infective shock



Overview

Definition

Infectious shock refers to the invasion of pathogenic microorganisms and their toxins into the blood circulation, causing tissue cell hypoxia, metabolic and functional disorders, and even multi-organ failure, resulting in shock, which is a life-threatening critical syndrome.

The onset and development of infectious shock is related to the virulence and quantity of microorganisms, as well as the body’s internal environment and response.

Pathogenesis

Sepsis and infectious shock have long been important problems of public health worldwide, with up to 40% or more of patients dying despite aggressive treatment. It is often secondary to infections dominated by gram-negative bacilli, often secondary to acute peritonitis, biliary tract infections, and urinary tract infections [1-3].

Etiology

Pathogenesis

Infection by pathogenic microorganisms

Bacterial infectious diseases

The common clinical diseases that cause infectious shock include gram-negative bacterial sepsis, fulminant rheumatism, toxic pneumonia, septic cholangitis, abdominal infections, and toxic bacillary dysentery. Common bacteria are as follows:

Gram-negative bacteria: Enterobacteriaceae bacteria, such as Escherichia coli, Klebsiella, Enterobacter, etc.; non-fermenting bacteria, such as Pseudomonas spp. and Fusobacterium spp.; as well as meningococcus and bacillus-like bacteria.

Gram-positive bacteria: such as staphylococcus, streptococcus, streptococcus pneumoniae, and clostridium difficile can also cause shock.

Viral, fungal infectious diseases

Such as hemorrhagic fever of renal syndrome, invasive fungal infections, etc., shock is also prone to occur during the course of the disease.

Low or impaired immune function

Patients with chronic underlying diseases, as well as those who have received immunosuppressants such as glucocorticoids, antimetabolites, cytotoxic drugs and radiation therapy for a long period of time, or those who have indwelling urinary catheters or intravenous catheters, are prone to concurrent infectious shock after secondary bacterial infections.

High risk factors or susceptibility factors

Elderly: Elderly patients usually have poorer resistance and are susceptible to pathogen infections, and are prone to overstress under the stress of infection, leading to sepsis and even infectious shock.

Pre-existing chronic underlying diseases: such as cirrhosis, diabetes, malignant tumors, leukemia, burns, organ transplantation, etc., and people with low immunity.

Long-term treatment: patients on long-term antibiotics, glucocorticoids, or artificial respiratory devices, patients with a history of combined urinary tract infections, biliary or gastrointestinal infections, and patients with the presence of invasive built-ins including catheters, drains, and other foreign bodies.

OTHER: Infectious shock also occurs frequently in neonates, pregnant women, and patients with severe immunocompromise due to primary disease [4].

Pathogenesis

Pathogenic microorganisms bind to complement, antibodies, and other components in the body, stimulate the sympathetic nerves to cause vasospasm, damage vascular endothelial cells, and prompt the release of inflammatory mediators, such as histamine, prostaglandins, and lysosomal enzymes, which cause systemic inflammatory response syndrome (SIRS), ultimately leading to microcirculatory disorders, metabolic disorders, and organ dysfunction [4-5].

Invasion of pathogenic microorganisms

Pathogenic microorganisms, such as bacteria, viruses, and fungi, invade the organism through the site of infection, and the endotoxins and exotoxins of pathogens, as well as their own toxicity, can lead to the development of infectious shock.

Infection is only the initiating factor of infectious shock, and bacteria and toxins only serve to trigger acute systemic infection.

Dysregulation of the immune response

When a microorganism invades, the body mobilizes an immune response in which immune cells are activated to release cytokines or inflammatory mediators, leading to inflammation. The strength of the immune response is influenced by factors such as microbial virulence and the immune status of the body.

When the inflammatory response develops to a certain degree, an anti-inflammatory response ensues, and a state of immunosuppression occurs, leading to secondary infection and increasing the initiating factors of infectious shock. The interaction between the two leads to dysregulation of the immune response, which aggravates the systemic inflammatory response and leads to tissue and organ damage.

