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Q: Medical research infectious disease ( Answered 5 out of 5 stars,   2 Comments )
Subject: Medical research infectious disease
Category: Miscellaneous
Asked by: housaga-ga
List Price: $100.00
Posted: 26 Sep 2005 14:43 PDT
Expires: 26 Oct 2005 14:43 PDT
Question ID: 572952
Medical Research- How long does it take for someone to progress from
systemic inflammatory response syndrome to multiple organ dysfunction
in the continuum of sepsis? I need medical studies to support your

Request for Question Clarification by pafalafa-ga on 26 Sep 2005 16:48 PDT

There is a lot of statistical information on the epidemiology of
sepsis, such as the numbers of patients with SIRS who progress to
failure of 1 organ, 2 organs, 3 organs, and so on, and the percentage
of mortality in each case.

There's also some overall data on the length of hospital stays for sepsis patients.

However, there doesn't seem to be any overview statistics of how
rapidly, on average, patients progress through various stages of

There is certainly a good deal of individual case information,
however, and it is clear that multiple organ failure can occur very
rapidly in some cases, and much less so in others.

Would a few individual case reports suit your needs?  Or are you
looking only for broad-based statistical studies of the progress of
sepsis in a large cohort?

Let me know a bit more about what, specifically, you need, and I'll
see what I can do.


Subject: Re: Medical research infectious disease
Answered By: crabcakes-ga on 26 Sep 2005 23:27 PDT
Rated:5 out of 5 stars
Hello Housaga,

   The best estimate I can give you on the time it might take a
patient with SIRS to develop MODS would be a few weeks at best. A
patient can survive SIRS 1-3 weeks, from what I have found, until they
develop MODS due to sepsis. (Covered further down in the answer) Then,
they either recover or succumb. Realize that multiple factors come
into play, and that no constant time can be given. The patient?s age,
condition, other underlying conditions, site of infection, kind of
organism (gram positive vs. gram negative) can alter the course of
SIRS and whether or not the patient may develop MODS.

    SIRS is a fairly new phenomena to medicine, and not only because
of the recent nomenclature updates! Its only been in the last 30 years
that seriously ill patients could be kept alive long enough to develop

   Because the terms sepsis, shock, bacteremia, septicemia, toxic
shock have been incorrectly interchanged for so many years, the
decision to standardize this terminology was made in 1991 by the
American College of Chest Physicians/Society of Critical Care
Medicine. Old terms die slowly however, and these terms are still
confusing medical personnel and patients alike!

?New definitions were offered for some terms, while others were
discarded. Broad definitions of sepsis and the systemic inflammatory
response syndrome were proposed, along with detailed physiologic
parameters by which a patient may be categorized. Definitions for
severe sepsis, septic shock, hypotension, and multiple organ
dysfunction syndrome were also offered. The use of severity scoring
methods when dealing with septic patients was recommended as an
adjunctive tool to assess mortality. Appropriate methods and
applications for the use and testing of new therapies were
recommended. The use of these terms and techniques should assist
clinicians and researchers who deal with sepsis and its sequelae.?

This is the current definition of SIRS:
Systemic Inflammatory Response Syndrome (SIRS)
The systemic inflammatory response to a wide variety of severe
clinical insults, manifested by two or more of the following
·Temperature > 38°C or < 36°C 
·Heart rate > 90 beats/min 
·Respiratory rate > 20 breaths/min or PaCO2 < 32 mm Hg 
·WBC count > 12,000/mm3 , < 4000/mm3 , or > 10% immature (band) forms. 

This is the definition of sepsis:
The systemic inflammatory response to infection. In association with
infection, manifestations of sepsis are the same as those previously
defined for SIRS. It should be determined whether they are a direct
systemic response to the presence of an infectious process and
represent an acute alteration from baseline in the absence of other
known causes for such abnormalities. The clinical manifestations would
include two or more of the following conditions as a result of a
documented infection.

Definition of Septic Shock
Septic shock is sepsis with hypotension (systolic BP <90 mm Hg or a
reduction of 40 mm Hg from baseline) despite adequate fluid
resuscitation. Concomitant organ dysfunction or perfusion
abnormalities (eg, lactic acidosis, oliguria, obtundation) are present
in the absence of other known causes.
Definition of Severe Sepsis/SIRS. 

