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Septic Shock Medication

  • Author: Andre Kalil, MD, MPH; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM  more...
 
Updated: May 17, 2016
 

Medication Summary

The most important aspects of medical therapy for patients with sepsis include adequate oxygen delivery, crystalloid fluid administration, and broad-spectrum antibiotics. Although colloid solution is mentioned, a mortality benefit of colloid over crystalloid solution has not been proved. Blood transfusion may also be beneficial for patients with low hemoglobin concentrations.

Vasopressors are important for patients whose conditions are refractory to adequate fluid resuscitation. Steroid administration should be considered in patients whose conditions are refractory to both fluids and vasopressors.

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Alpha-/Beta-Adrenergic Agonists

Class Summary

In cardiovascular disorders, vasopressors are used for their alpha1 and beta1 properties. They induce vasoconstriction and elevate mean arterial pressure, as well as provide hemodynamic support in acute heart failure and shock.

Vasopressors are used as second-line agents in the treatment of septic shock. There is no evidence that one vasopressor is superior compared to the other.

Norepinephrine (Levophed)

 

Norepinephrine is used in protracted hypotension after adequate fluid replacement. It stimulates beta1- and alpha-adrenergic receptors, thereby in turn increasing cardiac muscle contractility and heart rate as well as vasoconstriction. As a result, it increases systemic blood pressure and cardiac output. Adjust and maintain the infusion to stabilize the blood pressure (eg, 80-100 mm Hg systolic blood pressure) sufficiently to perfuse vital organs.

Dopamine (Intropin)

 

Dopamine stimulates both adrenergic and dopaminergic receptors. Its hemodynamic effect depends on the dose. Lower doses stimulate mainly dopaminergic receptors that produce renal and mesenteric vasodilation. Higher doses produce cardiac stimulation and renal vasodilation. After therapy is initiated the dosage may be increased by 1-4 µg/kg/min every 10-30 minutes until a satisfactory response is attained. Maintenance dosages lower than 20 µg/kg/min are usually satisfactory for 50% of the patients treated.

Dobutamine

 

Dobutamine is a sympathomimetic amine with stronger beta than alpha effects. It produces systemic vasodilation and increases the inotropic state. Vasopressors augment the coronary and cerebral blood flow during the low-flow state associated with shock. Sympathomimetic amines with both alpha- and beta-adrenergic effects are indicated in cardiogenic shock.

Dobutamine is used in early goal-directed therapy if there is evidence that tissue hypoperfusion and myocardial dysfunction is related to sepsis. Dopamine and dobutamine are the drugs of choice for improving cardiac contractility, with dopamine the preferred agent in hypotensive patients. Higher dosages of dobutamine may cause an increase in heart rate, exacerbating myocardial ischemia.

Epinephrine (Adrenalin)

 

Epinephrine is used for hypotension that is refractory to dopamine or norepinephrine. It stimulates alpha- and beta-adrenergic receptors, resulting in relaxation of bronchial smooth muscle, increased cardiac output, and increased blood pressure.

Vasopressin (Pitressin)

 

Vasopressin (Pitressin)

Vasopressin has vasopressor and antidiuretic hormone (ADH) activity. It increases water resorption at the distal renal tubular epithelium (ADH effect). Vasopressin promotes smooth muscle contraction throughout the vascular bed of the renal tubular epithelium (vasopressor effects). Vasoconstriction is increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels.

Phenylephrine

 

Phenylephrine is a strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity. It produces vasoconstriction of arterioles and increased peripheral vascular resistance. This agent causes reflex myocardial depression and decreased heart rate; therefore, it must be used with caution. Phenylephrine is a first-line agent in patients with hypotension and extreme tachycardia. It can be used as an adjunct to norepinephrine or dopamine to augment peripheral vasoconstriction.