Organ dysfunction

Organ and tissue ischemia and hypoxia due to microbial attack, dysregulated immune response, tissue hypoperfusion and many other factors thus causing dysfunction. Abnormal activation of coagulation, microcirculatory disorders and organ dysfunction will further aggravate the systemic inflammatory response, contributing to further aggravation of infectious shock.

Symptoms

Main Symptoms

Infectious shock is the most serious stage of infectious disease. Symptoms may appear simultaneously or sequentially, mainly characterized by symptoms of infection and shock, including fever/hypothermia, drop in blood pressure, irritability/fuzzy consciousness, decreased urine output, rapid pulse, and cold and clammy extremities.

Temperature changes

In the early onset of infectious shock, as this is the initial stage of infection and inflammation, patients usually present with an elevated body temperature, usually with a maximum temperature greater than 38°C.

With the progress of the disease, microcirculation disorder occurs, the body circulating blood volume is insufficient, the patient will appear hypothermia, the body temperature will usually be lower than 36 ℃, or even the body temperature does not rise.

Decrease in blood pressure

In the early stage of shock, i.e. the compensatory stage of shock, the patient’s blood pressure tends to be normal or slightly below normal, and the systolic blood pressure even has a mild increase, but the pulse pressure will be lowered, and there is an accelerated pulse rate.

As the shock continues to progress, there is a progressive drop in blood pressure, which may even be difficult to measure, and a poor response to vasoactive drugs such as norepinephrine.

Impaired consciousness

When the patient’s blood pressure decreases, due to insufficient blood supply to the heart and brain, the most important manifestation is different degrees of consciousness disorder, such as depression, drowsiness, coma and so on.

Skin florid

When peripheral circulation is impaired due to shock, the skin of the patient’s extremities usually appears pale, cyanotic, flushed, florid or even marbled.

Skin temperature changes

Some patients with infectious shock have a less common form of “warm shock,” in which the skin is warmer and drier. During the course of the disease, this may progress to “cold shock”, which is characterized by cold, clammy or cold sweating [4-5].

Oliguria, anuria

Anuria or oliguria occurs when low blood pressure leads to insufficient blood supply to the kidneys or renal insufficiency.

Complications.

Infectious shock can cause multi-organ dysfunction, resulting in appropriate clinical manifestations.

Acute kidney injury: the kidney is the most common organ involved in the early stage of infectious shock, which is manifested by weakness, lack of appetite, nausea, vomiting, decreased urine output and deepening of urine color, hematuria, etc. [5].

Coagulation disorders/diffuse intravascular coagulation: bleeding spots on the skin and mucous membranes, difficulty in stopping bleeding at puncture sites, etc., bleeding from certain internal organs, and intracranial hemorrhage in severe cases, etc.

Acute respiratory distress syndrome/respiratory failure: shortness of breath, hypoxia, cyanosis, dyspnea, etc.

Abnormal liver function: jaundice, pain and discomfort in the liver area, etc.

Myocardial injury/heart failure: manifested as chest pain, chest tightness, breath-holding, edema, inability to lie down at night, coughing pink foamy sputum, etc.

Gastrointestinal dysfunction: bloating, vomiting, constipation/diarrhea, stress ulcers, gastrointestinal bleeding, etc.

Ischemic-hypoxic encephalopathy: manifested by different degrees of consciousness disorders, such as lethargy and coma.

Consultation

Department of Medicine

Emergency Department

Patients presenting with symptoms such as low blood pressure, shortness of breath, impaired consciousness, decreased urine output, etc. are advised to seek medical treatment promptly.

Immunocompromised patients presenting with fever are advised to seek prompt medical attention.

Department of Intensive Care Medicine (ICU)

The emergence of infectious shock after emergency treatment requires admission to the ICU for further treatment, including continuous monitoring and intensive treatment, and replacement therapy for organ function.

Preparation for medical treatment

Preparation for medical consultation: registration, preparation of documents, common problems

Tips for medical care

Keep warm.

Family members should accompany the patient to the clinic and observe the patient’s consciousness.

Preparation List

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

Is there fever, cough and sputum?

Is there nausea, vomiting, abdominal pain and diarrhea?

