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15 Sepsis andSeptic Shock
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tion, particularly during the early phase following penetrating
injury, other signs such as shaking chills or rigors are more
specic indicators of infection and in particular, the presence
of bacteremia. Further clinical signs of infection depend on
the site of infection and may range from erythema and drainage or aspiration of pus (e.g. in surgical site infection) to
cough, sputum changes and crackles on lung auscultation
(such as in chest infection) to abdominal pain, guarding and
rebound tenderness (e.g. in secondary peritonitis).
Although some biomarkers have been shown to perform
well in differentiating between infectious and non-infectious,
mostly community-acquired acute illnesses, the specicity
of these laboratory investigations to identify an infection in
patients following severe trauma is controversial. The trend
of biomarkers such as C-reactive protein (CRP), interleukin 6 and procalcitonin (PCT) may, however, be used to assess
the level of systemic inammation. A renewed and otherwise
unexplained increase in the serum concentrations of these
inammatory biomarkers, especially during the second or
subsequent weeks after severe trauma, should prompt the
physician to closely assess the patient for the presence of a
new underlying infection. Laboratory investigations of specimens sampled from the site of a suspected infection (e.g.
retained uid collection, cerebrospinal uid, pleural uid)
may be diagnostic for selected infectious processes.
Microbiological (e.g. blood or urine cultures) and molecular biological (e.g. polymerase chain reaction-based tests)
methods as well as imaging techniques (e.g. computer
tomography) are used to conrm the presence of an underlying infection. Microbiological cultures with susceptibility
patterns are critical to inform adequate antimicrobial therapy. Models to predict the risk of fungal infections such as
the Candida Score combine clinical indicators with the nd-
ing of multifocal candida colonisation. Because of their high
negative predictive value, they can be used to select high-risk
patients for microbiological workup and biomarker sampling. In these patients, laboratory tests for detection of cell
wall components of fungi such as the 1,3-beta--glucan test
and galactomannan are useful and valuable laboratory
adjuncts for the early diagnosis of posttraumatic invasive
fungal infections.
15.3.2 Diagnosis ofAcute Organ Dysfunction
All patients sustaining penetrating trauma should be repeatedly screened for the development of acute organ dysfunction during their post-traumatic course. Sepsis-induced acute
organ dysfunction has been dened as an acute change in the
total Sequential Organ Failure Assessment score (Table15.1)
of ≥2 points consequent to infection. A Sequential Organ
Failure Assessment score count of ≥2 points is associated
with an overall mortality risk of 10% in a general hospital
population with suspected infection. Since the Sequential
Organ Failure Assessment score requires the results of specic laboratory investigations, simplied screening tools
based on vital parameters have been suggested to assess
patients for their risk of developing acute organ dysfunction
from an underlying infection. Although these tools such as
the quick Sequential Organ Failure Assessment score or
early warning scores can predict the early mortality risk in
patients with severe trauma, they have so far not been rigorously validated to screen trauma patients for the presence of
sepsis. From a practical point of view, however, no screening
tool can outperform good clinical acumen to detect new
organ dysfunction. Therefore, patients following penetrating
Table 15.1 The sequential organ failure assessment score
Organ system 0 point 1 point 2 points 3 points 4 points
Lungs PaO2/FiO2
(mmHg)
Coagulation Platelets (G/L)
Liver Bilirubin (mg/dL) <1.2 1.2–1.9 2–5.9 6–11.9
Cardiovascular
CNS Glasgow Coma
Renal Creatinine
CNS central nervous system, FiO2 fractional inspiratory oxygen concentration, MAP mean arterial blood pressure, PaO2 partial arterial oxygen
pressure
a
Catecholamine doses are given as μg/kg/min for at least 1h
*
to convert creatinine mg/dL to micromol/L multiply by 88.4
a
Scale
(mg/dL)*
Urine output
(mL/d)
≥400
≥150
MAP≥70mmHg
15 13–14 10–12 6–9 <6
<1.2 1.2–1.9 2–3.4 3.5–4.9
<400 <300 <200 <100
<150 <100 <50 <20
MAP<70mmHg Dopamine>5
or dobutamine
(any dose)
Dopamine
5.1–15 or
epinephrine
≤0.1 or
norepinephrine
≤0.1
<500 <200
≥12
Dopamine>15 or
epinephrine>0.1 or
norepinephrine>0.1
≥5
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M. Mer and M. W. Dünser
trauma should undergo repeated clinical assessments during
their post-traumatic course. Given that, with few exceptions,
acute organ dysfunctions can be diagnosed clinically, and
laboratory investigations should primarily be used to conrm
clinical impressions and assess whether denitions of acute
organ dysfunction as indicated by an increase of the
Sequential Organ Failure Assessment score of ≥2 points are
being met.