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Isotonic crystalloids

Class Summary

Isotonic sodium chloride solution (normal saline [NS]) and lactated Ringer (LR) solution are isotonic crystalloid fluids, the standard intravenous (IV) fluids used for initial volume resuscitation. Another crystalloid solution used is Plasmalyte. These solutions expand the intravascular and interstitial fluid spaces. Typically, about 30% of administered isotonic fluid stays in the intravascular space; therefore, large quantities may be required to maintain adequate circulating volume.

NS and LR solution are isotonic and have equivalent volume-restoring properties. Although some differences exist in the metabolic changes observed with the administration of large quantities of the 2 fluids, for practical purposes and in most situations, the differences are clinically irrelevant. No demonstrable difference in hemodynamic effect, morbidity, or mortality exists between resuscitation with NS and resuscitation with LR solution.

Normal saline (NS, 0.9% NaCl)

 

Normal saline restores interstitial and intravascular volume. It is used in initial volume resuscitation.

Lactated Ringer

 

LR solution restores interstitial and intravascular volume. It is used in initial volume resuscitation.

Plasmalyte

 

Normal saline restores interstitial and intravascular volume. It is used in initial volume resuscitation.

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Volume Expanders

Class Summary

Colloids are used to provide oncotic expansion of plasma volume. They expand plasma volume to a greater degree than isotonic crystalloids and reduce the tendency toward pulmonary and cerebral edema. About 50% of the administered colloid stays intravascular.

Albumin (Buminate, Albuminar)

 

Albumin is given for certain types of shock or impending shock. It is useful for plasma volume expansion and maintenance of cardiac output. A solution of NS and 5% albumin is available for volume resuscitation. The 5% solutions are indicated for expanding plasma volume, whereas the 25% solutions are indicated for raising oncotic pressure.

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Antibiotics

Class Summary

Early empiric antibiotic therapy is the only other proven medical treatment in septic shock. Use of broad-spectrum or multiple antibiotics provides the necessary wide coverage. In children who are immunocompetent, monotherapy with a third-generation cephalosporin (eg, cefotaxime, ceftriaxone, or ceftazidime) is possible. In immunocompetent adults, an antipseudomonal penicillin or carbapenem is used as monotherapy.

Penicillinase-resistant synthetic penicillins and a third-generation cephalosporin are used for combination therapy in children. Combination therapy in adults involves a third-generation cephalosporin plus anaerobic coverage (ie, clindamycin or metronidazole) or a fluoroquinolone plus clindamycin. All antibiotics should initially be administered IV.

Cefotaxime (Claforan)

 

Cefotaxime is a third-generation cephalosporin with broad-spectrum gram-negative activity. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Cefotaxime is used to treat against an increasing prevalence of penicillinase-producing microorganisms. This agent inhibits bacterial cell-wall synthesis by binding to 1 or more penicillin-binding proteins. Cell-wall autolytic enzymes lyse bacteria, and cell-wall assembly is arrested.

Ticarcillin-clavulanate (Timentin)

 

Ticarcillin-clavulanate consists of an antipseudomonal penicillin plus a beta-lactamase inhibitor that provides coverage against most gram-positive organisms (except for variable coverage against Staphylococcus epidermidis and no coverage against methicillin-resistant Staphylococcus aureus [MRSA]), gram-negative organisms, and anaerobes.

Piperacillin-tazobactam (Zosyn)

 

Piperacillin-tazobactam inhibits the biosynthesis of cell-wall mucopeptide and is effective during the stage of active multiplication. It has antipseudomonal activity.

Imipenem-cilastatin (Primaxin)

 

Imipenem-cilastatin is a carbapenem with activity against most gram-positive organisms (except MRSA), gram-negative organisms, and anaerobes. It is used for treatment of multiple organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of their potential for toxicity.

Meropenem (Merrem)

 

Meropenem is a carbapenem with slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci relative to imipenem. Compared with imipenem, it is less likely to cause seizures and better able to penetrate the blood-brain barrier.

Clindamycin (Cleocin)

 

Clindamycin is primarily used for its activity against anaerobes. It has some activity against Streptococcus species and methicillin-sensitive S aureus (MSSA).