Is there any urinary urgency, frequent urination, back pain, blood in urine?

Are there skin, soft tissue, perianal infections?

Is there oliguria, thirst, cold, clammy extremities, agitation or confusion?

Is a catheter (urinary or hemodialysis catheter) being carried?

List of medical history

Any cirrhosis, diabetes mellitus, malignancy, leukemia, burns, organ transplantation, etc.?

Is there prolonged use of antibiotics, glucocorticoids, or artificial respiratory devices?

Is there a history of urinary tract infections, biliary or gastrointestinal infections, chronic alcoholism, drug abuse?

Presence of invasive built-ins, including catheters, drains and other foreign bodies?

Checklist

Test results from the last six months, which can be brought to the doctor’s appointment

Laboratory tests: routine blood tests, pathogenetic tests, C-reactive protein, coagulation, urine/stool routine, blood biochemistry, cardiac enzymes, blood gas analysis, etc.

Imaging tests: head, chest and abdomen CT, ultrasound

Medication List

Medications used in the last 3 months, if there is a box or package, you can bring it with you to the doctor.

Glucocorticoid drugs: methylprednisolone, dexamethasone, etc.

Immunosuppressive drugs: cyclosporine, cyclophosphamide, tacrolimus, etc.

Anti-tumor drugs: Capecitabine, Crizotinib, etc.

Antibiotics: penicillin, cefixime, etc.

Diagnosis

Diagnosis is based on

Medical history

Presence of cirrhosis, diabetes mellitus, malignancy, leukemia, burns, organ transplantation.

Prolonged use of antibiotics, glucocorticoids, or artificial respiratory devices.

History of urinary tract infection, biliary or gastrointestinal infection.

Presence of invasive built-ins, including catheters, drains and other foreign bodies.

Clinical manifestations

Fever or hypothermia; shortness of breath, dyspnea, or hyperventilation; decreased blood pressure; pale, cyanotic, or florid skin; impaired consciousness, coma.

Auxiliary examination

Blood routine

Find out the elevation of white blood cells and neutrophils, as well as platelets and hemoglobin.

Pathogenetic examination

Blood, sputum, alveolar lavage fluid, bone marrow, cerebrospinal fluid, urine, stool and exudate from purulent lesions should be collected for bacterial and fungal culture (including anaerobic culture) and drug sensitivity test, so as to clarify the cause of the disease and guide the treatment.

Urine routine examination

Small amounts of protein, red blood cells and tubular pattern may be seen in the presence of renal failure.

Blood biochemistry test

Helps to understand tissue and organ damage, including kidney damage, liver damage, etc. Helps to understand the degree of hypoxia and assess the prognosis.

Blood gas analysis

Helps to understand the respiratory and metabolic conditions, determine acid-base imbalance, electrolyte disorders and hypoxia.

Procalcitonin

Calcitonin is used to determine the presence and severity of bacterial infection.

C-Reactive Protein

Helps to understand the presence of inflammation, trauma and assists in identifying bacterial, viral and other infections.

Blood rheology and DIC related tests

Infectious shock may present with abnormal coagulation function, to understand the presence of intravascular hemolysis, etc., to guide the treatment.

Diagnostic criteria

The diagnosis of infectious shock must have two necessary conditions: sepsis due to infection and shock.

Bacteriologic evidence of infection: fever/hypothermia, elevated white blood cells. Positive bacterial culture or clinical evidence of infection such as elevated procalcitoninogen, C-reactive protein.

Sepsis: a systemic inflammatory response based on infection, such as changes in temperature, respiration, and circulation [6].

Infectious shock (septic shock) is on the basis of sepsis and the presence of persistent sepsis is defined as a systemic inflammatory response caused on the basis of infection. hypotension, the need for vasoactive drugs to maintain a mean arterial pressure (MAP) ≥ 65 mm Hg despite adequate volume resuscitation, and a blood lactate level > 2 mmol/L [6].

Differential diagnosis

Differentiation from other types of shock

Including hemorrhagic shock, cardiogenic shock, anaphylactic shock, and neurogenic shock.

