Sepsis Stages Causes Symptoms Diagnosis Complications and Treatment Methods

Sepsis is one of the most serious medical emergencies. It develops as a result of an abnormal and dysregulated response of the body to an infection, which may lead to dysfunction of vital organs and, in severe cases, progress to septic shock and multiple organ failure. The danger of sepsis lies in its rapid progression and the difficulty of predicting its clinical course in some cases. Therefore, early diagnosis and prompt treatment are essential factors in improving survival rates and reducing complications.Sepsis can result from bacterial, viral, or fungal infections and may originate from various sources, including the lungs, urinary tract, gastrointestinal tract, skin, and soft tissues. Its symptoms and severity vary from one patient to another. Clinical manifestations may include fever, increased heart rate, and rapid breathing, as well as low blood pressure, altered mental status, and reduced urine output. These signs require urgent medical evaluation.The management of sepsis relies on a comprehensive set of interventions, including clinical assessment, appropriate laboratory tests and imaging studies, resuscitation and organ support, administration of appropriate antimicrobial therapy, and source control when necessary. Source control may involve medical treatment, surgical intervention, or minimally invasive procedures.This article by Dalili Medical Guide aims to provide a comprehensive overview of sepsis by discussing its definition, stages, causes, and associated risk factors; identifying its major signs and symptoms and diagnostic methods; and reviewing its complications and the key therapeutic principles used to prevent disease progression and improve clinical outcomes.

What Is Sepsis?

Sepsis is a serious, life-threatening condition that develops when the body's response to an infection becomes dysregulated, leading to dysfunction of vital organs. If not diagnosed and treated promptly, it may progress to multiple organ failure.

What Is the Difference Between Infection, Sepsis, Bacteremia, and Septic Shock?

- Infection: Occurs when pathogenic microorganisms, such as bacteria, viruses, or fungi, enter the body and multiply, causing a disease process.

- Bacteremia: Refers to the presence of bacteria in the bloodstream. It may occur without progressing to sepsis.

- Sepsis: A life-threatening organ dysfunction caused by a dysregulated host response to infection.

- Septic Shock: A severe form of sepsis associated with profound circulatory and metabolic abnormalities that may result in inadequate organ perfusion and organ failure.

Is an Elevated White Blood Cell Count Required to Diagnose Sepsis?

No. An elevated white blood cell count is not a prerequisite for diagnosing sepsis. The white blood cell count may be elevated, within the normal range, or decreased. Therefore, diagnosis relies on a comprehensive clinical assessment, the presence of suspected or confirmed infection, evidence of organ dysfunction, and appropriate laboratory findings.

Causes of Sepsis

Sepsis is a serious, life-threatening condition that occurs when the body's dysregulated response to an infection causes dysfunction of vital organs. If not diagnosed and treated promptly, it may progress to septic shock or organ failure.

Sepsis can result from an infection originating in any part of the body, triggering an inflammatory response and disrupting organ function. The most common sources of infection that may lead to sepsis include the following:

What Pathogens Cause Sepsis?

Sepsis can develop from various types of pathogenic microorganisms, including:

What Factors Increase the Risk of Sepsis?

The likelihood of developing sepsis is higher in certain populations, including:

Types of Sepsis

Sepsis can be classified according to the severity of the condition, the source of infection, or the type of causative pathogen.

1. Types of Sepsis According to Severity

Note: The term severe sepsis was previously used as a separate diagnostic category. However, it is no longer considered an independent category under modern definitions because the definition of sepsis already includes organ dysfunction.

2. Types of Sepsis According to the Source of Infection

Sepsis may be classified according to the site where the infection originates.

3. Types of Sepsis According to the Causative Pathogen

Type	Examples
Bacterial sepsis	Escherichia coli and Staphylococcus species
Viral sepsis	Severe influenza or coronavirus infection
Fungal sepsis	Candida infection
Severe parasitic infection	Severe malaria, which may be associated with serious organ dysfunction

Symptoms of Sepsis

First: Early Symptoms of Sepsis

Patients with sepsis may develop a range of early symptoms, including:

Abnormally high or low body temperature.
Shivering and chills.
Rapid heart rate.
Increased respiratory rate.
Severe fatigue and general malaise.
Excessive sweating or cold, clammy skin.