Sepsis (SIRS) associated with organ dysfunction, hypoperfusion, or
hypotension. Hypoperfusion and perfusion abnormalities may include,
but are not limited to, lactic acidosis, oliguria, or an acute
alteration in mental status.
Definition of Multiple Organ Dysfunction Syndrome (MODS). 
MODS is the presence of altered organ function in a patient who is
acutely ill such that homeostasis cannot be maintained without
intervention. Primary MODS is the direct result of a well-defined
insult in which organ dysfunction occurs early and can be directly
attributable to the insult itself. Secondary MODS develops as a
consequence of a host response and is identified within the context of
SIRS. The inflammatory response of the body to toxins and other
components of microorganisms causes the clinical manifestations of

?Early studies focused on uncontrolled invasive infection (sepsis) as
the driving force of multiple organ dysfunction syndrome (MODS).
However, some patients with adequately controlled infection and those
without sepsis nevertheless develop MODS and signs of systemic
inflammation. This discrepancy led to investigations of systemic
activation of inflammation by a wider variety of biological modulators
than just infection. Despite the apparent involvement of biological
modulators such as endotoxin, tumor necrosis factor, and interleukin-1
receptor in MODS, agents that neutralize these modulators have failed
to thwart the progression of sepsis, septic shock, and organ failure.
A new paradigm suggests that, in the critically ill patient at risk
for organ failure, an integrated process propagates an excessive
systemic inflammatory response and/or an inadequate compensatory
anti-inflammatory response.?;jsessionid=jXpsfoK8gjNe?cookieSet=1&journalCode=sur

?There is as yet no precise definition of the multiple organ failure
syndrome, or what is today more appropriately termed the multiple
organ dysfunction syndrome (MODS). Clinically MODS can be considered
as a sequential or concomitant occurrence of a significant derangement
of function in two or more organ systems of the body, against a
background of a critical illness. Organ dysfunction may be mild,
moderate or severe, and multiple organs may show varying degrees of
dysfunction. There is no universally acceptable classification system
which defines parameters of organ specific failure. An ACCP/SCCM
Consensus Conference which was held in 1991, defined MODS as ?the
presence of altered function in an acutely ill patient such that
homeostasis cannot be maintained without intervention?.[1] This
concept is clinically acceptable as it has a practical bearing on
management.? ?Sepsis (which is SIRS due to infection), trauma, and
shock from any cause, remain the most important causes of MODS all
over the world?

According to this site, multiple organ dysfunction syndrome, or MODS
is actually an extension of a SIRS response, and considered present
when any two or more of the following are present; fever, rapid
respiration, rapid pulse, and an elevated white blood count.;year=2003;volume=7;issue=4;spage=233;epage=236;aulast=Udwadia

The following is excerpted from one of the best papers I found on
SIRS, from Neal R. Chamberlain, Ph.D, Kirksville College of
Osteopathic Medicine:

?Sequence of events: Sepsis can be simply defined as a spectrum of
clinical conditions caused by the immune response of a patient to
infection that is characterized by systemic inflammation and
coagulation. It includes the full range of response from systemic
inflammatory response (SIRS) to organ dysfunction to multiple organ
failure and ultimately death.
This is a very complex sequence of events and much work still needs to
be done to completely understand how a patient goes from SIRS to
septic shock. Patients with septic shock have a biphasic immunological
response.  Initially they manifest an overwhelming inflammatory
response to the infection. This is most likely due to the
pro-inflammatory cytokines Tumor Necrosis Factor (TNF), IL-1, IL-12,
Interferon gamma (IFNgamma), and IL-6.?

?Septic shock is the most common cause of mortality in the intensive
care unit. It is the 10th leading cause of death overall (2000) and is
the most common cause of shock encountered by internists in the U.S.
Despite aggressive treatment mortality ranges from 15% in patients
with sepsis to 40-60% in patients with septic shock. There is a
continuum of clinical manifestations from SIRS to sepsis to severe
sepsis to septic shock to Multiple Organ Dysfunction Syndrome (MODS).?

?Systemic Inflammatory Response Syndrome (SIRS): Patient presents with
two or more of the following criteria.
1.temperature > 38°C or < 36°C
2.heart rate > 90 beats/minute
3.respiration > 20/min or PaCO2 < 32mm Hg
4.leukocyte count > 12,000/mm3, < 4,000/mm3 or > 10% immature (band) cells

?Sepsis: SIRS plus a documented infection site (documented by positive
culture for organisms from that site). Blood cultures do NOT need to
be positive. While SIRS, sepsis, and septic shock are associated
commonly with bacterial infection, bacteremia may not be present.
Bacteremia is the presence of viable bacterial within the liquid
component of blood. Bacteremia may be transient, as is seen commonly
after injury to a mucosal surface, primary (without an identifiable
focus of infection), or more commonly secondary, to an intravascular
or extravascular focus of infection.?

?Mortality increases with increase in number of SIRS symptoms and in
severity of the disease process.?

?The evidence that sepsis results from an exaggerated systemic
inflammatory response induced by infecting organisms is compelling;
inflammatory mediators are the key players in the pathogenesis.

The gram-positive and gram-negative bacteria induce a variety of
proinflammatory mediators, including cytokines. Such cytokines play a
pivotal role in initiating sepsis and shock. The bacterial cell wall
components are known to release the cytokines; these include
lipopolysaccharide (gram-negative bacteria), peptidoglycan
(gram-positive and gram-negative bacteria), and lipoteichoic acid
(gram-positive bacteria).