15.4 Management Principles
Once sepsis is suspected or conrmed, timely and adequate
therapeutic management is critical to facilitate survival and
best possible functional recovery. A principled approach
involving several elements needs to be adhered to in the
management of sepsis and septic shock. Amongst main pillars of sepsis therapy are adequate source control, appropriate antimicrobial therapy and symptomatic management of
acute organ dysfunction. Since sepsis outcome critically
depends on the timeous nature with which it was recognised
and adequate therapy initiated, early recognition and diagnosis should be followed by prompt initiation of sepsis therapy
with effective source control measures and organ support
ideally occurring simultaneously. In view of the substantial
mortality risk associated with sepsis and particularly septic
shock, patients suffering from these conditions should be
cared for in a monitored setting such as a high-dependency
or intensive care unit.
The Surviving Sepsis Campaign (SSC) guideline, a joint
initiative of the European Society of Intensive Care Medicine
(ESICM) and the Society of Critical Care Medicine (SCCM)
in the USA, provides evidence-based recommendations on
the management of sepsis and septic shock. This guideline
has recently been updated and the new iteration serves as a
valuable resource for the management of sepsis and septic
shock. Several important, helpful and benecial elements
contained within this document are referred to in the subsequent content of this chapter.
15.4.1 Treating theUnderlying Infection
As pointed out earlier, critical pillars in the management of
patients with sepsis and septic shock include the important
and fundamental concept of source control and antimicro-
bial therapy. Important antimicrobial therapy considerations
may be best addressed and covered by the terms “when,
what, how, de-escalation and duration”. These elements are
discussed below.
The timely administration of appropriate antimicrobial
therapy is vitally important to reduce morbidity and mortality from sepsis. Antimicrobial therapy should ideally begin
immediately or within the rst hour of recognition of septic
shock or sepsis. Several observational studies have shown a
mortality benet with each hour of early antimicrobial therapy administration in patients with septic shock. For patients
with possible sepsis but without shock, rapid assessment of
the likelihood of infection versus non-infectious illness
should be undertaken. If concern for infection persists after a
time-limited course of rapid investigation of the underlying
aetiology, then antimicrobial therapy should be commenced
within 3h from when sepsis was rst recognised. For patients
with a low likelihood of infection and without shock, antimicrobial therapy should be deferred and the patient should be
closely monitored.
The initiation of antimicrobials should be directed to
cover likely culprit microorganisms as well as being effective at limiting superinfection and resistant microorganisms.
The choice of agent(s) is based on a variety of factors and
includes site of infection, patient history, details and timing
of surgical procedures, previous antibiotic use, local pathogen susceptibility patterns, immunosuppression and risk factors for resistant microorganisms. Risk factors for resistance
include antimicrobial exposure and acquisition of infection
in a healthcare setting. Appropriate empiric coverage of the
pathogens involved is particularly relevant as various studies
have demonstrated a mortality reduction of approximately
50% with appropriate versus inappropriate antimicrobial
choice. A vefold increase in hospital mortality was demonstrated in a 5700-patient retrospective study involving 22 different institutions in patients with septic shock who received
inappropriate antimicrobial therapy. In a study of hospitalacquired intra-abdominal infection, inadequate coverage was
shown to an independent predictor of mortality. In patients
with gram-negative sepsis, recent antibiotic exposure was
associated with hospital mortality of 51% compared with
34% in those patients who had no recent exposure.
Relevant cultures of blood, urine, pulmonary secretions,
wound drainage or other potential infection sites should be
performed prior to initiation of antimicrobials, provided that
obtaining the cultures does not delay antimicrobial administration. Appropriate cultures prior to initiation of antimicrobial therapy are associated with improved outcomes. Blood
cultures may be negative in as many as 50% of cases of sepsis if empiric therapy is administered.
In general, in patients at high risk for MDR microorganisms, two gram-negative agents are advocated for empiric
antimicrobial treatment to increase the likelihood of adequate coverage, while in patients with low risk for MDR
microorganisms, use of a single agent for empiric treatment
is deemed appropriate, as there is no compelling benet of
using two agents, and the risks of antimicrobial-associated
undesirable effects, Clostridioides difcile infection and the
development of antimicrobial resistance are enhanced.
Empiric double coverage of gram-negative bacilli is most
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important in patients at high risk for resistant microorganisms with severe illness, particularly septic shock.
Patients at high risk of methicillin-resistant Staphylococcus
aureus (MRSA) should be considered for empiric use of
agents with MRSA cover. Patient-related risk factors for
MRSA include a prior history of MRSA infection or colonisation, recent intravenous antibiotic therapy, hemodialysis,
history of recurrent skin infections or chronic wounds, presence of invasive devices, recent hospital admission and
severity of illness. The incidence of MRSA varies by geographic region and by patient characteristics. For patients at
low risk of MRSA, empiric use of antimicrobials with MRSA
coverage is not advocated.
Over the past several years, there has been a signicant
rise in the incidence of sepsis due to fungal organisms.