Similarities: all may present with clinical manifestations of shock such as intractable hypotension and elevated lactate.

Differences: according to the cause of shock, in addition to the shock manifestations, the cause of different accompanying symptoms are different, and the basis of different auxiliary examination is different.

Treatment

Aim of treatment: replenish blood volume, correct acidosis, adjust vasoconstriction function, maintain important organ function and other measures.

Treatment principle: comprehensive assessment, early intervention, multiple rescue and overall management, including anti-infection and anti-shock treatment.

General treatment

Oxygenation: Patients with infectious shock need to maintain an adequate supply of oxygen, and often need to be given high concentrations of oxygen therapy.

Monitoring: closely monitor vital signs, urine output and consciousness.

Open venous access: Establish two or more peripheral venous accesses or central venous cannulation, to ensure large amounts of fluid resuscitation and at the same time can meet the conditions of vasoactive drugs, and can be carried out to monitor the CVP.

Fluid resuscitation

Once the clinical diagnosis of infectious shock is made, active fluid resuscitation should be performed as soon as possible [6-7,11].

Crystalline fluids: Early fluid resuscitation was based on crystalloid fluids, and now it is advocated to use balanced salt solution as the main resuscitation fluid, avoiding hyperchloremic acidosis as much as possible.

Colloid fluids: colloid fluids are not firstly chosen as volume expanding drugs; if colloid fluids are needed, albumin and plasma are preferred, and artificial colloids such as hydroxyethyl starch are not recommended.

Fluid resuscitation should make timely adjustments according to individual differences and changes in condition.

Anti-infection treatment

After clear infectious shock, early application of antibiotics before identifying the pathogen, the earlier the better, the sooner the better, administered within 1 hour after diagnosis, delayed no more than 3 hours.

Broad-spectrum antibiotics are preferred; common antibiotics include imipenem, vancomycin, linezolid, and levofloxacin, and generally need to cover all likely pathogens.

Combinations of antibiotics may be used empirically in the early stages. The antibiotic dosing regimen is adjusted according to the pathogenetic findings after a pathogenetic basis is available [6-11].

Vasoactive drugs

When using vasoactive drugs, it is necessary to closely observe the changes in blood pressure, as well as the patient’s skin color, temperature and other related conditions. If possible, an arterial catheter can be placed for invasive blood pressure monitoring.

Vasoconstrictor drugs

After adequate fluid resuscitation, if the blood pressure is still suboptimal, consideration may be given to initiating vasoconstrictor drugs to elevate the blood pressure in order to achieve a mean arterial pressure greater than 65 mmHg.

Norepinephrine is preferred, and in cases where it is still difficult to maintain mean arterial pressure with larger doses of norepinephrine, a combination of epinephrine and vasopressin can be slowly pumped to maintain circulation and organ perfusion. Dopamine may be used as an alternative drug in patients at low risk for tachyarrhythmia or in bradycardia.

Drugs to enhance myocardial contraction

In the presence of cardiac insufficiency and decreased cardiac output, dopamine or levosimendan may be used to increase cardiac output.

Drugs to improve microcirculation

For patients with adequate fluid resuscitation or myocardial contraction-enhancing drugs, but with continued decrease in cardiac output, increase in systemic peripheral vascular resistance and normal blood pressure, the addition of microcirculation-improving drugs can be expected to reverse shock.

Commonly used drugs are scopolamine, scopolamine and other anticholinergic drugs. Adverse reactions include dry mouth, skin flushing, dilated pupils, excitement, rapid heartbeat, etc. Glaucoma is contraindicated.

Maintenance of vital organ function

Respiratory function support: maintain airway patency, give nasal cannula/mask oxygen, take ventilator-assisted ventilation if necessary. Cevirolastat sodium inhibits the damage of inflammatory mediators to the lungs and improves oxygenation [12].

Renal function support/maintaining the stability of the internal environment: bedside continuous blood purification, generally choose CVVHDF mode of treatment can then maintain the water electrolyte acid-base balance at the same time can help to remove the inflammatory mediators in the blood, reduce the inflammatory response.