Metronidazole (Flagyl)

 

Metronidazole is an imidazole ring-based antibiotic that is active against various anaerobic bacteria and protozoa. It is usually combined with other antimicrobial agents, except when used for Clostridium difficile enterocolitis, in which monotherapy is appropriate.

Ceftriaxone (Rocephin)

 

Ceftriaxone is a third-generation cephalosporin with broad-spectrum, gram-negative activity. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Ceftriaxone is used for increasing prevalence of penicillinase-producing microorganisms. It inhibits bacterial cell-wall synthesis by binding to 1 or more penicillin-binding proteins. Cell-wall autolytic enzymes lyse bacteria, and cell-wall assembly is arrested.

Ciprofloxacin (Cipro)

 

Ciprofloxacin is a fluoroquinolone with variable activity against Streptococcus species, activity against methicillin-sensitive S aureus and Staphylococcus epidermidis, activity against most gram-negative organisms, and no activity against anaerobes. It is a synthetic broad-spectrum antibacterial compounds with a novel mechanism of action, targeting bacterial topoisomerase II and IV, thus leading to a sudden cessation of DNA replication. Oral bioavailability is near 100%.

Cefepime (Maxipime)

 

Cefepime is a fourth-generation cephalosporin. It has gram-negative coverage comparable to that of ceftazidime but has better gram-positive coverage (comparable to that of ceftriaxone). Cefepime is active against Pseudomonas species. It has increased effectiveness against extended-spectrum beta lactamase (ESBL)-producing organisms. Its poor capacity to cross the blood-brain barrier precludes its use for treatment of meningitis.

Levofloxacin (Levaquin)

 

Levofloxacin is a fluoroquinolone with excellent gram-positive and gram-negative coverage. It is an excellent agent for pneumonia and has excellent abdominal coverage as well. Its high urine concentration necessitates reduced dosing in urinary tract infection.

Vancomycin

 

Vancomycin provides gram-positive coverage and good hospital-acquired MRSA coverage. It is being used increasingly often because of the high incidence of MRSA. Vancomycin should be given to all septic patients with indwelling catheters or devices. It is advisable for skin and soft-tissue infections.

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Corticosteroids

Class Summary

Corticosteroids are powerful anti-inflammatory agents. They may maintain vascular tone in states of shock. These agents are most likely to be beneficial if therapy is initiated within 8 hours of the onset of severe septic shock, but no consistent proof of increased survival outcomes have been seen in clinical trials.

Hydrocortisone (A-Hydrocort, Solu-Cortef)

 

Endogenous cortisol is a stress hormone that acts in part to maintain vascular tone in states of shock. Some evidence suggests that exogenous hydrocortisone administration may increase mean arterial pressure and improve outcomes in patients with septic shock who have persistent hypotension despite adequate crystalloid resuscitation and vasopressor support.

Dexamethasone

 

Dexamethasone has many pharmacologic benefits, but it also has significant adverse effects. This agent stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines (eg, tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-2, and interferon gamma). The inhibition of chemotactic factors and factors that increase capillary permeability hinders recruitment of inflammatory cells into affected areas.

Dexamethasone suppresses lymphocyte proliferation through direct cytolysis, and it inhibits mitosis. It breaks down granulocyte aggregates and improves pulmonary microcirculation. Adverse effects include hyperglycemia, hypertension, weight loss, gastrointestinal (GI) bleeding or perforation, cerebral palsy, adrenal suppression, and death. Most of the adverse effects of corticosteroids are dose- or duration-dependent.

Dexamethasone is readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. It lacks the salt-retaining property of hydrocortisone. Patients can be switched from an IV to PO regimen in a 1:1 ratio.

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Contributor Information and Disclosures
Author

Andre Kalil, MD, MPH Professor of Medicine, Department of Medicine, Section of Infectious Diseases, University of Nebraska College of Medicine; Director, Transplant ID Program, University of Nebraska Medical Center

Disclosure: Received research grant from: Received grant/research funds from Spectral Diagnostics; Received grant/research funds from Asahi Kasei; Received grant/research funds from Ferring.