Several of the harmful effects of bacteria are mediated by
proinflammatory cytokines induced in host cells (macrophages/monocytes
and neutrophils) by the bacterial cell wall component. The most toxic
component of the gram-negative bacteria is the lipid A moiety of
lipopolysaccharide. The gram-positive bacteria cell wall leads to
cytokine induction via lipoteichoic acid. Additionally, gram-positive
bacteria may secrete the super antigen cytotoxins that bind directly
to the major histocompatibility complex (MHC) molecules and T-cell
receptors, leading to massive cytokine production.?

Characteristics of sepsis that influence outcomes
Clinical characteristics that relate to the severity of sepsis include
the following:
·	An abnormal host response to infection 
·	Site and type of infection 
·	Timing and type of antimicrobial therapy 
·	Offending organism 
·	Development of shock 
·	Any underlying disease 
·	Patient's long-term health condition 
·	Location of the patient at the time of septic shock

?Staging: Two well-defined forms of MODS of sepsis exist. In either,
the development of acute lung injury or ARDS is of key importance to
the natural history, although ARDS is the earliest manifestation in
all cases.
·In the more common form of MODS, the lungs are the predominant, and
often the only, organ system affected until very late in the disease.
These patients most often present with primary pulmonary disorder (eg,
pneumonia, aspiration, lung contusion, near drowning, chronic
obstructive pulmonary disease [COPD] exacerbation, hemorrhage,
pulmonary embolism). Progression of lung disease occurs to meet the
ARDS criteria. Pulmonary dysfunction may be accompanied by
encephalopathy or mild coagulopathy and persists for 2-3 weeks. At
this time, the patient either begins to recover or progresses to
develop fulminant dysfunction in other organ systems. Once another
major organ dysfunction occurs, these patients often do not survive.

·The second form of MODS presents quite differently. These patients
often have an inciting source of sepsis in organs other than the lung
(the common source being intra-abdominal sepsis), extensive blood
loss, pancreatitis, and vascular catastrophes. Acute lung injury or
ARDS develops early, but dysfunction in other organ systems also
develops much sooner. The organ systems affected are hepatic,
hematologic, cardiovascular, CNS, and renal. Patients remain in a
pattern of compensated dysfunction for several weeks and then either
recover or deteriorate further and die.?

·Acute lung injury leading to ARDS is a major complication of patients
with severe sepsis and septic shock. Incidence of ARDS is
approximately 18% in patients with septic shock.
·Acute renal failure occurs in 40-50% of patients with septic shock.
Acute renal failure complicates therapy and worsens the overall
·DIC occurs in 40% of patients with septic shock.
·Death occurs in 40-50% of patients with septic shock.
?n 1995, a multicenter prospective study published by Brun-Buisson
(1995) reported a mortality rate of 56% during ICU stays and 59%
during hospital stays. Twenty-seven percent of all deaths occurred
within 2 days of the onset of severe sepsis, and 77% of all deaths
occurred within the first 14 days. The risk factors for early
mortality in this study were higher severity of illness score, the
presence of 2 or more acute organ failures at the time of sepsis,
shock, and a low blood pH (<7.3).?

This page has illustrations of MODS and its steps, covering the role
of GALT, the thyroid, cortisol, ARDS, inflammatory mediators, etc.

?Multi-Organ Dysfunction Syndrome (MODS) When sepsis progresses to
severe sepsis or septic shock, progressive organ dysfunction can
develop. Microscopic coagulation plays a role in the development of
MODS, however, the cause of the organ dysfunction is likely
multi-factorial. Although individually, organ dysfunction is
reversible upon resolution of the septic shock, morbidity and
mortality increases as the number of organs involved becomes higher.
Organ dysfunction includes: 
	? Hypoxia, hypercarbia, increased ventilation requirements 
	? Hypotension, decreased cardiac output 
	? Oliguria, increased creatinine 
	? Decreased level of consciousness 
	? Metabolic derangements, including lactic acidosis 
	? Rising hepatic enzymes 
	? Coagulopathies 

Troponin levels are indicators of mortality due to MODS. ?Troponin
levels can rise during septic shock, and ejection fractions can become
low. This myocardial dysfunction is reversible if the septic shock is

MSOF is what MODS used to be named:
?Multiple system organ failure (MSOF) remains a principal cause of
death after major operative procedures and/or severe trauma. We
studied multiple parameters in 553 consecutive emergency surgical
patients to determine the incidence of MSOF, the predisposing factors
to MSOF, and the sequelae of MSOF. Thirty-eight patients had MSOF;
mortality was 74% for these patients. Evaluation of multiple factors
demonstrated that (1) MSOF is primarily due to infection, (2) the
temporal sequence of organ failure is lung, liver, gastric mucosa, and
kidney, and (3) MSOF is the most common fatal expression of
uncontrolled infection.?