Maintaining brain function: cerebral edema, increased intracranial pressure and even cerebral herniation are easy to occur in shock, head cooling should be given, and mannitol, tachycardia, adrenocorticotropic hormone should be used as appropriate; scopolamine can be given to relieve cerebral vasospasm if necessary.

Prevention and treatment of stress ulcers can be given H2 receptor blockers or acid suppressants such as omeprazole and gastric mucosal protectants such as aluminum thioglycollate.

Nutritional support: enteral nutrition should be started as early as possible after the circulation is stabilized, and parenteral nutrition should be given to those who are intolerant of gastrointestinal function, and it is recommended to do it in moderation and step by step.

Others

Immunomodulatory therapy: Hormones and immunosuppressants should not be applied first, and continuous drip of hydrocortisone can be used after the immunosuppressive state is discharged only if the resuscitation goal is still not achieved after adequate fluid resuscitation and use of vasoactive drugs.

Caution is required in patients with an immunosuppressed state and cefoperazones are avoided when hydrocortisone is applied to avoid disulfiram reactions.

Ustatin is a natural anti-inflammatory substance in the body, can inhibit the production and release of inflammatory mediators, effectively blocking the process of inflammatory storm, can effectively improve the tissue hypoperfusion and microcirculation condition, improve the prognosis.

Reasonable supplementation of energy, vitamins and trace elements to improve cellular metabolism.

Prognosis

Cure

Despite aggressive anti-infection and anti-shock treatment, the morbidity and mortality rate is still as high as 40% or more.

Even in patients discharged from the hospital after active treatment, the morbidity and mortality rate one year after discharge is significantly higher than that of patients with other diseases, and there is still a decline in the quality of life, cognitive dysfunction and physical fitness in the long term.

Prognostic factors

Prognosis is related to the response to treatment, whether the infection is controlled in time, whether it is accompanied by organ failure, whether there is a serious primary disease (leukemia, malignancy, etc.), and whether there is a combination of other diseases (diabetes mellitus, cirrhosis, heart disease).

Harmfulness

Patients with infectious shock have a high rate of near- and long-term mortality and may have a poorer quality of life than patients with other diseases, often accompanied by cognitive dysfunction and physical decline.

Daily

Daily management

Pay attention to keep warm, avoid catching cold, strengthen nutrition, monitor and control blood pressure, blood sugar and blood lipid.

Physical cooling is preferred for patients with high fever: e.g., ice packs, ice blankets, wet towels to wipe the skin.

When using ice packs, you should avoid placing them on the soles of the feet, chest and abdomen to avoid discomfort.

When using ice blankets, the circulating water temperature should be adjusted to be greater than 16 ℃ to avoid frostbite caused by too low a temperature.

Proper attention to warmth is needed when using wet towels to wipe the skin to avoid chills and other discomforts.

Disease monitoring

Regularly monitor blood pressure, heart rate, state of consciousness, and urine output.

If there are skin wounds or catheters, they should be cleaned and disinfected and changed/replaced regularly. Pay attention to the condition of the skin at the catheter puncture point, as well as the color, nature and amount of drainage fluid, and seek medical attention promptly for signs of infection.

Follow-up

Follow up as prescribed by the doctor.

The items to be reviewed include routine blood tests, routine urine tests, and monitoring of liver and kidney function and electrolytes for patients with liver and kidney function impairment.

Regular review of imaging studies, including examination of the site of primary infection and lung CT for patients with lung injury, is needed to avoid interstitial fibrosis or further progression of interstitial fibrosis.

Prevention

If there are symptoms of infection including fever, cough and sputum, urinary frequency and urgency, vomiting and diarrhea, etc. should actively seek medical attention to avoid progression to infectious shock.

Patients with cirrhosis, diabetes mellitus, malignant tumors, leukemia, burns, organ transplants, etc., should actively treat the primary disease, pay attention to avoiding infections, and seek timely medical treatment for symptoms of infection.

Reasonable use of antibiotics, glucocorticoids, avoid long-term application.

Invasive built-in objects, including catheters, drainage tubes and other foreign bodies, should follow the doctor’s instructions to take good care of them to avoid infection.