Septic Shock Medication

  • Author: Michael R Pinsky, MD, CM, FCCP, FCCM; Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM   more...
 
Updated: Oct 25, 2011
 

Medication Summary

The most important aspect of medical therapy for septic patients includes adequate oxygen delivery, crystalloid fluid administration, and broad-spectrum antibiotics. Although colloid solution is mentioned, mortality benefit of colloid over crystalloid has never been proven. Blood transfusion may also be beneficial for patients with low hemoglobin concentrations.

Vasopressors are important for patients who are refractory to adequate fluid resuscitation. Steroid administration should be considered in patients refractory to both fluids and vasopressors, and recombinant human activated protein C (APC) is a therapy that should be considered for the patients in the most critical condition in the intensive care unit (ICU).

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Vasopressors

Class Summary

In cardiovascular disorders, vasopressors are used for their alpha1 and beta1 properties. They provide hemodynamic support in acute heart failure and shock.

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Norepinephrine (Levophed)

 

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

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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. Cardiac stimulation and renal vasodilation is produced by higher doses. After initiating therapy, the dose may be increased by 1-4 µg/kg/min q10-30min until a satisfactory response is attained. Maintenance doses lower than 20 µg/kg/min usually are satisfactory for 50% of the patients treated.

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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 EGDT if there is evidence that tissue hypoperfusion and myocardial dysfunction is related to sepsis. Dopamine and dobutamine are the drugs of choice to improve cardiac contractility, with dopamine the preferred agent in hypotensive patients.

Higher dosages may cause an increase in heart rate, exacerbating myocardial ischemia.

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Epinephrine (Adrenalin)

 

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

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Vasopressin (Pitressin)

 

Vasopressin has vasopressor and antidiuretic hormone (ADH) activity. It increases water resorption at the distal renal tubular epithelium (ADH effect). It 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.

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Phenylephrine

 

Phenylephrine is a strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles and increased peripheral vascular resistance. It will result in 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 crystalloids, the standard intravenous (IV) fluids used for initial volume resuscitation. They expand the intravascular and interstitial fluid spaces. Typically, about 30% of administered isotonic fluid stays intravascular; therefore, large quantities may be required to maintain adequate circulating volume.

Both fluids are isotonic and have equivalent volume restorative properties. While some differences exist between metabolic changes observed with the administration of large quantities of either fluid, 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 either NS or LR.

Normal saline (NS, 0.9% NaCl)

 

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

Lactated Ringer

 

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

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Colloids

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 of pulmonary and cerebral edema. About 50% of the administered colloid stays intravascular.

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Albumin (Buminate, Albuminar)

 

Albumin is used 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. Five percent solutions are indicated to expand plasma volume, whereas 25% solutions are indicated to raise oncotic pressure.

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Antibiotics

Class Summary

Early treatment with empirical antibiotics is the only other proven medical treatment in septic shock. Use of broad-spectrum and/or multiple antibiotics provide the necessary coverage. In children who are immunocompetent, monotherapy is possible with a third-generation cephalosporin (eg, cefotaxime, ceftriaxone, ceftazidime). An antipseudomonal penicillin or carbapenem is used as monotherapy for adults who are immunocompetent.

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, metronidazole) or a fluoroquinolone plus clindamycin. All antibiotics should be administered IV initially.

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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 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, while cell wall assembly is arrested.

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Ticarcillin and clavulanate (Timentin)

 

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

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Piperacillin and tazobactam (Zosyn)

 

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

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Imipenem and 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 due to their potential for toxicity.

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Meropenem (Merrem)

 

Meropenem is a carbapenem with slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared to imipenem. It is less likely to cause seizures and superior penetration of blood-brain barrier compared to imipenem.

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Clindamycin (Cleocin)

 

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

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Metronidazole (Flagyl)

 

Metronidazole is an imidazole ring-based antibiotic 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.

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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, while cell wall assembly is arrested.

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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%.

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Cefepime (Maxipime)

 

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

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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. High urine concentration necessitates reduced dosing in urinary tract infection.

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Vancomycin

 

Vancomycin provides gram-positive coverage and good hospital-acquired MRSA coverage. It is now used more frequently 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.

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Hydrocortisone (A-Hydrocort, Solu-Cortef)

 

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.

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Dexamethasone

 

Dexamethasone has many pharmacologic benefits but significant adverse effects. It stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines (eg, TNF-alpha, IL-6, IL-2, and IFN-gamma). The inhibition of chemotactic factors and factors that increase capillary permeability inhibits recruitment of inflammatory cells into affected areas. It suppresses lymphocyte proliferation through direct cytolysis, and it inhibits mitosis. Dexamethasone breaks down granulocyte aggregates and improves pulmonary microcirculation. Adverse effects include hyperglycemia, hypertension, weight loss, 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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Human Activated Protein C, Recombinant

Class Summary

APC is an endogenous protein that has natural anticoagulant and anti-inflammatory effects. In the PROWESS-SHOCK trial, administration of recombinant human APC was not shown to improve mortality, and, therefore, the drug was withdrawn from the worldwide market on October 25, 2011.

