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Sepsis

Sepsis is a potentially life-threatening, systemic complication of an infection resulting from the spread of bacteria or their toxic products from a focus of infection. Pneumonia is the most common cause, followed by intraabdominal and urinary tract infections. No source is found in about one third of cases. The clinical presentation of sepsis is highly variable depending on the etiology.


Presentation

The clinical features of septicemia intensify over time from mild to severe.

The cardinal symptoms of sepsis include:

These features may be preceded by lethargy, headache and minor changes in consciousness.

In the elderly and immunocompromised patients, the clinical features may be quite subtle.

Tachypnea
  • Tachycardia and tachypnea are extremely common in mild pediatric illness; these are not as useful in selecting for septic patients. Therefore either a temperature or leukocyte abnormality must be present to meet pediatric SIRS criteria.[mdcalc.com]
  • Components of SIRS include tachycardia, tachypnea, hyperthermia or hypothermia, and elevated white blood count.[medpagetoday.com]
  • […] play \ ˈsep-ˌsēz \ : a systemic response typically to a serious usually localized infection (as of the abdomen or lungs) especially of bacterial origin that is usually marked by abnormal body temperature and white blood cell count, tachycardia, and tachypnea[merriam-webster.com]
  • Local inflammation is recognized as rubor (redness), tumor (swelling), calor (heat) and dolor (pain), and when a systemic response is elicited, it is called SIRS (Systemic Inflammatory Response Syndrome), which consists of tachypnea, tachycardia, hyperpyrexia[blogs.biomedcentral.com]
Fever
  • Often, if they develop signs of an infection such as fever, infants have to receive antibiotics and be admitted to hospital.[webmd.boots.com]
  • In older babies and children, symptoms may include a fever, irritability, difficulty breathing, and drowsiness.[kidshealth.org]
  • When to Use Pearls/Pitfalls Why Use Children Fever in patients There is good agreement to do full neonatal fever workups for neonates 28 days.[mdcalc.com]
  • Patients with nonspecific symptoms are usually acutely ill with fever, with or without shaking chills. Mental status may be impaired in the setting of fever or hypoperfusion.[emedicine.medscape.com]
  • Common symptoms of sepsis are fever, chills, rapid breathing and heart rate, rash, confusion and disorientation.[cottagehealth.org]
Chills
  • Chills are subjective—a patient feels chills but it cannot be observed by a health-care provider,” Dr. Dellinger says.[rd.com]
  • Common symptoms of sepsis are fever, chills, rapid breathing and heart rate, rash, confusion and disorientation.[cottagehealth.org]
  • People with weakened immune systems Infants and children The elderly People with chronic illnesses, such as diabetes, AIDS, cancer, and kidney or liver disease People suffering from a severe burn or physical trauma Common symptoms of sepsis are fever, chills[nlm.nih.gov]
  • At first, people have a high (or sometimes low) body temperature, sometimes with shaking chills and weakness. As sepsis worsens, the heart beats rapidly, breathing becomes rapid, people become confused, and blood pressure drops.[msdmanuals.com]
  • Patients with nonspecific symptoms are usually acutely ill with fever, with or without shaking chills. Mental status may be impaired in the setting of fever or hypoperfusion.[emedicine.medscape.com]
Weakness
  • Sepsis: Bacteremia or another infection triggers a serious bodywide response ( sepsis ), which typically includes fever, weakness, a rapid heart rate, a rapid breathing rate, and an increased number of white blood cells.[merckmanuals.com]
  • […] feeding not drinking for more than eight hours (when awake) bile-stained (green), bloody or black vomit/sick Activity and body soft spot on a baby's head is bulging eyes look "sunken" child cannot be encouraged to show interest in anything baby is floppy weak[nhs.uk]
  • At first, people have a high (or sometimes low) body temperature, sometimes with shaking chills and weakness. As sepsis worsens, the heart beats rapidly, breathing becomes rapid, people become confused, and blood pressure drops.[msdmanuals.com]
  • Gastrointestinal bleeding and infection (19 trials) and neuromuscular weakness (three trials) were not increased. We found sparse data on effects of corticosteroids in children with sepsis.[cochrane.org]
  • People with suspected sepsis can show: · low blood pressure · high temperature (fever) or low temperature · fast heartbeat · breathlessness · feeling weak or loss of consciousness · being confused or disorientated · loss of appetite · diarrhoea, nausea[nice.org.uk]
