U.S. patent application number 13/850662 was filed with the patent office on 2013-11-07 for system and method for diagnosis and management of sepsis.
The applicant listed for this patent is Bruce A. McKinley. Invention is credited to Bruce A. McKinley, Frederick A. Moore, Laure J. Moore, R. Matthew Sailors, Joseph F. Sucher, S. Rob Todd, Krista L. Turner.
Application Number | 20130296720 13/850662 |
Document ID | / |
Family ID | 48225407 |
Filed Date | 2013-11-07 |
United States Patent
Application |
20130296720 |
Kind Code |
A1 |
McKinley; Bruce A. ; et
al. |
November 7, 2013 |
SYSTEM AND METHOD FOR DIAGNOSIS AND MANAGEMENT OF SEPSIS
Abstract
Embodiments of systems and methods for providing protocols for
administering an aspect of care are presented. Specifically,
certain embodiments relate to a sepsis diagnosis and management
protocol which may have been segmented according to the severity of
the sepsis, where the care directives provided by the differing
segments of the protocol will be of differing intensity or
invasiveness based upon the severity of the patient's disease.
Embodiments of such protocols may be implemented in conjunction
with computer systems to aid in providing that aspect of care in
conjunction with a particular patient.
Inventors: |
McKinley; Bruce A.;
(Micanopy, FL) ; Moore; Frederick A.; (Fulshear,
TX) ; Sailors; R. Matthew; (Houston, TX) ;
Moore; Laure J.; (Houston, TX) ; Todd; S. Rob;
(Houston, TX) ; Turner; Krista L.; (Houston,
TX) ; Sucher; Joseph F.; (Katy, TX) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
McKinley; Bruce A. |
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|
US |
|
|
Family ID: |
48225407 |
Appl. No.: |
13/850662 |
Filed: |
March 26, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12495023 |
Jun 30, 2009 |
8439835 |
|
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13850662 |
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61133469 |
Jun 30, 2008 |
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Current U.S.
Class: |
600/484 ;
705/2 |
Current CPC
Class: |
G16H 10/60 20180101;
A61B 5/024 20130101; G06Q 10/0633 20130101; G16H 70/20 20180101;
A61B 5/021 20130101; A61B 5/412 20130101; G16H 50/20 20180101; A61B
5/02055 20130101; A61B 5/0816 20130101; A61B 5/0205 20130101 |
Class at
Publication: |
600/484 ;
705/2 |
International
Class: |
G06Q 10/06 20060101
G06Q010/06; G06Q 50/22 20060101 G06Q050/22; A61B 5/0205 20060101
A61B005/0205 |
Claims
1. A method for determining a protocol for an aspect of care,
comprising: identifying an aspect of care, ascertaining a current
state of the aspect of care; assessing the current state of the
aspect of care; identifying the set of therapeutic interventions
associated with the current state of the aspect of care;
identifying variables associated with each of the therapeutic
interventions; characterizing the set of therapeutic interventions;
sequencing the therapeutic interventions based upon the
characterization of the set of therapeutic interventions; and
devising a master routine of the set of therapeutic interventions;
and devising iterative logic for each of the therapeutic
interventions.
2. The method of claim 1, wherein the protocol is a protocol for
the diagnosis and management of sepsis.
3. The method of claim 1, wherein the protocol for the diagnosis
and management of sepsis comprises: a first segment comprising a
first set of rules corresponding to sepsis; and a second segment
comprising a second set of rules corresponding to severe
sepsis.
4. The method of claim 3, wherein the first set of rules comprising
the first segment comprises one or more rules for detecting
sepsis.
5. The method of claim 4, wherein the one or more rules are
configured to generate a score based on a heart rate, temperature,
respiration rate and white blood cell count.
6. The method of claim 3, wherein the second set of rules of the
second segment are further segmented according to clinical
independency.
7. The method of claim 6, wherein the second set of rules is
further segmented into a fluid/blood therapy segment, a
vasopressor/inotrope therapy segment, an adrenal
insufficiency/steroid therapy segment and a pulmonary arterial
catheter directed therapy segment.
8. The method of claim 1, further comprising implementing the
protocol on a protocol system coupled to one or more presentation
devices.
9. The method of claim 8, wherein implementing the protocol on the
protocol system comprises: executing an instance of the protocol by
a protocol execution module, determining a first rule of the
protocol by the protocol execution module, presenting one or more
interfaces corresponding to the first rule through a first
presentation device, wherein the one or more interfaces comprises
at least one request to obtain data corresponding to a patient,
receiving the data corresponding to the patient at the protocol
execution module from the first presentation device using the one
or more interfaces, storing the data corresponding to the patient
and associating the stored data with the instance of the protocol,
and determining a second rule of the protocol based on the stored
data corresponding to the patient and the instance of the protocol,
wherein the second rule is determined by the protocol execution
module.
10. The method of claim 9, wherein the data corresponding to the
patient is received from a medical device coupled to the patient
and the protocol system.
11. A system for computerized implementation of a protocol,
comprising: one or more presentation devices configured to present
interfaces; and a protocol system coupled to the one or more
presentation devices, the protocol system comprising: a processor,
a data store, and a computer readable medium comprising
instructions executable by the processor for implementing a
protocol for an aspect of care, where the protocol was devised by:
identifying an aspect of care, ascertaining a current state of the
aspect of care; assessing the current state of the aspect of care;
identifying the set of therapeutic interventions associated with
the current state of the aspect of care; identifying variables
associated with each of the therapeutic interventions;
characterizing the set of therapeutic interventions; sequencing the
therapeutic interventions based upon the characterization of the
set of therapeutic interventions; and devising a master routine of
the set of therapeutic interventions; and devising iterative logic
for each of the therapeutic interventions.
12. The system of claim 12, wherein implementing the protocol
comprises: executing an instance of the protocol by a protocol
execution module, determining a first rule of the protocol by the
protocol execution module, presenting one or more interfaces
corresponding to the first rule through a first presentation
device, wherein the one or more interfaces comprises at least one
request to obtain data corresponding to a patient, receiving the
data corresponding to the patient at the protocol execution module
from the first presentation device using the one or more
interfaces, storing the data corresponding to the patient and
associating the stored data with the instance of the protocol, and
determining a second rule of the protocol based on the stored data
corresponding to the patient and the instance of the protocol,
wherein the second rule is determined by the protocol execution
module.
13. The system of claim 12, wherein the protocol is a protocol for
the diagnosis and management of sepsis.
14. The system of claim 13, wherein the protocol for the diagnosis
and management of sepsis comprises: a first segment comprising a
first set of rules corresponding to sepsis; and a second segment
comprising a second set of rules corresponding to severe
sepsis.
15. The system of claim 14, wherein the first set of rules
comprising the first segment comprises one or more rules for
detecting sepsis.
16. The system of claim 15, wherein the one or more rules are
configured to generate a score based on a heart rate, temperature,
respiration rate and white blood cell count.
17. The system of claim 15, wherein the second set of rules of the
second segment are further segmented according to clinical
independency.
18. The system of claim 17, wherein the second set of rules is
further segmented into a fluid/blood therapy segment, a
vasopressor/inotrope therapy segment, an adrenal
insufficiency/steroid therapy segment and a pulmonary arterial
catheter directed therapy segment.
19. The system of claim 12, wherein the patient specific data is
received from a medical device coupled to the patient and the
protocol system.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of, and claims a benefit
of priority under 35 U.S.C. 120 of the filing date of U.S. patent
application Ser. No. 12/495,023 filed Jun. 30, 2009, entitled
"SYSTEM AND METHOD FOR DIAGNOSIS AND MANAGEMENT OF SEPSIS", by
inventors McKinley et al., which in turn claims the benefit of
priority under 35 U.S.C. .sctn.119 to U.S. Provisional Patent
Application No. 61/133,469 filed Jun. 30, 2008 entitled "System and
Method for Diagnosis and Management of Sepsis" by McKinley et al.,
which are hereby fully incorporated by reference herein for all
purposes.
TECHNICAL FIELD
[0002] This invention relates generally to the field of medical
informatics, biomedical engineering and surgical intensive care.
More specifically, embodiments of the present invention relate to
clinical decision support using rule-based systems for the care of
patients who are septic. Even more particularly, embodiments of the
present invention relate to rule-based systems for the care of
patients who are septic which may be implemented in a computerized
medical environment.
BACKGROUND
[0003] Sepsis is a serious medical condition characterized by a
whole-body inflammatory state and the presence of a known or
suspected infection. The body may develop this inflammatory
response to microbes in the blood, urine, lungs, skin, or other
tissues. Sepsis is characterized by evidence of acute inflammation
present throughout the entire body, and is, therefore, frequently
associated with higher than normal heart rate, fever or lower than
normal temperature and elevated white blood cell count
(leukocytosis) or lower than normal white blood cell count.
[0004] The modern concept of sepsis is that the host's immune
response to the infection causes most of the symptoms of sepsis,
resulting in hemodynamic consequences and damage to organs. This
host response has been termed systemic inflammatory response
syndrome (SIRS) and is characterized by hemodynamic compromise and
metabolic derangement. Outward physical symptoms of this response
frequently include a high heart rate, high respiratory rate,
elevated white blood cell count, and elevated or lowered body
temperature. Sepsis is differentiated from SIRS by the presence of
a pathogen. Without infection the above symptoms may not be
classified as sepsis, only SIRS.
[0005] Severe sepsis occurs when sepsis leads to organ dysfunction,
low blood pressure (hypotension), or insufficient blood flow
(hypoperfusion) to one or more organs (causing, for example, lactic
acidosis, decreased urine production, or altered mental status).
Sepsis can lead to septic shock, multiple organ dysfunction
syndrome (sometimes known as multiple organ failure) and death.
Organ dysfunction may result from sepsis-induced hypotension and
diffuse intravascular coagulation, among other things.
[0006] In the United States, sepsis is the second-leading cause of
death in non-coronary intensive-care unit (ICU) patients, and the
tenth-most-common cause of death overall according to data from the
Centers for Disease Control and Prevention (the first being
multiple organ failure). Sepsis is common and also more dangerous
in elderly, immunocompromised, and critically-ill patients. It
occurs in 1-2% of all hospitalizations and accounts for as much as
25% of ICU bed utilization. It is a major cause of death in
intensive-care units worldwide, with mortality rates that currently
range from 20% for sepsis to 40% for severe sepsis to >60% for
septic shock.
[0007] Sepsis is usually treated in the intensive care unit with
intravenous fluids and antibiotics. If fluid replacement is
insufficient to maintain blood pressure, specific vasopressor drugs
can be used. Artificial ventilation and dialysis may be needed to
support the function of the lungs and kidneys, respectively. To
guide therapy, a central venous catheter and an arterial catheter
may be placed to monitor intravascular pressures. Sepsis patients
require preventive measures for deep vein thrombosis, stress ulcers
and pressure ulcers, unless other conditions prevent this. Some
patients might benefit from tight control of blood sugar levels
with insulin (targeting stress hyperglycemia), low-dose
corticosteroids or activated drotrecogin alfa (recombinant protein
C).
[0008] Presently there is great variability in the diagnosis and
management of sepsis generally across health care institutions,
between and among physicians, and between and among differing
patients, even within the same health care institution.
Additionally, mortality and cost of intensive care unit (ICU) care
of patients with sepsis remain prohibitive. To apply current
standard of care to sepsis patients typically requires frequent or
constant bedside presence of an expert physician to guide decision
making for monitoring or therapeutic interventions. Available
evidence based guideline and other literature evidence for
management of sepsis are difficult for the bedside clinician to use
to direct the care process for the individual patient, and ad hoc
treatment with haphazard application of literature evidence or
guideline recommendations is common.
