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Sepsis, SIRS and MODSBen Griffiths
Iain D Anderson
AbstractSepsis, a systemic inflammatory process triggered by infection, is the
commonest mode of death in modern surgical practice. Sepsis exists as
a spectrum of severity from the Systemic Inflammatory Response
Syndrome (SIRS) through to Multiple Organ Dysfunction Syndrome
(MODS). The surgeon must be able to recognize patients within this spec-
trum rapidly because early identification and intervention is the key to
reducing mortality. Rapid, accurate assessment and management are
facilitated by using a structured approach such as that described in the
Care of the Critically-Ill Surgical Patient (CCrISP) programme. Control of
the source of sepsis is fundamental to success and this should be led
by senior surgeons. Key steps and timelines are described in the
evidence-based care bundles of the Surviving Sepsis Campaign.
Keywords resuscitation; source control; sepsis; SIRS; MODS
Sepsis is a major cause of morbidity and mortality worldwide
with around 36,800 sepsis-related deaths in the UK per annum.
Only coronary heart disease kills more people in the UK and it is
anticipated that worldwide rates of sepsis will increase year on
year. Sepsis is the leading mechanism of death in modern
surgical practice and the surgeon must understand common
definitions and their place in the sepsis spectrum. SIRS is
extremely common and patients will be seen with this on most
ward rounds. The surgeon should aim to identify cases early by
conducting structured ward rounds (progress/history, examina-tion, observations, laboratory results) with the aim of preventing
the slide of a patient with SIRS on the surgical ward to a criti-
cally-ill patient with MODS on ICU. This slippery slope from SIRS
to MODS can be rapid and difficult to halt but the earlier the
intervention the better the outcome.
Systemic Inflammatory Response Syndrome (SIRS) d can be
diagnosed when any two of the following criteria exist:
body temperature 38 C
heart rate >90 beats/min
respiratory rate >20 breaths/min or PCO2
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Intravenous fluid and vasopressors
If the serum lactate is >4 mmol/l (or the patient is under-
perfused) then an intravenous fluid bolus of 20 ml/kg crystal-
loid should be given rapidly and the response evaluated.
Crystalloid or colloid can be used as there is no evidence thatone is superior to the other, but 5% dextrose should be
avoided. In patients unresponsive to fluid challenges, vaso-
pressors should be started to aim at a mean arterial pressure
(MAP) of 65 mmHg. In sepsis the most common first-line
vasopressor is noradrenaline which raises MAP primarily by
vasoconstriction. Goals in patients with septic shock are
a central venous pressure of >8 mmHg and either a central
venous oxygen saturation (ScvO2) of>70% or a mixed venous
oxygen saturation (SvO2) of>65%.
Blood cultures
Two sets of peripheral blood cultures should be taken as well as
cultures from any in-dwelling vascular device. Blood cultures are
positive in 30e50% of septic patients and the identification of the
correct organism in these patients enables antibiotic therapy to
be targeted subsequently.
Broad-spectrum antibiotics
Give broad-spectrum antibiotics as soon as blood cultures
have been sent, the choice depending on local policy. If
necessary, get advice from your microbiologist. There is good
evidence that outcome is improved if antibiotics are given
within an hour of ward admission and within 3 h if seen in
Accident and Emergency.
Next steps in management
Source control
After resuscitation, controlling the source of sepsis is essential to
halting progress down the sepsis slope. Experienced surgical
input is needed to lead the search for the source of sepsis and
arrange urgent control. This may involve appropriate imaging if
the site is not obvious or immediate intervention once the source
has been identified (see Table 2). Source control may simplyinvolve removal of an in-dwelling vascular or urinary catheter or
a course of appropriate antibiotics. Radiologically-guided
drainage is a minimally invasive technique used to drain suitable
solitary intra-abdominal/pelvic abscesses. Clearly, in a patient
with perforated diverticular disease and faecal peritonitis the
only effective method of source control will be an urgent
laparotomy and definitive surgical management of the source is
the gold standard. However, a limited damage control
laparotomy may occasionally be necessary for rapid control of
sepsis in a patient too ill (acidotic, coagulopathic) to survive
complex definitive surgery. The patient returns to the ICU for
physiological improvement before delayed definitive surgery.