Antifungal therapy should be considered in patients at high
risk for such infections. Risk factors include the use of total
parenteral nutrition, recent broad-spectrum antibiotics, perforated abdominal viscus, anastomotic bowel leaks or breakdown, peritoneal contamination with bowel content,
immunosuppressed status or when clinical suspicion of fungal infection is high.
Patients should be assessed daily for opportunities to de-
escalate antimicrobial therapy. This assists in limiting unnecessary antibiotic exposure and the risk of developing resistant
microorganisms. The practice is both safe and cost-effective.
De-escalation involves using the narrowest spectrum antimicrobial based on local susceptibility patterns. If the clinical
course suggests that the illness is not actually due to infection, the antimicrobials should be stopped. Antimicrobial deescalation should form part of the discussion of daily rounds.
Shorter durations of antimicrobial therapy are recom-
mended over longer durations. Limiting antimicrobial duration to a period that is supported by prospective data also
limits unnecessary antimicrobial therapy and its sequelae.
The use of biomarkers such as CRP and procalcitonin (PCT)
to guide antimicrobial therapy has been the subject of much
debate and controversy. Clinical evaluation and acumen play
a key role in determining the duration of antimicrobial
administration. Biomarkers may, however, assist as a useful
adjunct in helping to determine when to discontinue antimicrobials. The decision to initiate antimicrobials is based on
clinical judgement with available information. For most
infections, a 5–7-day course of antimicrobial therapy is
appropriate in conjunction with suitable and relevant source
control. Longer courses may be required in certain circumstances such as for Staphylococcus aureus bacteremia, endocarditis, deep-seated bone and joint infections, fungal
infections, immunocompromised hosts and if adequate
source control cannot be achieved. Several well-performed
prospective randomised trials now exist to guide shorter
durations of antimicrobial therapy in a variety of disease pro-
cesses. In intra-abdominal infections, 4–8days of antimicrobial therapy with suitable source control has been shown to
be equivalent to any longer courses and similarly, 7–8days
of treatment for ventilator-associated pneumonia.
For adults with sepsis and septic shock, the administration
of beta-lactams using prolonged infusions following an initial loading dose is now preferred over conventional bolus
infusion. Prolonged infusions include extended infusions in
which the antibiotic is infused over at least 50% of the dosing interval, as well as continuous infusions. Reduced shortterm mortality has been demonstrated in two meta-analyses
addressing prolonged infusion of beta-lactams. Additionally,
antimicrobial dosing should be based on accepted pharma-
cokinetic (PK) and pharmacodynamic (PD) principles and
drug properties, as this is likely to result in effective and safe
drug concentrations as compared to dosing provided in manufacturer’s product information. The utilisation of these principles and considerations, particularly in critically ill
patients, is of benet in addressing such elements as augmented renal clearance, hypoalbuminemia, renal replacement therapy and extracorporeal circuits, all of which may
affect the concentration of some antimicrobials (Fig.15.2).
Therapeutic drug monitoring, where available, should be
employed to further assist with optimal dosing of
antimicrobials.
15.4.2 Source Control
Appropriate source control is a key principle and imperative
in the management of sepsis and septic shock. The process
may include drainage of an abscess, debridement of infected
necrotic tissue, removal of infected devices including intravascular access devices or denitive control of a source of
ongoing microbial contamination. Foci of infection readily
amenable to source control include intra-abdominal
abscesses and collections, gastrointestinal perforation(s),
ischemic bowel, cholecystitis, obstructive uropathy associated with abscess formation or pyelonephritis, necrotising
soft tissue infections, other deep space infections such as
empyema or septic arthritis, septic hematomas and implanted
device infections. Source control should be achieved as soon
as feasible following initial resuscitation and initiation of
antimicrobial therapy as alluded to previously. An identied
source should always be sampled and cultured for targeted
therapy. Source control of infected foci has been shown to be
associated with improved survival in several studies. This
should ideally be achieved within a time frame not exceeding
6–12 h (preferably ≤ 6 h). Studies beyond this time frame
have generally shown reduced survival. In a prospective
study examining time to source control in patients with peritonitis and septic shock, time to initiation of surgery was
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M. Mer and M. W. Dünser
Plasma antimicrobial concentrations in sepsis
Hypodynamic
circulation
Augmented
renal CL
These often coexist
Fig. 15.2 Pathophysiological changes in sepsis affecting antimicrobial concentrations
demonstrated to be an independent predictor of survival.
Abdominal source control within 2h was associated with a
Leaky capillaries and/or
altered protein binding
Increased
extravascular water
Increased Vd
Low plasma
concentrations
Normal organ
function
Unchanged
Vd
Normal plasma
concentrations
Vd = volume of distribution; CL = clearance
factors such as surgical or interventional staff availability
may also be a factor in the ultimate decision.
98% 60-day survival as compared to no survivors in the
group that waited for more than 6h for initiation of surgery.
In necrotising soft tissue infections, delay in debridement
15.5 Organ Support
beyond 24h has been associated with clear effects on mortality. The two most common clinical settings in which sur-
15.5.1 Fluid Therapy andHemodynamic
geons are involved in source control are in the treatment of
peritonitis and soft tissue infections.