[0009] Consequently, it is desired to substantially ameliorate
these problems.
SUMMARY
[0010] Embodiments of systems and methods for providing a sepsis
diagnosis and management protocol are presented. Specifically,
certain embodiments of the sepsis diagnosis and management protocol
may have been derived from currently available guidelines and
literature evidence where the protocol is intended to be utilized
to identify a patient with sepsis and direct and determine a logic
path of care for that particular patient. Specifically, embodiments
of the sepsis diagnosis and management protocol may be segmented
according to the severity of the sepsis, where the care directives
provided by the differing segments of the protocol will be of
differing intensity or invasiveness based upon the severity of the
patient's disease. These segments may correspond to a set of rules
and logic which are clinically distinct, independent processes that
are part of the overall aspect of care where the sets of rules and
associated logic may be logically distinct within the protocol.
Within such a segment, the set of rules may have thresholds or
interventions changed without affecting the basic process or other
segments. A segment may be useful in other aspects of care. Thus,
the segment could be used to manage that process for another
patient or as part of another aspect of care. The modularity of
certain segments permits edition, update and other change without
extensive revision to a protocol, and thereby permits immediate
incorporation of new guideline or literature evidence to maintain
clinical currency and improved standard of care for all
patients.
[0011] Embodiments of such a sepsis diagnosis and management
protocol may therefore be a rule based protocol developed based on
a number of sources, including any combination of published
guidelines, literature evidence or expert consensus opinion and
ongoing protocol analysis.
[0012] Specifically, embodiment of a protocol presented herein is
designed to direct clinician assessment of the severity of sepsis
according to specific criteria for sepsis, severe sepsis and septic
shock, to direct hemodynamic monitoring that is appropriate for the
sepsis severity and related hemodynamic instability that is
present, to prescribe immediate IV fluid administration in
calibrated volumes to regain hemodynamic stability defined as
numeric blood pressure and heart rate measurement thresholds for
intervention, to prescribe immediate antibiotic agent therapy that
is appropriate for the individual patient and suspected source of
infection, and to direct specific interventions to maintain
hemodynamic stability and systemic oxygenation using specific
measurements and numeric thresholds for intervention for at least
the 1.sup.st 24 ICU hours after diagnosis of sepsis.
[0013] The efficacy of embodiments of the present invention is
demonstrable. In a time period of 15 months, 172 patient encounters
for sepsis, severe sepsis and septic shock were managed using this
protocol. Summary demographics and outcomes are described in the
table below. As can be seen, patients with severe sepsis and septic
shock have survival rates that are much less than patients with
sepsis, but much greater than 50% that is a commonly cited survival
rate. Overall, sepsis survival rate utilizing embodiments of the
protocols described herein was 72%. In the year after sepsis
management protocol introduction, mortality rate decreased from 35
to 23%.
TABLE-US-00001 Sepsis Severe sepsis Septic shock (n = 30) (n = 101)
(n = 41) Age 54 .+-. 3 60 .+-. 2 61 .+-. 3 (mean .+-. SEM) gender
(male) 16 (52%) 47 (47%) 16 (39%) MAP t = 0 (mmHg) 85 .+-. 2 81
.+-. 1 66 .+-. 2 (mean .+-. SEM) [lactate] t = 0 (mM) 1.4 .+-. 0.1
3.2 .+-. 0.4 4.2 .+-. 0.5 (mean .+-. SEM) ICU free days 20.1 .+-.
1.4 15.0 .+-. 1.0 12.1 .+-. 1.6 (mean .+-. SEM) ICU survival 31
(100%) 85 (85%) 27 (66%) MAP t = 0, mean arterial pressure at start
of sepsis management protocol; [lactate] t = 0, blood lactate
concentration at start of sepsis management protocol; ICU free
days, 28 minus number of days spent in ICU after sepsis diagnosis
or 0 if death in ICU before 28 days after sepsis diagnosis; ICU
survival, survival extending beyond number of days spent in ICU
after sepsis diagnosis
[0014] In some cases, embodiments of a protocol for an aspect of
care, such as for the diagnosis and management of sepsis may be
implemented in a computerized system. These computerized protocols
are capable of directing complex care processes to provide evidence
based care that is comprehensive, individualized, appropriately
timed, and based on standardized bedside clinical decisions that
are replicable among patients. For sepsis management, a complex
process, the potential impact of guideline recommendations,
literature evidence and protocol implementation is likely to be
realized using the computerized protocol.
[0015] The efficacy of implementing embodiments of the protocol
described herein is also demonstrable. In a 3 month period 35
patients had sepsis diagnosed and the computerized protocol was
used by bedside clinicians to manage each patient's sepsis
encounter. Computerized protocol compliance by bedside clinicians
was 90% (833 of 930 computerized protocol generated instructions to
bedside clinicians) during these three months. Early effects of
computerized sepsis management protocol implementation are
indicated below:
TABLE-US-00002 Sepsis Severe sepsis Septic shock (n = 7) (n = 25)
(n = 14) ICU free days 19.4 .+-. 3.1 16.4 .+-. 1.9 12.0 .+-. 3.0
(mean .+-. SEM) ICU survival 7 (100%) 21 (84%) 12 (79%) ICU free
days, 28 minus number of days spent in ICU after sepsis diagnosis
or 0 if death in ICU before 28 days after sepsis diagnosis; ICU
survival, survival extending beyond number of days spent in ICU
after sepsis diagnosis.
[0016] One embodiment of a protocol for sepsis management may be
segmented as a process for management of relatively less severe
sepsis and a process for management of relatively more severe
sepsis (including septic shock). The process for management of less
severe sepsis may comprise a rule set for low risk patient
monitoring (e.g. non invasive blood pressure, heart rate) and for
interventions with lesser therapeutic intensity and risk (e.g. IV
fluid dose volumes) that are sufficient to maintain adequate
hemodynamic function as measured by minimally invasive monitors and
according to threshold rules for intervention. In a (hospital)
patient setting for which onset of sepsis is deemed likely and in
which low risk monitors (e.g. non invasive blood pressure, heart
rate) are routinely used, the process for management of less severe
sepsis may comprise a set of rules to detect the onset or existence
of sepsis. The process for management of less severe sepsis may
also comprise a set of threshold rules to detect development of
more severe sepsis or septic shock and for transition to the
process for management of severe sepsis or septic shock. The
process for management of severe sepsis or septic shock may
comprise a rule set for more invasive patient monitoring (e.g.
invasive intravascular blood pressure) and for interventions with
greater therapeutic intensity and risk (e.g. vasopressor drug
therapy) that are sufficient to maintain adequate hemodynamic
function as measured by invasive monitors and according to
threshold rules for intervention.
[0017] These, and other, aspects of the invention will be better
appreciated and understood when considered in conjunction with the
following description and the accompanying drawings. The following
description, while indicating various embodiments of the invention
and numerous specific details thereof, is given by way of
illustration and not of limitation. Many substitutions,
modifications, additions or rearrangements may be made within the
scope of the invention, and the invention includes all such
substitutions, modifications, additions or rearrangements.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] The drawings accompanying and forming part of this
specification are included to depict certain aspects of the
invention. A clearer impression of the invention, and of the
components and operation of systems provided with the invention,
will become more readily apparent by referring to the exemplary,
and therefore nonlimiting, embodiments illustrated in the drawings,
wherein identical reference numerals designate the same components.
Note that the features illustrated in the drawings are not
necessarily drawn to scale.
[0019] FIG. 1 is an illustration of one embodiment of a process for
development and implementation of a protocol for clinical care.
[0020] FIG. 2 is a flow diagram representing one embodiment of a
method for deriving a protocol.
[0021] FIGS. 3A-3D (FIG. 3) comprise a flow diagram representing
one embodiment of the rules of a segment of a protocol for sepsis
diagnosis and management.
[0022] FIGS. 4A-4D (FIG. 4) comprise a flow diagram representing
one embodiment of the rules of a segment of a protocol for sepsis
diagnosis and management.
[0023] FIGS. 5A-5B (FIG. 5) comprise a flow diagram representing
one embodiment of the rules of a segment of a protocol for sepsis
diagnosis and management.
[0024] FIGS. 6A-6D (FIG. 6) comprise a flow diagram representing
one embodiment of the rules of a segment of a protocol for sepsis
diagnosis and management.
[0025] FIG. 7A-7B (FIG. 7) comprise a flow diagram representing one
embodiment of the rules of a segment of a protocol for sepsis
diagnosis and management.
[0026] FIG. 8 is a flow diagram representing one embodiment of the
rules of a segment of a protocol for sepsis diagnosis and
management.
[0027] FIG. 9A is a representation of one embodiment of a scoring
method for use with the protocol for sepsis diagnosis and
management.
[0028] FIG. 9B is a representation of one embodiment of a scoring
method for use with the protocol for sepsis diagnosis and
management.
[0029] FIG. 10 is a block diagram of one embodiment of an
architecture for the computerized implementation of a protocol.
[0030] FIG. 11 a block diagram of one embodiment of an architecture
for the computerized implementation of a protocol.
[0031] FIGS. 12A-12E are representations of embodiments of
interfaces which may be utilized by a system for a computerized
implementation of a protocol.
DETAILED DESCRIPTION
[0032] The invention and the various features and advantageous
details thereof are explained more fully with reference to the
nonlimiting embodiments that are illustrated in the accompanying
drawings and detailed in the following description. Descriptions of
well known starting materials, processing techniques, components
and equipment are omitted so as not to unnecessarily obscure the
invention in detail. It should be understood, however, that the
detailed description and the specific examples, while indicating
preferred embodiments of the invention, are given by way of
illustration only and not by way of limitation. Various
substitutions, modifications, additions and/or rearrangements
within the spirit and/or scope of the underlying inventive concept
will become apparent to those skilled in the art from this
disclosure. Embodiments discussed herein can be implemented in
suitable computer-executable instructions that may reside on a
computer readable medium (e.g., a HD), hardware circuitry or the
like, or any combination.
[0033] Before discussing specific embodiments, embodiments of a
hardware architecture for implementing certain embodiments is
generally described herein and will be discussed in more detail
later. One embodiment can include one or more computers
communicatively coupled to a network. As is known to those skilled
in the art, the computer can include a central processing unit
("CPU"), at least one read-only memory ("ROM"), at least one random
access memory ("RAM"), at least one hard drive ("HD"), and one or
more input/output ("I/O") device(s). The I/O devices can include a
keyboard, monitor, printer, electronic pointing device (such as a
mouse, trackball, stylus, etc.), or the like. In various
embodiments, the computer has access to at least one database over
the network.
[0034] ROM, RAM, and HD are tangible computer readable medium for
storing computer-executable instructions executable by the CPU.
Within this disclosure, the term "computer-readable medium" is not
limited to ROM, RAM, and HD and can include any type of data
storage medium that can be read by a processor. In some
embodiments, a tangible computer-readable medium may refer to a
data cartridge, a data backup magnetic tape, a floppy diskette, a
flash memory drive, an optical data storage drive, a CD-ROM, ROM,
RAM, HD, or the like.
[0035] At least portions of the functionalities or processes
described herein can be implemented in suitable computer-executable
instructions. The computer-executable instructions may be stored as
software code components or modules on one or more computer
readable media (such as non-volatile memories, volatile memories,
DASD arrays, magnetic tapes, floppy diskettes, hard drives, optical
storage devices, etc. or any other appropriate computer-readable
medium or storage device). In one embodiment, the
computer-executable instructions may include lines of complied C++,
Java, HTML, or any other programming or scripting code.