Hypothermia
  • Components of SIRS include tachycardia, tachypnea, hyperthermia or hypothermia, and elevated white blood count.[medpagetoday.com]
  • This response includes an abnormally high temperature ( fever ) or low temperature ( hypothermia ) plus one or more of the following: Although many infections cause such symptoms throughout the body, in sepsis organs begin to malfunction and blood flow[msdmanuals.com]
  • The most prominent are: Decreased urine output Fast heart rate Fever Hypothermia (very low body temperature) Shaking Chills Warm skin or a skin rash Confusion or delirium Hyperventilation (rapid breathing) Cleveland Clinic is a non-profit academic medical[my.clevelandclinic.org]
  • The most prominent are: Decreased urine output Fast heart rate Fever Hypothermia (very low body temperature) Shaking Chills Warm skin or a skin rash Confusion or delirium Hyperventilation (rapid breathing) Next: Diagnosis and Tests Cleveland Clinic is[my.clevelandclinic.org]
  • In general, symptoms of sepsis can include: Chills Confusion or delirium Fever or low body temperature ( hypothermia ) Lightheadedness due to low blood pressure Rapid heartbeat Skin rash or mottled skin Warm skin A person with sepsis will be admitted[nlm.nih.gov]
High Fever
  • That’s why it’s crucial to learn the signs of sepsis, and the first and most important is a high fever. Sepsis occurs when “toxins from the infecting organism get into the bloodstream and produce inflammation,” says noted sepsis expert R.[rd.com]
  • fever, severe necrotizing pneumonia with haemoptysis, leucopenia, respiratory failure and shock.[oxfordjournals.org]
Vomiting
  • These can include: feeling dizzy or faint a change in mental state – such as confusion or disorientation diarrhoea nausea and vomiting slurred speech severe muscle pain severe breathlessness less urine production than normal – for example, not urinating[nhs.uk]
  • So call your doctor immediately or get emergency medical care if your baby shows any of these symptoms: vomiting no interest in feeding fever (100.4 F [38 C] or higher rectal temperature) in newborns and young infants labored or unusual breathing change[kidshealth.org]
  • If the body’s blood pressure drops to a dangerous level, a person will also feel dizzy, confused, experience diarrhoea and or vomiting and nausea. Their skin will also become cold, pale and clammy and they may slur their words.[independent.co.uk]
  • […] shaking Heart beating very fast, sometimes with rapid breathing Symptoms of severe sepsis or septic shock include: Confusion Disorientation Agitation Dizziness , particularly when standing up Fast respiratory rate Decreased urination Diarrhoea Nausea and vomiting[webmd.boots.com]
  • Other common warning signs include: Fever and chills Very low body temperature Peeing less than normal Rapid pulse Rapid breathing Nausea and vomiting Diarrhea Continued Sepsis Treatment If your doctor believes you might have sepsis, he’ll do an exam[webmd.com]
Nausea
  • People with suspected sepsis can show: · low blood pressure · high temperature (fever) or low temperature · fast heartbeat · breathlessness · feeling weak or loss of consciousness · being confused or disorientated · loss of appetite · diarrhoea, nausea[nice.org.uk]
  • If the body’s blood pressure drops to a dangerous level, a person will also feel dizzy, confused, experience diarrhoea and or vomiting and nausea. Their skin will also become cold, pale and clammy and they may slur their words.[independent.co.uk]
  • […] severe shaking Heart beating very fast, sometimes with rapid breathing Symptoms of severe sepsis or septic shock include: Confusion Disorientation Agitation Dizziness , particularly when standing up Fast respiratory rate Decreased urination Diarrhoea Nausea[webmd.boots.com]
  • Other common warning signs include: Fever and chills Very low body temperature Peeing less than normal Rapid pulse Rapid breathing Nausea and vomiting Diarrhea Continued Sepsis Treatment If your doctor believes you might have sepsis, he’ll do an exam[webmd.com]
Abdominal Pain
  • Diffuse abdominal pain may suggest pancreatitis (not sepsis) or generalized peritonitis, whereas right upper abdominal quadrant (RUQ) tenderness may suggest a gallbladder etiology (eg, cholecystitis, cholangitis ), and tenderness in the right lower abdominal[emedicine.medscape.com]
  • Narrow your results Refine your results RSS feed Highlighted Cochrane Review Pharmacological interventions for recurrent abdominal pain in childhood Alice E Martin, Tamsin V Newlove‐Delgado, Rebecca A Abbott, Alison Bethel, Joanna Thompson‐Coon, Rebecca[cochranelibrary.com]