Inability to achieve adequate source control despite rapid
resuscitation and initiation of appropriate antimicrobials
may result in failure to obtain clinical stability or sustained
patient improvement. With this consideration, prolonged
efforts at medical stabilisation in lieu of source control for
severely ill patients, particularly those with septic shock, are
generally not advised. In general, the least invasive option
that will effectively achieve source control should be pursued. Consideration should be given to open surgical intervention when other interventional approaches are inadequate
or cannot be provided in a timely fashion. Surgical intervention may also be indicated when diagnostic uncertainty is
present despite imaging studies, when success with percutaneous procedures is uncertain and when the undesirable
effects of a failed procedure are high. Institutional logistic
Hypovolemia due to endothelial dysfunction and interstitial
uid accumulation is frequent in patients with sepsis.
Reduced venous return results in decreased cardiac output
with resultant tissue hypoperfusion and impaired oxygen
delivery to organs. Restoring adequate intravascular volume
status is, therefore, an essential step to secure adequate organ
perfusion and oxygen supply. In view of the fact, however,
that not all patients with sepsis are hypovolemic and that
uid overload is as detrimental to organ function recovery
and survival as hypovolemia, it is crucial to correctly identify
sepsis patients in need for uid resuscitation.
The diagnosis of hypovolemia is largely based on tachycardia and clinical signs of peripheral hypoperfusion (e.g.
cold peripheries, prolonged capillary rell time, fast and
thready peripheral pulses, skin mottling) in the absence of
End organ
dysfunction (e.g.
renal or hepatic)
Decreased Vd
High plasma
concentrations
Support
Extracorporeal
circuits
Altered CL and
increased Vd of
sepsis
Plasma
concentrations
high or low
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symptoms of congestive heart failure (e.g. absence of
engorged external jugular veins or ne bibasilar crackles on
lung auscultation, no abdomino-jugular reux). The pathophysiological mechanisms causing oliguria in sepsis are far
more complex than simple renal hypoperfusion. As a consequence, reduced urine output cannot be regarded as a reliable
indicator of hypovolemia, particularly beyond 6–12h following the onset of sepsis. Furthermore, it is important to
underline that due to capillary leakage and loss of intravascular uid into the interstitium, sepsis patients may present
with clinical signs of hypovolemia despite the presence of
peripheral oedema. Only in patients with clinical signs of
hypovolemia should uid resuscitation be commenced. The
latest SCC guideline recommends commencing with a uid
bolus of 30 mL/kg within the rst 3 h of resuscitation.
Although this is the average volume of uid a patient with
sepsis is likely to need in order to restore intravascular volume status, it appears prudent to closely re-evaluate the
patient after each infusion of 500 mL and decide whether
further uid loading is required or not. As there is typically a
lag phase of approximately 15–30min until peripheral hypoperfusion starts to reverse, it is valuable to adjust reevaluation intervals to this period of time unless hypovolemic
shock is present and further uid loading is clearly needed.
Dynamic measures to assess uid responsiveness (prediction
of the likelihood whether another uid bolus will increase
stroke volume or not; e.g. stroke volume or pulse pressure
variation, passive leg raise manoeuvre) can further help to
inform the decision as to whether further uid boluses should
be given or not. It is, however, important to remember that
the primary goal of uid resuscitation is not to administer
uids until the patient is no longer uid responsive, but to
administer uids until peripheral perfusion is restored and
lactate levels (if initially elevated) are decreasing. The SSC
guideline recommends the use of balanced crystalloid solutions over normal saline as the rst-line uid for resuscitation although the recent BaSICS Trial showed no difference
in 90-day mortality. Synthetic colloids such as starches and
gelatins are not advocated as they may be associated with
adverse effects on both renal and coagulation functions. In
sepsis patients who have received large volumes of crystalloids, albumin may be used to limit positive uid balances.
Recent data have shown that restoration of intravascular
volume status will only improve capillary perfusion if uid
resuscitation is initiated early after the onset of sepsis. The
SSC guidelines recommend commencing uid resuscitation
within 3h of diagnosing sepsis. Initiating uid resuscitation
at a later stage (e.g. >48h following the onset of sepsis) is
unlikely to benecially affect microcirculatory dysfunction
and improve organ perfusion. This may be explained by the
complex derangement of endothelial function in sepsis,
including uncoupling of the macro- from the microcirculation in untreated or prolonged sepsis. These ndings support
the currently proposed approach of early aggressive uid
resuscitation followed by a restrictive uid strategy to avoid
excessive uid balances.
In case uid resuscitation does not result in restoration of
adequate tissue perfusion or reversal of arterial hypotension,
vasopressor drugs and ideally, invasive arterial blood pressure measurement are required. Norepinephrine (noradrenaline) is recommended as the rst-line vasopressor agent with
an initial target of a mean arterial blood pressure of 65mmHg.