Nutrition
Nutrition should be considered as part of every definitive
management plan. All septic patients are catabolic and their
calorie requirement increases significantly. The enteral route
should be utilized wherever possible and this may involve
accessing the gastrointestinal tract by tube (typically nasogastric/
nasojejunal tube, or radiological or open gastrostomy/jejuno-
stomy). The enteral route also maintains mucosal integrity and
may protect against further septic complications originating from
the gut, through colonisation/translocation, but if unavailable,
then parenteral nutrition should be used with meticulous care of
central venous catheters to prevent further sepsis.
Immuno-modulating feeds containing immunonutrients suchas arginine, glutamine, and omega-3 fatty acids are conceptually
appealing but data from multiple individual trials and several
meta-analyses have failed to produce convincing evidence of
general benefit.
Sepsis resuscitation bundle
The goal is to perform all indicated tasks within the first 6 h of
identification of severe sepsis in all patients.The tasks are:
1. Measure serum lactate
2. Obtain blood cultures prior to antibiotic administration
3. Administer broad-spectrum antibiotic,within 3 h of emergencyadmission and within 1 h otherwise
4. In the event of hypotension and/or a serum lactate >4 mmol/l
a. Deliver an initial minimum of 20 ml/kg of crystalloid or an
equivalent
b. Apply vasopressors for hypotension not responding to initial
fluid resuscitation to maintain mean arterial pressure (MAP)
>65 mmHg
5. In the event of persistent hypotension despite fluid resuscitation
(septic shock) and/or lactate >4 mmol/l
a. Achieve a central venous pressure (CVP) of>8 mmHg
b. Achieve a central venous oxygen saturation (ScvO2) >70 %
or mixed venous oxygen saturation (SvO2) >65%
(Reproduced with permission. Copyright 2008. European Society of Inten-
sive Care Medicine, International Sepsis Forum and Society of Critical Care
Medicine.)
Table 1
Source control in sepsis.
Techniques Examples
Antibiotics Urinary tract infection
CellulitisDrainage of pus Aspiration of breast abscess
Radiological paracolic abscess drainage
Device removal Central venous catheter
Hernia mesh excision
Debridement of
dead tissue
Necrotising fasciitis
Amputation gangrenous limb
Definitive surgery Colonic resection with stoma
Small bowel anastomosis
Damage control
laparotomy
Stapling ends of bowel
Drain pus, leave abdomen open
Table 2
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Prevention of complications
Septic patients are at increased risk of venous thromboembolism
and peptic ulceration. National Institute of Health and Clinical
Excellence (NICE) guidelines recommend mechanical prophy-
laxis with low molecular weight heparin in patients with severe
infection.3 Gastric acid suppression or preferably cytoprotective
therapy is used for ulcer prophylaxis. Meticulous intravascular
line care reduces line sepsis, and hand washing by medical andnursing staff reduces cross-infection.
Critical care
The critical care team should be informed of the presence of
a patient with severe sepsis as early as possible to enable them to
plan appropriate intervention and to decide on the appropriate
level of care. They may employ the sepsis managementbundle
for ICU care of severe sepsis,Table 3.
Steroid therapy
Intravenous corticosteroids (hydrocortisone 200e300 mg/day,
for 7 days in divided doses or by infusion) are recommended in
patients with septic shock who, despite adequate fluid replace-
ment, require vasopressor therapy to maintain adequate blood
pressure. A meta-analysis has shown significant reductions in
ICU and all-cause mortality as well as numbers of patients whose
septic shock was reversed.4
Activated protein C (APC)
APC has anticoagulant, anti-inflammatory and fibrinolytic prop-
erties. It is used in patients with severe sepsis and multiple organ
dysfunction in addition to standard care. Its anticoagulant action
means it is contraindicated in patients with a risk of significant
bleeding. The PROWESS study5 demonstrated a 6.1% absolute
reduction in 28-day mortality using recombinant human activ-
ated protein C in patients with severe sepsis and a recent Cana-
dian study has shown improved mortality if activated protein C
was given within the first 24 h of developing sepsis-induced
organ dysfunction.6 NICE has recommended APC for patients
with severe sepsis and organ failure.