  • pain Septic shock To be diagnosed with septic shock, you must have the signs and symptoms of severe sepsis — plus extremely low blood pressure that doesn't adequately respond to simple fluid replacement.[mayoclinic.org]
Diarrhea
  • Sepsis symptom: nausea, vomiting, and diarrhea iStock/monkeybusinessimages Unfortunately, GI symptoms are what threw off Rory Staunton’s doctors—they thought he just had a stomach virus.[rd.com]
  • Other common warning signs include: Fever and chills Very low body temperature Peeing less than normal Rapid pulse Rapid breathing Nausea and vomiting Diarrhea Continued Sepsis Treatment If your doctor believes you might have sepsis, he’ll do an exam[webmd.com]
  • Dizziness or feelings of faintness Confusion or a drop in alertness, or any other unusual change in mental state, including a feeling of doom or a real fear of death Slurred speech Diarrhea , nausea, or vomiting Severe muscle pain and extreme general[medicalnewstoday.com]
  • These include fever plus chills, shortness of breath, rapid breathing, increased heart rate, diarrhea, vomiting, rash, or pain, which many survivors describe as the worst they’ve ever felt. Disorientation or confusion can also be signs of sepsis.[consumerreports.org]
  • While symptoms can be subtle and nonspecific some signs include: listlessness not breastfeeding well low body temperature apnea (temporary stopping of breathing) fever pale color poor skin circulation with cool extremities abdominal swelling vomiting diarrhea[healthline.com]
Hypotension
  • Administration of 30 ml/kg IV crystalloid for hypotension or lactate 4 mmol/L.[cdemcurriculum.com]
  • […] or Lactate 4 mmol/L The 6-Hour Septic Shock Bundle contains the following elements, to be completed within 6 hours of the time of presentation with severe sepsis: Apply Vasopressors (for Hypotension That Does Not Respond to Initial Fluid Resuscitation[ihi.org]
  • In severe sepsis, resuscitation is performed during the first six hours to enhance the heart function in order to correct hypoxia, hypotension and hypoperfusion.[symptoma.com]
  • Individuals who suffer from septic shock will experience persistent hypotension despite adequate fluid resuscitation (Singer et al. 2016).[ausmed.com]
  • Hypotension 100 mmHg SBP, 2, Altered consciousness, Tachypnea 22 breath/minute are at increased risk of prolonged ICU stay and mortality.[clinicaladvisor.com]
Tachycardia
  • Tachycardia and tachypnea are extremely common in mild pediatric illness; these are not as useful in selecting for septic patients. Therefore either a temperature or leukocyte abnormality must be present to meet pediatric SIRS criteria.[mdcalc.com]
  • Components of SIRS include tachycardia, tachypnea, hyperthermia or hypothermia, and elevated white blood count.[medpagetoday.com]
  • […] sepsis plural sepses play \ ˈsep-ˌsēz \ : a systemic response typically to a serious usually localized infection (as of the abdomen or lungs) especially of bacterial origin that is usually marked by abnormal body temperature and white blood cell count, tachycardia[merriam-webster.com]
  • Includes normal responses to infection (eg. fever and tachycardia is not dysregulated infection; it’s just infection) SIRS even MISSES up to ⅛ very septic ICU pts (NEJM 2015) [5]. qSOFA is in. a qSOFA score of 2 or 3 or a rise in the SOFA score of 2.[foamcast.org]
Costovertebral Angle Tenderness
  • angle tenderness with a temperature of 102 F suggests acute pyelonephritis .[emedicine.medscape.com]
  • angle tenderness (suggesting pyelonephritis) Special considerations include the following: Elderly patients may present with peritonitis and may not experience rebound tenderness of the abdomen An acute surgical abdomen in a pregnant patient may be difficult[emedicine.medscape.com]
Warm Skin
  • The most prominent are: Decreased urine output Fast heart rate Fever Hypothermia (very low body temperature) Shaking Chills Warm skin or a skin rash Confusion or delirium Hyperventilation (rapid breathing) Cleveland Clinic is a non-profit academic medical[my.clevelandclinic.org]
  • The most prominent are: Decreased urine output Fast heart rate Fever Hypothermia (very low body temperature) Shaking Chills Warm skin or a skin rash Confusion or delirium Hyperventilation (rapid breathing) Next: Diagnosis and Tests Cleveland Clinic is[my.clevelandclinic.org]
  • In general, symptoms of sepsis can include: Chills Confusion or delirium Fever or low body temperature ( hypothermia ) Lightheadedness due to low blood pressure Rapid heartbeat Skin rash or mottled skin Warm skin A person with sepsis will be admitted[nlm.nih.gov]
Eruptions