To restore mean arterial blood pressure, norepinephrine
should be started as early as possible. This can be initiated
via a peripheral line if necessary, so that there is no delay
until a central venous catheter has been secured. Based on
the individual response, the mean arterial blood pressure target should then be adjusted to the patient’s needs. Whereas
some patients require higher mean arterial blood pressures,
others will exhibit signs of adequate tissue and organ perfusion even when lower mean arterial blood pressures are targeted. Since higher doses of norepinephrine are known to
cause a myriad of adverse cardiac side effects (e.g. tachycardia, tachyarrhythmias) in a dose-dependent fashion, particularly when cardiac comorbidities are present, it is
recommended to add intravenous corticosteroids (e.g.
200mg of hydrocortisone per day) and consider the addition
of vasopressin (where available) instead of escalating the
dose of norepinephrine. Should the combination of norepinephrine and vasopressin not allow for adequate attainment
of target blood pressure levels, the addition of epinephrine
should be considered. As the mortality risk in these patients
is very high, it is recommended to re-evaluate the targeted
mean arterial blood pressure level necessary to allow for survival. In many instances, acceptance of lower mean arterial
blood pressures (e.g. 50–60mmHg) can be life-saving as this
may allow for exit of the vicious circle of escalating vasopressor doses which then cause additional side effects further
aggravating hemodynamic instability. This concept has been
referred to as permissive hypotension.
In sepsis patients with signs of congestive heart failure or
those in whom systemic hypoperfusion persists despite restoration of intravascular uid status and adequate mean arterial blood pressures, the introduction of dobutamine or
epinephrine should be considered. The use of levosimendan
in patients with septic shock is discouraged because of the
drug’s relevant vasodilatory side effects.
15.5.2 Ventilatory Support
In sepsis, impairment of lung function is common. This can
be due to respiratory tract infection with associated alveolar
damage and ventilation-perfusion mismatch, but may also
occur in sepsis patients who have an extra-pulmonary infectious focus as a consequence of inammatory changes in the
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M. Mer and M. W. Dünser
lungs. Similar to severe pneumonia, this can lead to diffuse
alveolar damage, increases in extravascular lung water and
ventilation-perfusion mismatch. Hypoxemia and reduced
pulmonary compliance are frequent ndings in patients with
sepsis irrespective of the underlying infection. Tachypnoea
may accompany lung dysfunction but may also be a nonspecic sign of systemic inammation in sepsis. Taking these
aspects into consideration, ventilatory support is frequently
needed in patients with sepsis. The overall goals of care are
to secure an oxygen saturation>90% and to avoid respiratory decompensation due to an increased work of breathing.
The SSC guidelines could not identify sufcient scientic
evidence to provide guidance as to whether conservative
(oxygen saturation 91–96%) or usual oxygen (oxygen saturation≥91%) targets should be applied.
Figure 15.3 summarises a pragmatic approach in keeping
with current international recommendations to manage ventilatory dysfunction in patients with sepsis. Once a patient
with sepsis develops acute respiratory distress syndrome
(ARDS) and/or requires endotracheal intubation and invasive mechanical ventilation, it is imperative to use a low tidal
volume ventilation strategy (6mL/kg ideal body weight) as
this has repeatedly been shown to minimise ventilatorinduced lung injury. Furthermore, the upper limit for plateau
(in volume-controlled ventilation) or peak (in pressurecontrolled ventilation) pressures should not exceed
30 cmH2O. In patients with moderate or severe sepsisinduced ARDS, it is recommended that a higher positive
end-expiratory pressure (PEEP) strategy is preferred over a
lower one and that traditional (instead of incremental PEEP
titration) recruitment manoeuvres are used when lung derecruitment is suspected. In addition, mechanical ventilation
in the prone position for >12h daily and intermittent use of
neuromuscular blocking agents are recommended in these
patients too. When conventional mechanical ventilation fails
to provide adequate ventilatory support, the use of venovenous extracorporeal membrane oxygenation should be
considered in experienced centres with the infrastructure in
place to support its use.
mobilisation. Elements pertaining to mechanical ventilation
and use of corticosteroids have already been alluded to
earlier.
Renal Replacement Therapy
Septic shock is the most common cause of acute kidney
injury (AKI) in the intensive care unit (ICU) accounting for
approximately half of all AKIs and is associated with the
highest mortality. Renal replacement therapy may be indicated for the treatment of uremia, uid overload and metabolic derangement such as hyperkalemia and metabolic
acidosis. Early use of renal replacement therapy is theoretically attractive as it may limit organ injury and uid overload, as well as remove inammatory mediators responsible
for the clinical manifestations of sepsis.
