Surgical Critical Care

The Sepsis Six Samurai – Part 2

Nature makes penicillin; I just found it.

Alexander Fleming

Ehi guys… Happy to have you here again…

Last time we saw how to raise clinical suspicion of sepsis and how to make a diagnosis out of it. This time we are going to discuss how to treat these patients.

The Diagnostic Flowchart

The Magnificent Sepsis Six

The management of septic patients must start as soon as possible. Any delay in treating sepsis leads to increased mortality.

Sepsis management has three main goals: supporting organ functions, treating the most common pathogens responsible for sepsis, and identifying the specific agent involved. All these can be achieved with 6 easy steps:

  1. Fluid resuscitation;
  2. Blood cultures & source control;
  3. Measure serum lactate level & hemoglobin;
  4. IV empiric broad-spectrum antibiotics;
  5. Oxygen;
  6. Measure hourly urine output (it means inserting a urinary catheter).

Remember that this immediate care bundle must be started within one hour or the risk of death is doubled, and it should be completed within 3 hours. Every hour of delay increases the risk of mortality by an OR of 1.04.

To identify patients at higher risk, needing closer monitoring, it is possible to use the following parameters:

  • Systolic blood pressure <90 mmHg or MAP <65 mmHg;
  • Lactate >2 mmol/L;
  • Heart rate >130 bpm;
  • Respiratory rate >25 bpm;
  • SatO2 <91%;
  • Responds only to voice or pain / unresponsive;
  • Purpuric rash.

If a patient has at least one of them, he/she must be red-flagged and monitored.

Fluid Resuscitation

If a patient is hypotensive or his/her lactate levels are ≥4 mmol/L, give Ringer Lactate boluses (30 mL/kg within 3 hours, additional fluids may be given according to the patient’s hemodynamic status).

Do not use colloids (the reason has been explained in the post The Art of Alchemy – Part 2 under the Fluids & Permissive Hypotension section). However, if a high volume of crystalloids is required, the use of albumin is acceptable.


To overcome refractory hypotension, vasopressors must be added to the normal therapy. The decision whether to start vasopressors or not must be taken within the first 6 hours. The first-choice vasopressor to be used is norepinephrine (at a starting dose of ≈0.05 μg/kg/min). A second-line vasopressor may be required in addition to norepinephrine, and the choice is between vasopressin (at a dose 0.03 units/min, to decrease the dose of norepinephrine), epinephrine, and dopamine (in patients with bradycardia and low risk of arrhythmias).

Dobutamine may be used in hypotensive patients not responding to fluids and vasopressors.


Matter of discussion is the use in shocked patients of the “cocktail” vitamin C (1.5 g IV 4 times/day), thiamine (200 mg IV 2 times/day), and hydrocortisone (50 mg IV 4 times/day) until shock resolution or up to 10 days. However, it seems this combination does not perform better than IV hydrocortisone alone. Hydrocortisone should be used only if extensive fluid therapy and vasopressors fail to obtain acceptable hemodynamic parameters.

Source Control

Specific anatomic diagnosis of infection should be made or excluded as soon as possible, and, if confirmed, source control must be performed right after the definitive diagnosis is made.

Source control can be obtained through interventional radiology or surgery.

Blood Tests

Take at least two sets of blood cultures (aerobic & anaerobic) plus all relevant blood tests (full blood count, creatinine, urea, electrolytes, liver function tests, CRP, procalcitonin, arterial blood gas, etc…). Consider urine, sputum, and swab samples.

Serum lactate level helps in assessing the metabolic response to the therapy provided. Normalization of lactates is one of the main goals of sepsis management.

Antimicrobial Therapy

Broad-spectrum antibiotics must be started within the first hour. Do not wait for the blood culture results before starting their administration.

Once the infecting pathogen has been identified, the antibiotic regimen must be reassessed to determine if the one administered is appropriate; otherwise, it must be changed according to the culture’s results and antibiogram. Remember that up to 30% of septic patients may have negative blood cultures.

Antibiotics de-escalation should be done as soon as the clinical conditions allow it to reduce the risk of developing antimicrobial resistance. Therefore, daily assessment of the clinical conditions is mandatory to titrate the therapy. The duration of the treatment should not exceed 7-10 days for infections with sepsis or septic shock; however, the decision should be made on a case by case basis.

In patients with septic shock, the management must be more aggressive. In fact, at least two antibiotics of different antimicrobial classes should be used.

Blood Products

Hemoglobin values should be maintained above 7 g/dL. A higher cutoff (usually around 10 g/dL) should be used in patients with severe hypoxemia, myocardial ischemia, acute hemorrhage, or active ischemic heart disease.

Fresh-frozen plasma should be reserved for patients with coagulation abnormalities and active bleeding or planned invasive procedures.

Platelets should be given when levels are ≤10’000/mm3, ≤20’000/mm3 in patients with a high risk of bleeding, or ≤50’000/mm3 in patients actively bleeding or waiting for planned invasive procedures.

Ventilatory Support

Some authors support the concept of giving high-flow oxygen support (e.g. 15 L/min) via a non-rebreathable mask (target SatO2 >94%). However, we recommend not to abuse oxygen. Titrate the flow according to the patient’s saturation and blood gas.

If mechanical ventilation is required, the ventilation settings should follow the protective ventilation strategies (tidal volume 6 mL/predicted body weight, plateau pressure ≤30 cmH2O, positive end-expiratory pressure should be used).

In patients with sepsis-induced acute respiratory distress syndrome, a prone position should be used in patients with PaO2/FiO2 ≤150 mmHg. Moreover, neuromuscular blockade agents are recommended for ≤48 h in these patients.

In mechanically ventilated patients, sedation should be reduced at a minimum (when possible).

Nutrition & Glucose Levels

Remember that septic patients are in a high catabolic state; so, nutritional support must be started as soon as possible, preferably via enteral feeding.

The blood glucose level should be maintained <180 mg/dL. Therefore, patients with higher levels should be treated accordingly. In these patients, glucose levels should be measured every 2 h until a stable insulin regimen has been reached, and every 4 h thereafter.

Other Treatments

Proton pump inhibitors for stress ulcer prophylaxis should be administered only in patients with risk factors for upper gastrointestinal bleeding.

Deep venous thrombosis prophylaxis should be given to all patients, and low molecular weight heparin is the preferred method. In case of contraindications to heparin, mechanical prophylaxis should be used.

Bicarbonate therapy follows the same rules as in trauma (read The Art of Alchemy – Part 3): it should not be used if pH is higher than 7.15.

Renal replacement therapy (preferably in a continuous fashion) should be used in septic patients who develop acute kidney injury.

With this, we have finished our brief overview of sepsis. We know in this specific post we have been quite straight-to-the-point, and we apologize for that. This topic is huge, and we had to cut off some parts to lighten the speech. However, our goal is to discuss in detail some of the sections overlooked in future posts.

Remember that not all infections lead to sepsis, but you must not underestimate them.

See you next time…

  1. Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:801-10.
  2. Seymour CW, et al. Assessment of clinical criteria for sepsis for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;762-74.
  3. Howell MD, et al. Management of sepsis and septic shock. JAMA 2017;317:847-8.
  4. Rhodes A, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017;43:304-77.
  5. Plevin R, et al. Update in sepsis guidelines: what is really new? TSACO 2017;0:1-6.
  6. Fujii T, et al. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock – The VITAMINS randomized clinical trial. JAMA 2020:323:423-31.
How to Cite This Post

Bellio G, Marrano E. The Sepsis Six Samurai – Part 2. Surgical Pizza. Published on February 20, 2021. Accessed on June 24, 2022. Available at [].


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