  • And then it escalates, quickly erupting into widespread infection and inflammation that can cause organ failure and death if not treated fast enough.[statnews.com]
Oliguria
  • The cardinal symptoms of sepsis include: Fever, chills or hypothermia Hypotension and oliguria Hyperventilation Mental status changes Skin manifestations These features may be preceded by lethargy, headache and minor changes in consciousness.[symptoma.com]
  • […] of the body, most readily seen in the fingers/arms, toes/legs Sepsis is diagnosed when there is an infection somewhere in the body AND one of the following: Organ dysfunction (organ failure) Hypoxemia (inability to circulate oxygen to your tissues) Oliguria[christopherreeve.org]
  • The many signs and symptoms of sepsis include abnormalities in the individual’s body temperature, heart rate, respiratory rate and white blood cell count, in addition with hypoxaemia , oliguria, lactic acidosis, elevated liver enzymes and altered cerebral[ausmed.com]
  • […] systolic blood pressure 2 standard deviations below normal for age, or vasopressor requirement, or two of the following criteria: unexplained metabolic acidosis with base deficit 5 mEq/l lactic acidosis : serum lactate 2 times the upper limit of normal oliguria[en.wikipedia.org]
Confusion
  • Common symptoms of sepsis are fever, chills, rapid breathing and heart rate, rash, confusion and disorientation.[cottagehealth.org]
  • Although sepsis can easily be treated with antibiotics if caught early, sepsis symptoms can be confused with other conditions, so it often goes undiagnosed until it’s too late.[rd.com]
  • […] of the following symptoms may be present: Infection Elevated temperature, greater than 38.30C or 101.30F Fast heart rate, greater than 90 beats per minute Fast respiratory rate, greater than 20 breaths per minute Other symptoms that may be present: Confusion[christopherreeve.org]
  • […] children The elderly People with chronic illnesses, such as diabetes, AIDS, cancer, and kidney or liver disease People suffering from a severe burn or physical trauma Common symptoms of sepsis are fever, chills, rapid breathing and heart rate, rash, confusion[nlm.nih.gov]
Altered Mental Status
  • Severe sepsis is diagnosed when the septic patient has organ dysfunction (for example, low or no urine flow, altered mental status).[medicinenet.com]
  • Classic Presentation The classic presentation is that of an elderly patient with multiple comorbidities who presents to the ED with fever, tachycardia, tachypnea, and/or hypotension with altered mental status coming in from a nursing home.[cdemcurriculum.com]
  • It is defined by the presence of 2 or more criteria from the following: temperature 38.3 C (101 F) or 90 bpm; tachypnoea 20 breaths/minute or PaCO2 7.7 mmol/L [ 140 mg/dL]) in the absence of diabetes mellitus; acutely altered mental status; leukocytosis[bestpractice.bmj.com]
  • In the central nervous system , direct damage of the brain cells and disturbances of neurotransmissions causes altered mental status. [47] Cytokines such as tumor necrosis factor , interleukin 1 , and interleukin 6 may activate procoagulation factors[en.wikipedia.org]
  • Outside classic presentations, suspect sepsis for unexplained altered mental status, tachypnea with a clear chest and normal oxygenation, or if clinical instinct suggests something is “not right” in a patient with a seemingly routine infection or suspected[acep.org]
Lethargy
  • […] potential infections Prevent infections that can lead to sepsis by: Cleaning scrapes and wounds and practicing good hygiene by washing hands and bathing regularly If you have an infection, look for signs like: Fever and chills Extreme weakness, dizziness, lethargy[cottagehealth.org]
  • The cardinal symptoms of sepsis include: Fever, chills or hypothermia Hypotension and oliguria Hyperventilation Mental status changes Skin manifestations These features may be preceded by lethargy, headache and minor changes in consciousness.[symptoma.com]
  • If a child younger than 2 months of age has fever, lethargy, poor feeding, a change in normal behavior, or an unusual rash, call the doctor and proceed to the hospital.[emedicinehealth.com]
  • Children may show signs of lethargy and decreased age-appropriate mental status. Neonatal sepsis (sepsis neonatorum) is suspected in neonates up to 28 days old if the rectal temperature is 100.4 F or higher.[medicinenet.com]
Headache
  • The cardinal symptoms of sepsis include: Fever, chills or hypothermia Hypotension and oliguria Hyperventilation Mental status changes Skin manifestations These features may be preceded by lethargy, headache and minor changes in consciousness.[symptoma.com]