Venous Thromboembolism (VTE) Prophylaxis
Pharmacological prophylaxis using unfractionated heparin
(UFH) or low-molecular-weight heparin (LMWH) is recommended in the absence of contraindications to the use of
these agents. LMWH is recommended over UFH in patients
with no contraindications to LMWH, assuming availability
of both medications. Non-pharmacological prophylaxis
includes graduated compression stockings (GCS), intermittent pneumatic compression (IPC) devices and passive and
early mobilisation where appropriate. GCS and IPC devices
may be used in the setting where contraindications to the use
of pharmacologic prophylaxis exist and in high-risk patients
for VTE.
Glucose Control
Blood glucose should be managed using a protocolised
approach, commencing when blood glucose levels are
>10mmol/L (180mg/dL), with a target blood glucose value
of ≤10mmol/L (≤180mg/dL) aiming to keep the blood glucose in the range of 6–10mmol/L (108–180mg/dL) to avoid
detrimental hypoglycemia. Measurements should be conducted every 1–2h until values and insulin infusion rates
stabilise and then every 4h thereafter in patients receiving
insulin infusions.
15.5.3 General Interventions
15.5.3.1 Other Supportive Therapies inPatients
withSepsis andSeptic Shock
Additional supportive therapies for patients with sepsis and
septic shock are closely aligned with the general management of critically ill patients (Table15.2) and include such
elements as renal replacement therapy, nutrition, glycemic
control, venous thromboembolism prophylaxis, sedation and
analgesia, use of neuromuscular blocking agents, stress ulcer
prophylaxis, red blood cell transfusion, positioning and early
Sedation andAnalgesia
Continuous or intermittent sedation should be minimised in
mechanically ventilated patients targeting specic titration
end points from sedation scales. Common approaches
include implementation of nurse-directed protocols, administration of intermittent sedation and daily sedation interruption. Short-acting sedatives including propofol and
dexmedetomidine may result in improved outcomes.
Adequate pain control should be attained in all patients
where necessary (analgesia-rst sedation), and lighter sedation targets aimed for in general.
Hypoxemic
Venlatory Respiratory Failure
CV
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133
no
Respiratory Failure
(SaO2≤90%)
Standard
Oxygen Therapy
CV
normalWOB
+no respiratory acidosis
yes
SaO2≤90%
ja
(increased WOB or acute respiratory acidosis)
±Hypoxemic Respiratory Failure
Non-Invasive Venlaon
no
CV
High Flow Nasal
Oxygen Therapy
CV
no
relevantly increased WOB,
severe respiratory acidosis or SaO
≤90%
yes
2
Invasive Mechanical Venlaon
CV
Fig. 15.3 Therapeutic approach to patients with sepsis-induced acute respiratory failure. SaO2, arterial oxygen saturation; WOB, work of breath-
ing. Icons by Flaticom.com
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M. Mer and M. W. Dünser
Table 15.2 Core elements of general supportive care in patients with
sepsis and septic shock
Intervention Comment
Mechanical
ventilation
Renal replacement
therapy
Nutrition Commence enteral feeding early
Glucose control Maintain blood glucose < 10mmol/L
Venous
thromboembolism
prophylaxis
Blood transfusion If hemoglobin level <7.0g/dL (70g/L) in
Sedation and
analgesia
Neuromuscular
blocking agents
Stress ulcer
prophylaxis
Corticosteroids Consider in patients with septic shock and
Positioning and
mobilisation
Psychological
support
UFH unfractionated heparin, LMWH low-molecular-weight heparin,
ARDS acute respiratory distress syndrome, GI gastrointestinal
Lung protective ventilation strategy. Includes
tidal volume 6mL/kg ideal body weight,
plateau airway pressures ≤ 30cmH2O
As may be indicated for uid overload,
metabolic derangement (severe uremia,
hyperkalemia, acidosis)
(180mg/dL)
UFH or LMWH (LMWH preferred);
mechanical prophylaxis, e.g. pneumatic
compressive devices in select cases or where
contraindications to pharmacologic
prophylaxis exist; continue until patient fully
mobile
stable non-bleeding patients
Adequate pain control in all patients where
required and minimise sedation
In setting of respiratory dyssynchrony to
facilitate mechanical ventilation in patients
with moderate-severe ARDS
In patients with risk factors for GI bleeding
an ongoing requirement for vasopressor
support where adequate uid resuscitation
has occurred. Typical dose– hydrocortisone
200mg/day given as 50mg every 6 h
intravenously or as a continuous infusion
Elevate head of bed 30–45° in mechanically
ventilated patients; meticulous pressure area
care-document; active early mobilisation
Ongoing patient encouragement where
feasible and constructive and meaningful
family interaction
Use ofNeuromuscular Blocking Agents
Neuromuscular blocking agents may be considered in
mechanically ventilated septic patients with moderate-severe
acute respiratory distress syndrome (ARDS) in the setting of
respiratory dyssynchrony and to facilitate mechanical ventilation. These agents may improve chest wall compliance,
prevent dyssynchrony and reduce peak airway pressures.
Intermittent neuromuscular blockade boluses are preferred
to continuous infusions.
