptive
treatment of bacteremia with a reduction in associated
complications. It is prudent to at least culture those central
line tips that are suspected of being infected or removed
following an associated positive blood culture.
In most critically ill adults, removal of a catheter
suspected of being the source of infection is a low-
morbidity procedure. However, an approach where
a catheter could be classified as infected or not while in
situ with removal of only those infected catheters would be
preferred. Several methods have been developed in an
attempt to define whether a line may be infected prior toremoval and include differential quantitative blood cul-
tures and the differential time to positivity. Differential
quantitative blood cultures with a ratio 5:1 (comparingcolony counts from peripheral blood samples with colony
counts of blood samples from catheter hubs) has
a sensitivity of 70% and specificity of 95% relative to the
Maki-method. Differential time to positivity (comparing
time to positivity between cultures of blood samples
obtained from peripheral veins and from catheter hubs)
has a sensitivity of 95% and a specificity of 90% relative to
the Maki-method. It must be recognized that these
approaches require maintaining potentially infected cath-
eters in situ while cultures are incubated. While this may
be done safely in selected stable patients, suspected
infected catheters should be promptly removed in hemo-
dynamically unstable patients or in those where compli-
cations are suspected prior to the availability of blood
culture results.
Diagnostic imaging procedures frequently play an
important role in evaluating potential sources for bacter-
emia. Roentgenograms of the chest may identify pneumo-
nia. Free air due to a perforated viscus is readily identified
by typical views of the abdomen. Plain radiographs may
also be useful to identify bone and joint sources. While
often a reasonable first investigation, plain radiographs
suffer from limited sensitivity, and other modalities may
be indicated. Computed tomography has generally good
sensitivity and specificity to detect infective foci at most
body sites. Ultrasound is readily available at the bedside
and is particularly valuable for assessing the liver and
biliary tree, and can potentially identify infected large
vessel thrombi using Doppler mode. Magnetic resonance
imaging has markedly improved resolution as compared
to computed tomography and is particularly valuable in
defining infections of the head, neck, and spine. A main
limitation of these mentioned modalities is that they
require the clinician to select the body site to be imaged.
In many cases, clinical clues may suggest a potential focus
of infection, but in many cases, the site of infection is
clinically unapparent.
Nuclear medicine scans have been employed in
evaluation of bacteremia of unknown origin, and it may
allow a full body assessment. Traditionally, 67Gallium,111Indium, and 99mTechnetium radiotracers have been
employed but are limited in their specificity for localizing
bacterial infection. Scans using autologous leukocytes
labeled with either 111Indium or 99mTechnitium, while
specific for leukocyte infiltration, do not detect infection
per se. Several newer nuclear technologies are now being
evaluated in the diagnosis of bacterial infections.
delays in providing adequate antifungal therapy are asso-
patients who do not have implanted prosthetic material.
284 B Bacteremia, Primary of Unknown Originciated with adverse outcome. Once the etiology of bacter-
emia has been established, antimicrobial therapy should
be revised to provide optimum coverage. Generally speak-
ing, high doses of bactericidal/fungicidal agents are pre-
ferred and, with few exceptions, should be administered at
least initially through the intravenous route.
Catheter-related bacteremias may be classified as
uncomplicated or as complicated being associated with
one or more metastatic foci of infection. Complicated
catheter-related infections are secondary bacteremias
that require treatment directed at both the catheter source
and the complicated focus, and are discussed elsewhere in
the Encyclopedia. Of note, a negative transesophageal18-Fluorodeoxyglucose positron emission tomography
(18-FDG PET) scans have been investigated with consid-
erable success in identifying metastatic foci of infection.
However, 18-FDG is poorly taken up into the brain, heart,
kidneys, and bladder and therefore is complementary to
other imaging modalities. In addition, 18-FDG PETmay
have similar specificity issues as the radiotracers men-
tioned above. Another new imaging technology using99mTechnitium-ciprofloxacin has also been developed.
This tracer has the advantage of being specific to bacterial
enzymes. Performance in defining sources of bacteremia
as compared to other techniques is limited.
TreatmentThe treatment of primary bacteremia depends on
a number of factors not limited to patient factors includ-
ing severity of disease and comorbid illness, microbiolog-
ical factors including infecting species and in vitro
antimicrobial susceptibilities, evidence of metastatic foci
of infection, and whether the primary bacteremia is
catheter-related or is of unknown origin.
In patients suspected of having primary bacteremia, or
among those where preliminary blood culture results indi-
cate a presumptive infection, empiric therapy should be
initiated pending confirmation of true bacteremia.
Numerous observational studies have emphasized the
importance of early administration of effective antimicro-
bial therapies on the mortality outcome of serious infec-
tions including bacteremia. The selection of empiric
therapy involves an evaluation of the most likely agent(s)
causing disease and expected antimicrobial susceptibili-
ties. While generally one or more agents may be required
to cover a broad spectrum of potential bacterial patho-
gens, it should be recognized that evidence is emerging
that Candida species are frequent causes of primary
bloodstream infection in critically ill patients and thatOn the other hand, 4 or more weeks of treatment is
considered standard in primary catheter-related bacter-
emia due to most multidrug resistant organisms, includ-
ing methicillin-resistant Staphylococcus aureus [5]. The
treatment duration for primary bacteremia of unknown
origin is less well defined, but because a possible deep body
site focus has potentially not been recognized, treatment
durations are frequently prolonged as a precaution, par-
ticularly with Gram-positive and antimicrobial resistant
pathogens. Primary bacteremia of unknown origin caused
by susceptible Gram-negative organisms can generally be
treated for shorter courses (1014 days).
References1. Weinstein MP, Reller LB, Murphy JR, Lichtenstein KA (1983) The
clinical significance of positive blood cultures: a comprehensive anal-
ysis of 500 episodes of bacteremia and fungemia in adults. I. Labo-
ratory and epidemiologic observations. Rev Infect Dis 5:3553
2. Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL, Briggs JP
et al (2002) Health careassociated bloodstream infections in adults:
a reason to change the accepted definition of community-acquired
infections. Ann Intern Med 137:791797
3. Renaud B, Brun-Buisson C (2001) Outcomes of primary and
catheter-related bacteremia cohort case control study critically ill
patients. Am J Respir Crit Care Med 163:15841590
4. OGrady NP, Barie PS, Bartlett JG, Bleck T, Carroll K, Kalil AC et al
(2008) Guidelines for evaluation of new fever in critically ill adult
patients: 2008 update from the American college of critical care
medicine and the infectious diseases society of America. Crit Care
Med 36:13301349
5. Mermel LA, AllonM, Bouza E, Craven DE, Flynn P, OGrady NP et al
(2009) Clinical practice guidelines for the diagnosis and manage-
ment of intravascular catheter-related infection: 2009 update by the
infectious diseases society of America. Clin Infect Dis 49:145echocardiogram is required to define an uncomplicated
episode of S. aureus bacteremia. The approach to manage-
ment of primary (uncomplicated) catheter-related bacter-
emia involves prompt removal of the infected catheter
source in addition to providing optimal antimicrobial
therapy [5].
The duration of antimicrobial therapy for primary
bacteremia has not been well defined in clinical trials and
is largely based on anecdotal experience. In uncomplicated
primary catheter-related bacteremia, the duration of ther-
apy will depend on clinical response and the infecting
organism. A typical therapy duration for a primary
uncomplicated catheter-related bacteremia is 2 weeks
following catheter removal as long as there is good clinical
response. However, it is common practice to prescribe
either no antimicrobials or only a brief course of therapy
in primary catheter-related bacteremias specifically due to
coagulase-negative staphylococci after catheter removal in
Some of these procedures can be lifesaving and are often
important to implement early. Specifically in the case of
cardiopulmonary resuscitation (CPR) and defibrillation
with automatic external defibrillators (AEDs), BLS pro-
medical technician (EMT)-basics.