Workup

Early diagnosis and treatment of sepsis is the basic key in preventing the morbidity and mortality resulting from the sepsis.
Cardiac monitoring, blood pressure monitoring and pulse oxymetry are indicated in patients with septic shock. Once the patient is stabilized, the clinicians can move forward to the diagnostic workup. This involves the use of the following investigation to determine the cause and site of infection:

  • Blood CP
  • Blood culture
  • Chest radiography
  • Ultrasound abdomen and pelvis
  • Urea & creatinine levels
  • Liver function tests
  • Sputum culture
  • Urine culture
  • Arterial blood gases
  • Coagulation profile

Treatment

The following goals should be kept in mind while treating the patients with septic shock:

  • Adequate antibiotic therapy should be started as early as possible (within one hour of making the diagnosis in severe sepsis) [8].
  • In severe sepsis, resuscitation is performed during the first six hours to enhance the heart function in order to correct hypoxia, hypotension and hypoperfusion [9]. This is known as early goal directed therapy and effectively reduces mortality in these patients [10].
  • The source of infection should be identified identify and should be managed with anti-microbial therapy, surgery or both.
  • Adequate organ system function should be maintained.

Prognosis

The mortality resulting from sepsis is usually quoted to be in the range of 20-50% [7]. However, with the advances in the clinical trials in the past ten years, the mortality rate has been limited to 24 to 41%. The mortality greatly depends on the severity of illness.

The severity of the illness and the prognosis depend on the causative organism, site of infection, the strength of the patient’s immune system, the presence of any underlying disease and the developmet of septic shock.

Etiology

There are number of causes which lead to the development of sepsis. Most of these causes are bacterial in nature but viruses and fungi can also cause sepsis.

The common gram positive organisms that cause sepsis include Staphylocossus, Streptocossus and Enterococcus; whereas Proteus, Pseudomonas and Klebsiella are the common gram negative organisms.

In previously healthy adults, the most common sources of infection are intraabdominal infections, urinary tract infections and pneumonia. In many cases of septicemia, the focus of infection may not be apparent.

Few other rare causes include parasites, fungi, viruses and mycobacteria.

The common predisposing conditions for gram negative bacteremia include diabetes mellitus, lymphoproliferative disorders, cirrhosis of liver, burns, invasive procedures and neutropenia.

In contrast, intravenous drug abuse, vascular catheterization, the presence of indwelling mechanical devices and burns are the predisposing conditions for gram positive bacteremia.

Immunosuppression and broad-spectrum antimicrobial therapy predispose the patient to fungemia.

Epidemiology

In the United States, the per annum episodes of sepsis are 400,000 to 750,000. Sepsis is more common in the extremes of ages such as infancy or old age. Statistical data shows that the male gender more commonly develops sepsis; the sex ratio being 1.5:1.

The development of sepsis is favored by poor hygienic conditions and overcrowding. 5-10% of gram positive bacteremias and 50-60% of gram negative bacteremias are complicated by sepsis.

Sex distribution
Age distribution

Pathophysiology

The septic response results from the microbial signals or toxins coupled with the body response in the form of formation of cytokines, prostaglandins and the activation of complement C5a.

Microbial factors

Bacterial signals initiate the release of inflammaory mediators from leukocytes and endothelial cells. Exotoxins (such as peptoglycan and lipoteichoic acid produced by gram positive organisms) and endotoxins (such as lipopolysacchardie produced by gram negative organisms) are the important microbial factors in this regard.