[0036] Additionally, the functions of the disclosed embodiments may
be implemented on one computer or shared/distributed among two or
more computers in or across a network. Communications between
computers implementing embodiments can be accomplished using any
electronic, optical, radio frequency signals, or other suitable
methods and tools of communication in compliance with known network
protocols.
[0037] As used herein, the terms "comprises," "comprising,"
"includes," "including," "has," "having" or any other variation
thereof, are intended to cover a non-exclusive inclusion. For
example, a process, process, article, or apparatus that comprises a
list of elements is not necessarily limited to only those elements
but may include other elements not expressly listed or inherent to
such process, process, article, or apparatus. Further, unless
expressly stated to the contrary, "or" refers to an inclusive or
and not to an exclusive or. For example, a condition A or B is
satisfied by any one of the following: A is true (or present) and B
is false (or not present), A is false (or not present) and B is
true (or present), and both A and B are true (or present).
[0038] Additionally, any examples or illustrations given herein are
not to be regarded in any way as restrictions on, limits to, or
express definitions of, any term or terms with which they are
utilized. Instead, these examples or illustrations are to be
regarded as being described with respect to one particular
embodiment and as illustrative only. Those of ordinary skill in the
art will appreciate that any term or terms with which these
examples or illustrations are utilized will encompass other
embodiments which may or may not be given therewith or elsewhere in
the specification and all such embodiments are intended to be
included within the scope of that term or terms. Language
designating such nonlimiting examples and illustrations includes,
but is not limited to: "for example," "for instance," "e.g.," "in
one embodiment."
[0039] A brief discussion of context particularly with respect to
treatment of sepsis may now be helpful. As discussed above, there
is great variability in the diagnosis and management of sepsis.
However, recent data gives significant indications that the early
treatment of sepsis according to evidence based guidelines is
effective in improving mortality rates and decreasing the length of
intensive care unit (ICU), or hospital, stays for these patients.
These evidence based guidelines (for example, `Surviving Sepsis
Campaign: Guidelines for Management of Severe Sepsis and Septic
Shock` and its revision `Surviving Sepsis Campaign: International
Guidelines for Management of Severe Sepsis and Septic Shock: 2008`
(Dellinger et al. Crit. Care Med 2008)), while desirable in the
abstract, are often difficult, if not impossible, to use to help
guide care of the individual patient in a particular health care
institution. While many reasons contribute to this difficulty, one
of the major reasons has to do with the generality of these
guidelines. These guidelines provide neither patient specific
directives nor explicit directives or instructions for individual
patient care by the bedside clinician. Additionally, and along the
same lines, for bedside clinicians (which in many cases, may not be
physicians, but instead may be physician extenders, nurses or
clinician assistants) these guidelines are too many and too complex
to recall, or too general to provide sufficient guidance in
individual cases.
[0040] While certain attempts have been made to fashion guidelines,
these attempts have resulted in significant clinician frustration
due to complexity of the disease and therapy process, and due to
the need for specific, timely instructions for measurements of
physiologic functions and for interventions to treat sepsis using
the best available information. What is desired then, is a sepsis
diagnosis and management protocol that is based on the currently
available evidence and guidelines and that can provide specific
instructions to a bedside clinician for timely care of the
individual patient based on patient specific information. Protocols
are precise, detailed plans for management or study of a medical
problem or regimen of therapy. Protocols provide specific
instruction for individual clinical decisions, and, importantly,
elicit the same decision from different clinicians. Protocols
standardize decision making among bedside clinicians, and make
decisions for specific interventions replicable among patients.
Furthermore, it is desired that such sepsis diagnosis and
management protocols may be implemented on computerized systems to
allow the automated requests for, or gathering of, measurements
associated with the patient, the patient's clinical status, and the
presentation of protocol derived instructions for care specifically
tailored for the individual patient in accordance with both the
patients' information and the sepsis diagnosis and management
protocol.
[0041] To that end, attention is now directed to the systems and
methods of the present invention. Embodiments of these systems and
methods provide a sepsis diagnosis and management protocol which
has been derived from currently available guidelines and evidence
where the protocol is intended to be utilized to identify a patient
with sepsis (including severe sepsis or septic shock) and direct
and determine a logic path of care for that particular patient.
Specifically, embodiments of the sepsis diagnosis and management
protocol may be segmented according to the severity of the sepsis,
where the care directives provided by the differing segments of the
protocol will be of differing intensity or invasiveness based upon
the immediate severity of the individual patient's disease. For
example, one segment may comprise rules associated with all cases
of sepsis and some cases of severe sepsis and another segment may
comprise rules associated with some cases of severe sepsis
including cases of septic shock, where the rules to apply to the
care of a particular patient may be determined according to one or
the other of the segments based upon that specific patient's
condition. Rules of the protocol may also be segmented based upon
any number of other criteria, such as for example clinical
dependency or independency or the like.
[0042] Embodiments of such a sepsis diagnosis and management
protocol may therefore be a rule based protocol developed based on
a number of sources, including any combination of published
guidelines, literature evidence or expert consensus opinion, and
ongoing analysis of protocol performance. Such a protocol may
comprise rules including instructions, interventions, requests for
patient specific information, thresholds for measurements etc.
organized in a logical sequence that may accommodate bedside
workflow, thereby providing patient based rules for care that are
based on patient specifics, including patient condition and
responses to interventions, and which are replicable among
different patients. The modular design of embodiments of these
types of protocols permit modifications to incorporate new
guideline or literature evidence, change of threshold or therapy
intervention, or to accommodate specific hospital or care unit
workflow.
[0043] The application, revision, etc. of embodiments of a sepsis
diagnosis and management protocol may therefore be facilitated by
the implementation of embodiments of these protocols as a computer
based system such that requests for information, instructions for
interventions or the presentation of information related to other
rules associated with protocol may be delivered via computer to any
interface, such as a computer screen, personal digital assistant
(PDA), laptop, cell phone screen, speaker, etc. The logic for
selecting a certain rule of the protocol to apply, the time certain
actions occurred, patient-specific data (as non-limiting examples,
demographics, criteria, related measurements, etc.) and patient
responses to specific interventions may be recorded and the next
rule in the protocol to implement with respect to that patient may
be determined in conjunction with the protocol as applied to that
specific patient's information. Thus, the protocol will tailor the
care administered to the current conditions of the individual
patient by applying rules of the protocol selected based upon that
patient's immediate condition.
[0044] As the rules (for example, instructions related to
interventions, request to obtain or enter measurements, etc.)
issued through the interface are tailored to the specific patient
being cared for, the bedside presence of an expert physician for
stepwise decision making throughout the protocol care process is
not necessarily required. In fact, in certain embodiments such a
computer based protocol system may be connected to one or more
medical devices from which patient information (including, for
example, medical or demographic data) may be obtained or rules
implemented (for example, adjustment of amount of medication being
delivered through an intravenous line, etc.) such that one or more
rules associated with the protocol may occur substantially without
the involvement of a bedside clinician. Additionally, as the data
is recorded during the administration of care to the patient
according to the protocol it can be retrospectively analyzed to
optimize and improve the care process, including the protocol
itself.
[0045] Turning now to FIG. 1, it may be helpful to give an overview
of the lifecycle of protocols, including those protocols for the
diagnosis and management of sepsis. Accordingly, FIG. 1 depicts one
embodiments of a method for development and use of a protocol for
the diagnosis and management of sepsis. More specifically, a
knowledge base for the diagnosis and management of sepsis may be
developed at step 110. The development of such a knowledge base may
entail the review of published references, guidelines journal
articles or other documents related to the diagnosis and treatment
of sepsis, obtaining information from experts in the area of
diagnosis and management of sepsis, obtaining information from one
or more consensus groups regarding diagnosis and management of
sepsis or obtaining information from any other desired source
regarding the diagnosis and management of sepsis.
[0046] Once this information is obtained, it can be distilled into
a knowledge base comprising the protocol, where the knowledge base
comprises a protocol including a set of rules organized according
to a logical sequence. This knowledge base may be tested at step
120 and the knowledge obtained from testing used to develop/revise
the knowledge base at step 110. The testing of such a knowledge
base may comprise a review or other testing procedures done in a
patient independent manner at step 130, or may comprise testing of
the protocol in conjunction with patient care or treatment at step
140.
[0047] At some point then, at step 150 the protocol may be given to
a programmer to develop a computer system implemented version of
the protocol. This computer implemented protocol may be configured
to guide a clinician or other user through the implementation of a
protocol such that requests for information, instructions for
interventions or the presentation of information related to other
rules associated with protocol may be delivered via computer to an
interface and patient-specific data including patient responses to
specific interventions or patient specific measurements may be
obtained through an interface and rules of the protocol evaluated.
The computer implemented protocol may also be tested at step 120
and the knowledge obtained from testing used to develop/revise the
knowledge base at step 110. The testing of such a knowledge base
may comprise a review or other testing procedures done in a patient
independent manner at step 130, or may comprise testing of the
protocol in conjunction with patient care or treatment at step
140.
[0048] Once the protocol is implemented in a computer system at
step 150, before implementation in conjunction with an actual
patient, at step 160, it may be desirable to train clinicians with
respect to the protocol or the computer system on which the
protocol is implemented. Thereafter, the computer implemented
protocol may be used in a clinical setting at step 170, for example
at the patient's bedside such that the patient's care is based on
the protocol. Any feedback generated from the use of the protocol
in conjunction with actual patient care base may be also used to
develop/revise the knowledge base at step 110.
[0049] As can be seen then, in certain embodiments, initially a
protocol may be created from the extant literature, including any
articles or guidelines, and the knowledge of clinicians and
consensus groups formed with respect to that aspect of care. FIG. 2
depicts a flow diagram for a method of creating such a protocol.
Initially, before creating a protocol, at step 210 an aspect of
care for which the protocol is to apply can be identified. In the
example embodiments illustrated herein, the aspect of care is
sepsis diagnosis and management, however, the use of this example
should not be construed as a constraint upon other embodiments of
the present invention which may be effectively utilized with other
aspects of care.
[0050] Once the desired aspect of care for which a protocol is to
be created is identified, the current state of that aspect of care
may be ascertained at step 220. Ascertaining the current state of
that aspect of care may, in general, comprise a search of the
literature, querying experts in that aspect of care, a review of
articles, guidelines or other literature pertinent to that aspect
of care. The experts queried may, for example, be local experts
associated with, for example, a particular health care institution
or setting or unit within a health care institution (for example, a
hospital, an ICU within a hospital, etc.), such that expert
knowledge pertaining to the current state of the aspect of care
with respect to a particular location may ascertained.
[0051] The depth or nature of this review may depend, at least in
part, on the aspect of care. For example, in the case of
ascertaining the current state of care for sepsis diagnosis and
management, peer reviewed literature may be reviewed along with
querying local expert clinicians (for example, affiliated with a
particular locale where a protocol is to be implemented) and
intensivists. In particular, when reviewing this information
(literature, guidelines, expert knowledge, etc.), in one
embodiment, this information may be analyzed to determine various
processes, where these processes comprise a set of linked or
otherwise related steps involved in that aspect of care.
[0052] After a review of the information pertaining to the
identified aspect of care, the current state of the aspect of care
may be assessed at step 230. The assessment of the aspect of care
may involve determining a setting or locale where the aspect of
care is administered and the associated availability of resources
(for example, the ICU, the operating room (OR), the emergency room
(ER), during transport of a patient, some combination, etc.), the
duration over which the aspect of care is administered (an hour,
week, month, etc.) and the complexity of the current state of the
aspect of care, such as the initial criteria associated with the
implementation of that aspect of care, the number and types of
interventions associated with that aspect of care, the number of
variables involved in determining whether to administer an
intervention, how many measurements are required to determined if
an intervention should be implemented and how often these
measurements are required, how many interventions are required and
in what time period, etc.