Characteristics
Basic Life Support B 285
BBangs Disease
BrucellosisBAL
Bronchoalveolar Lavage (BAL).Bailout Surgery
Damage Control SurgeryBag-Valve-Mask Ventilation
Airway ManagementBacteriuria
Urinary Tract InfectionsBacterial Pneumonia
Burns, PneumoniaBacterial Meningitis
MeningitisBacterial Endocarditis
Cardiac and Endovascular InfectionsBLS can be provided by first responders or EMTs. EMTs
are classified as EMT-basic (EMT-b), EMT-advanced,or EMT-paramedic (please see Prehospital Care fora more detailed description of each level of provider).cedures can have a significant impact on survival, and are
typically delivered by initial responders (sometimes
referred to as first-responders) until more advanced and
definitive medical care can be implemented. BLS is typi-
cally provided by either first responders or emergencyDefinitionBasic life support (BLS) is defined as a variety of nonin-
vasive emergency procedures performed to assist in the
immediate survival of a patient, including cardiopulmo-
nary resuscitation, hemorrhage control, stabilization of
fractures, spinal immobilization, and basic first aid.SynonymsEMT-basic; Field medicine; First responder; Out-of-
hospital careBarlows Disease
Mitral Valvular Disease
Barotrauma
Diving SicknessPleural Disease and Pneumothorax
Basic Life Support
CHRISTOPHER B. COLWELL, GINA SORIYA
Department of Emergency Medicine, Denver Health
Medical Center, Denver, CO, USA
tila
wh
the
and
pat
sug
ma
not
a p
thr
2.
286 B Basic Life Supportshock is indicated, and deliver that electric shock. It can
detect pulseless ventricular tachycardia (VT) and ventric-
ular fibrillation (VF), which then stimulates the machine
to indicate to the provider that a shock is advised. The
AED is also able to recognize a non-shockable rhythm,
such as asystole and pulseless electrical activity (PEA), and
will not designate a shock advisory. The AED is designed
for use by first responders or laypeople that have ideally
been trained in the use of the machine although the use of
AEDs by members of the public that have not been previ-
ously trained in its use has been increasing. Lack of train-
ing on AEDs should never discourage a member of the
public from using thesemachines. Early use of AEDs in the
appropriate setting by trained or untrained responders
can have a significant impact on mortality [2].
Pre-existing Condition1. Unconsciousness/apnea/pulselessness
2. Foreign body obstruction/choking
3. Drowning
4. Hypothermia
5. Stabilization of basic injuries
Application1. Adult BLS/CPR sequence for the unconscious/apneic/
pulseless patient:
Establish scene safety. Assess victims level of consciousness: (1) ask are
you okay? (2) stimulate the patient physically to
check responsiveness.
Activate local emergency system: instructa bystander to call 911.
Apply an AED if available, and shock if advised. If no suspected spinal injury, open the airway
via head-tilt/chin-lift (image). If spinal injury is
suspected, open the airway via jaw-thrust (image).
Look, listen, and feel for 10 s: (1) Look forforeign body; if any are visible, remove with
finger-sweep technique. Blind finger sweep is notCardiopulmonary resuscitation (CPR) integrates ven-
tions and chest compressions in the setting of a patient
o is pulseless and/or apneic. The purpose of performing
se maneuvers in sequence is to provide oxygenation
circulation in an attempt to prevent brain injury in
ients whose heart has stopped. Recent research has
gested the early access to quality CPR and defibrillation
y be the most significant determinants of whether or
someone survives and recovers from cardiac arrest [1].
An automatic external defibrillator (AED) is
ortable computerized device that can diagnose a life-
eatening arrhythmia, direct the provider if an electric If no chest rise occurs, reposition the airway uti-lizing the appropriate technique and attempt arti-
ficial ventilations again. If ventilations continue to
be unsuccessful, and the patient is unresponsive,
consider an airway foreign body. Begin chest com-
pressions. Check airway after each set of 30 com-
pressions, removing any foreign body found, and
reattempting ventilations.
If ventilations are successful, check for a carotidpulse. If a pulse is found, continue with appropri-
ate ventilations and await immediate transport. If
there is no pulse, begin CPR with 30 compressions
followed by two ventilations at 100 compressions
per minute for five cycles.
After five cycles of CPR have been completed, thecycle should be repeated, starting with reassessing
the patients airway, breathing, and circulation.
The BLS sequence should be continued until oneof the following conditions has been met: (1) the
patient regains a pulse, (2) the initial provider is
relieved by another rescuer of equal or higher
medical training, (3) the rescuer is physically
unable to continue with CPR, or (4) the patient
is pronounced dead by a physician.
Foreign body obstruction/choking:
Airway obstruction from a foreign body may pre-
sent in a variety of ways, ranging from minimal symp-
toms to respiratory compromise and death. The death
rate nears 2,000 annually in the USA, with children
aged 13 as the primary victims. Mortality rates are up
to 3.3% [3].
Assess severity of obstruction. If the patient is ableto cough effectively, the patient should be encour-
aged to cough and monitored for deterioration.
If the patient is unable to speak or breathe, iscyanotic, or has a silent cough, abdominal thrusts
should be administered in rapid progression until
the obstruction is relieved. If the patient isforming a seal. Ensure chest rise with ventilations.recommended. Look for chest rise. (2) Listen
for breath sounds. (3) Feel for breath; feel for
chest rise.
If the patient is breathing normally, place patientin the lateral recumbent (recovery) position and
await transport. Continue to check for breathing.
If the patient is not breathing, administer two artifi-cial ventilations using mouth-to-mouth technique,
mouth-to-mask technique, or bag-valve-mask. If
usingmouth-to-mouth technique, close the patients
nostrils between the thumb and forefinger on one
hand, covering the mouth with that of the rescuers,
3.
4.
5. Sta
(a)
(b)
Basic Life Support B 287
BFor hypothermia patients with no perfusing
rhythm:
Assess the ABCs, keeping in mind it may takelonger to detect a pulse or respiratory rate.
If no respirations are detected, begin rescuebreathing. If there is no detectable pulse, or if
there is any doubt that a pulse may be present,
begin compressions. Compression-to-ventilation
ratio is 30:2.ister warm, humidified oxygen.obstruct the trachea.
There is no need to perform the Heimlich maneu-ver or abdominal thrusts in an attempt to clear
water from the lungs, as these moves are ineffective
and can be dangerous for the patient.
Patient emesis is not uncommon during resuscita-tion of the drowning victim. If this occurs, vomitus
from the airway should be removed via finger
sweep with the patients head turned laterally. If
the patient has a suspected cervical spine injury,
the patient should be logrolled to the side, and
vomitus swept from the airway.
Hypothermia:
For hypothermic patients with a perfusing rhythm:
Assess airway, breathing, and circulation. Thepulse and respiratory rate may be difficult to
detect, therefore it may take longer to adequately
assess, such as 4560 s.
Remove wet garments and prevent any furtherexposure to the cold environment.