Nutrition
Early enteral feeding should be commenced in patients who
can tolerate it within 48h provided that they are adequately
resuscitated and hemodynamically stable. Either trophic/
hypocaloric or full enteral feeding strategies may be
employed. If trophic/hypocaloric feeding is the initial strategy, then feeds should be advanced according to patient tolerance to reach feeding goals. If enteral feeding is not fully
established within a week, parenteral supplementation
should be considered. A feeding protocol is useful to optimise delivery of enteral nutrition.
Stress Ulcer Prophylaxis
Stress ulcer and septic shock prophylaxis is recommended in
patients with sepsis and septic shock who have risk factors
for gastrointestinal (GI) bleeding. Risk factors for GI bleeding include mechanical ventilation ≥48 h, coagulopathy,
renal replacement therapy, liver disease, multiple comorbidities, and higher organ failure scores.
Red Blood Cell (RBC) Transfusion
Use of a restrictive over liberal transfusion policy is recommended in patients who have been fully and adequately
resuscitated and where there is no ongoing bleeding. A
restrictive transfusion strategy typically includes a hemoglobin concentration transfusion trigger of 7 g/dL (70 g/L).
RBC transfusion however should not be guided by hemoglobin concentration alone. Assessment of the overall clinical
status of a patient and consideration of various circumstances
such as acute myocardial ischemia severe hypoxemia, or
acute hemorrhage, is required.
Positioning andEarly Mobilisation
This includes elevating the head of the bed to between 30 and
45 degrees for mechanically ventilated patients and regular
meticulous pressure area care. Active and early mobilisation
should commence as soon as the patient is stable enough to
participate. This assists in improving both mobility status
and muscle strength. The role of physiotherapists is hugely
relevant.
Based on currently available evidence, the SSC guideline
specically recommends against the use of certain therapies
and interventions (Table15.3).
Table 15.3 Therapies of the Surviving Sepsis Campaign guidelines
recommends against using in patients with sepsis
• Polymyxin B hemoperfusion
• Intravenous immunoglobulins
• Renal replacement in patients without denitive indications
for renal replacement therapy
• Intravenous vitamin C
• Sodium bicarbonate therapy to improve hemodynamics or to
reduce vasopressor requirements in patients with septic shock
and hypoperfusion-induced lactic acidosis
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15.6 Transition ofCare
Following recovery from sepsis, the transition from the
intensive care unit to the normal ward is both an important
step in the psychological healing process of the patient (moving forward and not being dependent on life support any longer), but also a critical one exposing the patient to certain
risks, including respiratory and infectious complications.
Respiratory complications often arise as a consequence of
less intense physical and respiratory therapy outside of the
intensive care unit. In addition, dysphagia as a result of prolonged endotracheal intubation or tracheostomy is well
known to make post-intensive care unit patients particularly
vulnerable to respiratory complications including pulmonary
infections. Due to the compensatory anti-inammatory
response to both trauma and sepsis, patients recovering from
these conditions are considered immunosuppressed and specically prone to acquire further infections and septic episodes. Despite being associated with very high mortality
rates, recurrent septic episodes tend to occur in a fashion that
is less acute and fulminant than the rst septic episode. This
may put patients at high risk as the acuity and severity of
recurrent sepsis may not be as overt or obvious and thus may
be overlooked, with adequate management and early readmission to an intensive care or high dependency unit being
delayed.
It is, therefore, critical to identify the correct time point to
transition care from an intensive to a non-intensive care setting and to prepare this step as best as possible. Although the
optimum time to transfer a patient from the intensive care unit
to a normal ward may depend on several institutional factors
(including the availability of step-down or high dependency
unit), the patient should be free of the need for organ support
and stable for an adequate time period. Experience indicates
that the longer the period of organ dysfunction has lasted, the
longer this observational phase without need for organ support should be (e.g. up to 48–72h in patients with prolonged
critical illness). In selected patients, transition from an intensive to a non-intensive care setting may not only depend on
the absence of organ dysfunction but also on the need for
intensive nursing care or physical therapy (e.g. patients with
high spinal cord injuries and reduced consciousness or those
with critical illness acquired weakness). In order to make the
transition process as safe as possible for the patient, the use of
structured hand over processes from the intensive care unit to
the ward is advocated. In addition, reconciliation of medications at intensive care unit discharge as well as close followup during the rst days following discharge from the intensive
care unit is recommended.
While respiratory and infectious complications pose
immediate threats to patients recovering from sepsis, critical
illness due to sepsis is associated with multiple long-term
sequelae. These include, but are not limited to, reduced func-
tionality including pulmonary capacities, cognitive impairment and post-traumatic stress disorders. Furthermore,
recent research has indicated that patients following an overwhelming pro-inammatory stimulus such as sepsis, exhibit
increased levels of pro-inammatory mediators that last for
weeks to months. This prolonged sub-clinical inammation
is the likely explanation for the increased risk of cardiovascular events during the rst year following a septic episode.