[0053] For example, with respect to the current state of the aspect
of care of sepsis diagnosis and management it may be determined
that the criteria for implementation of that aspect of care
comprises numeric thresholds for one or more of temperature (T),
heart rate (HR), respiration rate (RR), blood pressure (BP), white
blood cell count (WBC), or a subjective assessment of a patient
based upon the presence of infection. The setting for sepsis
diagnosis and management is an ICU or other full resource setting,
an ER, during transport, or some combination, while the duration
may be between 1 day and 1 week as the typical ICU length of stay
(LOS) is less than one month. The complexity of the current
standard of care is that usually 3-5 interventions are required and
5-10 variables are associated with those interventions. The
assessment may also involve the association of various processes or
interventions with setting or duration or complexity. For example,
processes may be correlated with the setting in which they are
implemented or the duration over which they are implemented.
[0054] In conjunction with assessing the aspect of care, as
described above, therapeutic interventions associated with current
state of the aspect of care may be identified at step 240. The
identification of therapeutic interventions may entail prioritizing
the set of therapeutic interventions that comprise at a least a
portion of the current state of the aspect of care and determining
dose rates, iterative doses, any incremental escalation or an
empiric dose related to one or more of the therapeutic
interventions.
[0055] For example, in the case of sepsis diagnosis and management,
therapeutic interventions may include IV fluid delivery, antibiotic
administration, blood component therapy, vasopressor therapy,
inotrope therapy, activated protein C therapy, etc. where the
therapeutic interventions are prioritized according to the best
available evidence (such as efficacy statistics or the like) as
therapeutic interventions including: IV fluid, antibiotics, blood,
vasopressor, inotrope, activated protein C which are prioritized
according to best evidence as: IV fluid, antibiotic, vasopressor
(increased risk, need invasive monitor); inotrope (increased risk,
need invasive monitor); activated protein C (increased risk of
hemorrhage). The dosage determined for the above are: IV fluids:
empiric dosing; and initial, repeated dose to a mean arterial
pressure (MAP) or central venous pressure (CVP) threshold;
antibiotic: empiric dose regimen (depending on suspected infection
source); vasopressor: incremental dose (MAP threshold); inotrope:
incremental dose; activated protein C: empiric (prioritize with
expert clinician opinion).
[0056] The variables associated with the aspect of care and the
determined interventions may be identified at step 250. This
identification process may entail the identification of a set of
variables whose values can identify a need for the aspect of care.
Additionally, any variables which may be affected by each
intervention, including variable derangements associated with a
poor outcome for an intervention, (for example, blood glucose
concentration greater than 150 mg/dl, etc.), measurement techniques
for each variable and the character of each technique (for example,
invasive, non-invasive, continuous, periodic or random, ease of
measurement or repetition, etc.) and the character of a measurement
result (numeric, binary, subjective, etc.) and turn-around time to
obtain a result.
[0057] In one embodiment, as pertinent to the aspect of care of
sepsis diagnosis and management a variable set that identifies need
for aspect of care (for example, criteria for diagnosis of sepsis)
including BP, HR, RR, T, WBC and a suspected source of infection.
Variables affected by each intervention including blood creatinine
concentration increase in the previous 24 hour period compared with
the current value may be used to identify renal failure, and need
for more intensive monitoring or therapy. Measurement technique(s)
for each variable may be identified and used to qualify variable
and measurement technique for use during protocol (for example,
turnaround time is less than the maximum time after intervention to
obtain accurate measurement of effect of intervention). These
measurement techniques can then be characterized, for example, BP
at 5 or 15 minute intervals may be non-invasive and adequately
accurate for hemodynamically stable patient, but invasive arterial
cannula and continuous real time monitoring may be required for
monitoring status during shock and therapy). Whether a technique is
continuous, periodic or random: may be determined by assessing the
time needed to keep a measurement `clinically current` and such
criteria (for example, 2 minute limit for MAP, 4 hour limit for
[lactate], etc.) are required for protocol function. Ease of
measurement and need for repetition may be used to determine logic
sequence for measurement-intervention-re-measurement and such
measurement results will be characterized (for example, as numeric,
binary or subjective, etc.).
[0058] The therapeutic interventions identified may be further
characterized at step 260. This may entail a determination of
whether the therapeutic intervention is generally required for the
aspect of care, a rating of the importance of the timing of the
intervention, a rating of the risk/benefit of the intervention, the
complexity of implementing the intervention at the bedside, if the
intervention can be implemented as a clinically independent
iteration and if a constant support process is needed or available
for such an intervention.
[0059] For example, in an embodiment of protocol generation where
the aspect of care is sepsis diagnosis and management the following
interventions may be determined to be required for sepsis mgt: IV
fluid (lactated Ringer's solution, LR), antibiotic (local regimen,
pharmacy), vasopressor (norepinephrine or other agent), inotrope
(dobutamine or other agent), drotrecogin alpha (activated protein
C; Xigris, Eli Lilly Corp). The importance of the timing of the
various interventions may be IV fluid (volume determined by empiric
considerations based on patient's estimated weight), antibiotic
(optimally, to be administered within the first hour after start of
protocol); vasopressor (possibly required within first hour after
start of protocol, possibly ongoing at time of sepsis diagnosis and
start of protocol). The risk--benefit analysis for the
interventions may be IV fluid (low risk); vasopressor/inotrope
(intermediate risk); blood component therapy (packed red blood
cell, PRBC, intermediate risk; fresh frozen plasma, FFP, low risk);
Xigris (expensive, last resort, risk of hemorrhage).
[0060] Based upon the interventions identified for the aspect of
care, including identified therapeutic interventions and the
corresponding priority and characteristics, a sequence for the
therapeutic interventions may be determined at step 270. In one
embodiment, this sequence may be determined based on the rating of
the time criticality of each of the therapeutic interventions, the
rating of the risk of each/benefit of each of the therapeutic
interventions and the ability to measure the effectiveness of a
therapeutic intervention.
[0061] In one embodiment, to devise a master routine to direct
therapeutic interventions in a sequence for a sepsis diagnosis and
management protocol: it was determined that there was a difference
between hemodynamic stability (where, for example, hemodynamic
stability is defined as: MAP>=65, HR<120, UO>=0.5) and
severe sepsis (aka shock) and that the protocol should be segmented
accordingly, with a set of rules applicable to stability and a set
of rules applicable to severe sepsis with rules applicable to
transition between the two segments. If a patient was stable
(explicit immediate determination), then rules which monitor and
maintain stability using minimal invasiveness would be used and
periodic measurements and threshold as systemic indicator of
hemodynamic stability and perfusion adequacy with hourly or more
frequent re-check of ongoing hemodynamic stability with key
variable set. A cumulative IV fluid volume threshold for transition
to the severe sepsis segment was determined along with a
hemodynamic instability threshold for transition to the severe
sepsis segment and checks for organ dysfunction or failure
thresholds for transition to the severe sepsis segment.
[0062] In general it was determined that in the severe sepsis
segment would be an explicitly time limited sepsis management
protocol, (for example, 24 hours) based on a determination
(critically unstable; explicit immediate determination, for example
based on thresholds)) where the rules would entail more invasive
monitoring and more intensive therapy set such as fluid/blood or
vasopressor/inotrope therapy, as needed by the individual patient
with a reduction or gradual curtailment of such vasopressor therapy
if possible.
[0063] The sequence of therapeutic interventions may be used, at
step 280, to devise a master routine to direct therapeutic
interventions in sequence. This sequencing may, in one embodiment,
entail a comparison of thresholds associated with each
intervention, where therapeutic interventions can be sequenced
based upon the thresholds (for example, if one set of thresholds is
less than another the therapeutic intervention associated with the
first set of thresholds may be sequenced before the other
therapeutic intervention). The sequencing may also entail a
determination of time intervals between one or more measurements
and the implementation of an intervention, or a re-check of a
measurement. Additionally, such a sequence may be based on the
feasibility of implementing simultaneous interventions and the
coordination of therapeutic interventions.
[0064] Once the sequence of therapeutic interventions is determined
iterative logic for each therapeutic intervention can be devised at
step 290. Devising this iterative logic may entail forming rules to
iterate a therapeutic intervention or when to proceed to another
therapeutic intervention in the sequence. Such rules may be
associated with measurements of an intervention specific variable
for threshold comparison, such that if the threshold(s) is
exceeded, then an intervention request (for example, for the
intervention) is made and the quantity and rate of intervention is
determined. If the threshold is not exceeded, then a time interval
for a recheck may be determined. A time interval for recheck after
the completion of the intervention may also be determined. If the
physiologic variable threshold measurement--therapeutic
intervention--recheck threshold process is clinically independent,
then this process can be described as an independent algorithm
(which may be utilized as an independent segment), with call from
and return to the master routine may be added.
[0065] In one embodiment applicable to a protocol for sepsis
diagnosis and management, devising an iteration subroutine for each
therapeutic intervention comprises determination of logic for fluid
and blood therapy; vasopressor therapy, including explicit logic
for increment of continuous support therapy to obtain specific
variable effect (for example, MAP>=65) and complementary logic
to attempt decrease/stop of vasopressor therapy; inotrope therapy,
including explicit logic for increment of continuous support
therapy to obtain specific variable effect (for example, systemic
oxygenation, measured as systemic hemoglobin oxygen
saturation>70%) or, alternatively, explicit logic to direct a
more intensive monitor of hemodynamic function, for example
pulmonary artery catheter (PAC) directed therapy.
[0066] At this point, then, a protocol for use with the aspect of
care may have been developed, where the protocol comprises a number
of rules operable to implement a set of sequenced therapeutic
interventions and logic to select between the rules based upon
thresholds associated with various measurement. One outgrowth of
the application of embodiments of such a methodology to the
development of protocols for aspects of care is that the resulting
protocols may be segmented according to severity, clinical
independence of a particular therapy process, or based on a number
of other criteria.
[0067] Specifically, the segmentation of a protocol may comprise
the grouping of the rules into segments which can be substantially
independently utilized by a clinician, but which may be applied in
tandem to address an aspect of care. The segmentation of the
protocol may be based on a number of different criteria, including
the invasiveness of monitoring or of therapeutic intervention
involved with the implementation of the rules of the segments (for
example, more invasiveness involved with obtaining measurements or
administration of medication, etc.), the severity of the
application of the rules of the segment on a patient including risk
to the patient or the effects of medication to be administered in
conjunction with the segment, the ability to administer or perform
the rules of a segment in a separate clinical setting or in
conjunction with other protocols, or any of a number of other
criteria which may result in the grouping of rules into segments
when forming the protocol.
[0068] It may be useful to illustrate a particular protocol which
resulted from the application of the above methodology for
generating a protocol, where the protocol is segmented according to
one or more criteria. Accordingly, attention is now directed to
FIGS. 3-8 which illustrate one embodiment of a protocol for the
diagnosis and management of sepsis. The protocol may comprise a
number of rules which have been segmented according to various
criteria. It may be useful before delving into the specific
segments and rules of the protocol to give a general overview of
the segmentation of the protocol.