Apply warm dry blankets, hot packs, or othermodality to warm the patient. If available, admin-airway, as the amount is minimal and does notpregnant or obese, chest thrusts should be deliv-
ered as an alternative to abdominal thrusts. In
infants under 1 year of age, the rescuer should
alternate between back blows and chest thrusts.
If the patient subsequently becomes unresponsive,the patient should be lowered to the ground, EMS
activated, and CPR initiated. The airway should be
assessed for foreign body and removed if visualized.
Drowning:
Death from drowning reaches over 8,000 annually
in the USA, almost 25% of those being children.
Remove the patient from the body of water,maintaining cervical spine immobilization if
trauma is suspected.
Assess airway, breathing, and circulation asoutlined under Sect. I. Proceed with CPR. Com-
pression-to-ventilation ratio is 30:2.
There is no need to clear aspirated water from theseek immediate help.
If there is an open wound at the site of thefracture, cover the wound and apply direct
pressure for bleeding control. Splint as above
and elevate.
If there is a suspected spinal injury, do notmove the patient unless assisted by trained
medical personnel.
(c) Burn care
Extinguish the burn with a large amount ofwater.recheck circulation. If there continues to be
lack of circulation, splint in alignment andplace.
Do not remove debris from the wound. If thereis a protruding foreign object, such as a knife,
leave in place and bandage securely so the
object is immobilized.
For chest wounds, seal open sucking woundswith hand or an air-tight dressing.
For abdominal wounds, cover with clean ban-dage. Do not replace protruding intestines into
the wound.
Fracture splinting
Immobilize the joints above and below thefracture site with a splint.
Check distal circulation, motion, and sensa-tion (CMS) before and after immobilization.
If the fracture is angulated and there is nonoted distal circulation, attempt to straighten
the fracture into anatomical alignment and Apply a clean dressing and bandage firmly inshould be delivered one time, then CPR imme-
diately resumed. The number of defibrillation
attempts in the hypothermic cardiac arrest is
controversial; however, further defibrillation
attempts should be postponed until the patients
core body temperature warms, in order to
improve the chance of conversion to a normal
rhythm.
bilization of basic injuries
Bleeding control
Check airway, breathing, and circulation.Resuscitate as indicated.
Expose area by removing or cutting clothing. Apply direct pressure to the bleeding wound. Check for circulation distal to the wound by
assessing pulse or capillary refill.
Elevate the wound if possible.the machine advises a defibrillation, the shockIf an AED is available, it should be applied. If
2. Bobrow BT et al (2008) Minimally interrupted cardiac resuscitation
by emergency Medical services for out-of-hospital cardiac arrest.
Cardiopulmonary Resuscitation
Pressure Ulcer Evaluation, Prevention and Treatment
Monitoring
DefinBedside
of phys
technol
vital sig
rate, te
logicall
288 B Basic Life Support (BLS)itionmonitoring refers to the systematic recording
iological data over time. This extends from the
ogically very simple and noninvasive collection of
ns such as heart rate, blood pressure, respiratory
mperature, and urine output, to the more techno-
y demanding noninvasive techniques such pulseSHELDEN MAGDER
Critical Care Division, McGill University Health Centre,
Royal Victoria Hospital, Montreal, QC, Canada
SynonymsHemodynamic monitoring; Pressure monitoring; Vital
signsBedside HemodynamicBed SoreJAMA 299:11581165
3. Soroudi A et al (2007) Adult foreign airway obstruction in the
prehospital setting. Prehosp Emerg Care 11(1):2529
Basic Life Support (BLS) Check airway, breathing, circulation, andresuscitate as indicated.
Remove smoldering clothing, as well as jew-elry, belts, and shoes.
Cover with sterile burn dressing if available;otherwise use any clean dry dressing.
Do not open or drain blisters.
References1. Eisenberg MS, Psaty BM (2009) Defining and improving survival
rates from cardiac arrest in US communities. JAMA 301:860862oximetry, end-tidal CO2, and techniques for the assess-
ment of cardiac output, and to invasive intravascular
measurements of pressures such as the central venous
pressure (CVP), arterial pressure, pulmonary artery pres-
sure, measurements of cardiac output, airway pressures
and flows, and cerebrospinal pressure. Measurement of
variables over times allows trend analysis so that changes
in the patients underlying condition or changes in
response to therapy can be assessed. In this entry, I will
concentrate on the hemodynamic components of bedside
monitoring. (I assume that respiratory and neuro
monitoring are covered elsewhere). For the purpose of this
discussion, a central assumption is that for an individual
patient there is a range of parameters such as heart rate,
blood pressure, cardiac output, and markers of metabolic
stability (e.g., arterial oxygen, lactate, base excess,
central venous oxygen content) that have been identified
by the treating team and there is a desire to maintain the
patients values in a given range. When a patients
values are in the desired range, the patient is defined as
hemodynamic stabile.
Pre-existing Condition
IndicationsHemodynamic monitoring has the following roles. (1) It
alerts the medical team to deterioration in a patients
hemodynamic status and the requirement for urgent
interventions. This includes the development of an inad-
equate heart rate response or rhythm disturbance, exces-
sively high or low blood pressure or inadequate cardiac
output for tissue needs. (2) It can be used to predict
potential responses to therapeutic interventions. (3) It
allows assessment of the response to therapeutic interven-
tions. (4) The pattern of hemodynamic wave patterns
themselves can have diagnostic information for the under-
lying condition.
In choosing a monitoring tool one must consider
potential benefits, costs, and risks. Costs and risks gener-
ally are more readily available but the benefits are much
harder to define. Although there is no rigorous evidence
that supports the utility of any hemodynamic tools
including vital signs, it is important to appreciate that
a monitoring tool is only as good as the algorithm
that makes use of the information. This is well illustrated
by studies in which investigators have tried to assess the
roles of the pulmonary artery catheters for the manage-
ment of critically ill patients [1, 2]. No benefit has been
observed in these studies, but in reality they have only
tested the presence of a catheter and not an algorithm and
there is no reason to expect that the catheter itself should
Bedside Hemodynamic Monitoring B 289
Bhave a benefit. Even a stethoscope has no value if the
clinician does not know how to interpret the sounds that
are heard and to put them into the context of the patients
overall condition.
Perhaps the most significant use of hemodynamic
monitoring is that it allows physicians to continuously
assess responses to therapeutic interventions and to cor-
relate these responses with the patients overall condition.
The important phrase here is overall condition. When
the predefined targets have been met as assessed by the
monitoring tool, the physician can limit further interven-
tions and potentially prevent harm from excess use of the
interventions. Physicians deal with individual patients,
not populations and hemodynamic monitoring allows
the physician to determine the response to a therapy in
an individual patient. If the expected response does not
occur, it does not make sense to continue the therapy
in that patient even if it is recommended as a standard
treatment from large population studies.
Conditions in which there is a greater potential for
hemodynamic instability to occur and close monitoring is
warranted include: (1) patients with known cardiovascu-
lar disease who have either developed new cardiac
dysfunction or who are under increased risk of hemody-
namic or rhythmic instability because of surgery or a new
medical condition; (2) patients undergoing high-risk
surgical procedures and who are expected to have major
fluid losses as well as large fluctuations in blood pressure
and cardiac output and in whom the subsequent use of
careful volume resuscitation and vasoactive drugs are
likely to be required to maintain hemodynamic stability;
(3) Patients with recent large blood losses from trauma,
gastrointestinal sources, or large surgical losses;
(4) patients with severe sepsis or septic shock, (5) patients
with major burns and who will have challenging volume
management; (6) patients requiring ongoing analysis
of their respiratory status. In all these conditions
the changing pattern of the measurements are more
important than the actual values.