?Sepsis is a clinical syndrome that complicates severe infection and
is characterized by systemic inflammation and widespread tissue
injury. In this syndrome, tissues remote from the original insult
display the cardinal signs of inflammation, including vasodilation,
increased microvascular permeability, and leukocyte accumulation.
Although inflammation is an essential host response, current beliefs
regarding the onset and progression of sepsis center upon a
"dysregulation" of the normal response, with a massive and
uncontrolled release of proinflammatory mediators creating a chain of
events that leads to widespread tissue injury.

Tissue injury secondary to activation of the inflammatory system may
also complicate noninfectious disorders (eg, acute pancreatitis or
pulmonary contusion). The term systemic inflammatory response syndrome
(SIRS) is used in this setting to refer to the consequences of a
dysregulated host inflammatory response when infection is not present.

We therefore distinguish between an underlying disease (infection or
pancreatitis) and the host's response (sepsis or SIRS). This
distinction is important clinically since it is the latter, not the
primary disease, that is responsible for the multiple organ
dysfunction syndrome (MODS). MODS is the usual explanation for the
high mortality rates associated with these syndromes.?

?Multiple organ dysfunction is a continuum, with incremental degrees
of physiological derangements in individual organs; it is a process
rather than an event. Alteration in organ function can vary widely
from a mild degree of organ dysfunction to frank organ failure. The
degree of organ dysfunction has a major clinical impact. The term MODS
is defined as a clinical syndrome in which the development of
progressive and potentially reversible physiological dysfunction in 2
or more organs or organ systems induced by a variety of acute insults,
including sepsis, is characteristic.?

   A study done on 4,887 trauma hospital admissions during an 18 month
period, where patients were classified by using  two scoring systems.
The Injury Severity Score (ISS), and a SIRS severity score (1 to 4)
were calculated on each patient. One point was given for each
component: fever, rapid breathing, rapid heartbeat, and a high white
blood cell count. The study revealed that was the SIRS score was
accurate in predicting the patient?s outcome. A score of 2 or greater
predicted greater mortality.

?Background: Recent studies have documented that the systemic
inflammatory response syndrome (SIRS) score is a useful predictor of
outcome in critical surgical illness. The duration and severity of
SIRS are associated with posttrauma multiple organ dysfunction and
mortality. We sought to determine whether the severity of SIRS at
admission is an accurate predictor of mortality and length of stay
(LOS) in trauma patients.

Results: Trauma patients (n = 4,887, 83% blunt injuries, 72% male) had
the following characteristics: 73.1% were age 18 to 45 years, 17.5%
were age 46 to 65 years, and 9.4% were age >=66 years; 77.7% had ISS
less than 15, 18.8% had ISS 16 to 29, and 3.5% had ISS greater than
29. Analysis of variance adjusting for age and ISS determined that
SIRS score of 2 was a significant predictor of LOS. Furthermore, the
relative risk of death increased significantly with SIRS score of 2
when age and ISS were held constant.

Conclusion: Logistic regression analysis confirmed that a SIRS score
of 2 was a significant independent predictor of increased mortality
and LOS in trauma patients. These data suggest that admission SIRS
scoring in trauma patients is a simple tool that may be used as a
predictor of outcome and resource utilization.?;jsessionid=D46cSlJdb7c9KzOl55dlDVlGpFN9I3OLn7W6Uvao6a3z1f9CTWY1!1277578804!-949856144!9001!-1

  eMedicine says 
Systemic Inflammatory Response Syndrome is also known as SIRS. ?Note
that SIRS is separate and distinct from sepsis, severe sepsis, and
septic shock. Each of these latter entities has unique diagnostic
criteria that are different from those for SIRS. The key transition
from SIRS to sepsis according to definition is the presence of an
identified pathogen.?
?The hallmark of SIRS is the creation of a proinflammatory state that
is marked by tachycardia, tachypnea or hyperpnea, hypotension,
hypoperfusion, oliguria, leukocytosis or leukopenia, pyrexia or
hypothermia, and the need for volume infusion. This condition
characteristically does not include a documented source of infection
(eg, bacteremia). Metabolic acidosis is a frequent accompaniment to
SIRS, and it is derived principally from lactate.
SIRS may affect all organ systems and may lead to multiple organ
dysfunction syndrome (MODS)?

·	Morbidity and mortality from SIRS are highly variable, and they
depend principally on the success of therapy for the underlying
disorder and the progression to MODS. Mortality ranges from 25% to
nearly 100% as the number of organ failures increases.
·	SIRS is a reflection of host inflammation. The morbidity associated
with SIRS is related to hypoperfusion from effective circulating
volume maldistribution and the work of breathing associated with
respiratory compensation for metabolic acidosis. Once end-organ damage
begins (eg, renal failure from acute tubular necrosis [ATN]), the
entity is no longer SIRS but has progressed to early MODS. This
progression also is associated typically with the progression to
sepsis or severe sepsis.

