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## Complete Summary

#### GUIDELINE TITLE

Practice parameters for hemodynamic support of sepsis in adult patients:
2004 update.

#### BIBLIOGRAPHIC SOURCE(S)

Hollenberg SM, Ahrens TS, Annane D, Astiz ME, Chalfin DB, Dasta JF,
Heard SO, Martin C, Napolitano LM, Susla GM, Totaro R, Vincent JL,
Zanotti-Cavazzoni S. Practice parameters for hemodynamic support of
sepsis in adult patients: 2004 update. Crit Care Med 2004
Sep;32(9):1928-48. \[230 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15343024)

#### GUIDELINE STATUS

This is the current release of the guideline.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

-   Sepsis

-   Septic shock

#### GUIDELINE CATEGORY

> Management\
> Treatment

#### CLINICAL SPECIALTY

> Cardiology\
> Critical Care\
> Infectious Diseases\
> Internal Medicine

#### INTENDED USERS

> Health Care Providers\
> Physicians

#### GUIDELINE OBJECTIVE(S)

-   To provide guidelines for hemodynamic support in sepsis to maintain
    adequate organ system and cellular perfusion

-   To review the state of knowledge concerning hemodynamic therapy of
    sepsis and to supplement specific therapeutic recommendations with
    guidelines about how to optimize therapy and how to evaluate the
    results of therapeutic interventions

> **Note**: Consideration of activated protein C and other therapies not
> directed at hemodynamic stabilization is outside the scope of these
> practice parameters.

#### TARGET POPULATION

> Adult patients with sepsis and septic shock

#### INTERVENTIONS AND PRACTICES CONSIDERED

> **Monitoring**

1.  Continuous electrocardiography (ECG)

2.  Monitoring of:

    -   Heart rate

    -   Stroke volume

    -   Cardiac output

    -   Systemic vascular resistance

    -   Indexes of regional or global perfusion

    -   Urinary output

3.  Pulse oximetry

4.  Laboratory measurements

    -   Arterial blood gas

    -   Serum electrolytes

    -   Complete blood count

    -   Coagulation variables

    -   Lactate concentrations

    -   Creatinine clearance

    -   Hemoglobin

    -   Hematocrit

5.  Blood pressure (via arterial cannula)

    -   Systolic blood pressure (SBP)

    -   Mean arterial pressure (MAP)

6.  Hemodynamic assessment (via right heart catheterization)

    -   Central venous pressure

    -   Central venous oxygen saturation

    -   Mixed venous oxyhemoglobin saturation (SVO~2~)

7.  Glomerular filtration rate

8.  Splanchnic blood flow

> **Hemodynamic Therapy**

1.  Fluid resuscitation therapy

    -   Crystalloids

        -   0.9% sodium chloride (normal saline)

        -   Lactated Ringer\'s solution

        -   Hypertonic saline solutions

    -   Colloids

        -   Plasma protein fraction

        -   Albumin

        -   Gelatins

        -   Dextrans

        -   Hydroxyethyl starch

2.  Transfusion therapy

3.  Vasopressor therapy

    -   Dopamine

    -   Norepinephrine

    -   Phenylephrine

    -   Epinephrine

    -   Vasopressin

        -   Arginine-vasopressin

        -   Lysine-vasopressin (terlipressin)

    -   Corticosteroids

        -   Hydrocortisone

        -   Fludrocortisone

        -   Methylprednisolone

4.  Inotropic therapy

    -   Isoproterenol

    -   Dopamine

    -   Dobutamine

    -   Norepinephrine

    -   Epinephrine

    -   Phosphodiesterase inhibitors (e.g., milrinone)

#### MAJOR OUTCOMES CONSIDERED

-   Mortality

-   In-hospital mortality

-   Organ dysfunction

-   Predictive value of diagnostic tests

-   Survival rates

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

> Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

> The information and recommendations are predicated upon an
> expert-based review of the available scientific data, clinical
> investigations, and outcomes research. Where such data are unavailable
> or limited in scope, consensus was attained by considering published
> expert opinion and discussion among a wide range of experts.

