Introduction
Methods
Recognizing the septic patient
Suggested sepsis diagnosis with limited resources | Sepsis diagnosis according to international consensus (22, 23) | |
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Sepsis | Proven or highly suspected infection plus presence of ≥2 of the following conditions: | Proven or highly suspected infection plus presence of ≥2 of the following conditions: |
Heart rate >90 bpm | Heart rate >90 bpm | |
Respiratory rate >20 bpm | Respiratory rate >20 bpm or PaCO2 <32 mmHg | |
Temperature <36 or >38°C | Temperature <36 or >38°C | |
Malaise and/or apathy | WBC <4 or 12 g/L or >10% immature forms | |
Severe sepsis | Sepsis-induced tissue hypoperfusion or organ dysfunction | Sepsis-induced tissue hypoperfusion or organ dysfunction |
Tissue hypoperfusion | Tissue hypoperfusion | |
Decreased capillary refill or skin mottling | Decreased capillary refill or skin mottling | |
Peripheral cyanosis | Hyperlactatemia (>1 mmol/L) | |
Arterial hypotension | Arterial hypotension | |
Systolic arterial blood pressure <90 mmHg or a systolic arterial blood pressure decrease >40 mmHg | Systolic arterial blood pressure <90 mmHg; mean arterial blood pressure <70 mmHg; or a systolic arterial blood pressure decrease >40 mmHg | |
Pulmonary dysfunction | Pulmonary dysfunction | |
SpO2 <90% with or without oxygen | PaO2/FiO2 <300 | |
Central cyanosis | ||
Signs of respiratory distress (e.g., dyspnea, wheezing, crepitations, unability to talk sentences) | ||
Renal dysfunction | Renal dysfunction | |
Acute oliguria (urine output <0.5 mL/kg/h or 45 mL/h for at least 2 h despite adequate fluid resuscitation) | Acute oliguria (urine output <0.5 mL/kg/h or 45 mL/h for at least 2 h despite adequate fluid resuscitation) | |
Creati nine increase >0.5 mg/dL or 44.2 μmol/L | ||
Hepatic dysfunction | Hepatic dysfunction | |
Jaundice | Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 μmol/L | |
Coagulation dysfunction | Coagulation dysfunction | |
Petechiae or ecchymoses | Thrombocytopenia (platelet count, <100,000/μL) | |
Bleeding/oozing from puncture sites | Coagulation abnormalities (INR >1.5 or a PTT >60 s) | |
Gastrointestinal dysfunction | Gastrointestinal dysfunction | |
Ileus (absent bowel sounds) | Ileus (absent bowel sounds) | |
Septic shock | Sepsis-induced arterial hypotension despite adequate fluid resuscitation (note that patients on inotropics or vasopressors may not be hypotensive despite of presence of shock) and signs of tissue hypoperfusion | Sepsis-induced arterial hypotension despite adequate fluid resuscitation (note that patients on inotropics or vasopressors may not be hypotensive despite of presence of shock) and signs of tissue hypoperfusion |
Treating the septic patient
General considerations
Timing | Diagnose sepsis as early as possible (LoE: D) |
Initiate sepsis treatment as early as possible (LoE: B). Antimicrobials should be given within 1 h of recognizing sepsis (LoE: C). Hemodynamic endpoints should be achieved within 6 h of recognizing sepsis (LoE: C) | |
Hygienic precautions | Wash hands before and after each patient contact and whenever contaminated (LoE: B). Prefer alcohol rubs, otherwise use running water and soap |
Use sterile barrier precautions when performing invasive procedures or surgical interventions (LoE: A) | |
Patient monitoring | Never leave the septic patient alone. Ensure continuous observation (LoE: D) |
Perform clinical examinations several times per day (LoE: D) | |
Whenever available use a continuous patient monitor and set meaningful alarm limits (1D). Alarms for children should be set at age appropriate ranges (LoE: D) | |
Multidisciplinary care | Whenever applicable, seek consultation from experienced health care workers of other medical specialties (LoE: D) |
Data documentation | Keep a patient record and document vital signs at meaningful intervals (LoE: D) |
If the patient deteriorates or fails to improve look for the cause and seek medical review (LoE: D) | |
Convey essential information to all team members involved in the care of the septic patient (LoE: C) | |
Emergency drugs and equipment | Keep an emergency supply of drugs and equipment on the ward that is available 24 h/day and is checked and replenished daily (LoE: D) |
Patient transfer | Transfer of septi c patients to hospitals with more resources and/or medical expertise may save lives. However, the risks must always be critically weighed against benefits (LoE: D) |
Whenever possible transfer should be attended by a physician or other experienced medical personnel (LoE: D) | |
Estimating prognosis and | For each patient, critically assess the prognosis and extent of treatment (LoE: D) |
Treatment limitation | Limit treatment in adult patients with grave prognosis (LoE: D). Whenever possible make decisions together with other colleagues and compassionately communicate it to the patient and family |
Quality control | Whenever possible and compatible with local culture, perform autopsies in patients who died from sepsis. Communicate autopsy results to all team members and critically discuss points that could have been done better (LoE: D) |
Identify local strengths and weaknesses in sepsis management by documenting key aspects of sepsis care and outcome (LoE: D) |