[0069] In the embodiment illustrated, FIGS. 3 and 4 illustrate
segments of the embodiment of the protocol for the diagnosis and
management of sepsis where the rules comprising these various
segments have been grouped according to severity of diagnosis and
invasiveness of application of the rules. Generally, then, the
segment of FIG. 3 represents rules for the diagnosis and management
of sepsis which are applicable to relatively less severe sepsis
(also referred to as sepsis), wherein the rules may be applied (for
example, measurements taken, medications delivered, etc.)
relatively less invasively and with commensurately less risk to the
patient. In contrast, FIGS. 4-8 represent a segment of the protocol
for the diagnosis and management of relatively more severe sepsis
including septic shock (collectively referred to herein as severe
sepsis) where the application of the rules of this segment are
addressed to more severe sepsis and the application of these rules
entail invasive methods of monitoring the patient or delivery of
drugs with intensive physiologic effects, the administration of
drugs with potential side effects, etc. (for example, using a
pulmonary artery catheter, the use of a central venous catheter,
the administration of vasopressor or inotrope drugs, etc.).
[0070] Furthermore, it may be the case that certain segments of the
protocol may be further segmented based on certain criteria. Here,
FIGS. 5-8 further represent embodiments of segments of the protocol
where the rules have been grouped into segments based on the
ability to clinically separate the administration of the rules
comprising the segment, or the rules are separated based on their
applicability to a specific area, medication, measurement, etc.
[0071] In this embodiment then, FIG. 5 is represents one embodiment
of a segment of the protocol for sepsis diagnosis and management
where rules of the segment have been grouped according to
fluid/blood therapy. As can be seen then, rules comprised by the
fluid/blood therapy segment may also be considered to be comprised
by the grouping of rules according to sever sepsis or septic shock.
This may also be the case with the rules of the segments depicted
in FIGS. 6-8 as well. Moving on to FIG. 6, one embodiment of a
segment of the protocol for sepsis diagnosis and management where
rules of the segment have been grouped according to
vasopressor/inotrope therapy is depicted. FIG. 7 depicts one
embodiment of the protocol for sepsis diagnosis and management
where rules of the segment have been grouped according to adrenal
insufficiency/steroid therapy and FIG. 8 depicts one embodiment of
the protocol for sepsis diagnosis and management where rules of the
segment have been grouped according to pulmonary arterial catheter
(PAC) directed therapy.
[0072] Each of the various segments of the embodiment for a
protocol for sepsis diagnosis and management as represented in
FIGS. 3-8 may now be discussed in more detail. Turning first to
FIG. 3, at step 310 a patient can be assessed for sepsis. This
assessment may comprise applying one or more rules configured to
implement a point or score based screening where points are based
upon measurements of patient condition (referred to herein
collectively as scoring), including temperature, heart rate,
respiration rate, white blood cell count, etc. Additionally a
suspected source of infection may be identified. This scoring
system may, for example, generate a score based on if T>38 C or
T<36 C, HR>90 bpm, RR>20 bpm or PaCO.sub.2<32 mmHg or
WBC>12000 or WBC<4000 cells/mm.sup.3 and may ask a
practitioner to identify a suspected source of infection (for
example: line, pneumonia, abdomen, cellulitis/soft tissue, urinary
tract, etc.) FIGS. 9A and 9B depicts one embodiment of a sheet
which may be utilized by a clinician (such as nurse practitioner or
the like) to complete a sepsis screening process.
[0073] Returning to FIG. 3, at step 310 if the criteria for a
diagnosis of sepsis are met, at step 320 vital signs are recorded,
recent lab data reviewed, IV access established and a urine output
monitor utilized. More specifically in one embodiment the following
actions are taken: record body core temperature (T), heart rate
(HR), respiratory rate (RR), mean arterial pressure (MAP), urine
output rate (UO), partial pressure of carbon dioxide in arterial
blood (PaCO2), white blood cell count (WBC), blood lactate
concentration ([lactate]), Glasgow Coma Scale (GCS) score and
suspected source of infection. If catheters are not present, then
place: peripheral IV catheter (18 gauge), peripheral IV catheter
(20 gauge), foley catheter (with T sensor) and document catheter
placement procedures in chart. Determine need for new or existing
central venous catheter. If new central venous catheter is
required, then document placement in chart and document reason as:
congestive heart failure (CHF), pulmonary hypertension or
inadequate peripheral IV access. If required, then measure central
venous pressure (CVP). If CVP.gtoreq.15 mmHg, then notify
intensivist physician, and, based on information including current
MAP, HR, UO, [lactate], and CVP, decide whether to continue the
first segment of the protocol (one embodiment depicted in FIG. 3)
or start the second segment of the protocol (one embodiment
depicted in FIG. 4). This determination may include assessing for
septic shock, including assessing the suspected source of infection
and assessing hypotension (MAP<65 mmHg (measured and recorded)
or MAP.gtoreq.65 mmHg and vasopressor therapy ongoing).
[0074] At step 330 a diagnosis of septic shock may be confirmed.
More specifically in one embodiment the following actions are
taken: determine hypotension (MAP<65 mmHg) or normotension
(MAP.gtoreq.65 mmHg) with vasopressor therapy ongoing (for example,
post operation prior to ICU admit). If normotension (MAP.gtoreq.65
mmHg) with vasopressor therapy ongoing, then record vasopressor
agent and vasopressor agent dose rate. If hypotension (MAP<65
mmHg) or normotension (MAP.gtoreq.65 mmHg) with vasopressor therapy
ongoing, then give Lactated Ringer's (LR) fluid: 20 mL/kg, ideal
body weight; IV bolus (use pressure bag). Measure MAP within 5
minutes of completion of 20 mL/kg IV fluid bolus. If vasopressor
therapy is ongoing, then attempt to wean vasopressor to maintain
MAP.gtoreq.65 mmHg. Record vasopressor agent and vasopressor agent
dose rate. If vasopressor therapy is not ongoing, then determine if
hypotension (MAP<65 mmHg) persists after fluid administration.
If MAP<65 or unable to wean vasopressor (patient is unresponsive
to fluid and septic shock is ongoing) then go to step 396.
[0075] Otherwise, at step 340 antibiotic therapy is started after
record a suspected or confirmed microorganism. More specifically in
one embodiment the following actions are taken: select correct
antibiotic agent from table below.
TABLE-US-00003 Antibiotic drug if severe Vancomycin Regimen
allergy, then substitute 600 mg q12 hr Linezolid Indication 1.
1.sup.st line .sup.amonitor, adjust for renal 2. 2.sup.nd line
dysfxn .sup.bfor severe .beta. lactam allergies; kinetic monitoring
Pneumonia Community 1. Ceftriaxone + 1 g IV q24 h acquired
Azithromycin 500 mg IV/PO q24 h 2. Levofloxacin .sup.a 750 mg IV
q24 h Community Add Clindamycin 600 mg IV q8 h aspiration or change
Ceftriaxone .sup.a 4.5 g IV q6 h to Piperacillin/ Tazobactam
Ventilator associated early (<5 dy) 1. Cefepime .sup.a2 g IV q12
h 2. Ciprofloxacin .sup.a 400 mg IV q12 h late 1. Cefepime + .sup.a
2 g IV q24 h (pseudomonas Vancomycin + .sup.a 15 mg/kg IV q12 h
risk) Tobramycin .sup.a, b 7 mg/kg IV 2. Ciprofloxacin + .sup.a 400
mg IV q12 h Vancomycin + .sup.a 15 mg/kg IV q12 h Clindamycin 900
mg IV q8 h Catheter related Urinary catheter; 1. Piperacillin/
.sup.a 4.5 g IV q6 h UTI Tazobactam 2. Ciprofloxacin .sup.a 400 mg
IV q12 h IV, art cath; Vancomycin .sup.a 15 mg/kg IV q12 hr
bloodstream (after cath removal) Wound/Soft Tissue Necrotizing 1.
Piperacillin/ .sup.a 4.5 g IV q6 h fasciitis Tazobactam + .sup.a 15
mg/kg IV q12 h Vancomycin + 900 mg IV q8 h Clindamycin 2.
Ciprofloxacin + .sup.a 400 mg IV q12 h Vancomycin + .sup.a 15 mg/kg
IV q12 h Clindamycin 900 mg IV q8 h Surgical site 1. Piperacillin/
.sup.a 4.5 g IV q6 h infection Tazobactam + .sup.a 15 mg/kg IV q12
h Vancomycin 2. Ciprofloxacin + .sup.a 400 mg IV q12 h Vancomycin
.sup.a 15 mg/kg IV q12 h Intra abdominal 1. Imipenem/ .sup.a 500 mg
IV q6 h Cilistatin + .sup.a 15 mg/kg IV q12 h Vancomycin +/- .sup.a
800 mg IV q24 h Fluconazole 2. Ciprofloxacin + .sup.a 400 mg IV q12
h Metronidazole + 500 mg IV q8 h Vancomycin +/- .sup.a 15 mg/kg IV
q12 h Fluconazole .sup.a 800 mg IV q24 h
As soon as available, give selected antibiotic agent using
prescribed dose rate and schedule.
[0076] At step 350 give Lactated Ringer's (LR) fluid: 0.5 L; IV
bolus (use pressure bag) and at step 360 Measure and record MAP,
HR, UO, and (if monitored) CVP within 5 min of completion of IV
fluid bolus.
[0077] Following this, at step 370 it can be determined if
vasopressor therapy is ongoing. If vasopressor therapy is ongoing,
then attempt to wean vasopressor to maintain MAP.gtoreq.65 mmHg.
Then record vasopressor agent and vasopressor agent dose rate. If
MAP<65 mmHg or unable to wean vasopressor, i.e. patient is
unresponsive to fluid therapy, requires vasopressor therapy, and
septic shock is ongoing, then go to step 396. If MAP.gtoreq.65 mmHg
and able to wean vasopressor, i.e. patient is responsive to fluid
therapy, does not require ongoing vasopressor therapy, then go to
step 380.
[0078] At step 380 if vasopressor therapy is not ongoing, then
determine if hypotension (MAP<65 mmHg) or tachycardia (HR>120
beats per minute (bpm)) persists after fluid therapy. If MAP<65
mmHg and/or HR>120 bpm, then determine total IV fluid volume
given since protocol start. A decision can then be made whether to
repeat fluid bolus based and hemodynamic instability can be
assessed. More specifically in one embodiment the following actions
are taken: If MAP<65 mmHg and/or HR>120 bpm, and if total LR
volume.gtoreq.6 L (i.e. 20 mL/kg fluid challenge IV bolus+0.5 L LR
IV boluses, or 12 0.5 L LR IV boluses) has been given in past 6 hr,
then go to step 396. If total LR volume<6 L has been given in
past 6 hr (for example, total LR volume=20 mL/kg fluid challenge IV
bolus+0.5 L LR IV boluses<6 L, or <12 0.5 L LR IV boluses),
then go to step 350. Otherwise repeat 0.5 L IV LR fluid bolus, then
go to step 360. Re-measure MAP, HR UO, then go to step 370. With
respect to hemodynamic stability: If MAP.gtoreq.65 and
HR.ltoreq.120, then determine total LR volume given. If total LR
volume=20 mL/kg fluid challenge IV bolus+0.5 L LR IV boluses<6
L, or if <twelve 0.5 L boluses have been given in past 6 hr,
i.e. total LR volume<6 L in past 6 hr, then go to step 390.
Reassess hemodynamic stability and renal function within 1 hr. If
total LR volume=20 mL/kg fluid challenge IV bolus+0.5 L LR IV
boluses.gtoreq.6 L, or if .gtoreq.twelve 0.5 L boluses have been
given in past 6 hr, (for example, total LR volume.gtoreq.6 L in
past 6 hr) then notify intensivist physician, and, based on
information including LR volume past 6 hr, and current MAP, HR, UO,
[lactate], and CVP (if monitored), decide whether to continue the
first segment of the protocol (one embodiment depicted in FIG. 3)
or start the second segment of the protocol (one embodiment
depicted in FIG. 4). If decision to continue with the first segment
then go to step 390 reassess hemodynamic stability and renal
function within 1 hr. If the decision is made to start the second
segment, then go to step 396 at which point the sever sepsis
segment of the protocol may be implemented.