Second: Symptoms Indicating Clinical Deterioration

As sepsis progresses and organ function becomes impaired, more serious symptoms may develop, including:

Altered mental status: Confusion, difficulty concentrating, or unusual drowsiness.
Low blood pressure: Which may be accompanied by dizziness or fainting.
Reduced urine output: A noticeable decrease in the amount of urine produced.
Difficulty breathing: Or a significantly increased respiratory rate.
Cold extremities or pale skin: Mottled skin discoloration may also occur.
Severe pain or discomfort: Without an obvious cause.

Medical warning: Sepsis is a life-threatening medical emergency. If sepsis is suspected, particularly when accompanied by altered consciousness, difficulty breathing, or low blood pressure, seek emergency medical care immediately.

Third: Symptoms of Sepsis According to the Source of Infection

The symptoms associated with sepsis vary depending on the site of the initial infection. Common examples include:

Source of infection	Possible symptoms
Lungs	Cough, shortness of breath, and chest pain.
Urinary tract and kidneys	Pain or burning during urination, flank pain, and changes in urine color or appearance.
Abdomen	Abdominal pain, vomiting, and abdominal distension.
Skin and wounds	Redness, swelling, pain, and pus discharge.
Central nervous system	Severe headache, neck stiffness, and altered mental status.

Fourth: How Can Sepsis Be Distinguished from an Uncomplicated Infection?

Sepsis is not simply a fever or the presence of microorganisms in the bloodstream. It is a serious condition involving life-threatening organ dysfunction caused by the body's dysregulated response to infection.

The main concern is that sepsis can lead to rapid clinical deterioration and may occur even in the absence of an elevated body temperature. Therefore, distinguishing sepsis from an uncomplicated infection requires a comprehensive clinical assessment, identification of signs of organ dysfunction, and appropriate diagnostic investigations.

Common Sources of Infection That May Lead to Sepsis

Sepsis may originate from several sites in the body, including:

Respiratory tract infections: Such as pneumonia, a common source of sepsis.
Urinary tract and kidney infections: Particularly kidney infections or infections associated with urinary tract obstruction.
Intra-abdominal infections: Such as complicated appendicitis, peritonitis, cholecystitis, and intestinal perforation.
Skin and soft tissue infections: Including contaminated wounds, abscesses, infected burns, and necrotizing soft tissue infections.
Catheter- and medical device-associated infections: Such as infections related to intravenous catheters or certain implanted devices.
Central nervous system infections: Such as meningitis, which may lead to sepsis in severe cases.

Pathogens That Can Cause Sepsis

Sepsis may result from several types of pathogens, including:

Bacteria: Common causes include Escherichia coli (E. coli) and Staphylococcus species.
Viruses: Severe infections caused by influenza viruses or SARS-CoV-2 may lead to sepsis.
Fungi: Such as Candida, particularly in immunocompromised patients or those with prolonged hospital stays.
Parasites: Certain parasitic infections, including severe malaria, can cause serious systemic illness that resembles sepsis or may coexist with it.

Risk Factors for Sepsis

Certain populations are at an increased risk of developing sepsis, including:

Older adults and newborns.
People with weakened immune systems.
Patients with diabetes or chronic medical conditions.
Patients who have undergone major surgery or invasive medical procedures.
Patients hospitalized for prolonged periods or admitted to intensive care units.
Individuals with severe infections or delayed treatment.

Clinical Classification of Sepsis

Sepsis can also be described according to its severity or the source of infection.

Sepsis: Life-threatening organ dysfunction resulting from a dysregulated response to infection.
Septic shock: A severe subset of sepsis characterized by profound circulatory and metabolic abnormalities. It may require vasopressor medications to maintain blood pressure despite adequate fluid resuscitation.
Pulmonary sepsis: Sepsis originating from a respiratory infection, such as pneumonia.
Urinary sepsis: Sepsis originating from an infection of the urinary tract or kidneys.
Abdominal sepsis: Sepsis caused by an intra-abdominal infection, such as peritonitis, intestinal perforation, or an abdominal abscess.
Skin and soft tissue sepsis: Sepsis arising from infections affecting the skin and soft tissues, including infected wounds.
Catheter- and medical device-associated sepsis: Sepsis resulting from an infection associated with a catheter or medical device.
Sepsis associated with central nervous system infections: Sepsis that may develop in cases of meningitis or other severe infections affecting the central nervous system.

Diagnosis of Sepsis

First: Clinical Assessment

The physician begins by evaluating the patient's general condition, vital signs, and indicators that may suggest organ dysfunction. These include:

Body temperature: To identify an abnormally high or low temperature.
Heart rate: To detect tachycardia (an abnormally rapid heartbeat).
Respiratory rate: To identify an abnormally increased breathing rate.