Glycaemic control
Hyperglycaemia is common in septic patients and there is
evidence that maintaining blood glucose levels within a very
tight range (4.4e6.1 mmol/l) reduces morbidity and mortality in
critically-ill surgical patients.7 Maintaining glucose in such a tight
range is difficult and hypoglycaemic events are more common.
This has led to a relaxation of the acceptable range as shown in
the bundle above.
Inspiratory plateau pressure goal
Most septic patients need to be intubated and ventilated and
approximately 50% will have either acute lung injury or acute
respiratory distress syndrome (ARDS). Studies have shown that
aiming for a mean inspiratory plateau pressure of3.9 mmol/l, but
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Gut
The GI tract may help propagate the septic process. Bacteria in
the upper GI tract may be aspirated into the lungs, producing
nosocomial pneumonia and this process is made worse by the
necessary gastric acid suppression in critical illness. Alterna-
tively, cytoprotective therapy with drugs such as sucralfate can
be prescribed. There is evidence from animals that the normal
barrier function of the gut may be affected by splanchnic hypo-perfusion or reperfusion injury allowing translocation of bacteria
and endotoxins into the systemic circulation.
Liver
By virtue of the role of the liver in host defence, the abnormal
syntheticfunctions caused by liver dysfunction can contribute to
both the initiation and progression of sepsis. The reticuloendo-
thelial system of the liver acts as a first line of defence in clearing
bacteria and their products; liver dysfunction leads to a spill-over
these products into systemic circulation. Markers of liver
synthetic function can be useful in assessing response to treat-
ment (C-reactive protein, serum albumin).
Kidneys
Acute renal failure often accompanies sepsis due to acute tubular
necrosis. Systemic hypotension, direct renal vasoconstriction,
release of cytokines and activation of neutrophils by endotoxins
and other peptides all contribute to renal injury. Treatment
involves limiting ischaemic injury to the kidney, reducing iatro-
genic injury (nephrotoxic medication) and the use of renal
replacement therapy. Common methods of renal replacement on
the ICU include continuous veno-venous haemofiltration
(CVVH), continuous veno-venous diafiltration (CWHDF) and
continuous veno-venous haemodialysis (CVVHD).
Central nervous system
Involvement of the CNS in sepsis produces encephalopathy and
peripheral neuropathy, the pathogeneses being poorly
understood.
Coagulation
Subclinical coagulopathy signified by a mild elevation of the
thrombin or activated partial thromboplastin time (APTT) or
a moderate reduction in platelet count is extremely common, but
overt disseminated intravascular coagulation (DIC), with a dia-
gnostic rise in D-dimers, is less common. Thromboelastograms
are being used more commonly in ICUs to monitor haemostasis
as a dynamic process.
Novel therapies
It is hoped that widespread use of the evidence-based Surviving
Sepsis Campaign care bundles will translate into improvements in
mortality from sepsis over the next decade. Surgical advances are
likely to involve minimally invasive techniques of obtainingsource control. In the critical care setting there is interest in
improving understanding of the genetic polymorphisms which
have been shown to be important in an individuals susceptibility
and response to sepsis. There is interest in administering APC in
the inhaled form to patients with ALI as there is improved
oxygenation in animal models. Hydrogen sulphide has been
identified as the third gaseous transmitter (after nitric oxide and
carbonmonoxide) andhas been shown to be a signalling molecule
of the cardiovascular, neurological and inflammatory systems.
Animals continue to be studied in various shock models and we
wait to see whether any application in humans emerges. A
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