#### NUMBER OF SOURCE DOCUMENTS

> Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

> Expert Consensus (Committee)\
> Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

> **Level I**: Large, randomized trials with clear-cut results; low risk
> of false-positive (alpha) error or false-negative (beta) error
>
> **Level II**: Small, randomized trials with uncertain results;
> moderate to high risk of false-positive (alpha) error and/or
> false-negative (beta) error
>
> **Level III**: Nonrandomized, contemporaneous controls
>
> **Level IV**: Nonrandomized, historical controls and expert opinion
>
> **Level V**: Case series, uncontrolled studies, and expert opinion

#### METHODS USED TO ANALYZE THE EVIDENCE

> Review of Published Meta-Analyses\
> Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

> The experts reviewed the literature and classified the strength of
> evidence of human studies according to study design and scientific
> value.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

> Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

> Recommendations were drafted and graded levels based on an
> evidence-based rating system (See \"Rating Scheme for the Strength of
> the Recommendations\"). The recommendations were debated, and the task
> force chairman modified the document until \<10% of the experts
> disagreed with the recommendations.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

> **Strength of Recommendations**

A.  Supported by at least two level I investigations

B.  Supported by only one level I investigation

C.  Supported by level II investigations only

D.  Supported by at least one level III investigation

E.  Supported by level IV or level V investigations only

#### COST ANALYSIS

> A formal cost analysis was not performed and published cost analyses
> were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

> Not stated

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

> Not applicable

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

> The classes of recommendations (A-E) and levels of evidence (I-V) are
> defined at the end of the \"Major Recommendations\" field.
>
> **[Recommendations for Hemodynamic Support of Septic
> Patients]{.underline}**
>
> **Basic Principles**

1.  Resuscitation of patients with sepsis should be initiated
    expeditiously and pursued vigorously. Measures to improve tissue and
    organ perfusion are most effective when applied early.

2.  Patients with septic shock should be treated in an intensive care
    unit, with continuous electrocardiographic monitoring and monitoring
    of arterial oxygenation.

3.  Arterial cannulation should be performed in patients with shock to
    provide a more accurate measurement of intra-arterial pressure and
    to allow beat-to-beat analysis so that decisions regarding therapy
    can be based on immediate and reproducible blood pressure
    information.

4.  Resuscitation should be titrated to clinical end points of arterial
    pressure, heart rate, urine output, skin perfusion, and mental
    status, and indexes of tissue perfusion such as blood lactate
    concentrations and mixed venous oxygen saturation.

5.  Assessment of cardiac filling pressures may require central venous
    or pulmonary artery catheterization. Pulmonary artery
    catheterization also allows for assessment of pulmonary artery
    pressures, cardiac output measurement, and measurement of mixed
    venous oxygen saturation. Echocardiography may also be useful to
    assess ventricular volumes and cardiac performance.