Acute interventions
Circulation | Use adequate tissue perfusion as the principal endpoint of resuscitation (LoE: A). In addition, target a systolic arterial blood pressure >90 mmHg in adults, as well as normal heart rate and arterial blood pressure in children (LoE: 2D) |
In patients with tissue hypoperfusion, infuse fluids aggressively and continue liberal infusions for 24–48 h (LoE: C). More than 4 L during the first 24 h may be required to adequately resuscitate the adult septic patient | |
Use crystalloids and/or colloids for fluid resuscitation (LoE: B). When available, use colloid solutions for fluid resuscitation in children with severe Dengue shock syndrome (LoE: B) | |
Use dopamine or epinephrine (adrenaline) in patients with persistent tissue hypoperfusion despite liberal fluid resuscitation (LoE: C) | |
In patients requiring dopamine or epinephrine (adrenaline) measure arterial blood pressure and heart rate frequently (LoE: D) | |
Administer intravenous hydrocortisone (up to 300 mg/day) or prednisolone (up to 75 mg/day) to adult patients requiring escalating dosages of epinephrine (adrenaline) or dopamine (LoE: B). Consider the use of equivalent hydrocortisone or prednisolone doses in children with severe shock (LoE: C) | |
Ventilation | Apply oxygen to achieve an oxygen saturation >90% (LoE: B). If no pulse oximeter is available administer oxygen empirically in patients with severe sepsis or septic shock (LoE: C) |
Place patients in a semi-recumbent position (head of the bed raised to 30–45°) (LoE: C) | |
Unconscious patients should be placed in the lateral position. The patient’s airway should be kept clear (LoE: D) | |
If available and medical staff is adequately trained, use non-invasive ventilation in patients with dyspnea and/or persistent hypoxemia despite oxygen therapy (LoE: C) | |
Antimicrobial therapy | Initiate sepsis treatment as early as possible (LoE: B). Antimicrobials should be given within 1 h of recognizing sepsis (LoE: C) |
Administer intravenous antimicrobials at adequate dosages and with a high likelihood to be active against the suspected bacterial pathogens (LoE: C) | |
Diagnosis | Perform a detailed patient history and thorough clinical examination to identify the source of infection (LoE: D). Use imaging techniques when available (LoE: D) |
Whenever possible and without harm to the patient, sample fluid or tissue from the site of infection (LoE: C) | |
Examine the sampled fluid or tissue by Gram stain, culture and whenever possible by antibiogram (LoE: C) | |
Source control | Whenever possible drain or debride the source of infection (LoE: C) |
Remove any foreign body or device that may potentially be the source of infection (LoE: C) |
Circulation
Normal capillary refill timea
|
Absence of skin mottling |
Warm and dry extremities |
Well felt peripheral pulses (e.g., radial or dorsalis pedis pulses) |
Return to baseline mental status before sepsis onset |
Urine output >0.5 (adults) or 1 (children) mL/kg/hourb
|
Ventilation
Antimicrobial therapy
Diagnosis
Source control
Post-acute interventions
Antimicrobial therapy | Reassess the effectiveness of the antimicrobial regimen regularly (LoE: C) |
Administer antimicrobials for an adequate but not prolonged time (LoE: D) | |
Glucose control | Whenever possible check blood sugar levels in every septic patient (LoE: D) |
Aim to keep blood glucose >70 mg/dL (>4 mmol/L) by providing a glucose calorie source (LoE: B). Do not target upper blood glucose levels <150 mg/dL (<8.3 mmol/L) (LoE: D) | |
DVT prophylaxis | Use prophylactic heparin and/or apply elastic bandages on both legs in post-pubertal children and adults (LoE: A). No deep vein thrombosis prophylaxis is required in pre-pubertal children |
Enteral nutrition | Allow the patient to eat and drink small amounts once she/he is fully resuscitated and awake (LoE: C) |
Sedation and pain relief | Use opioids to relieve pain. Titrate opioids cautiously in unstable patients (LoE: D) |
Only sedate the agitated and uncooperative patient (LoE: D) | |
As soon as the patient is stable encourage mobilization (LoE: A) | |
Wean invasive support | As soon as the patient is improving, try to actively wean the extent of invasive support (LoE: D) |
Antimicrobial therapy
Inadequate empirical anti-infective therapya
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Missed or insufficient control of the infectious focus |
Insufficient supportive therapy (suboptimal fluid resuscitation) |
Development of new antimicrobial resistance |
Occurence of a new, hospital-acquired infection |
Clinical symptoms are due to other diseases than sepsis |
Glucose control
Deep vein thrombosis prophylaxis
Enteral nutrition
Sedation and pain relief
Wean invasive support
Background | |
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DO NOT use hypotonic fluids (e.g., glucose solutions) for fluid resuscitation | Hypotonic fluids only have a little effect on intravascular volume status but carry a high risk of tissue edema, brain edema and dyselectrolytemia |
DO NOT use fluid balance as a guide to administer or withhold further volume loading | Fluid resuscitation should always be indicated by the patient’s condition and the individual response to fluid loading. Significant under-resuscitation may occur |