The presence of a suspected infection accompanied by altered mental status, low blood pressure, or difficulty breathing requires urgent medical evaluation in a hospital.

Second: Laboratory Tests and Investigations for Diagnosing Sepsis

The physician may order a range of investigations depending on the patient's clinical condition and the suspected source of infection.

Test	Purpose
Blood culture	To identify the microorganism responsible for the infection and guide appropriate treatment.
Complete blood count (CBC)	To assess white blood cell and platelet counts and identify abnormalities.
Serum lactate	To help assess impaired tissue perfusion and the severity of the patient's condition.
Kidney and liver function tests	To detect dysfunction of these organs.
Blood gas analysis	To assess acid–base balance and oxygenation, as indicated by the clinical condition.
Inflammatory markers, such as CRP and procalcitonin	To support the assessment of infection and the inflammatory response; these markers cannot independently confirm sepsis.
Urine, sputum, or wound cultures	To help identify the source of infection and the causative microorganism.

Medical Treatment of Sepsis

First: Antibiotics

Antibiotics are a cornerstone of treatment for sepsis caused by bacterial infections. The appropriate medication is selected according to the suspected source of infection, disease severity, local antimicrobial resistance patterns, kidney and liver function, and the patient's medication history and allergies.

In cases of septic shock or when the likelihood of sepsis is high, appropriate intravenous antibiotics should be administered as soon as possible, ideally within the first hour of recognizing the condition.

Blood cultures and other appropriate specimens should preferably be collected before starting treatment, provided that doing so does not cause a significant delay in antibiotic administration.

Once culture and antimicrobial susceptibility results become available, treatment should be adjusted to select the most appropriate antibiotic. The need for continued treatment and its duration should be reassessed regularly.

Which Antibiotics Are Used to Treat Sepsis?

Several intravenous antibiotics may be used in hospital settings. The choice depends on the suspected infection, likely pathogens, and the patient's individual risk factors.

Medication or drug class	Potential indications
Piperacillin/tazobactam	Broad-spectrum coverage against many bacteria, including Pseudomonas aeruginosa and certain anaerobic bacteria.
Cefepime	Coverage against many Gram-negative bacteria, including Pseudomonas aeruginosa. Metronidazole may be added when anaerobic coverage is needed.
Meropenem	Used in selected severe infections, particularly when resistant bacteria are suspected, including certain extended-spectrum beta-lactamase (ESBL)-producing organisms.
Vancomycin	Added when there is a significant risk of methicillin-resistant Staphylococcus aureus (MRSA) infection or another appropriate indication.
Ceftriaxone	May be used for selected community-acquired infections, depending on the source and severity of infection and the likelihood of antimicrobial resistance.
Metronidazole	Provides anaerobic coverage in selected infections, such as certain intra-abdominal infections, when the primary antibiotic does not provide adequate coverage.
Azithromycin	May be added in selected cases of pneumonia to provide coverage against atypical pathogens, depending on the clinical assessment.

These medications are examples of potential treatment options, not a standardized prescription for every patient with sepsis.

Examples of Antibiotic Selection According to the Source of Infection

Sepsis caused by a urinary tract infection: Ceftriaxone, cefepime, or piperacillin/tazobactam may be considered, depending on disease severity and the likelihood of resistant organisms.
Sepsis caused by a pulmonary infection: Treatment depends on whether the infection was acquired in the community or in the hospital, as well as the likely pathogens and relevant risk factors.
Sepsis caused by an intra-abdominal infection: Piperacillin/tazobactam, meropenem, or cefepime combined with metronidazole may be used in selected cases.
Suspected MRSA infection: Vancomycin or an appropriate alternative may be added, depending on the infection site and clinical condition.
Suspected highly resistant bacteria: Treatment is selected based on previous culture results, recent antibiotic exposure, and local antimicrobial resistance data.

Important note: Vancomycin and meropenem should not automatically be prescribed to every patient with sepsis. Unnecessary use of broad-spectrum antibiotics can increase drug toxicity and antimicrobial resistance. Dosing varies according to age, body weight, kidney and liver function, and infection severity.

Second: Vasopressors for Septic Shock

Septic shock can cause a severe drop in blood pressure, threatening the delivery of blood and oxygen to vital organs. If hypotension persists despite appropriate fluid resuscitation, the patient may require vasopressor medications, with close monitoring in a hospital or intensive care unit.