> **Fluid Resuscitation**
>
> ***Recommendation 1 - Level B***. Fluid infusion should be the initial
> step in hemodynamic support of patients with septic shock. Initial
> fluid resuscitation should be titrated to clinical end points.
>
> ***Recommendation 2 - Level B***. Isotonic crystalloids or iso-oncotic
> colloids are equally effective when titrated to the same hemodynamic
> end points.
>
> ***Recommendation 3 - Level D***. Invasive hemodynamic monitoring
> should be considered in those patients not responding promptly to
> initial resuscitative efforts. Pulmonary edema may occur as a
> complication of fluid resuscitation and necessitates monitoring of
> arterial oxygenation. Fluid infusion should be titrated to a level of
> filling pressure associated with the greatest increase in cardiac
> output and stroke volume. For most patients, this will be a pulmonary
> artery occlusion pressure in the range of 12 to 15 mm Hg. An increase
> in the variation of arterial pressure with respiration may also be
> used to identify patients likely to respond to additional fluid
> administration.
>
> ***Recommendation 4 - Level C***. Hemoglobin concentrations should be
> maintained between 8 and 10 gm/dL. In patients with low cardiac
> output, mixed venous oxygen desaturation, lactic acidosis, widened
> gastric-arterial PCO~2~ gradients, or significant cardiac or pulmonary
> disease, transfusion to a higher concentration of hemoglobin may be
> desirable.
>
> **Vasopressor Therapy**
>
> ***Recommendation 1 - Level C***. Dopamine and norepinephrine are both
> effective for increasing arterial blood pressure. It is imperative to
> ensure that patients are adequately fluid resuscitated. Dopamine
> raises cardiac output more than norepinephrine, but its use may be
> limited by tachycardia. Norepinephrine may be a more effective
> vasopressor in some patients.
>
> ***Recommendation 2 - Level D***. Phenylephrine is an alternative to
> increase blood pressure, especially in the setting of
> tachyarrhythmias. Epinephrine can be considered for refractory
> hypotension, although adverse effects are common, and epinephrine may
> potentially decrease mesenteric perfusion.
>
> ***Recommendation 3 - Level B***. Administration of low doses of
> dopamine to maintain renal function is not recommended.
>
> ***Recommendation 4 - Level C***. Patients with hypotension refractory
> to catecholamine vasopressors may benefit from addition of replacement
> dose steroids.
>
> ***Recommendation 5 - Level D***. Low doses of vasopressin given after
> 24 hours as hormone replacement may be effective in raising blood
> pressure in patients refractory to other vasopressors, although no
> conclusive data are yet available regarding outcome.
>
> **Inotropic Therapy**
>
> ***Recommendation 1 - Level C***. Dobutamine is the first choice for
> patients with low cardiac index and/or low mixed venous oxygen
> saturation and an adequate mean arterial pressure following fluid
> resuscitation. Dobutamine may cause hypotension and/or tachycardia in
> some patients, especially those with decreased filling pressures.
>
> ***Recommendation 2 - Level B***. In patients with evidence of tissue
> hypoperfusion, addition of dobutamine may be helpful to increase
> cardiac output and improve organ perfusion. A strategy of routinely
> increasing cardiac index to predefined \"supranormal\" levels (\>4.5
> L·min^-1^·m^-2^) has not been shown to improve outcome.
>
> ***Recommendation 3 - Level C***. A vasopressor such as norepinephrine
> and an inotrope such as dobutamine can be titrated separately to
> maintain both mean arterial pressure and cardiac output.
>
> **[Definitions]{.underline}**
>
> **Level I**: Large, randomized trials with clear-cut results; low risk
> of false-positive (alpha) error or false-negative (beta) error
>
> **Level II**: Small, randomized trials with uncertain results;
> moderate to high risk of false-positive (alpha) error and/or
> false-negative (beta) error
>
> **Level III**: Nonrandomized, contemporaneous controls
>
> **Level IV**: Nonrandomized, historical controls and expert opinion
>
> **Level V**: Case series, uncontrolled studies, and expert opinion
>
> **Strength of Recommendations**

A.  Supported by at least two level I investigations

B.  Supported by only one level I investigation

C.  Supported by level II investigations only

D.  Supported by at least one level III investigation

E.  Supported by level IV or level V investigations only

#### CLINICAL ALGORITHM(S)

> A clinical algorithm is provided in the original guideline document
> for hemodynamic support of adult patients with severe sepsis and
> septic shock.

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

> The type of supporting evidence is identified and graded for some of
> the recommendations (see the \"Major Recommendations\" field).

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

> An organized approach to the hemodynamic support of sepsis including
> use of fluid resuscitation, vasopressor therapy and inotropic therapy

#### POTENTIAL HARMS

-   The primary risk when using hypertonic saline solution is
    iatrogenically induced hypertonic states due to sodium load.

-   There have been reports suggesting that hydroxyethyl starch
    molecules may adversely affect renal function by causing tubular
    injury.

-   Hydroxyethyl starch can cause dose-dependent decreases in factor
    VIII activity and prolongation of partial thromboplastin time.

-   The major undesirable effects of dopamine are tachycardia and
    arrhythmogenesis, both of which are more prominent than with other
    vasopressor agents. Other side effects include increased pulmonary
    artery occlusion pressure, increased pulmonary shunt, and the
    potential for decreased prolactin release and consequent
    immunosuppression.