Applications
TechniquesMeasurements can be categorized as those related to
(1) rhythm and rate, (2) pressure, (3) flow measurements,
and (4) metabolic consequences of flow and oxygen
delivery.
Rhythm and RateHeart rate and rhythm are easily assessed with surface elec-
trodes and the amplified signal of the electrocardiogram. Theidentification of rapid or bradycardic rhythms is a subject by
itself and will not be dealt with here. However, a cautionary
note is worthwhile related to the significance of rapid sinus
rhythm. A rapid heart rate is always abnormal and should
alert the physician to look for causes. However, it does not
necessarily indicate that the rate should be slowed pharma-
cologically and I would suggest that unless the patient man-
ifests evidence of myocardial ischemia or is known to be at
high risk of myocardial ischemia, there currently is no evi-
dence that slowing the rate pharmacologically is beneficial.
Tachycardia also is not a reliable indicator of a patients
intravascular volume status. Patients with inflammation in
the area of the celiac axis (e.g., pancreatitis, post-surgery, or
who has abdominal abscesses), can often be tachycardic but
volume replete. This likely occurs from activation of sympa-
thetic afferents from local sympathetic ganglia, which
increase central sympathetic output. On the other side,
a normal heart rate does not rule out hypovolemia.
Pressures
General PrinciplesPressures that we measure are primarily due to the elastic
force that stretches the walls of vessels and the heart [3].
A key principle is that measured pressures are relative to
a reference value. Since we are normally surrounded by
atmospheric pressure, we are interested in deviations from
atmospheric pressure and atmospheric pressure actually is
the reasonable starting value or zero for our measure-
ments. A pressure of zero is actually not zero but around
760 mmHg and an arterial systolic pressure of 120 mmHg
is really about 880 mmHg. The commonly used units of
pressure as millimeters of mercury (mmHg) or centime-
ters of water (cmH2O) are based on the force produced by
the height of a column of fluid and the density of that
fluid. The density of mercury is 13.6 times greater than
that of water and this value can be used to interconvert the
values in cmH20 and mmHg.
The use of fluid-filled tubes to connect the patient to
a transducer introduces an additional gravitational com-
ponent to the pressure measurement. The difference in
height of the column of fluid between the reference level
on the patient and the transducer produces an addition
pressure of around 8 mmHg for every 10 cm height.
Standard and consistent leveling of the transducer to the
patient is thus essential for the comparison of values in
a particular patient to other patients and for trending
measurement over time in the same patient. The generally
accepted (although arbitrary) physiological reference
level is the midpoint of the right atrium for that is where
the blood comes back to the heart before it is pumped out
this level gives values of vascular pressures that are approx-
290 B Bedside Hemodynamic Monitoringimately 3mmHg higher than the value obtained by using 5
cm below the sternal angle. The appropriate level on the
transducer is the level of the stopcock that is used to open
the system to atmospheric pressure for zeroing.
It is the pressure across the wall of elastic structures
that determines the stretch of the wall; this is called
transmural pressure. The pressure outside the heart is
pleural pressure and not atmospheric pressure and
pleural pressure changes relative to atmospheric pressure
during the ventilator cycle. However, transducers that are
used to measure intrathoracic pressure are outside the
chest and referenced to atmospheric pressure and it is
not possible to easily obtain the pleural pressure to
calculate the transmural pressure. To minimize the error
produced by of changes in pleural pressure during the
ventilatory cycle, pressures are measured at the end of
expiration (which is also the point just before inspiration)
whether ventilation occurs with negative or positive
pressure ventilation. However, this does not account for
positive end-expiratory pressure and there is no simple
solution for this error. Although expiration is normally
passive, critically ill patients often have active expiratory
efforts and if these increase during the expiratory
phase, they increase the end-expiratory pressure that is
measured relative to atmosphere. In these situations,
the valid pressure is likely at the beginning of the
expiratory phase, before the patient begins to recruit
expiratory muscles.
Arterial PressureArterial pressure is themost commonly measured vascular
pressure and can be measured invasively with intravascu-
lar catheters or noninvasively by the classic auscultation
method or by devices that use oscillometry. These latter
devices are frequently used for repeated automatic mea-
surements, but it is important to appreciate that the values
obtained with these devices need to be validated with
occasional auscultatory measured pressures for they can
sometimes produce artifactual values of pressure.again. That level is approximately 5 cm vertical distance
below the sternal angle which is where the second rib
meets the sternum and is valid when the patient is flat or
sitting at up to 60. Accurate measurement of this levelrequires a carpenters leveling device and a marker of 5 cm
below the device so that it is more popular to reference
transducers to the midpoint of the thorax at the fourth rib.
This position, though, should only be used in the supine
position for it will vary relative to themidpoint of the right
atrium when the upper body is elevated. Referencing atIn patients in the ICU following surgical procedures
upper limits for pressure are often set to reduce the risk of
bleeding. Identification of high pressure is also important
in patients with hypertensive crisis, aortic dissection, or an
unstable aneurysm, but not as important in the short run
in most other patients. In the majority of cases, decreased
arterial pressure is the primary concern. Despite the fre-
quency of the hypotension and its aggressive treatment, it
is amazing how little empiric knowledge there is for
acceptable limits of low pressures and whether the impor-
tant pressure is the systolic, mean, or diastolic pressure. It
is important to remember that flow to the tissues, or even
more precisely delivery of oxygen and nutrients and
clearance of waste is what counts and not pressure.
The pressure is used as a surrogate for potential
flow. The patients clinical status provides an important
guide. A low pressure in patient who is awake with normal
sensorium, who has stable renal function, and no acidosis,
is likely of no consequence. However, in many patients
some or all of these are abnormal. The pressure may or
may not be a contributor and empiric values must be
chosen to guide therapy.
There are advantages and disadvantages for the
choices of any one of systolic, diastolic, or mean pressure.
When the pressure is measured by auscultation, it is gen-
erally a low systolic pressure that triggers clinical responses
and provides a convenient signal. When arterial catheters
and transducers are used to measure pressure, the charac-
teristics of the measuring device can affect the observed
systolic pressure and one must be careful to make sure that
the waveform of the signal is appropriate and not over- or
under-damped. The mean pressure should be related to
overall flow to organs with higher flows, but does not give
a good guide to regions that receive more of their flow in
systole. There are some patients who also have a low
diastolic pressure but high systolic pressure and targeting
the mean can result in high doses of vasopressor. Finally,
diastolic pressure is important for coronary flow, but
excess use of vasopressors to raise the diastolic pressure
could end up increasing myocardial oxygen demand by
increasing systolic pressures and cardiac ionotropy
and also decrease coronary flow by constricting the
coronary arteries.
Ideal pressures really need to be established empiri-
cally, but there are few rigorous studies to provide guid-
ance. Optimal arterial pressures have been studied best for
the kidney and it is suggested that a minimal mean pres-
sure of 80 mmHg is required for normal renal function.
However, this value is primarily derived from animal
studies over short periods of time and without underlying
vascular or intrinsic renal disease. Septic patients are an
It is also the change in CVP in relation to other hemody-
pulmonary vascular changes, obstructive processes, or
Bedside Hemodynamic Monitoring B 291
Bobliterative processes.
Inflation of a balloon at the end of a pulmonary cath-
eter or advancing a pulmonary catheter until the end-hole
occludes the vessel gives the pressure distal to the end-hole
which after equilibration is equal to the left atrial pressure.