[0079] At step 390 hemodynamic stability and renal function may be
assessed. More specifically in one embodiment the following actions
are taken: if MAP<65, HR>120, UO<0.5, and/or vasopressor
therapy ongoing, then determine if CVP is being monitored. If CVP
is being monitored, then record CVP. If CVP.gtoreq.15, then notify
an intensivist physician, and, based on information including LR
volume past 6 hr, and current MAP, HR, UO, [lactate], and CVP (if
monitored), decide whether to continue with the first segment of
the protocol (one embodiment depicted in FIG. 3) or start the
second segment of the protocol (one embodiment depicted in FIG. 4).
If CVP<15, then go to step 350 and give another 0.5 L LR IV
bolus. If .gtoreq.24 hr since start of the protocol, then patient
care under the protocol may end, which may entail notifying an
intensivist physician and record in the protocol end time and
orders to proceed with standard monitoring orders. If
UO.gtoreq.0.5, then go to step 392. Otherwise, determine time since
last 0.5 L LR IV bolus. If <4 hr since last 0.5 L LR IV bolus,
then determine time since last [lactate] analysis. If .gtoreq.4 hr
since last [lactate] analysis, then go to step 394.
[0080] At step 392 If <4 hr since last 0.5 L LR IV bolus, then
determine time since last [lactate] analysis. If .gtoreq.4 hr since
last [lactate] analysis, then go to step 394 where if .gtoreq.4 hr
since last [lactate] analysis, then: order [lactate] analysis. If
[lactate]>4 mM, then go to step 350. Otherwise repeat 0.5 L IV
LR fluid bolus, then go to step 360. Then re-measure MAP, HR UO,
then go to 370 and reassess hemodynamically stability.
[0081] At step 396 proceed to the segment of the protocol for
sepsis diagnosis and management intended for severe sepsis, one
embodiment of which is depicted in FIG. 4. At step 410 hemodynamic
stability can be assessed and established. If vasopressor
administration is ongoing (for example, post op prior to ICU
admit), then determine if norepinephrine IV is the agent being
administered. If norepinephrine is being administered, and if
MAP<55, then: increase norepinephrine (Levophed) dose rate by 5
mcg/min; IV; titrate dose rate to obtain 65.ltoreq.MAP.ltoreq.75
mmHg. If vasopressor agent other than norepinephrine is being
administered, then: order norepinephrine (Levophed), IV; set up IV
infusion; after norepinephrine infusion set up is complete, D/C
other vasopressor agent; increase or start norepinephrine
(Levophed) dose rate by 5 mcg/min; IV; titrate dose rate to obtain
65.ltoreq.MAP.ltoreq.75 mmHg. If no vasopressor administration is
ongoing, then measure MAP. If MAP.gtoreq.55 mmHg, then go to step
420. If MAP<55 mmHg, then: order norepinephrine (Levophed), IV
and set up IV infusion. After norepinephrine infusion set up is
complete, D/C other vasopressor agent; increase (start)
norepinephrine (Levophed) dose rate by 5 mcg/min; IV and titrate
dose rate to obtain 65.ltoreq.MAP.ltoreq.75 mmHg.
[0082] At step 420 central venous and arterial catheters may be
placed. Monitoring and antibiotic therapy started. More
specifically in one embodiment the following actions are taken: If
not present, place: 1) foley catheter (with T sensor); 2)
peripheral arterial line; 3) central venous line (triple lumen) and
4) systemic oxygenation monitor (e.g. noninvasive tissue hemoglobin
oxygen saturation, StO.sub.2 monitor). If not ordered, order and
obtain samples for clinical laboratory analyses: 1) peripheral
blood culture (x3; 3 different sites; 20 mL/site); 2) [lactate] 3)
arterial blood gas analysis (measurements of: acid base balance,
pH; partial pressure oxygen, PaO2, partial pressure carbon dioxide,
PaCO2); 4) Ca.sup.++, magnesium, phosphorus 5) complete blood count
with differential WBC analysis; 6) international normalization
ratio (INR), partial thromboplastin time (PTT), fibrinogen
concentration ([fib]), D-dimer concentration; 7) cytokine+basic
metabolic panel (BMP): IL-1ra, IL-6, IL-8, IL-10, ICAM-1,
TNF-.alpha., caspase-3, procalcitonin, K+, Na+, Cl-, [gluc],
[creat], [BUN], [tot CO.sub.2], [tot Ca]; 8) hepatic function
panel; 9) thyroid function panel: T3, T4, TSH; 10) B-type
natriuretic protein concentration (BNP); 11) C-reactive protein
concentration (CRP); 12) blood type and screen (possible blood
product transfusion); 13) urine screen; 14) if clinical pulmonary
infection score (CPIS)>6, then perform mini bronchoalveolar
lavage (BAL); or sputum culture if not intubated and 15) if patient
is receiving vasopressor therapy, then order chest x ray. Probable
source of infection and StO.sub.2 are recorded, antibiotic agents
(broad spectrum; IV) are given, the patient is screened for
possible Xigris therapy. Order and obtain samples for clinical
laboratory analyses: [lactate], arterial blood gas, INR, PTT,
[fib], [D-dimer] and CBC with differential.
[0083] Additionally, in one embodiment the following actions may
also be taken: blanket ICU consent obtained, or make chart entry
explaining why consent could not be obtained. Pre printed orders
signed and placed in chart. Notify intensivist physician when
baseline monitoring is complete and document catheter placement
procedures in chart. Antibiotic therapy may then be started, by
recording a suspected or confirmed microorganism and selecting and
administering the correct antibiotic agent from the table:
TABLE-US-00004 if severe Vancomycin allergy, then substitute
Regimen Antibiotic drug Linezolid 600 mg q12 hr Indication 1.
1.sup.st line .sup.amonitor, adjust for renal 2. 2.sup.nd line
dysfxn .sup.bfor severe .beta. lactam allergies; kinetic monitoring
Pneumonia Community 1. Ceftriaxone + 1 g IV q24 h acquired
Azithromycin 500 mg IV/PO q24 h 2. Levofloxacin .sup.a 750 mg IV
q24 h Aspiration Add Clindamycin 600 mg IV q8 h or change
Ceftriaxone .sup.a 4.5 g IV q6 h to Piperacillin/ Tazobactam
Ventilator associated early (<5 dy) 1. Cefepime .sup.a 2 g IV
q12 h 2. Ciprofloxacin .sup.a 400 mg IV q12 h late 1. Cefepime +
.sup.a 2 g IV q24 h (pseudomonas Vancomycin + .sup.a 15 mg/kg IV
q12 h risk) Tobramycin .sup.a,b 7 mg/kg IV 2. Ciprofloxacin +
.sup.a 400 mg IV q12 h Vancomycin + .sup.a 15 mg/kg IV q12 h
Clindamycin 900 mg IV q8 h Catheter related Urinary catheter; 1.
Piperacillin/ .sup.a 4.5 g IV q6 h UTI Tazobactam 2. Ciprofoxacin
.sup.a 400 mg IV q12 h IV, art cath; Vancomycin .sup.a 15 mg/kg IV
q12 hr bloodstream (after cath removal) Wound/Soft Tissue
Necrotizing 1. Piperacillin/ .sup.a 4.5 g IV q6 h fasciitis
Tazobactam + .sup.a 15 mg/kg IV q12 h Vancomycin + 900 mg IV q8 h
Clindamycin 2. Ciprofloxacin + .sup.a 400 mg IV q12 h Vancomycin +
.sup.a 15 mg/kg IV q12 h Clindamycin 900 mg IV q8 h Surgical site
1. Piperacillin/ .sup.a 4.5 g IV q6 h infection Tazobactam + .sup.a
15 mg/kg IV q12 h Vancomycin 2. Ciprofoxacin + .sup.a 400 mg IV q12
h Vancomycin .sup.a 15 mg/kg IV q12 h Intra abdominal 1. Imipenem/
.sup.a 500 mg IV q6 h Cilistatin + .sup.a 15 mg/kg IV q12 h
Vancomycin +/- .sup.a 800 mg IV q24 h Fluconazole 2. Ciprofloxacin
+ .sup.a 400 mg IV q12 h Metronidazole + 500 mg IV q8 h Vancomycin
+/- .sup.a 15 mg/kg IV q12 h Fluconazole .sup.a 800 mg IV q24 h
[0084] At step 430 an effort is made to achieve hemodynamic
stability. More specifically in one embodiment the following
actions are taken: determine if steroid therapy is ongoing (pre or
post hospital admit) and if steroid therapy is ongoing, then go to
step 490. If steroid therapy is not ongoing, then go to step 430.
Measure MAP and determine adrenal sufficiency. If MAP.gtoreq.65
mmHg and vasopressor support ongoing, or if MAP<65 mmHg and
vasopressor support not ongoing, then determine if adrenal
stimulation test is complete, or if excluded as meaningful test. If
no adrenal stim test exclusion criteria or if adrenal stim test
complete and change in [cortisol]<9 .mu.g/dL (results indicate
adrenal insufficiency), then go step 490. If adrenal stim test
exclusion criteria or if adrenal stim test complete and change in
[cortisol].gtoreq.9 .mu.g/dL (i.e. results indicate adrenal
sufficiency), then determine hypotension: MAP<65 mmHg. If
MAP<65 mmHg, then go to step 440. If MAP.gtoreq.65 mmHg, then
determine if norepinephrine infusion rate>0 (vasopressor support
ongoing) or previous attempt to wean vasopressor support was >1
hr ago. If MAP.gtoreq.65 mmHg, and if norepinephrine infusion
rate=0 (no vasopressor support ongoing) or previous attempt to wean
vasopressor support was <1 hr ago, then determine tachycardia:
HR>120 bpm, or oliguria: UO<0.5 mL/kg-hr. If MAP.gtoreq.65
mmHg, and if norepinephrine infusion rate>0 (vasopressor support
ongoing) or previous attempt to wean vasopressor support was >1
hr ago, then go to step 440 (attempt to wean norepinephrine
infusion rate to minimum dose rate to maintain MAP.gtoreq.65 mmHg).
If MAP.gtoreq.65 mmHg, and if norepinephrine infusion rate=0 (no
vasopressor support ongoing) or previous attempt to wean
vasopressor support was <1 hr ago, and if HR>120 bpm or
UO<0.5 mL/kg-hr, then go to step 450.
[0085] At step 440 cardiac sufficiency may be determined. More
specifically in one embodiment the following actions are taken: if
CVP.gtoreq.15 mmHg and norepinephrine dose rate.gtoreq.15
.mu.g/min, then go to step 402. If CVP<15 mmHg or norepinephrine
dose rate<15 .mu.g/min, then determine vascular volume and
cardiac sufficiency: CVP.gtoreq.10 mmHg. If CVP<10 mmHg, then go
to step 450. If CVP.gtoreq.10 mmHg and norepinephrine infusion
rate=0 (or previously decreased within past hour to minimum
necessary to maintain MAP.gtoreq.65 mmHg), then determine
hypotension: MAP<65 mmHg. If MAP<65 mmHg, then go to step
470. If MAP.gtoreq.65 mmHg, and if norepinephrine infusion
rate>0 (vasopressor support ongoing) or previous attempt to wean
vasopressor support was >1 hr ago, then attempt to wean
norepinephrine infusion rate to minimum dose rate to maintain
MAP.gtoreq.65 mmHg.