DO NOT use high dose steroids (e.g., hydrocortisone >300 mg/day or prednisolone >75 mg/day) | High dose steroids do not change mortality but relevantly increase the risk of hospital-acquired infection, hyperglycemia, gastrointestinal bleeding and/or delirium. Note relevant exceptionsa
|
DO NOT use muscle relaxants except for endotracheal intubation and in mechanically ventilated patients with severe respiratory distress | Muscle relaxants increase the risk of neuromuscular weakness and prolonged paralysis from sepsis |
DO NOT use succinylcholine in patients immbolized >3 days or with neuromuscular diseases | Succinylcholine may cause hyperkalemia resistant to treatment when administered to patients immbolized >3 days or with neuromuscular diseases |
DO NOT use furosemide unless hypervolemia, hyperkalemia and/or renal acidosis are/is present | Furosemide cannot improve kidney function but may even be harmful to the kidney. Treat the patient and not the urine output! |
DO NOT use dopamine in an attempt to improve renal function | Dopamine cannot prevent renal failure in sepsis but may even cause adverse side effects |
DO NOT use sodium bicarbonate to treat metabolic acidosis arising from tissue hypoperfusion | Effectiveness of sodium bicarbonate to correct metabolic acidosis is unsure. Although a marker of disease severity, acidosis may have protective effects |
DO NOT use non-steroidal anti-inflammatory analgesics | Non-steroidal anti-inflammatory analgesics cannot improve sepsis outcome but may impair renal and coagulation function as well as increase the risk of stress ulcer formation |
DO NOT restrict oxygen because of considerations to reduce respiratory drive | Only few patients with chronic obstructive pulmonary disease have their respiratory drive suppressed by oxygen. The risk of accepting hypoxia in the majority of patients is unacceptably higher than the risk of inducing hypoventilation in a few |
DO NOT diagnose “fever of unknown origin” | “Fever of unknown origin” is a diagnosis by exclusion. Resource limitations usually do not allow for full work-up of patients to make this diagnosis. Always assume and treat infection in the patient in whom fever cannot be explained by other pathologies |
DO NOT use insulin if blood sugar cannot be measured regularly | If blood sugar is not measured regularly liberal insulin use may result in hypoglycemia with devastating neurological results. Depending on the availability of blood sugar tests adjust the upper glucose limit. If blood sugar can be measured several times a day the optimum blood sugar range would be 70–180 mg/dL (4–10 mmol/L) |
Specific considerations for sepsis management
Malaria | Prompt start of parenteral artesunate in adults and children (2.4 mg/kg STAT followed by the same dose at 12 h, 24 h, and then daily until oral medication can be taken) (LoE: A) |
If injectable artesunate is unavailable intramuscular artemether (3.2 mg/kg on admission followed by 1.6 mg/kg daily), artesunate by suppositories (8–16 mg/kg at 0 and 12 h and then daily) or intravenous quinine (20 mg/kg loading dose over 4 h followed by 10 mg/kg over 4 h 8 hourly until oral medication is possible) can be used (LoE: A) | |
In children, parenteral antibiotics should be given in addition to antimalarial treatment (LoE: A) | |
Parenteral antibiotics should be given to adults with slide proven malaria and who present with a clinical syndrome requiring parenteral antibiotics (meningitis/encephalopathy, malnutrition, very severe or severe pneumonia) (LoE: A) | |
Seizures should be treated with rectal or intravenous diazepam, intravenous lorazepam, paraldehyde or other standard anticonvulsants (LoE: B) | |
In the absence of shock, fluid management should be performed judiciously and more restrictively than in patients with bacterial sepsis (LoE: B) | |
In case of severe anemia (e.g., hemoglobin level <6 g/dL), blood transfusion should be considered (LoE: A) | |
Empirical antibiotic therapy needs to cover Gram-positive, Gram-negative and anaerobic bacteria (LoE: B) | |
Puerperal sepsis | Treatment of tuberculosis infection in resource-limited settings is best performed by timely initiation of the combination of isoniazid, rifampicin, pyrazinamide and ethambutol for 2 months followed by isoniazid and rifampicin alone for another 4 months (LoE: A) |
Septic patients with HIV/AIDS | Patients with open mycobaterial infections require isolation/cohorting (LoE: A) |
In Pneumocystis jiroveci pneumonia, the therapy of choice is trimethoprim/sulfamethoxazole administered for 3 weeks. In patients with hypoxemia, prednisolone (40 mg bid for 5 days followed by 40 mg/day for 5 days and then 20 mg/day for 11 days) should be added (LoE: B) | |
In malnourished patients, energy supply should be re-started slowly with a stepwise increase of daily caloric intake and avoidance of large amounts of carbohydrates to prevent the re-feeding syndrome (LoE: B) |
Implementing current recommendations into clinical practice
Acute care bundle | Oxygen therapy |
Fluid resuscitation | |
Early and adequate antimicrobial therapy | |
Surgical source control | |
Post-acute care bundle | Re-evaluation of antimicrobial therapy |
Deep venous thrombosis prophylaxis | |
Glucose control | |
Weaning of invasive support |