> **Complications of Fluid Resuscitation Therapies**

-   The major complications of fluid resuscitation are pulmonary and
    systemic edema. These complications are related to three principal
    factors: a) increases in hydrostatic pressures; b) decreases in
    colloid osmotic pressure; and c) increases in microvascular
    permeability associated with septic shock. The controversy
    concerning crystalloid and colloid resuscitation revolves around the
    importance of maintaining plasma colloid osmotic pressure. Large
    volume crystalloid resuscitation results in significant decreases in
    plasma colloid osmotic pressure, whereas plasma colloid osmotic
    pressure is maintained with colloid infusion. In experimental
    studies, decreases in plasma colloid osmotic pressure increase
    extravascular fluid flux in the lungs and lower the level of
    hydrostatic pressure associated with lung water accumulation. Some,
    but not all, clinical reports have observed a correlation between
    decreases in the colloid osmotic pressure-pulmonary artery occlusion
    pressure gradient and the presence of pulmonary edema. Several
    clinical studies have randomized subjects to crystalloid or colloid
    infusion and examined the development of pulmonary edema with mixed
    results, demonstrating either no differences between solutions or an
    increased incidence of pulmonary edema with crystalloids.
    Experimental reports in septic models demonstrate no increase in
    extravascular lung water when hydrostatic pressures are maintained
    at low levels, indicating that in sepsis the primary determinant of
    extravascular fluid flux appears to be microvascular pressure rather
    than colloid osmotic pressure. Together, these data suggest that
    when lower filling pressures are maintained there is no significant
    difference in the development of pulmonary edema with crystalloids
    or colloids. However, if higher filling pressures are required to
    optimize cardiac performance in patients with ventricular
    dysfunction, colloids may mitigate against extravascular fluid flux.

-   The acute respiratory distress syndrome occurs in 30-60% of patients
    with septic shock. Of concern has been the possibility that in the
    setting of increased microvascular permeability, colloid particles
    could migrate into the interstitium where they would favor fluid
    retention in the lung and worsen pulmonary edema. A number of
    studies, including a variety of models of increased microvascular
    permeability, as well as clinical studies in patients with septic
    shock and the acute respiratory distress syndrome, have not found
    evidence of increased lung water or compromised lung function with
    colloids.

-   Systemic edema is a frequent complication of fluid resuscitation.
    The relative roles of increased microvascular permeability,
    increases in hydrostatic pressure, and decreases in plasma colloid
    osmotic pressure in the development of this complication during
    sepsis are unclear. Tissue edema may reduce tissue oxygen tensions
    by increasing the distance for diffusion of oxygen into cells.
    During experimental peritonitis, crystalloid therapy was associated
    with increased endothelial cell swelling and decreased systemic
    capillary cross-sectional area when compared with colloid infusion.
    In contrast, other studies comparing the impact of large volume
    crystalloid infusion on skeletal muscle and intestinal oxygen
    metabolism have observed no impairment of oxidative metabolism
    despite significant edema formation. The integrity of the
    gastrointestinal mucosa as a barrier to bacterial translocation also
    does not appear to be affected by decreases in colloid osmotic
    pressure and the development of tissue edema following crystalloid
    resuscitation. A comparison of crystalloid and colloid resuscitation
    in thermal injury found that the extent of resuscitation and not the
    choice of fluids was the major determinant of bacterial
    translocation.

-   Finally, there have been multiple meta-analyses of the clinical
    studies comparing crystalloids with colloids, which have examined
    the effect of resuscitation with these solutions on mortality rate.
    The results have been conflicting, with some of the reports
    suggesting differences in mortality rate favoring crystalloids,
    whereas others have shown no differences. These differences reflect
    the poor quality of many of the underlying studies, the
    heterogeneity in patient populations, and the fact that none of the
    clinical studies was ever designed with mortality as an end point.

> **Complications of Vasopressor Therapy**

-   All of the catecholamine vasopressor agents can cause significant
    tachycardia, especially in patients who are inadequately volume
    resuscitated. Tachyarrhythmias can occur as well. In patients with
    significant coronary atherosclerosis, vasopressor-induced coronary
    artery constriction may precipitate myocardial ischemia and
    infarction; this is of particular concern in patients treated with
    vasopressin. In the presence of myocardial dysfunction, excessive
    vasoconstriction can decrease stroke volume, cardiac output, and
    oxygen delivery. Should this occur, the dose of vasopressor should
    be lowered, or the addition of an inotropic agent such as dobutamine
    should be considered. Vasopressors can also cause limb ischemia and
    necrosis.