[0086] At step 450 fluid blood therapy may initiated. FIG. 5
depicts one embodiment of a segment of a protocol for sepsis
diagnosis and management where the segment comprises rules for
administering fluid or blood therapy. More specifically in one
embodiment the following actions are taken: measure CVP and if
CVP.gtoreq.15 mmHg, then measure blood hemoglobin concentration
([Hb]). If [Hb].ltoreq.6 g/dL, then order 2 units PRBC. If
CVP.gtoreq.15 mmHg, then give 2 units IV over next hour. If
CVP<15 mmHg, then give 2 units IV bolus (within 10 min; use
pressure bag). If 6<[Hb]<8 g/dL, then order 1 unit PRBC and
give IV bolus (within 5 min; use pressure bag). If CVP<15 mmHg,
then determine if latest INR measurement.gtoreq.6 hr old. If latest
INR measurement.gtoreq.6 hr old, then measure INR. If latest
INR<6 hr old, then determine if latest INR.gtoreq.2. If latest
INR.gtoreq.2, then determine if there is risk of hemorrhage or
recent abdominal surgery. If hemorrhage risk or recent abdominal
surgery, then determine if .gtoreq.4 units FFP were given. If
.gtoreq.4 units FFP have not been given, then order and give 2
units FFP IV bolus (within 10 min; use pressure bag). After
administration of 2 units FFP, re measure INR, and re measure CVP.
If if latest INR<2, or if no risk of hemorrhage or recent
abdominal surgery, or if .gtoreq.4 units FFP have been given, then
give I L LR IV bolus (within 5 min; use pressure bag). Measure CVP
within 5 min of completion of IV infusion. If CVP<10 mmHg, then
determine if .gtoreq.2 L LR have been given. If 2 L LR have not
been given, then give 2.sup.nd L LR IV bolus (within 5 min; use
pressure bag). Measure CVP within 5 min of completion of IV
infusion. If .gtoreq.2 L LR have been given, then measure [Hb]. If
[Hb].ltoreq.6 g/dL, then order 2 units PRBC. If CVP.gtoreq.15 mmHg,
then give 2 units PRBC IV over next hour. If CVP<15 mmHg, then
give 2 units PRBC IV bolus (within 10 min; use pressure bag). If
6<[Hb]<8 g/dL, then order 1 unit PRBC and give IV bolus
(within 5 min; use pressure bag) or, if StO.sub.2.gtoreq.70%, if
[Hb]<10, then order 1 unit PRBC and give IV bolus. If
[Hb].gtoreq.8 g/dL (or .gtoreq.10), then go to step 460.
[0087] At step 460 systemic oxygen consumption may be assessed.
More specifically in one embodiment the following actions are
taken: measure and record StO.sub.2 and, if StO.sub.2.gtoreq.70%,
then go to step 412. If time since start of sepsis
protocol.gtoreq.24 hr, then go to step 422. If time since start of
sepsis protocol<24 hr, then go to step 432. If StO.sub.2<70%,
then determine if total isotonic fluid volume for last 6 hr (for
example, fluid challenge 20 mL/kg+fluid therapy 2 L+other) given is
>60 mL/kg ideal body weight. If total isotonic fluid
volume>60 mL/kg, then determine if .gtoreq.2 L Hextend
(hetastarch colloid balanced crystalloid solution; BioTime Inc) has
been given in last 24 hr. If Hextend volume<2 L, then order and
give Hextend 0.5 L IV bolus. Re measure and record StO.sub.2. If
StO.sub.2.gtoreq.70%, then go to step 412. If Hextend volume<2
L, then repeat Hextend 0.5 L IV bolus. Re measure and record
StO.sub.2. If StO.sub.2.gtoreq.70%, then go to step 412. If Hextend
volume<2 L, then determine persistent hypotension. If MAP<65
mmHg despite fluid challenge and fluid blood therapy interventions,
then go to step 470. If StO.sub.2<70% and total isotonic fluid
volume (fluid challenge 20 mL/kg+fluid therapy 2 L+other) given for
during administration of the protocol is .ltoreq.60 mL/kg ideal
body weight, then reassess within 1 hour.
[0088] At step 470 vasopressor/inotrope therapy may initiated. FIG.
6 depicts one embodiment of a segment of a protocol for sepsis
diagnosis and management where the segment comprises rules for
administering vasopressor/inotrope therapy. More specifically in
one embodiment the following actions are taken: If MAP<65 mmHg,
determine if norepinephrine (Levophed) infusion is ongoing. If
norepinephrine (Levophed) infusion is not ongoing, then start
norepinephrine (Levophed) infusion, 6 .mu.g/min, IV. Reassess MAP
for effect of norepinephrine (Levophed) infusion in 5 min. If
MAP<65 mmHg, then determine if norepinephrine (Levophed)
infusion rate.gtoreq.15 .mu.g/min.
[0089] If norepinephrine (Levophed) infusion rate<15 .mu.g/min,
then increase dose rate by 3 .mu.g/min. Reassess MAP for effect of
norepinephrine (Levophed) infusion rate increase in 5 min. If
norepinephrine (Levophed) infusion rate.gtoreq.15 .mu.g/min, then
notify an intensivist physician. If norepinephrine (Levophed)
infusion rate.gtoreq.15 .mu.g/min, then determine if vasopressin
infusion is ongoing. If vasopressin infusion is not ongoing, then
start vasopressin infusion, 0.04 unit/min, IV. Reassess MAP for
effect of vasopressin (and norepinephrine) infusion in 5 min.
[0090] If MAP<65 mmHg, norepinephrine (Levophed) infusion
rate.gtoreq.15 .mu.g/min, and vasopressin infusion rate=0.04
unit/min are ongoing, then determine if an echo cardiogram was
ordered and completed, and if results are available, and consult an
intensivist physician to continue. If an echo cardiogram was not
ordered, then order an echo cardiogram, and consult an intensivist
physician to continue. If MAP<65 mmHg, norepinephrine (Levophed)
infusion rate.gtoreq.15 .mu.g/min and vasopressin infusion
rate=0.04 unit/min are ongoing, and if echo cardiogram results are
available or pending, then, in consult with the intensivist, order
increase of norepinephrine (Levophed) infusion rate by 3 .mu.g/min
increments with MAP reassessment after each increment to a maximum
limit of 30 .mu.g/min to obtain MAP.gtoreq.65 mmHg, or order no
further increase of norepinephrine (Levophed) infusion rate.
[0091] If MAP<65 mmHg, norepinephrine (Levophed) infusion
rate.gtoreq.15 .mu.g/min (or .gtoreq.30 .mu.g/min), and vasopressin
infusion rate=0.04 unit/min are ongoing, and if no further increase
of norepinephrine (Levophed) infusion rate is ordered, then assess
echo cardiogram results and, in consult with SICU intensivist,
assess systemic oxygenation (StO.sub.2). If MAP<65 mmHg,
norepinephrine (Levophed) infusion rate.gtoreq.15 .mu.g/min (or
.gtoreq.30 .mu.g/min), and vasopressin infusion rate=0.04 unit/min
are ongoing, and if no further increase of norepinephrine
(Levophed) infusion rate is ordered, then order increase of
dobutamine infusion rate to obtain StO.sub.2.gtoreq.70%. If
MAP.gtoreq.65 mmHg with norepinephrine (Levophed) infusion
rate<15 .mu.g/min, or with norepinephrine (Levophed) infusion
rate.gtoreq.15 .mu.g/min and vasopressin infusion=0.04 unit/min,
then assess systemic oxygenation (StO.sub.2). If StO.sub.2<70%,
then determine if dobutamine infusion is ongoing. If dobutamine
infusion is not ongoing, then start dobutamine infusion, 2.5
.mu.g/kg-min, IV.
[0092] Reassess MAP and StO.sub.2 for effect of dobutamine infusion
in 5 min. If StO.sub.2<70%, then then determine if dobutamine
infusion rate.gtoreq.10 .mu.g/kg-min. If dobutamine infusion
rate<10 .mu.g/kg-min, then increase dose rate by 2.5
.mu.g/kg-min. Notify an intensivist physician and reassess MAP and
StO.sub.2 for effect of dobutamine infusion rate increase in 5 min.
If dobutamine infusion rate.gtoreq.10 .mu.g/kg-min, then consult an
intensivist physician to continue. If MAP.gtoreq.65 mmHg and
StO.sub.2.gtoreq.70% with or without norepinephrine (Levophed)
infusion, norepinephrine (Levophed) and vasopressin infusion, or
dobutamine infusion, then re assess systemic oxygenation
(StO.sub.2) within 1 hr. If MAP<65 mmHg or StO.sub.2<70%,
norepinephrine (Levophed) infusion rate.gtoreq.15 .mu.g/min (or
.gtoreq.30 .mu.g/min) and vasopressin infusion=0.04 unit/min or
dobutamine infusion rate.gtoreq.10 .mu.g/kg-min, then go to step
480.
[0093] At step 480 pulmonary artery catheter directed therapy may
be initiated. FIG. 7 depicts one embodiment of a segment of a
protocol for sepsis diagnosis and management where the segment
comprises rules for administering pulmonary artery catheter (PAC)
directed therapy. More specifically in one embodiment the following
actions are taken: an intensivist physician is notified and if the
intensivist physician concurs, then order and place pulmonary
artery catheter. If the intensivist physician does not concur with
order to place pulmonary artery catheter, then instruction is
provided to consider echo cardiogram and confirm whether steroid
therapy ongoing.
[0094] In one embodiment, PAC directed therapy would proceed
according to the protocol segment of FIG. 7, using [Hb], cardiac
index (CI), and pulmonary capillary wedge pressure (PCWP) as the
key measurement variables to guide protocol logic. Referring to
FIG. 7, a PAC with continuous cardiac output (CCO) monitoring
capability and an arterial catheter would be placed (A). Protocol
logic would direct maintenance of DO.sub.2I.gtoreq.500 mL
O.sub.2/min-m.sup.2 (B) with interventions of: PRBC if [Hb]<10
g/dL and DO.sub.2I<500 mL O.sub.2/min-m.sup.2; crystalloid fluid
bolus (LR, 1 L) if [Hb].gtoreq.10 g/dL, PCWP<15 mmHg, and
DO.sub.2I<500 mL O.sub.2/min-m.sup.2 (C); PCWP-CI optimization
(`Starling curve`) if [Hb].gtoreq.10 g/dL, PCWP.gtoreq.15 mmHg and
DO.sub.2I<500 mL O.sub.2/min-m.sup.2 (D); inotrope infusion
(milrinone or dobutamine) if PCWP-CI was optimized, [Hb].gtoreq.10
g/dL, PCWP.gtoreq.15 mmHg and DO.sub.2I<500 mL
O.sub.2/min-m.sup.2; and, vasopressor infusion (norepinephrine) if
inotrope infusion was ongoing, PCWP-CI was optimized,
[Hb].gtoreq.10 g/dL, PCWP.gtoreq.15 mmHg, DO.sub.2I<500 mL
O.sub.2/min-m.sup.2 and MAP<60 mmHg (E). (from Sucher et al. J
Trauma 2008)
[0095] At step 490 adrenal insufficiency/steroid therapy may be
administered. FIG. 8 depicts one embodiment of a segment of a
protocol for sepsis diagnosis and management where the segment
comprises rules for administering adrenal insufficiency/steroid
therapy. More specifically in one embodiment the following actions
are taken: determine if steroid therapy is ongoing. If steroid
therapy is ongoing, then give 50 mg hydrocortisone IV bolus (Q 6
hr, 24 hr). Record: vasopressor dose rate, current MAP, when
MAP<65 mmHg during past 6 hr, LR volume past 6 hr. If steroid
therapy is not ongoing, then determine if vasopressor
(Levophed/vasopressin) therapy is ongoing. If vasopressor therapy
is ongoing, then determine if adrenal stimulation test is excluded
as a meaningful test where exclusion criteria for adrenal
stimulation test include: allergy to corticosteroid or
adrenocorticotropic hormone (ACTH), steroid therapy in last 6
months, steroid therapy this hospital stay or etomidate in last 12
hours. If vasopressor therapy is not ongoing, then go to step 402.