This wedged pressure provides diagnostic information
about the behavior of the left side of the heart. It also gives
an indication of the minimal pressures in the pulmonary
capillaries and thus the hydrostatic force that drives pul-
monary capillary filtration. On the other hand it does not
give an indication of the preload status of the heart as
a whole for that is related to the CVP for the left heart can
only put out what the right heart gives it. An important
use of these catheters is that they provide a simple tool for
measuring cardiac output which is discussed below.namic events that is helpful. Importantly, CVP by itself is
not an indicator of blood volume.
Pulmonary Arterial and Pulmonary ArterialOcclusion PressurePulmonary artery pressure is an important indicator of
the load on the right ventricle. It is also an indicator of
pathology in the pulmonary vasculature. The pulmonary
artery pressure can be elevated passively because of high
left heart pressures, high pulmonary flow and reactiveinteresting example where monitoring pressure and urine
output can allow individualization of pressure targets.
Elevation of arterial pressure with vasopressors can restore
renal blood flow and function and this individualized
pressure thus provides a useful pressure target for the use
of vasopressors in these patients.
One must be careful of some potential measurement
problems that can occur. Patients with a stenosis proximal
to the measuring device will appear to have low arterial
pressures, when in fact central pressure is normal.
In patients who have a distal arterial catheter and who
are receiving high doses of vasopressors, constriction of
the vessel can lead to underestimates of the central
pressure.
Central Venous PressureCentral venous pressure (CVP) is a commonly used mea-
sure and can even be estimated without a catheter by
examining the level of jugular venous distension [4].
A fuller discussion of the use of CVP with changes in
cardiac output will be given below for the CVP is only
useful in conjunction with an estimate of cardiac output.Cardiac OutputThe cardiac output, liter per minute, is a major compo-
nent of the ultimate clinical end-point which is the deliv-
ery of nutrients to the tissues and removal of waist and
thus a very desirable value to measure [5, 6]. Unfortu-
nately, flow is not as easy to measure as pressure. One of
the most reliable methods but a cumbersome one is based
on the dilution of an indicator that is injected at
a proximal site such as a major vessel and detected by
a sensor at a downstream site. Indocyannine green was
one of earliest indicators, but the development of thermal
sensing catheters allowed the use of temperature which is
a much simpler indicator to use although it has more
potential errors. Small doses of lithium can also be used
as an indicator. Placement of the thermistor in the pul-
monary artery allows injection of a solution that is cooler
than blood into the right atrium and sensing the change in
temperature in the pulmonary artery but this requires
passing a catheter through the right heart and the risks
of arrhythmias and perforation. The alternative is to place
the sensor in an artery which generally needs to be bigger
than a radial artery so that it also has an invasive compo-
nent and is not without risks. Two key requirements for
the use of an indicator dilution technique are that there
must be immediate complete mixing and no loss of indi-
cator. This can be a problem when the injection is made
in the right atrium and the patient has tricuspid insuffi-
ciency for some of the indicator (temperature) is poten-
tially lost when the blood goes back and forth and mixing
may not be complete because of the regurgitant flow.
Pulmonary catheters can also be equipped with a sensor
for oxygen saturation and these catheters allow the
measurement of cardiac output continuously.
Flow can also be measured with Doppler techniques
which detect the velocity of blood by the phase shift of the
Doppler wave when it hits the flow pulse and gives
a measure of the stroke volume which is then converted
to cardiac output by multiplying by the heart rate.
The calculation of flow from velocity requires a measure
of the cross-sectional area of the vessel for flow is equal to
the product of velocity and the cross-sectional area of the
vessel. The latter is not always easy to obtain and is often
assumed, which is reasonable under basal conditions but
not when a patient is in shock. Continuous assessment of
flow by Doppler probes can be made with a probe placed
in the esophagus but this is really only tolerable in
a heavily sedated or unconscious patient. Appropriate
positioning of the catheter must also be made.
Devices have also been developed to measure the elec-
trical impedance related to blood volume and the changes
during the cardiac cycle give a measure of stroke volume.
ascending part of its function curve. If the cardiac output
increases, more volume can be given to try to maintain the
desired values, but importantly a positive response only
means that the patient is volume responsive but it does not
indicate that the patient actually needs volume. That is
a clinical decision. If the cardiac output does not increase
with a bolus that increased the CVP by 2 mmHg or more,
the patient should be considered volume unresponsive
and further volume loading will not help and may be
harmful no matter what the starting CVP value. This
situation indicates limitation of right ventricular output
and even if the left heart is deemed to be underfilled based
on the pulmonary artery occlusion pressure or by
292 B Bedside Hemodynamic Monitoring
This too is multiplied by heart rate to give cardiac output.
These devises give reasonable estimates in normal subjects
but there are potential problems in critically ill patients
who have increased chest wall edema, pleural or pericar-
dial effusions, or hyperinflated chests
A number of techniques have been developed to try to
estimate stroke volume from the pulse pressure. This
requires knowledge of the elastic properties of the patients
vessels which is hard to predict in individual patients. It
will also vary with disease and likely be very sensitive to the
volume in the vessel for elastance is curvilinear against
the radius of vessels. These techniques can give trends in
patients who do not have major pathology but likely will
not be useful in patients who are hemodyanmically unsta-
ble which is when you really need them.
All techniques that attempt to measure stroke volume
and calculate cardiac output by multiplying stroke
volume by heart rate will always show at least a moderate
relationship to direct measurements of cardiac output for
populations but one must be cautious about extrapolating
this to individual patients. This is because the heart rate,
which provides a very reliable measure, is a large percent-
age of the product and therefore drives a large part of the
correlation. However, it is often the smaller changes in
stroke volume that are important for that it identifies
changes in cardiac muscle function.
Therapeutic ApplicationAs discussed above, the values of pressures and flow that
are adequate for a patients metabolic need are not well
empirically established and need to be customized to the
individual patient. However, hemodynamic monitoring
that includes a measure of cardiac output can be useful
for detecting a decrease from the values that the patient
had when deemed stable or becomes stable and also to
identify the dominant hemodynamic process. Clinical
responses are most often triggered by decreases in arterial
blood pressure. Arterial pressure is approximately equal to
the product of cardiac output and systemic vascular resis-
tance (SVR) (Fig. 1). The two measured values are arterial
pressure and cardiac output (or a surrogate) so that SVR is
a derived variable. This means that it is changes in cardiac
output that are key. If the blood pressure is low and cardiac
output is normal or elevated, the primary problem is
a decrease in SVR and the differential diagnosis for the
problem is specific. If the cardiac output is depressed, then
the next question is why is it decreased? The steady-state
cardiac output is determined by the interaction of cardiac
function (based on the FrankStarling relationship) and
the function that determines venous return. These twofunctions intersect at the working cardiac output and the
working right atrial pressure which is approximately the
same as the CVP. A low cardiac output with a high CVP
indicates that the cardiac function is the primary limiting
factor, whereas a low cardiac output with a low CVP
indicates that the return function is the primary limiting
factor and the most common cause is inadequate vascular
volume. The specific values are not as useful as the change
in values. A fall in cardiac output with a rise in
CVP indicates a decrease in cardiac function and a fall in
cardiac output with a fall in CVP indicates a return
problem, which is most commonly insufficient vascular
volume (Fig. 2).