Coauthor(s)

Kristina L Bailey, MD Assistant Professor, Department of Medicine, Section of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center

Kristina L Bailey, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, Research Society on Alcoholism

Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease, Clinical and Translational Science and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM is a member of the following medical societies: American College of Chest Physicians, Association of University Anesthetists, European Society of Intensive Care Medicine, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Shock Society, Society of Critical Care Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Masimo<br/>Received honoraria from LiDCO Ltd for consulting; Received intellectual property rights from iNTELOMED for board membership; Received honoraria from Edwards Lifesciences for consulting; Received honoraria from Masimo, Inc for board membership.

Acknowledgements

Fatima Al Faresi, MD Dermatologist, Tawam Hospital, Al Ain, UAE

Disclosure: Nothing to disclose.

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy ofSciences,and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

John L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Ismail Cinel, MD, PhD Visiting Associate Professor, Division of Critical Care Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey

Disclosure: Nothing to disclose.

Clara-Dina Cokonis, MD Staff Physician, Department of Medicine, Division of Dermatology, Cooper Hospital University Medical Center

Disclosure: Nothing to disclose.

R Phillip Dellinger, MD Professor of Medicine, Program Director, Critical Care Medicine Fellowship Program, Robert Wood Johnson School of Medicine, University of Medicine and Dentistry of New Jersey; Head, Division of Critical Care Medicine, Medical Director, Medical/Surgical/Cardiovascular Surgical Intensive Care Unit, Cooper University Hospital

Disclosure: Wyeth Consulting fee Consulting; BRAHMS Grant/research funds Other Clinical Trial; Artisan Grant/research funds Other Clinical Trial; Agenix Grant/research funds Other Clinical Trial

Daniel J Dire, MD, FACEP, FAAP, FAAEM Clinical Professor, Department of Emergency Medicine, University of Texas Medical School at Houston; Clinical Professor, Department of Pediatrics, University of Texas Health Sciences Center San Antonio

Daniel J Dire, MD, FACEP, FAAP, FAAEM is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American Academy of Pediatrics, American College of Emergency Physicians, and Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Michael R Filbin, MD Clinical Instructor, Department of Emergency Medicine, Massachusetts General Hospital

Michael R Filbin, MD is a member of the following medical societies: American College of Emergency Physicians, Massachusetts Medical Society, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Franklin Flowers, MD Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine

Franklin Flowers, MD, is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

Cory Franklin, MD Professor, Department of Medicine, Rosalind Franklin University of Medicine and Science; Director, Division of Critical Care Medicine, Cook County Hospital

Cory Franklin, MD is a member of the following medical societies: New York Academy of Sciences and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Theodore J Gaeta, DO, MPH, FACEP Clinical Associate Professor, Department of Emergency Medicine, Weill Cornell Medical College; Vice Chairman and Program Director of Emergency Medicine Residency Program, Department of Emergency Medicine, New York Methodist Hospital; Academic Chair, Adjunct Professor, Department of Emergency Medicine, St George's University School of Medicine

Theodore J Gaeta, DO, MPH, FACEP is a member of the following medical societies: Alliance for Clinical Education, American College of Emergency Physicians, Clerkship Directors in Emergency Medicine, Council of Emergency Medicine Residency Directors, New York Academy of Medicine, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Hassan I Galadari, MD Assistant Professor of Dermatology, Faculty of Medicine and Health Sciences, United Arab Emirates University

Hassan I Galadari, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Medical Student Association/Foundation, and American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Elsevier Royalty Other

Paul Krusinski, MD Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Steven M Manders, MD Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania; Associate Professor, Department of Internal Medicine, Division of Dermatology, University of Medicine and Dentistry of New Jersey

Disclosure: Nothing to disclose.