?All patients have a perfusion abnormality (eg, hypoperfusion), an
infectious focus, or both. Patients with multiple discrete diseases
have these pathophysiologic abnormalities in common, which span
diverse entities (eg, perforated diverticulitis, trauma, ruptured
aortic aneurysm, pneumonia, transfusion-related acute lung injury).
Despite having a relatively common final pathway for presentation, a
wide variety of triggers exists for SIRS.?
?Staging: A continuum exists from an immune trigger to SIRS to sepsis
to severe sepsis to septic shock that leads to MODS and death. The
"window of opportunity" for targeted intervention is immediately after
SIRS develops. The patient's course along this continuum may be
charted as a prognostic indicator. Clearly, progression towards the
latter elements in the continuum is a poor prognostic event.?

?No drugs of choice exist for this entity. Medication prescriptions
target preexisting comorbidities and prophylaxis regimens for
complications. No pharmacologic agents have been demonstrated to
improve the SIRS outcome. Trials that have established some benefit
have enrolled patients with sepsis, not SIRS. Examples include the
MONARCS trial of monoclonal anti-TNF (alpha). Another is the PROWESS
trial that evaluated the utility of activated protein-C to reduce
mortality is patients with severe sepsis. Thus far, these agents have
not been demonstrated to benefit patients with SIRS.?

·	?Education ideally should target the patient's family. Family
members need to understand the fluid nature of immune responsiveness
and that SIRS is a potential harbinger of other more dire syndromes.
·	Education has a negligible impact once patients are hospitalized
with SIRS. However, well-patient education regarding early
intervention may help intervene early in the inflammatory process to
reduce the frequency with which patients develop SIRS from an acute
illness. To date, such data are lacking, and the above represents an
educated guess of a potential educational intervention.

?A prospective evaluation of the proposed gradations of SIRS and
sepsis demonstrated increasing mortality as patients developed a
greater number of SIRS criteria or more advanced manifestations of
sepsis. Those mortality rates were 3% in patients with no SIRS
criteria, 7% with two SIRS criteria, 10% with three SIRS criteria, 17%
with four SIRS criteria, 16% with sepsis, 20% with severe sepsis, and
46% with septic shock.[4] Although there is marked variability in the
actual numbers, the incidence of sepsis is clearly on the rise;
incidence rates ranging from 1.06 episodes per 1000 patient days to up
to 16 to 260 episodes per 1000 patient days have been reported.?

?The outcome of a patient with severe sepsis is often related to the
occurrence of sepsis-induced multiple organ dysfunction syndrome.
Multiple organ dysfunction syndrome appears to result from a cascade
of organism-related factors, inflammatory mediators, endothelial
injury, disturbed hemostasis, and microcirculatory abnormalities. In
patients with severe sepsis, derangements of inflammation and
coagulation are tightly linked. Although numerous clinical trials
focused on interventions in one or the other of the inflammatory and
coagulation systems failed to show reduced mortality due to sepsis, a
member of a new class of drugs called "cogins" was effective.?

?Numerous clinical trials have enrolled thousands of patients in an
attempt to find a specific agent to modulate the underlying disease
process in sepsis. Candidate antisepsis therapies have included agents
that target host cell activation, mediators of the inflammatory
response, agents that boost the immune response, and prostaglandin
inhibitors. Until recently, however, no modulator therapy has reduced
28-day mortality due to all causes in patients with severe sepsis?

Clinical definitions for organ failure and shock
?Clinical entity Definition
Shock Systolic blood pressure £90 mmHg or mean £70 mmHg, or need for vasopressors

Renal Serum creatine ³2.0 mg/dl, the need for dialysis, or dysfunction
increase in serum creatine ³20 mg/dl above
pre-existing normal

Hepatic Two or more of the following: serum bilirubin dysfunction ³25
mg/dl; alanine aminotransferase or aspartate
aminotransferase ³2 times normal; and prothrombin time ³1.5 times normal

DIC Two or more of the following: prothrombin or partial
thromboplastin time ³1.2 times normal; platelet count
£100000 mm5; and fibrin split products or D-dimer >0.5 mg/l

ARDS Lung injury      score ³7 [20]

Cerebral Dysfunction     Glasgow Coma Scale score <11

Although predicting 28-day survival was not the primary focus of the
present study, it was predicted with moderate success using baseline
plus serial data SMART models.
Not surprisingly, possibly reflecting a more defined
mortality/survival population later during the course of severe
sepsis/septic shock, predictions of survival were most accurate from
serial data at 21 and 28 days. A similar phenomenon has been reported
for the APACHE III?