-   Administration of vasopressors may impair blood flow to the
    splanchnic system, and this can be manifested by stress ulceration,
    ileus, malabsorption, and even bowel infarction. Gut mucosal
    integrity occupies a key position in the pathogenesis of multiple
    organ failure, and countercurrent flow in splanchnic
    microcirculation gives the gut a higher critical threshold for
    oxygen delivery than other organs. If possible, episodes of
    intramucosal acidosis, which might be detected either by a decrease
    in gastric mucosal pHi or an increase in gastric mucosal PCO~2~,
    should be avoided, although no prospective randomized controlled
    trial has demonstrated a decrease in mortality rate with pHi or
    gastric PCO~2~-directed care in the management of patients with
    septic shock.

> **Complications of Inotropic Therapy**

-   In the septic patient who has been inadequately volume resuscitated,
    all of the inotropic agents can cause significant tachycardia and
    other cardiac arrhythmias. In patients with coexisting coronary
    disease, the change in myocardial oxygen consumption may precipitate
    myocardial ischemia and infarction. Excessive doses of
    catecholamines can also result in myocardial band necrosis
    independent of the presence of coronary disease.

-   Sole use of inotropic agents that also have vasodilatory activity
    (e.g., isoproterenol, milrinone) is likely to reduce blood pressure.
    These reductions can be long-lasting with agents that have long
    half-lives.

-   Administration of inotropic agents that have pressor activity may
    impair blood flow to other organ beds, such as the splanchnic
    circulation. Efforts to ensure adequate volume resuscitation and to
    assess end-organ function must be made.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

> These guidelines are for adult patients and do not cover all
> conceivable clinical scenarios.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

> An implementation strategy was not provided.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

> Getting Better

#### IOM DOMAIN

> Effectiveness\
> Timeliness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

> Hollenberg SM, Ahrens TS, Annane D, Astiz ME, Chalfin DB, Dasta JF,
> Heard SO, Martin C, Napolitano LM, Susla GM, Totaro R, Vincent JL,
> Zanotti-Cavazzoni S. Practice parameters for hemodynamic support of
> sepsis in adult patients: 2004 update. Crit Care Med 2004
> Sep;32(9):1928-48. \[230 references\]
> [PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15343024)

#### ADAPTATION

> Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

> 2004 Sep

#### GUIDELINE DEVELOPER(S)

> Society of Critical Care Medicine - Professional Association

#### SOURCE(S) OF FUNDING

> Society of Critical Care Medicine (SCCM)

#### GUIDELINE COMMITTEE

> Not stated

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

> *Primary Authors*: Steven M. Hollenberg, MD; Tom S. Ahrens, DNS, RN,
> CCRN, CS; Djillali Annane, MD, PhD; Mark E. Astiz, MD, FCCM; Donald B.
> Chalfin, MD, MS, FCCM, FCCP; Joseph F. Dasta, MSc, FCCM; Stephen O.
> Heard, MD, FCCM; Claude Martin, MD, FCCM; Lena M. Napolitano, MD,
> FCCM; Gregory M. Susla, PharmD, FCCM; Richard Totaro, MB, BS, FRACP,
> FJFICM; Jean-Louis Vincent, MD, PhD, FCCM; Sergio Zanotti-Cavazzoni,
> MD

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

> Not stated

#### GUIDELINE STATUS

> This is the current release of the guideline.

#### GUIDELINE AVAILABILITY

> Electronic copies: Available in Portable Document Format (PDF) from
> the [Society of Critical Care Medicine (SCCM) Web
> site](http://www.sccm.org/professional_resources/guidelines/table_of_contents/Documents/Hemodynamicsupport.pdf).
>
> Print copies: Available from the Society of Critical Care Medicine,
> 701 Lee Street, Suite 200, Des Plaines, IL 60016; Phone: (847)
> 827-6869; Fax: (847) 827-6886; on-line through the [SCCM
> Bookstore](http://www.sccm.org/SCCM_Store/Pages/default.aspx).

#### AVAILABILITY OF COMPANION DOCUMENTS

> None available

#### PATIENT RESOURCES

> None available

#### NGC STATUS

> This NGC summary was completed by ECRI on March 31, 2005.

#### COPYRIGHT STATEMENT

> This NGC summary is based on the original guideline, which is subject
> to the guideline developer\'s copyright restrictions.

### DISCLAIMER

#### NGC DISCLAIMER

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> © 1998-2008 National Guideline Clearinghouse
>
> Date Modified: 11/10/2008
>
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