If vasopressor therapy is ongoing and if adrenal stimulation test
is not excluded, then order adrenal stimulation test. Determine if
latest [cortisol].gtoreq.6 hr old. If latest [cortisol].gtoreq.6 hr
old, then order serum [cortisol] (random). Confirm that adrenal
stimulation test is not complete. If adrenal stimulation test is
not complete, then order and give 250 .mu.g Cosyntropin IV; wait 30
min; order serum [cortisol] (random); wait additional 30 min; order
2.sup.nd serum [cortisol] (random); determine
.DELTA.[cortisol]=1.sup.st or 2.sup.nd post Cosyntropin
[cortisol]-pre Cosyntropin [cortisol]. If adrenal stimulation test
is complete and .DELTA.[cortisol]<9 (i.e. +results, indicating
adrenal insufficiency), then order and give 50 mg hydrocortisone IV
bolus (Q 6 hr, 24 hr). Record: vasopressor dose rate, current MAP,
when MAP<65 during past 6 hr, LR volume past 6 hr. If adrenal
stimulation test is complete and .DELTA.[cortisol].gtoreq.9
(i.e.--results, indicating adrenal sufficiency), then go to step
460.
[0096] At step 402 conventional therapies may have been maximized,
thus criteria for recombinant activated protein C (Xigris) therapy
may be assessed. More specifically in one embodiment the following
actions are taken: confirm criteria for recombinant activated
protein C (Xigris) therapy. If criteria met, then order and give
recombinant activated protein C (Xigris). At step 412 hemodynamic
stability may be assessed, and therapy given within 1 hr of change
or previous assessment. At step 422 if 24 hours have elapsed since
the start of the administration of the protocol, the protocol may
be ended. Otherwise, at step 432: in reassess Q at 4 hours and
reassess metabolic status (BMP), oxygenation (ABG), coagulation
status (INR, PTT, [fib], [D dimer]), and blood cell counts.
[0097] As may be noted after a review of the protocol for the
diagnosis and management of sepsis described above, the practical
utilization of such a protocol may be relatively complex, as
embodiments of these protocols may comprise many rules including
many interventions. Thus, it is desirable from an implementation
standpoint to provide effective methodologies or systems for the
use of such protocols. Accordingly, in certain embodiments, a
protocol, such as the embodiments of the sepsis diagnosis and
management protocol described above, may be implemented in
conjunction with a computer system which is tailored for use by a
clinician in a health care environment.
[0098] More particularly, in one embodiment this computer
implemented protocol may be configured to guide a clinician or
other user through the implementation of a protocol such that
requests for information, instructions for interventions or the
presentation of information related to other rules associated with
protocol may be delivered via computer to a interface and
patient-specific data including patient responses to specific
interventions or patient specific measurements may be obtained
through an interface and rules of the protocol evaluated such that
a subsequent instruction may be presented based both on the
protocol being implemented by the computer system and the specifics
of the patient whom the protocol is being utilized to treat.
[0099] FIG. 10 depicts one embodiment of a high-level architecture
diagram for the implementation of a computer system implemented
protocol for an aspect of care. A computerized protocol system 1010
may comprise a processor operable to execute a protocol
implementation module 1012 configured to implement a protocol for
an aspect of care. The computerized protocol may comprise one or
more instructions stored on a tangible computer readable medium
which are configured to implement a state machine or other program
or logic according to the rules comprising the protocol for that
aspect of care. Thus, protocol implementation module 1012 may
deliver instructions to perform actions associated with the
implementation of a protocol, including to ascertain and provide
information, etc., through a notifier 1020 based on the rules
comprising the protocol. This delivery may entail the presentation
of certain displays or prompts on a visual, verbal or auditory
interface device, etc. These actions may then be carried out by the
clinician 1040 such that required therapeutic intervention or other
action is performed on the patient, the proper information on the
patient's current condition is ascertained, provided through the
notifier and stored in the data repository 1050, etc.
[0100] Alternatively, the notifier 1020 may be linked to one or
more medical devices such as physiological monitors 1060,
therapeutic devices 1070 and any one of a number of ancillary
systems 1080 such that at least of the actions associated with
protocol may be performed, information on the patient ascertained
and stored in data repository 1050, etc. substantially without the
involvement of clinician. For example, one or more medical devices
in may be able to accept instructions in the Health Level 7 (HL7)
Version 3 Messaging Standard messages and perform one or more
actions based on the instructions or return data pertaining to the
current state of the patient or other information to the data
repository 1050. Thus, one or more instructions associated with the
implementation of the protocol may be carried on substantially
between the computerized protocol system 1010 and one or more
medical devices 1060, 1070, 1080 substantially without any
involvement by the clinician 1040
[0101] Referring now to FIG. 11, a more detailed depiction of the
implementation of one embodiment of such a computerized protocol
system, which may be utilized in conjunction with computerized
implementation of protocols for aspects of care, including a
protocol for the diagnosis and management of sepsis, is depicted.
In particular, a clinical setting in which patient care is
implemented, such as a hospital or the like may desire to implement
protocols for one or more aspects of care being utilized to
diagnose or treat patients. To that end, a protocol system 1120 may
be employed in such a clinical setting to aid in the computerized
implementation of such protocols.
[0102] Such a protocol system 1120 may be attached to a data store
1110, where the data store 1110 comprises a set of executable
protocols 1132 and patient data 1134. An executable protocol 1132
may comprise a set of computer instructions configured to, when
executed, implement a protocol, such as the protocol for the
diagnosis and management of sepsis discussed above, in conjunction
with one or more computer systems. Thus, protocol system 1120 may
also comprise a protocol execution module 1140 executing on a
processor of protocol system 1120 and configured to execute an
executable protocol 1134 such that the protocol which the
executable computer protocol is configured to implement may be
utilized in conjunction with the care of a patient.
[0103] Specifically, in one embodiment, protocol system 1120 may be
coupled through a wired or wireless communication network 1170,
such as a LAN, WAN, Intranet, the Internet, etc. to one or more
presentation devices 1112 (for example, computers, laptops,
handheld devices, wireless handsets, mobile phones, etc.) residing
in proximity to a patient 1122 such as in the patient's room, a
unit of the clinical facility in which the patient resides, an
operating room, etc. A presentation application 1114 configured to
present one or more interfaces corresponding to the computerized
implementation of a protocol may be executed by presentation device
1112.
[0104] It is desired to utilize a protocol corresponding to a
particular aspect of care, a clinician 1102 may access protocol
system 1120 utilizing presentation application 1114 on presentation
device 1112 to select an executable protocol 1132 corresponding to
the desired aspect of care it is desired to administer to patient
1122. The selected executable protocol 1132 may be executed by
protocol execution module 1140 to implement the protocol in
conjunction with the patient 1122. The execution of the executable
protocol may comprise generating an instance 1136 of the selected
executable protocol 1132, where the instance 1136 of the executable
protocol 1132 comprises the rules and logic of the executable
protocol 1132 plus a state corresponding to the currently selected
rule of the protocol, where the instance 1136 of the executable
protocol 1132 is associated with at least one set of patient data
1134 in the data store 1110.
[0105] The execution of the selected executable protocol 1132
comprises utilizing the instance 1136 to select an applicable rule
and presenting one or more interfaces to the clinician 1102 on
presentation device 1112 using presentation application 1114. These
interfaces may include instructions for actions to be taken by
clinician 1102 (for example, to be performed on, or in conjunction
with patient 1122) or other types of instructions. These interfaces
may also include requests to obtain data and provide associated
interfaces to allow the clinician 1102 to enter the obtained
information. The obtained data may then be stored in patient data
1134 corresponding to that instance 1136, such that a record is
kept of data for that patient 1122 undergoing that particular
protocol at that particular time period. Other data may also be
stored in patient data 1134, for example, the logic or data that
led to a particular rule being selected by protocol execution
module 1140, the time certain actions occurred, patient-specific
data (as non-limiting examples, demographics, criteria, related
measurements, etc.) and patient responses to specific
interventions. In some embodiments, the requested data may also be
obtained automatically, from one or more medical devices 1172
coupled to the patient and to protocol system 1120 through network
1170.
[0106] Once the selected rule has been completed, protocol
execution module may determine a subsequent rule based upon the
state of the instance 1136 of the executable protocol 1136 and the
patient data 1134 corresponding to patient 1122. Interfaces
corresponding to the newly selected rule may then be presented
through presentation device 1112. In this manner, a protocol for an
aspect of care may be implemented on a computer system such that
the rules of the protocol may be selected and implemented based on
the state of a particular patient at a particular time period. This
ability leads advantageously to clinically replicable care derived
from currently known best practices and the like.
[0107] It will be apparent after a review of the above disclosure
that a protocol for the diagnosis and management of sepsis,
embodiments of which are discussed above may be advantageously
implemented by a computer. It may be useful to illustrate examples
of embodiments of visual interfaces which may be utilized by
embodiments of a computerized protocol system configured to
implement a protocol for the diagnosis and management of sepsis
where the interfaces may be presented to a clinician to provide
instructions to a clinician and provide interface to allow the
clinician to provide information when prompted by the
interface.
[0108] FIGS. 12A-12E depicts embodiments of such interfaces for a
computer implemented protocol for the diagnosis and management of
sepsis. More specifically, FIG. 12A one embodiment of an interface
which may be utilized in association with rule similar to that of
step 310 of FIG. 3 as discussed above is depicted, in FIG. 12B one
embodiment of an interface which may be utilized in association
with rule similar to that of step 320 of FIG. 3 as discussed above
is depicted, in FIG. 12C one embodiment of an interface which may
be utilized in association with rule similar to that of step 340 of
FIG. 3 as discussed above is depicted, in FIG. 12D one embodiment
of an interface which may be utilized in association with rule
similar to that of step 360 of FIG. 3 as discussed above is
depicted and in FIG. 12E one embodiment of an interface which may
be utilized in association with rule similar to that of step 320 of
FIG. 4 as discussed above is depicted
[0109] Notice with respect to the various interfaces, that a flow
diagram with representation of the rules of a protocol is displayed
to a clinician or other user, with the currently selected rule
highlighted. A "dialog box" comprising instructions to a clinician
is also presented using the interface, where the dialog box
comprises actions to be undertaken in conjunction with the selected
rule, including actions to perform certain interventions or obtain
certain information. Thus, utilizing these interfaces a clinician
may be effectively guided through the implementation of a protocol
with respect to an aspect of care in conjunction with
administration of that aspect of care to a patient and in
particular may be presented with rules and corresponding
instructions for implementing a protocol for that aspect of care
tailored to the state of a particular patient at a particular
time.
[0110] In the foregoing specification, the invention has been
described with reference to specific embodiments. However, one of
ordinary skill in the art appreciates that various modifications
and changes can be made without departing from the scope of the
invention as set forth in the claims below. Accordingly, the
specification and figures are to be regarded in an illustrative
rather than a restrictive sense, and all such modifications are
intended to be included within the scope of invention.
[0111] Benefits, other advantages, and solutions to problems have
been described above with regard to specific embodiments. However,
the benefits, advantages, solutions to problems, and any
component(s) that may cause any benefit, advantage, or solution to
occur or become more pronounced are not to be construed as a
critical, required, or essential feature or component of any or all
the claims.
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