?The present study prospectively validated multiple logistic
regression models from a population of septic surgical, medical, and
gynecologic patients that predicted shock, pulmonary edema, mechanical
ventilation, ARDS, DIC, and hepatobiliary, renal, and cerebral
dysfunction in septic surgical patients, up to 28 days in advance.?

   ?The systemic inflammatory response also damages the endothelial
lining of blood vessels and cell membranes. This causes fluid to leak
from the intravascular and intracellular spaces into the interstitial
space. The fluid shift from increased capillary permeability results
in reduced circulating fluid volume, which, in turn, causes the blood
pressure to drop. The blood vessels also dilate, which leads to a
further plunge in the blood pressure. Increased clotting, increased
capillary permeability, and the increased inflammatory response will
eventually cause impaired tissue perfusion and multiple organ failure.

Once organs begin to fail, sepsis is defined as severe and can
progress to septic shock?that is, sepsis with severe hypotension and
perfusion abnormalities. In severe sepsis, changes in vital signs and
lab test results, along with signs and symptoms of altered tissue
perfusion, reflect acute organ system dysfunction. See Signs of Acute
Organ System Failure for more details.?

?Besides the systemic inflammatory response syndrome (SIRS) criteria
discussed in Clinical Signs of Sepsis , signs and symptoms of severe
sepsis include clinical indicators of altered tissue perfusion, like
hypotension, oliguria (decreased urine output), and decreased skin
perfusion (such as decreased capillary refill, mottled skin, and
rashlike appearance). What you need to remember is that a patient who
exhibits two or more SIRS criteria and has symptoms of a known or
suspected infection is waving a big red flag at you; he needs to be
evaluated for sepsis.

The health care provider will order at least two blood cultures to
help identify the organism at the root of sepsis and to guide
antimicrobial therapy. If the patient has a vascular access device,
you can draw one sample from it and the other percutaneously.
Depending on the specifics of the case, the health care provider might
also want to culture the patient's urine, cerebrospinal fluid, wound
fluid, respiratory secretions, or other body fluids. Although lab
tests can confirm the presence of infection, a definitive source of
infection isn't identified in 20% to 30% of patients with sepsis.?

?To combat inflammatory and procoagulation responses, drotrecogin alfa
(recombinant human activated protein C [Xigris]) is indicated for
patients with severe sepsis who have at least two of the SIRS criteria
and evidence of early organ system failure. Drotrecogin alfa is the
first approved cogin, a class of agents that inhibit coagulation,
decrease the inflammatory response, and promote fibrinolysis in
sepsis. Although bleeding is a risk when drotrecogin alfa is given,
the health care provider should weigh this risk against the potential
benefits for patients with sepsis-induced organ failure, acute
respiratory distress syndrome, and septic shock.?

?However, once severe sepsis has begun, treatment options are limited.
In order to standardize treatment options, the Surviving Sepsis
Campaign provided several evidence-based treatments for severe sepsis.
The goal of providing these guidelines is to standardize the treatment
of severe sepsis and generate an improved outcome.?

A little more about GALT can be found here:

Further Reading

I hope this has adequately answered your question. If not, please do
not close this question by rating. Simply request an Answer
Clarification and I will be happy to assist you further with this

Regards, Crabcakes

Search Terms

SIRS progresses to MODS
SIRS induced organ failure
SIRS + mortality
MODS + sepsis
systemic inflammatory response syndrome
SIRS to MODS continuum sepsis

Request for Answer Clarification by housaga-ga on 27 Sep 2005 08:45 PDT
Is there any medical support or research for the position that one can
develop SIRS or sepsis and then progress to MODS within two hours?
What do you base your estimate on? Is there any medical research to
support your  estimate? MEdical texts journal article and or medical
research studies would be appreciated.Any and all help would Thanks

Request for Answer Clarification by housaga-ga on 27 Sep 2005 08:52 PDT
SOmeone has argued to me that a healthy individual can progress from
SIRS and/or sepsis to MODS in two hours. If you have individual case
information that is contained in medical texts, medical journals or
studies, I would appreciate it.

Clarification of Answer by crabcakes-ga on 27 Sep 2005 10:49 PDT
Hello Housaga,

   I've done extensive research, looking for a time frame for the
continuum of SIRS and sepsis to organ failure, and can not find any.
If you review the follwoing link, you'll see the numerous factors that
can affect the timing. One can not say with any certitude that one
will progress in a predetermined timeline.

?Damage to the organs in cases of MODS is not caused by exogenous
factors such as tissue damage, bacteria or toxins directly, but is
primarily a consequence of the harmful influence of endogenously
produced mediators.

