Dr
KK Aggarwal
Recipient
of Padma Shri
The conviction of Dr
Hadiza Bawa-Garba on the charges of manslaughter by gross negligence following
the death of Jack Adcock, a 6-year-old boy with Down syndrome in 2011 has
generated controversy. The successful appeal by the GMC to erase her name from
the medical register has shaken the medical community not only in the UK, but
outside UK also and angered many.
Missing the diagnosis of
sepsis and thus delaying initiating antibiotic treatment was among the series
of charges leveled against her.
Sepsis and septic shock
are life-threatening conditions if not detected and managed in time. A high index
of clinical suspicion along with a thorough clinical examination of the patient
supported by appropriate lab tests is essential for the early diagnosis of
sepsis.
Let’s revise some
important aspects of sepsis, a potentially avoidable cause of death
lSepsis is the
consequence of a dysregulated inflammatory response to an infectious
insult.
lSepsis exists
on a continuum of severity ranging from infection (invasion of sterile tissue
by organisms) and bacteremia (bacteria in the blood) to sepsis and septic
shock, which can lead to multiple organ dysfunction syndrome (MODS) and death.
lSeptic shock
is defined as sepsis that has circulatory, cellular, and metabolic
abnormalities that are associated with a greater risk of mortality than sepsis
alone; these abnormalities can be clinically identified as patients who fulfill
the criteria for sepsis who, despite adequate fluid resuscitation, require
vasopressors to maintain a mean arterial pressure (MAP) ≥65 mmHg and have a
lactate >18 mg/dL.
lPatients with
suspected or documented sepsis typically present with hypotension, tachycardia,
fever, and leukocytosis. As severity worsens, signs of shock (e.g., cool skin
and cyanosis) and organ dysfunction develop (e.g., oliguria, acute kidney
injury, altered mental status)
lPoor prognostic factors: Inability to mount a
fever, leukopenia, age >40 years, certain comorbidities (e.g., AIDS, hepatic
failure, cirrhosis, cancer, alcohol dependence, immunosuppression), a
non-urinary source of infection, a nosocomial source of infection, and
inappropriate or late antibiotic coverage. Sepsis is a clinical syndrome
characterized by systemic inflammation due to infection.
lThere is a
continuum of severity ranging from sepsis to septic shock. Mortality has been
estimated to be ≥10% and ≥40% when shock is present.
lFirst aid: Securing the
airway (if indicated) and correcting hypoxemia, and establishing venous access
for the early administration of fluids and antibiotics
lSupplemental oxygen should be supplied to all patients with sepsis and oxygenation
should be monitored continuously with pulse oximetry.
lVenous access should be
established as soon as possible in patients with suspected sepsis.
lAn initial
brief history and examination, as well as laboratory, microbiologic, and
imaging studies are often obtained simultaneously while access is being
established and the airway stabilized.
o TLC along with
differential count, blood chemistries, liver function tests, and coagulation
studies including D-dimer level.
o An elevated serum
lactate (eg, >2 mmol/L or greater than the laboratory upper limit of normal)
may indicate the severity of sepsis.
o Arterial blood gas (ABG)
analysis – ABGs may reveal acidosis, hypoxemia, or hypercapnia.
o Peripheral blood cultures
(aerobic and anaerobic cultures from at least two different sites), urinalysis,
and microbiologic cultures (eg, sputum, urine, intravascular catheter, wound or
surgical site, body fluids) from readily accessible sites – For patients with a
vascular catheter, blood should be obtained both from the catheter and from
peripheral sites.
o Imaging targeted at the
suspected site of infection is warranted (eg, chest radiography, computed
tomography of chest and/or abdomen).
o Procalcitonin –has
become increasingly popular.
lThe
cornerstone of initial resuscitation is the rapid restoration of perfusion and
the early administration of antibiotics.
lTissue
perfusion is predominantly achieved by the aggressive administration of
intravenous fluids (IVF), usually crystalloids (balanced crystalloids or normal
saline) given at 30 mL/kg (actual body weight) within the first three hours
following presentation. Empiric antibiotic therapy is targeted at the suspected
organism(s) and site(s) of infection and preferably administered within the
first hour.
lComponents of
the protocols usually included the early administration of fluids and
antibiotics (within 1 to 6 hours using the following targets to measure the
response: central venous oxyhemoglobin saturation (ScvO2) ≥70%, central venous
pressure (CVP) 8 to 12 mmHg, mean arterial pressure (MAP) ≥65 mmHg, and urine
output ≥0.5 mL/kg/hour.
lIntravenous
(IV) fluids (first three hours): In patients with sepsis, intravascular
hypovolemia is typical and may be severe, requiring rapid fluid resuscitation.
There is no difference in mortality when mean infusion volumes of 2 to 3 liters
were administered in the first three hours compared with larger volumes of
three to five liters, which was considered standard therapy at the time. Fluid
therapy should be administered in well-defined (e.g., 500 mL), rapidly infused
boluses.
lEmpiric antibiotic therapy (first hour): Optimal doses of appropriate IV antibiotic therapy should be
initiated within one hour of presentation, preferably after cultures
have been obtained.
lAlthough the
feasibility of a one hour target has not been assessed, the rationale for
choosing it is based upon several observational studies that report poor
outcomes with delayed (even beyond one hour), inadequately dosed, or
inappropriate (i.e., treatment with antibiotics to which the pathogen was later
shown to be resistant in vitro) antimicrobial therapy
lBroad
spectrum is defined as therapeutic agent(s) with sufficient activity to cover a
range of gram negative and positive organisms (eg, carbapenem,
piperacillin-tazobactam). Many patients with septic shock should receive
combination therapy with at least two antimicrobials from two different classes
(ie, combination therapy) depending on the organisms that are considered likely
pathogens and local antibiotic susceptibilities. Combination therapy is defined
as multiple antibiotics given with the intent of covering a known or suspected
pathogen with more than one agent.
lAmong
organisms isolated from patients with sepsis, the most common include
Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and
Streptococcus pneumoniae, such that coverage of these organisms should be kept
in mind when choosing an agent
lClinicians
should pay attention to maximizing the dose in patients with sepsis and septic
shock using a full "high-end" loading dose
lDe-escalation
and duration of antimicrobial agents should be assessed daily.
References
1.N Engl J Med
2001;345:1368.
2.N Engl J Med
2014;370:1683.
3.N Engl J Med
2014;371:1496.
4.N Engl J Med
2015;372:1301.
5.Intensive Care Med
2015;41:1549.
6.N Engl J Med 2017.
7.Upodate.com
Dr KK Aggarwal
Padma Shri
Awardee
Vice President CMAAO
Group Editor-in-Chief IJCP Publications
Vice President CMAAO
Group Editor-in-Chief IJCP Publications
President Heart
Care Foundation of India
Immediate Past
National President IMA
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