Early inclusion of sepsis survivors into rehabilitation
programs as well as screening for economic, social and religious support is currently recommended by the SSC
guidelines.
15.7 Prevention ofPost-traumatic Sepsis
Prevention of post-traumatic sepsis mainly focusses on
infection prevention. Since the pathogenesis of the dysregulated host response to infection resulting in sepsis is so far
only poorly understood, no current strategy exists to prevent
development of sepsis in patients acquiring an acute infection. Although the concept of timely recognition and adequate management of infection appears biologically sound, it
has not been proven that this can signicantly reduce the
occurrence of sepsis.
Infection prevention in patients with penetrating trauma
includes both prevention of wound infections and prevention of hospital-acquired infectious complications. The key
steps to prevent deep and supercial wound infections following penetrating trauma are optimal early (<6h) surgical
wound care including aseptic techniques, disinfection,
(high pressure) irrigation, debridement, appropriate timing
of wound closure and negative pressure wound therapy as
well as antibiotic prophylaxis. The efcacy of antibiotics to
prevent infections in patients with penetrating injuries
depends on several factors. Of particular relevance is appropriate timing. Data have shown that antibiotic prophylaxis
should be administered to patients with penetrating wounds
to deep tissue structures as early as possible, preferably
within the rst hour following injury. Antibiotic prophylaxis delivered only during or even after surgery is signicantly less effective to decrease the rate of wound infections.
Additionally, the choice of antibiotics depends on the injury
site and contamination of underlying tissues. Furthermore,
as prolonged duration of antibiotic prophylaxis has been
shown to paradoxically increase the risk of subsequent
infections, the duration of antibiotic prophylaxis in patients
with penetrating injuries should not in general exceed suggested time frames (24h). In general, a single dose of prophylactic antimicrobial(s) is often all that is required unless
there is signicant blood loss or the patient is subjected to
prolonged surgery, in which case repeat dosing is
indicated.
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after touching a patient’s surroundings
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Fig. 15.4 The ve moments
of hand hygiene. Adapted
from the World Health
Organization. Icons by
Flaticom.com
M. Mer and M. W. Dünser
before a procedure
before touching a patient
after a procedure or body fluid
exposure risk
after touching a patient
Prevention of hospital-acquired infectious complications
largely relies on strict hand hygiene (Fig.15.4). Dedicated bundles and protocols have been shown to decrease or even eliminate the risk of hospital-/ventilator-acquired pneumonia and
central line-associated bloodstream infections, respectively.
Consistent removal of urinary or central venous catheters and
wound drains when they are no longer needed is another important step to prevent device-related infections. Therapeutic strategies to hasten recovery from critical illness such as targeted
sedation, early mobilisation and adequate nutritional support
are strategies to reduce the risk of post-traumatic infections.
These elements have been addressed earlier.
Finally, vaccinations are highly effective in preventing
late infections and fulminant sepsis (e.g. the overwhelming
post-splenectomy infection syndrome) in patients following
splenectomy. Vaccinations are recommended to be administered at 14days after trauma or prior to hospital discharge,
whichever comes rst. Important exceptions include patients
who require ongoing organ support or those undergoing
major surgical procedures, as their immune systems may not
sufciently respond to vaccination. In-hospital vaccination is
recommended to include the pneumococcal 13-valent conjugate, Haemophilus inuenzae type b (Hib), quadrivalent
meningococcal and meningococcal serogroup B vaccines. It
is safe to administer all vaccinations at the same time either
as compound vaccines or using different injection sites.
Importantly, the patient must be informed on the need to
receive another dose of the pneumococcal 23-polysaccharide, quadrivalent meningococcal and meningococcal serogroup B vaccines 2months later, as well as further doses of
the pneumococcal 23-polysaccharide and quadrivalent
meningococcal vaccine every 5years, and the seasonal inuenza vaccine annually.
15.8 Conclusions
This chapter outlines the essentials and most current concepts
and understanding of the relevant epidemiology, denitions,
pathogenesis, diagnosis and investigation, and management
principles of patients with sepsis and septic shock in a pragmatic
and evidence-based fashion, and as may be pertinent to patients
with penetrating trauma. Sepsis and septic shock are common
and should be regarded as medical emergencies. Patients with
penetrating trauma are at high risk for the development of sepsis
and its associated sequelae. Early recognition, focussed uid
administration and hemodynamic support, source control, and
appropriate antimicrobial therapy are the cornerstones that offer
the best possible survival outcomes for patients suffering from
sepsis and septic shock. Appropriate supportive measures and
post-sepsis care are important and integral components of care
that further enhance outcomes. Adherence to these principles
which are based on current best practice, is key to reducing the
burden of resulting disease, death, and disability from sepsis and
septic shock in patients with penetrating trauma.
Key Messages
• Sepsis and septic shock are common syndromes of
immense clinical importance.
• Sepsis is a life-threatening organ dysfunction due to a
dysregulated host response to infection.
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