Body response

There is convincing evidence to support the belief that sepsis develops from exaggerated systemic inflammatory response which is induced by infecting organisms. Some of the inflammatory mediators include TNF (tumor necrosis factor), cytokines, leukotrienes, interleukins, eicosanoids, interferon gamma, selectins and complement C5a [3][4][5].

The interaction of these mediators leads to an inflammatory cascade of reactions that causes widespread endothelial damage, hypotension, refractory shock and multiorgan failure.

Abnormalities of coagulation and fibrinolysis

As a result of endothelial damage, clotting factors and the extrinsic clotting cascade are activated. This leads to disseminated intra-vascular coagulation (DIC) and microvascular thrombosis which ultimately results in organ dysfunction and death [6].

Circulatory abnormalities

Distributive shock is characterized by the pathological vasodilatation and shunting of blood from vital to non-vital tissues and organs. Septic shock falls under this category. Disturbances in blood flow, micro-circulation and peripheral shunting of oxygen result in the deficiency of oxygen and accumulation of lactic acid.

Organ dysfunction and failure

As a result of the abnormalities in circulation, coagulation, peripheral shunting and chemical mediators, the main systems and organs of the body fail to function properly. The improper oxygenation that develops ultimately leads to organ failure and death.

Prevention

Promotion of the hygienic conditions and prevention of overcrowding greatly prevents sepsis. High risk individuals must be identified beforehand to ensure early diagnosis.

Summary

Sepsis can be defined as the systemic inflammatory response to microbial invasion. It is characterized by the presence of two or more of the following  four conditions [1].

  • Oral temperature greater than 38°C or less than 36°C
  • Heart rate more than 90 beats/minutes
  • Respiratory rate more than 20 breaths/minute; or less than 32 torr partial pressure of carbon dioxide.
  • Leukocyte count of more than 12,000 cells/mm3 or less than 4000 cells/mm3 or greater than 10% band forms

Dysfunction of major organs occurs in severe sepsis and may lead to septic shock. Septic shock can be defined as sepsis with hypotension that is unresponsive to fluid resuscitation with signs of organ dysfunction and perfusion abnormalities such as metabolic acidosis, acute alteration in mental status, oliguria or adult respiratory distress syndrome.

Early sepsis is usually reversible whereas patients with septic shock often die even if aggressive therapy is provided. For this reason, it is necessary to detect the cause of sepsis and treat it as early as possible. Sepsis causes millions of death each year [2].

Patient Information

Sepsis is a condition in which in which microorganisms or their toxins are present in the blood. It is characterized by fever, fast breathing and heart rate and an increase in white blood cell count. Individuals at the extremes of ages (old age or infancy) or those who have poor health, or unhygienic living conditions are more prone to the development of sepsis. Sepsis can be fatal if not diagnosed and managed promptly.

References

Article

  1. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Critical care medicine. Apr 2003;31(4):1250-1256.
  2. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Critical care medicine. Jan 2008;36(1):296-327.
  3. Salles MJ, Sprovieri SR, Bedrikow R, et al. [Systemic inflammatory response syndrome/sepsis--review and terminology and physiopathology study]. Revista da Associacao Medica Brasileira. Jan-Mar 1999;45(1):86-92.
  4. Avdeeva MG, Shubich MG. [Pathogenetic mechanisms of the initiation of systemic inflammatory response syndrome (a literature review)].
  5. Klinicheskaia laboratornaia diagnostika. Jun 2003(6):3-10.
    Jaffer U, Wade RG, Gourlay T. Cytokines in the systemic inflammatory response syndrome: a review. HSR proceedings in intensive care & cardiovascular anesthesia. 2010;2(3):161-175.
  6. Nimah M, Brilli RJ. Coagulation dysfunction in sepsis and multiple organ system failure. Critical care clinics. Jul 2003;19(3):441-458.
  7. Russel JA. The current management of septic shock. Minerva medica. Oct 2008;99(5):431-458.
  8. Soong J, Soni N. Sepsis: recognition and treatment. Clinical medicine. Jun 2012;12(3):276-280.
  9. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. The New England journal of medicine. Nov 8 2001;345(19):1368-1377.
  10. Jones AE, Brown MD, Trzeciak S, et al. The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: a meta-analysis. Critical care medicine. Oct 2008;36(10):2734-2739.

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