Steven Mink, MD Head, Section of Pulmonary Medicine, Department of Internal Medicine, St Boniface Hospital; Professor of Medicine, University of Manitoba, Canada

Steven Mink, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Mark L Plaster, MD, JD Executive Editor, Emergency Physicians Monthly

Mark L Plaster, MD, JD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians

Disclosure: M L Plaster Publishing Co LLC Ownership interest Management position

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Vicken Y Totten, MD, MS, FACEP, FAAFP Assistant Professor, Case Western Reserve University School of Medicine; Director of Research, Department of Emergency Medicine, University Hospitals, Case Medical Center

Vicken Y Totten, MD, MS, FACEP, FAAFP is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Eric L Weiss, MD, DTM&H Medical Director, Office of Service Continuity and Disaster Planning, Fellowship Director, Stanford University Medical Center Disaster Medicine Fellowship, Chairman, SUMC and LPCH Bioterrorism and Emergency Preparedness Task Force, Clinical Associate Progressor, Department of Surgery (Emergency Medicine), Stanford University Medical Center

Eric L Weiss, MD, DTM&H is a member of the following medical societies: American College of Emergency Physicians, American College of Occupational and Environmental Medicine, American Medical Association, American Society of Tropical Medicine and Hygiene, Physicians for Social Responsibility, Southeastern Surgical Congress, Southern Association for Oncology, Southern Clinical Neurological Society, and Wilderness Medical Society

Disclosure: Nothing to disclose.

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Strawberry tongue in a child with staphylococcal toxic shock syndrome. Reproduced with permission from Drage, LE. Life-threatening rashes: dermatologic signs of four infectious diseases. Mayo Clin Proc. 1999;74:68-72.
Venn diagram showing the overlap of infection, bacteremia, sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction.
A 26-year-old woman developed rapidly progressive shock associated with purpura and signs of meningitis. Her blood culture results confirmed the presence of Neisseria meningitidis. The skin manifestation seen in this image is characteristic of severe meningococcal infection and is called purpura fulminans.
Gram stain of blood showing the presence of Neisseria meningitidis.
Acute respiratory distress syndrome (ARDS), commonly observed in septic shock as a part of multiorgan failure syndrome, results in pathologically diffuse alveolar damage (DAD). This photomicrograph shows early stage (exudative stage) DAD.
Acute respiratory distress syndrome (ARDS), commonly observed in septic shock as a part of multiorgan failure syndrome, results in pathologically diffuse alveolar damage (DAD). This is a high-powered photomicrograph of early stage (exudative stage) DAD.
Photomicrograph showing delayed stage (proliferative or organizing stage) of diffuse alveolar damage (DAD). Proliferation of type II pneumocytes has occurred; hyaline membranes as well as collagen and fibroblasts are present.
Photomicrograph showing delayed stage (proliferative or organizing stage) of diffuse alveolar damage (DAD). Fibrin stain depicts collagenous tissue, which may develop into fibrotic stage of DAD.
Acute respiratory distress syndrome (ARDS) in a patient who developed septic shock secondary to toxic shock syndrome.
Bilateral airspace disease and acute respiratory failure in a patient with gram-negative septic shock. The source of the sepsis was urosepsis.
A 45-year-old woman was admitted to the intensive care unit with septic shock secondary to spontaneous biliary peritonitis. She subsequently developed acute respiratory distress syndrome (ARDS) and multiorgan failure.
An 8-year-old boy developed septic shock secondary to Blastomycosis pneumonia. Fungal infections are rare causes of septic shock.
A 28-year-old woman who was a former intravenous drug user (human immunodeficiency virus [HIV] status: negative) developed septic shock secondary to bilateral pneumococcal pneumonia.
Diagram depicting the pathogenesis of sepsis and multiorgan failure. DIC = disseminated intravascular coagulation; IL = interleukin.
Soft-tissue infection secondary to group A streptococci, leading to toxic shock syndrome.
Necrotizing cellulitis of toxic shock syndrome.
Necrosis of the little toe of the right foot and cellulitis of the foot secondary to group A streptococcal infection.
Group A streptococci cause beta hemolysis on blood agar.
Gram stain of blood showing group A streptococci that was isolated from a patient who developed toxic shock syndrome. Image courtesy of T. Matthews.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. The leg was incised to exclude underlying necrotizing infection. Image courtesy of Rob Green, MD.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome (same patient as in previous image). This patient also had streptococcal pharyngitis. Image courtesy of Rob Green, MD.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome (same patient as in previous image). The patient had diffuse erythroderma, a characteristic feature of the syndrome. Image courtesy of Rob Green, MD.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome (same patient as in previous image). The patient had diffuse erythroderma, a characteristic feature of the syndrome. He improved with antibiotics and intravenous gammaglobulin therapy. Several days later, a characteristic desquamation of the skin occurred over his palms and soles. Image courtesy of Rob Green, MD.
Progression of soft-tissue swelling to vesicle or bullous formation is an ominous sign and suggests streptococcal shock syndrome. Image courtesy of S. Manocha.
Extensive debridement of necrotizing fasciitis of the hand.
Healing of the hand after aggressive surgical debridement of necrotizing fasciitis (same patient as in previous image).
A 58-year-old patient presented in septic shock. On physical examination, progressive swelling of the right groin was observed. On exploration, necrotizing cellulitis, but not fasciitis, was present. The wound cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). Computed tomography (CT) scanning helped to evaluate the extent of the infection and to exclude other pathologies (eg, psoas abscess, osteomyelitis, inguinal hernia).
Computed tomography (CT) scan from a 58-year-old patient who presented in septic shock (same patient as in previous image). Progressive swelling of the right groin was noted, and necrotizing cellulitis, but not fasciitis, was present. The wound cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). CT scanning helped in the evaluation of the extent of the infection and in the exclusion of other pathologies (eg, psoas abscess, osteomyelitis, inguinal hernia).
Computed tomography (CT) scan from a 58-year-old patient who presented in septic shock (same patient as in previous image). Progressive swelling of the right groin was noted, and necrotizing cellulitis, but not fasciitis, was present. The wound cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). CT scanning helped in the evaluation of the extent of the infection and in the exclusion of other pathologies (eg, psoas abscess, osteomyelitis, inguinal hernia).
Space-occupying lesion correlating with left temporoparietal metastatic infiltration associated with peritumoral edema.
Space-occupying lesion correlating with left temporoparietal metastatic infiltration associated with peritumoral edema (same lesion as shown in previous computed tomography image).
Table 1. Sepsis-Related SOFA Score (adapted froom Singer et al)
System 0 Points 1 Point 2 Points 3 Points 4 Points
Respiration



