Lets Revise Sepsis. An article by Dr KK Aggarwal, Recipient of Padma Shri.

Dr Bawa-Garba Case:Lets Revise Sepsis

Dr KK Aggarwal,  19 February 2018

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

• Sepsis is the consequence of a dysregulated inflammatory response to an infectious insult. 

• Sepsis 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.

• Septic 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.

• Patients 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) 

• Poor 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. 

• There is a continuum of severity ranging from sepsis to septic shock. Mortality has been estimated to be ≥10% and ≥40% when shock is present.

• First aid: Securing the airway (if indicated) and correcting hypoxemia, and establishing venous access for the early administration of fluids and antibiotics

• Supplemental oxygen should be supplied to all patients with sepsis and oxygenation should be monitored continuously with pulse oximetry. 

• Venous access should be established as soon as possible in patients with suspected sepsis. 

• An 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. 

• The cornerstone of initial resuscitation is the rapid restoration of perfusion and the early administration of antibiotics.

• Tissue 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.

• Components 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. 

• Intravenous (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. 

• Empiric 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.

• Although 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

• Broad 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.

• Among 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

• Clinicians should pay attention to maximizing the dose in patients with sepsis and septic shock using a full "high-end" loading dose 

• De-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