1. Norepinephrine (Noradrenaline)

Norepinephrine is generally the first-line vasopressor for adults with septic shock. It constricts blood vessels and raises blood pressure, helping improve organ perfusion.

It is administered by intravenous infusion, with the dose adjusted according to the patient's response and blood pressure measurements.

2. Vasopressin

Vasopressin may be added to norepinephrine when hypotension persists or higher doses of norepinephrine are required. Its use may improve blood pressure control and reduce the need to further increase the norepinephrine dose.

3. Epinephrine (Adrenaline)

Epinephrine may be added when the target blood pressure is not achieved with other vasopressors or used in specific clinical circumstances, according to the treating team's assessment.

4. Dobutamine

Dobutamine may be used in selected cases when there is evidence of impaired cardiac function and persistent organ hypoperfusion despite correction of fluid deficits and blood pressure abnormalities. It is not the primary medication for raising blood pressure alone.

The usual initial target for mean arterial pressure (MAP) in adults with septic shock is approximately 65 mmHg, although this target may be adjusted according to the patient's condition and clinical needs.

These medications require continuous monitoring of blood pressure, heart rate, and tissue perfusion. They must not be used at home or without specialist medical supervision.

Third: Intravenous Fluids and Supportive Medications

A. Intravenous Fluids

Intravenous fluids are used to restore circulating blood volume and support circulation when fluid depletion or impaired tissue perfusion is present.

Commonly used fluids include:

Balanced crystalloids: Such as lactated Ringer's solution, which are commonly preferred as initial resuscitation fluids.
0.9% normal saline: May be used in appropriate cases, depending on the clinical assessment.

Fluid administration should be individualized and reassessed frequently to evaluate the patient's response and reduce the risk of fluid overload, particularly in patients with cardiac or kidney dysfunction.

In adults with sepsis accompanied by hypoperfusion or septic shock, guidelines recommend considering the administration of approximately 30 mL of intravenous fluids per kilogram of body weight during the first three hours.

However, this volume is not mandatory for every patient. Fluid responsiveness should be reassessed frequently, taking into account blood pressure, respiratory status, cardiac and renal function, and the risk of fluid overload or pulmonary edema.

B. Corticosteroids

Hydrocortisone

Hydrocortisone may be used in selected patients with septic shock who continue to require vasopressor medications despite adequate fluid resuscitation.

It is not a routine treatment for all cases of sepsis, nor does it replace antibiotics or the interventions required to control the source of infection.

C. Insulin

Insulin may be used to control persistent hyperglycemia in critically ill patients.

Guidelines for critically ill adults generally recommend initiating insulin therapy when blood glucose levels reach 180 mg/dL or higher, with frequent glucose monitoring to prevent dangerous hypoglycemia.

D. Antifungal Medications

Physicians may prescribe antifungal medications, such as fluconazole or an echinocandin, in selected cases where an invasive fungal infection is strongly suspected.

The choice of antifungal agent depends on the suspected fungal species, the severity of the patient's condition, risk factors, and laboratory findings. These medications are not routinely used in all patients with sepsis.

Fourth: Source Control

Antibiotics alone may not be sufficient to treat sepsis if the source of infection requires direct intervention. Therefore, source control is an essential component of treatment.

The necessary procedures may include:

Abscess drainage: Performed surgically or through image-guided interventional radiology.
Management of an infected urinary tract obstruction: Urgent intervention may be required to relieve the obstruction.
Surgical intervention for certain intra-abdominal infections: Examples include cases requiring surgery for cholecystitis, intestinal infection, or other sources of infection.
Removal of a suspected infected intravenous catheter: When clinically indicated, with alternative venous access provided if necessary.

The type and timing of the intervention depend on the source of infection and the patient's clinical condition and stability. Necessary procedures should not be delayed.

Fifth: Duration of Antibiotic Therapy

There is no single antibiotic treatment duration suitable for all cases of sepsis. The duration depends on several factors, including:

The source of infection and the causative microorganism.
The severity of the illness and the degree of organ dysfunction.
The patient's clinical response to treatment.
Culture results and antimicrobial susceptibility testing.
The success of source control.

Antibiotic therapy should be reviewed daily, and treatment should be narrowed whenever culture results and the patient's clinical condition allow.