If inadequate volume is thought to be the primary
problem then the best test is to do a volume challenge
[4]. In this procedure, a small bolus is given quickly with
the aim of raising CVP. The faster the fluid is given the less
fluid that is needed. The hemodynamic variable that one is
trying to correct needs to be reassessed as soon as the CVP
is increased. A reasonable value for the increase in CVP is
2 mmHg because that is a value that can be detected with
certainty on a monitor. It also should produce an obvious
increase in cardiac output if the heart is functioning on the
Part = Q x SVR (+K)
CircuitStressed volumecomplianceresistancePra
SepsisDrugsSpinal
HeartHeart rateAfterloadContractilityPreload
Dobutaminemilrinone
VolumeNE NE
Bedside Hemodynamic Monitoring. Figure 1 Predictions of
changes of cardiac output and changes in CVP
Implications of changes in cardiac output and CVP
se
em
up
ed
ou
Bedside Hemodynamic Monitoring B 293
Bechocardiography, volume will not solve the problem for
the left heart can put out what the right heart gives it. This
raises an important limitation of the use of echocardiog-
raphy for hemodynamic monitoring as is sometimes
advocated [7]. Besides not being able to provide easy and
rapid assessment of serial values, it mainly assesses left
heart function, but the output of the left heart is totally
dependent upon right heart function which often does not
functioning well in critically ill even though left ventricu-
lar function is intact. In that situation, the volume status
of the left ventricle is no help for fluid management.
There have been many attempts to use the respiratory
variations in arterial pressure or pulse with positive
pressure ventilation to predict volume responsiveness
[8]. These techniques can be effective but are only valid
if there are no spontaneous inspiratory or expiratory ven-
tilatory efforts by the patients. The various values given for
these variations also are only valid when the patient is
ventilated with the same ventilator parameters as in the
original study and when the rhythm is regular. Their use is
thus limited.
An inspiratory fall in CVP with a spontaneous
(negative pressure swing) breath, whether the patient is
on a ventilator or not, has also been shown to predict
volume responsiveness [4]. The test works best in the
Cardiac Output CVPDecreased Decreased Decreased Increased Increased Increased Increased Decreased
Bedside Hemodynamic Monitoring. Figure 2 Approach to as
management. Part arterial pressure, Q cardiac output, SVR syst
downstream value of pressure because the true equation is
pressure (= CVP), NE norepinephrine. Cardiac output is determin
the preload of the cardiac function is the Pra which is also thenegative. Absence of an inspiratory fall in CVP in
a patient with an adequate effort indicates that the patient
will not have an increase in cardiac output in response to
an infusion of volume. When using this technique, one
must be careful to make sure that the inspiratory fall in
CVP is not in fact the release of a forced expiration that
looks like an inspiratory fall and produces an apparent
false positive.
Information can also be gathered by examining wave-
forms. As some examples, a wide arterial pulse pressure is
suggestive of a low SVR. Prominent y descents in the
CVP tracing suggest that the right heart is volume limitedand will not respond to further volume loading. A large
C-V wave in the CVP tracing is indicative of tricuspid
regurgitation. A prominent v in the pulmonary artery
occlusion pressure is indicative of mitral regurgitation but
is seen when there is excessive filling of the left heart.
A loss of a y descent in the CVP can be a sign of the
development of cardiac tamponade.
ConclusionThe important part of bedside monitoring is not the
actual values but the changes in the values as they related
to changes in the patients condition. In a sense, the
meaning of a patients values should be calibrated to
the clinicians impression of the patients overall status.
This is especially important when trying to gauge the
impact of therapeutic interventions. The value of
the information obtained by bedside monitoring can
only be as good as the skill of the clinicians and nurses
receiving them.
References1. Vincent JL, Pinsky MR, Sprung CL, Levy M, Marini JJ, Payen D,
Rhodes A, Takala J (2008) The pulmonary artery catheter: in medio
virtus. Crit Care Med 36:30933096
2. HadianM, PinskyMR (2006) Evidence-based review of the use of the
pulmonary artery catheter: impact data and complications. Crit Care
IndicatesDecreased return (most often volume )Decreased Pump functionIncreased return (likely volume ) Increased pump function
ssment of cause of hypotension and simplified approach to
ic vascular resistance, K a constant representing the
stream minus downstream pressure Q x SVR, Praright atrial
by the interaction of the cardiac function and return function;
tflow pressure for the venous return (circuit)10(Suppl 3):S8
3. Magder S (2007) Invasive intravascular hemodynamic monitoring:
technical issues. Crit Care Clin 23:401414
4. Magder S (2006) Central venous pressure: a useful but not so simple
measurement. Crit Care Med 34:22242227
5. Magder S (1997) Cardiac output measurement. In: Tobin MJ (ed)
Principles and practice of intensive care monitoring. McGraw-Hill,
Chicago, pp 797810
6. de Waal EE, Wappler F, Buhre WF (2009) Cardiac output monitor-
ing. Curr Opin Anaesthesiol 22:7177
7. Vignon P (2005) Hemodynamic assessment of critically ill patients
using echocardiography doppler. Curr Opin Crit Care 11:227234
8. Magder S (2004) Clinical usefulness of respiratory variations in
arterial pressure. Am J Resp Crit Care Med 169:151155
Being the Active Part of Fish Oil
Serum and Urinary Low Molecular Weight Proteins
JONATHAN BALL
General Intensive Care Unit, St. Georges Hospital &
Beta-adrenoceptor blocking drugs (b-blockers) have beena mainstay of therapy for hypertension, myocardial ische-
mia, and, more recently, cardiac failure. The current Brit-
b-blockers involves marked differences in their pharma-codynamics as well as differences in their pharmacokinet-
ics. Our understanding of adrenergic receptors and the
294 B Bedside Ultrasonographymyriad roles the sympathetic nervous system plays, in
both health and disease, continues to increase. Coupled
with the extensive body of trial data examining, the role ofish National Formulary [1] lists 15 b-blockers while themedical literature contains at least as many agents again,
either in development or consigned to history. Unlike
most other classes of drugs, the heterogeneity betweenMedical School, University of London, London, UK
IntroductionBeta-BlockersOmega-3 Fatty Acids
Beta-2-MicroglobulinBedside Ultrasonography
Ultrasound: Uses in ICU
Bedside Ultrasound
Shock, Ultrasound Assessmentb-blockers in a diverse group of settings has resulted inmuch ongoing controversy. In critical care, not only do we
need a clear understanding of the risks and benefits of
acute therapy with b-blockers, but we must also be awareof the consequences of chronic therapy in our patients.
Basic ScienceThe sympathetic nervous system has two principal trans-
mitters, noradrenaline (norepinephrine) and adrenaline
(epinephrine). The receptors for these endogenous ago-
nists have been classified into alpha and beta with more
recent identification of a number of subtypes. Beta-
adrenoceptors are found in nearly every human organ
and tissue. There are three subtypes: b1, b2, and b3. A b4subtype was believed to exist but has been proven to be the
b1-receptor in a different conformational state with dis-tinct agonist/antagonist binding [2]. Their tissue location
and agonist binding responses are detailed in Table 1.
Pathophysiologically and therapeutically cardiac beta-
adrenoceptors have been studied in the greatest detail
[3, 4]. A review of beta-adrenoceptor physiology, patho-
physiology, and polymorphisms can be found here [12].
Despite this body of research many questions remain
unanswered.
An important property of beta-adrenoceptors is the
autoregulatory process of receptor desensitization. This
process operates to prevent overstimulation of receptors
in the face of excessive beta-agonist exposure. Desensiti-
zation occurs in response to the association of receptor
with the agonist molecule, and is prevented by the inter-
action of the receptor with an antagonist. The mecha-
nisms by which desensitization can occur consist of three
main processes: (1) uncoupling of the receptors from
adenylate cyclase, (2) internalization of uncoupled recep-
tors, and (3) phosphorylation of internalized receptors.