Organ dysfunction can occur acutely, that is within a few minutes or
hours of a harmful influence on previously healthy persons (e.g. in
cases of extensive tissue damage, placental abruption or following a
bite from poisonous snake). In such cases, activation of proteases and
the release of innumerable mediators from a large number of different
cells leads to a critical condition that is characterised by
haemodynamic, respiratory and haemostatic instability. Even though the
symptoms can appear alarming, the prognosis is often better than in
cases involving the sub-acute systemic activation of these defence
Note that the above paragraph doe snot apply to sepsis or SIRS, but to
noninfective origin.

The continuum of events:
   1. Severe sepsis
   2. Septic shock
   3. Multiple organ dysfunction syndrome (MODS), which often results in death

See an animated cascade of events:

"Standard supportive care alone may not adequately treat severe
sepsis, which has mortality rates of 28-50%."

I?m reposting these paragraphs from the original answer:

?Staging: Two well-defined forms of MODS of sepsis exist. In either,
the development of acute lung injury or ARDS is of key importance to
the natural history, although ARDS is the earliest manifestation in
all cases.
·	In the more common form of MODS, the lungs are the predominant, and
often the only, organ system affected until very late in the disease.
These patients most often present with primary pulmonary disorder (eg,
pneumonia, aspiration, lung contusion, near drowning, chronic
obstructive pulmonary disease [COPD] exacerbation, hemorrhage,
pulmonary embolism). Progression of lung disease occurs to meet the
ARDS criteria. Pulmonary dysfunction may be accompanied by
encephalopathy or mild coagulopathy and persists for 2-3 weeks. At
this time, the patient either begins to recover or progresses to
develop fulminant dysfunction in other organ systems. Once another
major organ dysfunction occurs, these patients often do not survive.
·	The second form of MODS presents quite differently. These patients
often have an inciting source of sepsis in organs other than the lung
(the common source being intra-abdominal sepsis), extensive blood
loss, pancreatitis, and vascular catastrophes. Acute lung injury or
ARDS develops early, but dysfunction in other organ systems also
develops much sooner. The organ systems affected are hepatic,
hematologic, cardiovascular, CNS, and renal. Patients remain in a
pattern of compensated dysfunction for several weeks and then either
recover or deteriorate further and die.?
Scroll down to about the middle of the page:

If you?re discussing sepsis, we have a different time frame.
Anecdotally, I have seen septic patients go into DIC and then organ
failure who die in a matter of hours to a day or two. DIC during
sepsis is a major contributor to MODS.
?Disseminated intravascular coagulation (DIC), previously considered a
specific disease, is now considered part of a pathophysiologic process
 involving excess coagulation such as seen in sepsis and related
disorders, e.g. systemic inflammatory response syndrome (SIRS), or
multi-organ dysfunction syndrome (MODS) (1-5).
      ?Although DIC was previously thought to result solely from
activation of the coagulation system by endotoxin or tissue factor,
new data suggest that the changes in DIC may also reflect the
activation of pro-inflammatory cytokines. These same cytokines are
part of the inflammatory response of sepsis.?

?The survival of the patients differs with regard to the extent of the
infection and inflammation of the host.  Thus, survival is about 77%
in those with bacteremia, 65% in those with SIRS and septicemia, 50%
in severe sepsis, and 34% in those with septic shock (table 1). If the
patients present with acute renal failure survival is about 50%. It
decreases to about 30% if the patient also suffers from SIRS, and
about 20% or less if there is an additional septic shock with progress
into MODS (table 2). The interaction of various cascade systems is out
of control in these patients despite optimal treatment with adequate
antibiotics, fluid substitution, inotropic drugs, mechanical
respiration and dialysis.?

?Increased DIC score also was associated with increased mortality,
pressors requirements and mutiorgan failure. There was also a trend
for increased heart rate, BUN, and creatinine, and a lower blood
pressure, and Glasgow Coma Score with increased DIC score. An evolving
DIC score > 2 at 72 hours had an 81 % sensitivity and 73% specificity
of predicting mortality in patients with severe sepsis.?

?It is just two decades ago that it became clear that sepsis is often
accompanied by MODS. During severe sepsis a generalised activation of
the haemostatic system occurs, and fibrin is formed in the
microvasculature. This condition is known as DIC. DIC can also be
provoked by other mechanisms and may, by itself, cause MODS due to
microthrombosis and ischemia.?

?It occurs in approximately one hospital patient in every 10001 and it
may implicate that patients with primarily treatable conditions
develop critical illness or die as a result of dysfunction of one or
multiple organs.2?4 Damage to organs is the result of uncontrolled,
systemic activation of the haemostatic system and inflammatory
processes. The terminology used can sometimes be confusing. The terms
?disseminated intravascular coagulation?, ?systemic inflammatory
response syndrome? (SIRS) and multiple organ deficiency syndrome
(MODS) cover a number of closely related disorders and are often used
indiscriminately. DIC and SIRS, however, describe pathophysiological
conditions, while MODS describes the results of the processes.5?