A relatively short course of antibiotics may be sufficient for certain infections once source control has been achieved and the patient's condition has improved. Other conditions require longer treatment, such as some cases of infective endocarditis, osteomyelitis, and complicated bloodstream infections.

The physician may also decide to discontinue empirical antibiotics if the condition is found to have a noninfectious cause or if further evidence no longer supports continued treatment.

Important note: Antibiotics should not be discontinued, changed, or adjusted without consulting the treating physician.

Sepsis: Surgical Management

First: Surgical Procedures Used for Source Control

A. Abscess Drainage

Abscess drainage is performed to remove accumulated pus from tissues or body cavities, helping limit the persistence and spread of infection.

Drainage may be performed using either of the following methods:

Surgical drainage: The abscess is opened, its contents are evacuated, and the cavity is cleaned as needed.
Percutaneous drainage: A needle or catheter is inserted into the abscess under medical imaging guidance, such as ultrasound or computed tomography (CT).

Additional steps may include obtaining a pus sample for bacterial culture and antibiotic susceptibility testing and placing a drainage catheter when necessary.

Examples of conditions that may require abscess drainage include:

Intra-abdominal abscesses.
Pelvic abscesses.
Deep soft-tissue abscesses.

B. Surgical Debridement

Surgical debridement aims to remove dead or severely infected tissue that may serve as a persistent focus of infection.

Depending on the patient's condition, the procedure may involve:

Excision of nonviable tissue.
Opening infected tissue spaces and draining accumulated pus and secretions.
Cleaning the wound and assessing the extent of infection.
Reassessing the affected tissues and performing additional debridement if necessary.

Important conditions that may require this intervention include necrotizing fasciitis and severe infections associated with tissue necrosis.

Important note: When necrotizing fasciitis is suspected, urgent surgical intervention is essential. Surgery should not be delayed while awaiting imaging results if the clinical suspicion is high.

C. Exploratory or Therapeutic Abdominal Surgery

Sepsis may result from intra-abdominal conditions that require surgical repair or removal of infected tissue. The type of intervention is determined by the source of infection, its extent, and the patient's condition.

Important examples include:

Gastric or intestinal perforation: Repairing the perforation or resecting the affected segment, depending on the extent of damage.
Complicated appendicitis: Appendectomy, with abscess drainage when necessary.
Complicated cholecystitis: Cholecystectomy or temporary gallbladder drainage in selected cases.
Intestinal ischemia with necrosis: Resection of intestinal segments that have lost viability.

These procedures aim to eliminate the source of infection and prevent continued contamination of the abdominal cavity or the spread of inflammation to adjacent tissues.

D. Drainage of an Infected Obstruction

Sepsis may persist despite antibiotic treatment if an obstruction prevents the drainage of urine or bile. Relieving the obstruction may therefore be an urgent and essential intervention.

Examples include:

Infected urinary tract obstruction: May require ureteral stent placement or percutaneous nephrostomy to drain urine and relieve pressure.
Acute cholangitis with biliary obstruction: May require biliary drainage using endoscopic retrograde cholangiopancreatography (ERCP).

In these cases, antibiotics alone may not be sufficient. The obstruction must also be relieved and the source of infection controlled alongside medical treatment.

E. Removal of Infection Sources Associated with Medical Devices

Certain medical devices may serve as sources of persistent infection, including intravenous catheters and some implanted devices.

Potential interventions include:

Removing an intravenous catheter when it is suspected to be the source of infection, based on clinical assessment, and providing alternative venous access when necessary.
Evaluating infected implanted devices and determining whether removal, surgical cleaning, or another appropriate intervention is required.
Obtaining appropriate samples to identify the causative microorganism whenever indicated.

The decision depends on the type of device, the location of the infection, the suspected microorganism, and whether the infection can be controlled without removing the device.

Second: Differences Between Open Surgery and Minimally Invasive Interventions

The medical team selects the appropriate intervention according to the nature of the infection source, the extent of the infection, the patient's stability, and the available resources.

Type of intervention	Potential indications
Open surgery	Conditions requiring direct access to organs, such as certain cases of gastrointestinal perforation, extensive tissue necrosis, or severe intra-abdominal contamination.
Laparoscopic surgery	Cases in which the source of infection can be safely treated laparoscopically, depending on the patient's stability and the surgical team's expertise.
Percutaneous drainage	Abscesses suitable for image-guided drainage when this approach can provide adequate source control.
Endoscopy	Procedures such as biliary drainage and removal of certain causes of obstruction using ERCP.