PaO2a/FiO2b



 



≥400 mm Hg



 



<400 mm Hg



 



<300 mm Hg



 



<200 mm Hg



(with respiratory support)



 



<100 mm Hg



(with respiratory support)



Coagulation



Platelet count



 



≥150 x 103/µL



 



<150 x 103/µL



 



<100 x 103/µL



 



<50 x 103/µL



 



<20 x 103/µL



Liver



Bilirubin level



 



<1.2 mg/dL



 



1.2-1.9 mg/dL



 



2-5.9 mg/dL



 



6-11.9 mg/dL



 



>12 mg/dL



Cardiovascular MAPc ≥70 mm Hg MAP >70 mm Hg Dopamine <5 or



dobutamine (any dose)e



Dopamine 5.1-15 or



epinephrine ≤0.1 or



norepinephrine ≤0.1e



Dopamine >15 or



epinephrine >0.1 or



norepinephrine >0.1e



Central nervous system



GCSd score



 



15



 



13-14



 



10-12



 



6-9



 



<6



Renal



Creatinine



Urine output



<1.2 mg/dL 1.2-1.9 mg/dL 2-3.4 mg/dL  



3.5-4.9 mg/dL



<500 mL/day



 



>5 mg/dL



<200 mL/day



aPaO2=Partial pressure of oxygen.



bFiO2=Fraction of inspired oxygen.



cMAP=Mean arterial pressure.



dGCS=Glasgow Coma Scale (range, 3-15, with higher indicating better function).



eCatecholamine doses administered as µg/kg/min for ≥1 hour.