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Drotrecogin alfa (Xigris)

 

October 25, 2011: Withdrawn from worldwide market. levels of APC are low in septic shock, which is hypothesized to exacerbate the proinflammatory response and microthrombus formation in end-organ vascular beds that leads to organ dysfunction. Having an anticoagulant effect, use of APC increases the risk for serious bleeding.

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Contributor Information and Disclosures
Author

Michael R Pinsky, MD, CM, FCCP, FCCM  Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center

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

Disclosure: LiDCO Ltd Honoraria Consulting; iNTELOMED Intellectual property rights Board membership; Edwards Lifesciences Honoraria Consulting; Applied Physiology, Ltd Honoraria Consulting; Cheetah Medical Consulting fee Consulting

Coauthor(s)

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 of Sciences, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

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.

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.

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.

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 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.

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.

Specialty Editor Board

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.

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

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.

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.

Chief Editor

Michael R Pinsky, MD, CM, FCCP, FCCM  Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center

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

Disclosure: LiDCO Ltd Honoraria Consulting; iNTELOMED Intellectual property rights Board membership; Edwards Lifesciences Honoraria Consulting; Applied Physiology, Ltd Honoraria Consulting; Cheetah Medical Consulting fee Consulting

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors R Phillip Dellinger, MD, Ismail Cinel, MD, PhD,Steven Manders, MD, Clara-Dina Cokonis, MD, and Dane Salandy, MD†,to the development and writing of the source articles.

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Venn diagram showing 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. The blood culture confirmed Neisseria meningitidis. The skin manifestation is characteristic of severe meningococcal infection and is called purpura fulminans.
Gram stain of blood showing presence of Neisseria meningitidis.
Acute respiratory distress syndrome (ARDS), commonly observed in septic shock as a part of multiorgan failure syndrome, is pathologically diffuse alveolar damage (DAD). This photomicrograph shows an early stage (exudative stage) of DAD.
Acute respiratory distress syndrome (ARDS), commonly observed in septic shock as a part of multiorgan failure syndrome, is pathologically diffuse alveolar damage (DAD). This is a high-powered photomicrograph of an early stage (exudative stage) of DAD.
This photomicrograph shows a delayed stage (proliferative or organizing stage) of diffuse alveolar damage (DAD). Proliferation of type II pneumocytes has occurred, hyaline membranes are present, and collagen and fibroblasts are present.
This photomicrograph shows a delayed stage (proliferative or organizing stage) of diffuse alveolar damage (DAD). This is fibrin stain showing collagenous tissue, which may develop into the 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 sepsis was urosepsis.
A 45-year-old woman is 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 a rare cause of septic shock.
A 28-year-old woman who is a previous intravenous drug user (HIV-negative status) developed septic shock secondary to bilateral pneumococcal pneumonia.
Table 1. Mediators of Sepsis
TypeMediatorActivity
Cellular mediatorsLipopolysaccharideActivation of macrophages, neutrophils, platelets, and endothelium releases various cytokines and other mediators
Lipoteichoic acid
Peptidoglycan
Superantigens
Endotoxin
Humoral mediatorsCytokinesPotent proinflammatory effect



Neutrophil chemotactic factor



Acts as pyrogen, stimulates B and T lymphocyte proliferation, inhibits cytokine production, induces immunosuppression



Activation and degranulation of neutrophils



Cytotoxic, augments vascular permeability, contributes to shock



Involved in hemodynamic alterations of septic shock



Promote neutrophil and macrophage, platelet activation and chemotaxis, other proinflammatory effects



Enhance vascular permeability and contributes to lung injury



Enhance neutrophil-endothelial cell interaction, regulate leukocyte migration and adhesion, and play a role in pathogenesis of sepsis



TNF-alpha and IL-1β



IL-8



IL-6



IL-10



MIF



G-CSF



Complement
Nitric oxide
Lipid mediators



Phospholipase A2



PAF



Eicosanoids



Arachidonic acid metabolites
Adhesion molecules



Selectins



Leukocyte integrins



G-CSF = Granulocyte colony-stimulating factor; IL = interleukin; MIF = macrophage inhibitory factor; PAF = platelet-activating factor; TNF = tumor necrosis factor.
Table 2. Criteria for Organ Dysfunction
Organ System Mild Criteria Severe Criteria
PulmonaryHypoxia/hypercarbia requiring assisted ventilation for 3-5 dARDS requiring PEEP >10 cm H2 O and FiO2 < 0.5
HepaticBilirubin 2-3 mg/dL or other liver function tests more than twice normal, PT elevated to twice normalJaundice with bilirubin 8-10 mg/dL
RenalOliguria ( < 500 mL/d or increasing creatinine) 2-3 mg/dLDialysis
GastrointestinalIntolerance of gastric feeding for more than 5 dStress ulceration with need for transfusion, acalculous cholecystitis
HematologicaPTT >125% of reference range, platelets < 50-80,000DIC
CardiovascularDecreased ejection fraction with persistent capillary leakHyperdynamic state not responsive to pressors
CNSConfusionComa
Peripheral nervous systemMild sensory neuropathyCombined motor and sensory deficit
aPTT = Activated partial thromboplastin time; ARDS = acute respiratory distress syndrome; CNS = central nervous system; DIC = disseminated intravascular coagulation; FiO2 = fraction of inspired oxygen; PEEP = positive end-expiratory pressure; PT = prothrombin time.
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