The extent of desensitization depends on the degree and
duration of the receptor agonist or antagonist response
[13]. From the perspective of b-blockade, the physiologi-cal process of desensitization results in an increase in
sensitivity in subjects exposed to chronic blockade.
Indicationsb-blockers have been used for multiple indications formany decades. Perhaps surprisingly therefore, many gaps
remain in our knowledge with regard to the optimal use of
currently available agents. Commonly used b-blockersexhibit variable degrees of relative affinity to b1-, b2-,and b3-receptors [14]. The effect of drug receptor bindingalso produces variable effects with some agents producing
universal antagonism, while others produce partial
te
oat
ty
sti
Beta-Blockers B 295
BBeta-Blockers. Table 1 Subtypes of beta-adrenoceptors. Adap
Receptor Tissue Response to agonist
b1 Heart (b1:b2 70:30 atria,80:20 ventricles)
Increases heart rate (sin
node, cardiac contractili
Ubiquitous coupling toagonism or inverse agonism [15, 16]. Table 2 summarizes
the pharmacology of the most commonly used b-blockers.It should be stressed that b-blockers are a very heteroge-neous group of drugs. Indeed, much of the controversy
surrounding their optimal use results from the wide-
Pro-apoptotic
Chronic stimulation results
Lung (20%) [8] Bronchodilatation [9]?Juxtaglomerular cells Increases rennin secretion
Innate and adaptive
immune cells
Pro-inflammatory
Coagulation system May increase platelet aggr
Brain Poorly characterised [10]
b2 Heart (b1:b2 70:30 atria,80:20 ventricles)
Increases heart rate (sinoat
node, cardiac contractility
Coupled to both stimulato
Anti-apoptotic
Chronic stimulation results
Lung (180%) [8] Bronchodilatation and alveSmooth muscle Relaxation of smooth mus
tract
Skeletal muscle Glycogenolysis; uptake of
Liver Glycogenolysis; gluconeog
Pancreas Insulin and glucagon secre
Thyroid T4 to T3 conversion
Innate and adaptive
immune cells
Downregulate the synthes
anti-inflammatory cytokine
Coagulation system Reduces platelet aggregab
concentration; increases fib
Brain Poorly characterized [10]
b3 Heart Inactive during normal phyStimulation seems to prod
b1- and b2-receptors [11]
Smooth muscle Relaxation of smooth mus
genitourinary tract
Brain Present in discrete regions
cerebral cortex areas know
responsible for the negativ
disorder
Adipose tissue Lipolysis; thermogenesisd from [37]
rial firing), impulse conduction through the atrioventricular
(>b2), and rate of relaxationmulatory G-proteinsranging pharmacodynamic and pharmacokinetic proper-
ties of available agents and the lack of comparative studies
in patients. Thus, for each indication, the choice of b-blocker significantly influences the balance of risks and
benefits.
in endocytosis and reduction in functional density
egability; may decrease fibrinolytic activity
rial firing), impulse conduction through the atrioventricular
(
Beta-Blockers.Table
2Commonlyusedb-blockers
andtheirpharmacology[17,1
8]
Drug
Relativereceptoraffinity
Lipo*
PB(%
)Enteral
IVT1/2
Metabolism
andelimination
Notes
b1:b
2b
2:b
3b1:b
3
Atenolol
4.7:1
76:1
355:1
+10
50%
absorption
68h
100%
GF
Remove
dbyhemodialysis
Bisoprolol
13.5:1
10.7:1
145:1
++
30
100%
absorption10%
FPM
912h
50%
GF.RemainderCYP450
toinactive
metabolites
Carve
dilo
l1:4.5
12.6:1
2.8:1
+++
98
100%
absorption75%
FPM
610h
98%
CYP450to
active
metabolites,mostlyexcreted
inbile
Racemicmixture,o
nlyS(-)
enan
tiomerhas
b-blocking
activity.B
oth
enan
tiomers
areselectivea 1-adrenergic
antagonists.C
a2+entry
blockad
e.A
ntioxidan
t.
Antiproliferative
.
Vasodilating.W
eak
membranestab
ilizer
Esmolol
32:1
+55
9min
Rap
idlyan
dextensive
ly
metabolizedviaRBC
esterases.Inactive
metobilte
100%
GF
Moderatelyb 1
selective
Labetalol
1:2.5
71:1
28:1
+50
100%
absorption75%
FPM
48h
95%
conve
rtedto
inactive
glucu
ronideofwhich60%
GF
andremainderin
bile
Racemicmixture
withtw
o
opticalcenters.Selectivea 1-
adrenergican
tagonist.b 2
partial
agonist.Vasodilating
Metoprolol
2.3:1
54:1
126:1
++
12
100%
absorption50%
FPM
34h
510%
GF.Remainder
CYP450to
inactive
metabolites
Crossesnorm
alBBB(CSF
leve
ls78%
ofserum).Despite
minim
alprotein
bindingnot
significan
tlyremove
dby
hae
modialysis
296 B Beta-Blockers
Nevibolol
47:1
+++
98
100%
absorptionExtensive
FPM
827h
CYP450to
3metabolites,one
ofwhichisactive
.Subject
to
polymorphismshence
wide
spectrum
ofT1/2.A
ctive
metaboliteisdependan
t
uponGFforelim
ination
Racemicmixture.H
ighlyb 1
selectivean
tagonistan
db 3
agonist.Vasodilating
propertiesbydirect
actionon
endotheliu
m,p
ossiblybyNO
production/release
Propranolol
1:8.3
141:1
17:1
+++
90
100%
absorption
Extensive
FPM
34h
Eightmetabolites,at
least1
active
.Elim
ination
independentofGF
Racemicmixture,o
nly
l-isomeractive
.Moderate
membranestab
ilizingeffect.
DecreasesHbO2affinity.
Decreasesplatelet
aggregab
ility.C
rossesnorm
al
BBB
Sotalol
1:12
63:1
5.2:1
+10
100%
absorption
1020h
100%
GF
Racemicmixture.C
lass
IIan
d
IIIan
ti-arrhythmicactivity.
Potentiallypro-arhythmicin
thepresence
of
hyp
okalaemia.P
artially
remove
dbyhae
modialysis
Tim
olol
1:26
758:1
2.1:1
++
1030
90%
absorption50%
FPM
45h
80%
CYP450to
inactive
metabolites.20%
+
metabolitesviaGF
Commonlyusedin
ophthalmicpreparationsbut
associatedwithsignifican
t
systemiceffects
Notes:Relative
receptoraffinitydatatakenfrom
[14].Lipo*=lip
ophilicity.Lipophilicity
isassociatedwithCNSpenetrationan
dbetterCVSoutcomes[19].PB(%
)=percentageprotein
bound.