Table 2. Surviving Sepsis Guidelines Criteria for Organ Dysfunction
Organ System Sepsis Criteria Severe Sepsis Criteria
Pulmonary Arterial hypoxemia: PaO2/FIO2 < 300 Arterial hypoxemia: PaO2/FIO2 < 250 in absence of pneumonia and < 200 in presence of pneumonia
Hepatic Hyperbilirubinemia: Plasma total bilirubin >4 mg/dL or 70 µmol/L Hyperbilirubinemia: Plasma total bilirubin >2 mg/dL or 34.2 µmol/L
Renal Creatinine increase >0.5 mg/dL or 44.2 µmol/L



Acute oliguria: Urine output < 0.5 mL/kg/hr for ≥2 hr despite adequate fluid resuscitation



Creatinine >2 mg/dL or 176.8 µmol/L



Acute oliguria: Urine output < 0.5mL/kg/hr for ≥2 hr despite adequate fluid resuscitation



Gastrointestinal Ileus: Absent bowel sounds  
Hematologic INR >1.5, aPTT >60 s, or platelets < 100,000/µL INR >1.5 or platelets < 100,000/µL
Cardiovascular Hyperlactatemia >1 mmol/L; decreased capillary refill or mottling



Hemodynamic status: SBP < 90 mm Hg, MAP < 70 mm Hg, or SBP decrease >40 mm Hg



Hyperlactatemia: Above upper limits of laboratory normal



Hemodynamic status: SBP < 90 mm Hg, MAP < 70 mm Hg, or SBP decrease >40 mm Hg



Central nervous system Confusion, lethargy, coma  
     
aPTT = activated partial thromboplastin time; FIO2 = fraction of inspired oxygen; INR = international normalized ratio; MAP = mean arterial pressure; PaO2 = partial pressure of oxygen; PEEP = positive end-expiratory pressure; PT = prothrombin time; SBP = systolic blood pressure.



Source: Dellinger RP, Levy MM, Rhodes A, et al, for the Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637.[11]



Table 3. Mediators of Sepsis
Type Mediator Activity
Cellular mediators LPS Activation of macrophages, neutrophils, platelets, and endothelium releases various cytokines and other mediators
Lipoteichoic acid
Peptidoglycan
Superantigens
Endotoxin
Humoral mediators Cytokines Activate inflammatory pathways
  • TNF-α and IL-1β
Potent proinflammatory effect
  • IL-6
Acts as pyrogen, stimulates B- and T-cell proliferation
  • IL-8
Neutrophil chemotactic factor, activation and degranulation of neutrophils
  • IL-10
Inhibits cytokine production, induces immunosuppression
  • MIF
Activates macrophages and T cells
  • G-CSF
Promotes neutrophil and macrophage, platelet activation
Complement Promotes neutrophil and macrophage, platelet activation and chemotaxis, other proinflammatory effects
Nitric oxide Involved in hemodynamic alterations of septic shock; cytotoxic, augments vascular permeability, contributes to shock  
Lipid mediators Enhance vascular permeability and contribute to lung injury  
  • Phospholipase A2
   
  • PAF
   
  • Eicosanoids
   
Arachidonic acid metabolites Augment vascular permeability  
Adhesion molecules Enhance neutrophil-endothelial cell interaction, regulate leukocyte migration and adhesion, and play a role in pathogenesis of sepsis; increased levels of VAP-1 activity and anchor protein SDC-1 content have been found in critically ill patients with septic shock[12]  
  • Selectins
   
  • Leukocyte integrins
   
  • High mobility box–1
Late mediator of endotoxin-induced lethality and tissue repair  
G-CSF = granulocyte colony-stimulating factor; IL = interleukin; LPS = lipopolysaccharide; MIF = macrophage inhibitory factor; PAF = platelet-activating factor; SDC-1 = syndecan-1; TNF = tumor necrosis factor; VAP-1 = vascular adhesion protein–1.



Source:  Cinel I, Opal SM. Molecular biology of inflammation and sepsis: a primer. Crit Care Med. 2009 Jan;37(1):291-304.[13]



 
 
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