?Sepsis is the leading cause of morbidity and mortality in critically
ill patients in many intensive care units. The pathophysiology of
organ failure and death in patients with sepsis remain elusive. This
review focuses on recent advances in our understanding of the
mechanisms of cell death in sepsis, the types of cells that are dying,
and the consequences on immunity. The extensive apoptotic death
results in immune cell depletion and may compromise the ability of the
patient to eradicate the primary infection and predispose to secondary
nosocomial infections.?

?Patients treated with APC should have acute life-threatening
infection manifested by:
1) systemic inflammatory response syndrome (SIRS), defined as
abnormalities in 3 of the following 4 areas:
temperature, heart rate, respiratory status, and white blood cell count; and
2) acute organ failure, present for less than 24 hours, involving one
or more of the following systems: cardiovascular, pulmonary, renal,
hematologic, and/or metabolic.?

?Sepsis (both bacteremia and clinical sepsis syndrome) did not
significantly increase mortality rates in the groups with organ system
failure. Mortality rates for patients with sepsis before or within 24
hours of development of MOSF (early sepsis) did not differ from
mortality rates for those patients with onset of sepsis more than 24
hours after developing MOSF (late sepsis, 53% vs 33%, P = NS). We
conclude that underlying pathophysiologic mechanisms of MOSF other
than sepsis are as important as sepsis in critically ill pediatric

?Mortality from sepsis correlates with the number of failing organs
and the degree of organ dysfunction. Patients without organ failure
face a mortality rate of approximately 15% compared with 70% for those
with three or more failing organs.[3] Increasing number of organs
failing during the first 48 hrs of admission to an intensive care unit
is a good indicator of mortality.[4] Consequently, prevention of new
or worsening organ dysfunction is a primary goal in the treatment of
patients with severe sepsis.[5]?

This article ?Determinants of Mortality in Patients with Severe
Sepsis? can be purchased for $25.00


While this site is not helpful, it may give you some insight:
?Of the 52 privates in the 13th Light Dragoons wounded by sabre,
gunfire and cannon injuries at Waterloo, only two subsequently died.
Prof Singer says: "Despite the non-existence of antibiotics, blood
transfusions, life-support machines and other paraphernalia of modern
intensive care, most of these soldiers recovered, often from
life-threatening injuries. Yet with all our technical advances in
medicine, mortality rates from conditions such as sepsis (bacterial
infection of the bloodstream) haven't improved dramatically over the
past century.
Modern treatments trigger changes in the patient's inflammatory and
immune responses or influence circulatory, hormonal, bioenergetic and
metabolic systems in ways we don't appreciate. Even lowering the
temperature of a feverish patient may be counter-productive. We may
need to be more strategic in our treatments and therapies, tailoring
them to how the body responds naturally to sepsis and other critical
Survival statistics from the battle of Waterloo throw up an even more
radical theory - could it be that multiple organ failure, triggered by
severe trauma or subsequent infection, actually represents the body's
last-ditch attempt to survive in the face of a critical illness? By
switching itself off and becoming dormant, as with hibernating animals
during extreme cold, the body may thus be able to tide itself through
the critical period. Support for this theory comes from the fact that
the organs invariably recover, to the point of appearing remarkably
normal, within days to weeks when the patient survives.?

Two case histories

I hope this has helped!
Regards, Crabcakes

Clarification of Answer by crabcakes-ga on 27 Sep 2005 11:07 PDT
Hello again, I just saw your second clarification.

I don't consider a person with SIRS to be a "healthy" person. Could a
person with sepsis or SIRS progress to MODS within two hours?

How do you know when to start the timer? How do you determine the
point the organ failure starts? Is one organ failing? Two? One would
have to monitor body chemistry and coagulation constantly. Is dialysis
ongoing? A ventilator? I would guess two hours from SIRS or sepsis
*could* be possible, but it depends greatly on the causative organism
and its modus operandi! If the causative organism is resistant to
given antibiotics, one can assume MODS would occur more rapidly. If
two or more organisms were present, and producing toxins...  if DIC
has occurred...

I was unable to find documentation to prove or disprove the two hour time frame.

Regards, Crabcakes
housaga-ga rated this answer:5 out of 5 stars

Subject: Re: Medical research infectious disease
From: pinkfreud-ga on 26 Sep 2005 14:50 PDT
This article might be of interest to you:

"Gordon,L (1999). The sepsis continuum from systemic inflammatory
response syndrome to multiple organ dysfunction syndrome. Nursing in
Critical Care 4(5) 239-244"
Subject: Re: Medical research infectious disease
From: crabcakes-ga on 28 Sep 2005 10:07 PDT
Thank you for the 5 star rating! It is appreciated.
Sincerely, Crabcakes

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