IV=intravenouspreparationavailable
intheUK.T
1/2=elim
inationhalflife.G
F=glomerularfiltration/renal
clearan
ce
Beta-Blockers B 297
B
298 B Beta-Blockers
HypertensionThe optimal role of b-blockers as a class, and specificagents in particular, in the management of chronic hyper-
tension, remains controversial [20]. However, in patients
with hypertensive crises (malignant hypertension and pre-
eclampsia) or those in whom rapid reduction/control is
indicated (aortic dissection and spontaneous Intracerebral
hemorrhage) b-blockers have an established role. In thesesetting, intravenous (IV) labetolol, usually as an infusion
(15160 mg/h titrated to response), is commonly
employed as a first-line agent. Of the commonly available
b-blockers, labetolol has several pharmacodynamic andpharmacokinetic properties that make it the optimal
choice. In addition to its b1 antagonism, it is also a b2partial agonist and a1-adrenergic antagonist thus pro-duces a significant vasodilating effect. It is available as an
intravenous preparation and has a relatively short elimi-
nation half-life.
Ischemic Heart Disease (IHD)b-blockers have an established role in the management ofacute and chronic angina, acute coronary syndromes,
myocardial infarction [20], and during percutaneous cor-
onary intervention (PCI) [21]. Most of these effects are
mediated through b1 antagonism, which results in [20]:
1. A reduction of myocardial oxygen requirements by
a decrease in heart rate, systolic pressure, and ventric-
ular contractility
2. Bradycardia, which prolongs the coronary diastolic
filling period
3. A reduction in arrhythmogenic free fatty acids
4. A redistribution of coronary flow to vulnerable
subendocardial regions
5. A reduction of platelet stickiness
6. An increase in the threshold to ventricular fibrillation
7. A reduction in infarct size
8. A reduction in risk of cardiac rupture
9. A reduction in the rate of reinfarction
However, the evidence of efficacy of the use of b-blockers,especially in the acute setting, has been questioned by
some authors [22, 23]. Atenolol, metoprolol, and
bisoprolol are the most widely investigated and utilized
b-blockers in the management of IHD. Each agent has itsstrengths and weaknesses and no comparative trials exist.
Optimal dosing remains controversial; however, up-
titration to maximal tolerated doses is widely advocated.
Adequate dosing can be judged by both resting heart rate
(target
Beta-Blockers B 299
B(New York Heart Association class II, III and IV), regard-
less of etiology [36, 37]. b-blockers improve myocardialperformance (increase in ejection fraction of 510%) and
prevent complications of cardiac failure by the following
means [20]:
1. Bradycardia, leading to increased diastolic coronary
filling time (particularly relevant to ischemic heart
failure)
2. Reduction in myocardial oxygen requirements
3. Antiarrhythmic activity
4. Upregulation of b1 receptors5. Inhibition of the rennin/angiotensin system
6. Increasing atrial and brain naturetic peptide secretion
7. Inhibition of catecholamine-induced necrosis. This is
an effect of both b1 antagonism and b2 agonism
There have been positive outcome trials for carvedilol,
metoprolol, bisoprolol, and nevibolol and even a trial
comparing carvedilol and metoprolol. Whether b1 selec-tivity is an advantage or disadvantage remains controver-
sial, however, carvedilol may be the optimal agent [32]. Of
note, nevibolol, in addition to its marked b1 selectivity, isa b3 agonist. Whether b3 agonism is a good or bad thing inchronic cardiac failure remains unclear [11].
b-blocker therapy should not be initiated in patientswith acute decompensation of cardiac failure, until their
condition has been stabilized, however, long-term therapy
should not be stopped unless shock is evident. Therapy
should be started/restarted at the earliest opportunity.
Therapy should commence at a low dose and be up-
titrated to the maximal tolerated dose. Again, controversy
exists as to the best determinant of effective dose in an
individual.
Portal Hypertension and VaricealHemorrhageNonselective b-blockers have an established role both inthe primary and secondary prevention of variceal hemor-
rhage [38]. Propranolol is the most widely used agent. The
recommended starting dose is 40 mg twice daily, increased
as tolerated up to 160 mg twice daily. Carvedilol [39] and
nadolol [40] have also been investigated but their place in
therapy remains undefined.
To prevent bleeding/re-bleeding, nonselective
b-blockers must reduce the hepatic venous pressure gra-dient (HVPG) to
300 B Beta-Blockers
harm than good. The effects of selective or nonselective b-blockade on the innate and adaptive immuno-
inflammatory systems, remains speculative, but b1-blockade coupled with b2 stimulation is a potentiallyattractive therapeutic target.
Thyroid Storm [46]b-blockers relieve the symptoms of thyrotoxicosis but donot modify the underlying disease. Their use is advocated
in the acute management of a thyrotoxic crisis (storm) as
part of package of endocrine care. Nonselective b-blockersare usually recommended though this is predominantly
based on historical president.
Useful Neuropsychiatric effects?Agitation and aggressive behavior, following acquired
brain injury is a common and complex problem for
which numerous pharmacological and therapeutic strate-
gies have been trialled. There is some evidence from small-
scale trials to suggest propranolol and possibly pindolol
may form part of a useful strategy in reducing agitation
and aggression following moderate to severe brain injury
[47]. Early studies also suggest a potential role for pro-
pranolol in both the prevention and treatment of post-
traumatic stress disorder [48].
b-blockers appear to causemeasurable neuropyschiatriceffects including sleep disturbance, vivid dreams, anxiolysis,
and subtle effects on memory. When administered during
general anesthesia, they appear to exhit antinociceptive
and anesthetic-sparing effects [49, 50]. Whether this is
a synergistic effect or merely a result of b-blockers alteringthe pharmacokinetics of opiates and anesthetic agents
remains unclear.
Contraindications [1] Second- and third-degree heart block Cardiogenic shock Peripheral arterial insufficiency (relative contraindica-
tion as vasodilating agents may be well tolerated)
Asthma (relative contraindication as highly b1 selec-tive agents may be tolerated)
Recurrent hypoglycemia
Adverse Reactions [1]b-blocker therapy may be associated with the followingadverse reactions:
Generalized fatigue. Cardiovascular hypotension, bradycardia, asystole,
cardiogenic shock. A deterioration in symptoms of
peripheral arterial insufficiency. Respiratory bronchospasm, due to b2-blockade,which may be averted by using highly b1 selectiveagents. b-blockers are generally well tolerated inchronic obstructive pulmonary disease. The respira-
tory effects of b-blockers in chronic cardiac failure arecomplex and reviewed here [51]. In short, the overall
effect is beneficial but some drug-specific effects may
have detrimental effects in some individuals. Monitor-
ing of pulmonary function is advised.
Brain sleep disturbances with nightmares, believedto be less common with the less lipophilic agents.
Metabolic a small deterioration of glucose toleranceand interference with the metabolic and autonomic
responses to hypoglycemia. They may also cause an
increase in serum triglycerides, low density and very
low density lipoprotein cholesterol, and a decrease in
high density lipoprotein cholesterol.
b-Blocker Toxicity and Overdose [52]In addition to supportive care beta-adrenoceptor agonists,
phosphodiesterase inhibitors (e.g., milrinone), glucagon,
and hyperinsulinemic euglycemia have been investigated
as antidotes. Individually, none are reliably effective and
only anecdotal reports support combination therapy.
Atenolol and sotalol may be significantly cleared by
hemodialysis.
Drug Interactions Class Effects [1]Synergistic effects with other antihypertensives can lead to
symptomatic hypotension. Synergistic effects with other
negative chronotropes can lead to symptomatic bradycar-
dia and even asystole. Synergistic effects with other nega-
tive inotropes can lead to cardiogenic shock. Use with a1agonists can result in severe hypertension.
Drug Interactions Specific Agents [1]Propranolol decreases the threshold for lidocaine and
bupivacaine toxicity. Sotalol increases the risk of ventric-
ular arrhythmias when coadministered with any drug that
causes QT prolongation.
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