Sepsis
Recognise it early, give the Sepsis Six within one hour, then find and control the source. A normal temperature does not rule sepsis out.
A 58-year-old man with diabetes has had burning urine and fever for three days. Now he is confused. Pulse 124, BP 84/50, RR 28, SpO₂ 93%, temperature 38.9 °C.
What do you do in the first hour?
- Oxygen if SpO₂ is lowTarget 94–98% (88–92% if known CO₂ retainer such as severe COPD).
- Two cannulas, bloods and blood culturesTwo sets of blood cultures before antibiotics, plus lactate on a venous gas. Do not let cultures delay antibiotics by more than a few minutes.
- IV antibiotics within 1 hourChoose by the likely source and your hospital policy. Write the time given.
- Fluid bolus if BP is low or lactate is high500 mL crystalloid over 15 minutes, then reassess before the next.
- Measure lactateRepeat within 2 hours. A falling lactate means you are winning.
- Measure urine outputCatheter and hourly urine in shock. Aim for at least 0.5 mL/kg/hour.
- Find the sourceChest, urine, abdomen, skin, joints, lines, wounds, meninges.
- Call your seniorEarly, especially if BP stays low after fluids.
- NEWS2 of 5 or more with suspected infection
- Systolic BP below 90 or MAP below 65 after fluids
- Lactate 4 mmol/L or more
- New confusion or drowsiness
- Non-blanching rash
- Fever within 6 weeks of chemotherapy
- Pain out of proportion with spreading redness
| Antibiotics | Within 1 hour of recognising sepsis. Doses are in the antibiotics section below |
| Fluid bolus | 500 mL crystalloid over 15 minutes, reassess, up to about 30 mL/kg in the first 3 hours |
| Lactate | Above 2 mmol/L means poor perfusion. 4 or above means very high risk |
| Target MAP | 65 mmHg or more. Still below 65 after fluids: noradrenaline and ICU |
| Urine | At least 0.5 mL/kg/hour |
Check every dose against a current drug reference and your hospital protocol.
On this page
Why speed matters
Sepsis is a life-threatening failure of organs caused by the body's response to an infection. The infection itself may be ordinary (a urine infection, a chest infection), but the body's reaction drops the blood pressure, starves organs of oxygen and makes the blood clot abnormally. In septic shock, every hour of delay before the first antibiotic dose increases the risk of death. The first hour is yours.
A normal temperature does not rule out sepsis. Older people, diabetics, patients on steroids and anyone who has taken paracetamol may have a normal or low temperature.
Recognising sepsis
- Sepsis: infection plus organ dysfunction (confusion, low BP, low oxygen, low urine, high lactate, low platelets, jaundice).
- Septic shock: sepsis where, despite adequate fluids, the patient needs a vasopressor to keep the MAP at 65 or more, and the lactate is above 2 mmol/L.
- NEWS2: the observation score used on wards. A score of 5 or more with possible infection means think sepsis and call for review.
- qSOFA: a quick bedside check. One point each for RR 22 or more, new confusion, and systolic BP 100 or less. A score of 2 or more means high risk. It is a warning sign, not a test to rule sepsis out.
Signs to look for
- Fast breathing (often the first sign), fast pulse, low BP.
- Cold, mottled skin, slow capillary refill (more than 3 seconds), or warm flushed skin early on.
- New confusion, drowsiness or agitation.
- Passing little urine.
- Features of the source: cough, burning urine, belly pain, red swollen skin, headache with neck stiffness, a red and painful cannula site.
History
- Symptoms pointing to a source, and how long they have been going on.
- Diabetes, kidney or liver disease, cancer, chemotherapy, steroids, HIV, splenectomy.
- Recent surgery, hospital stay, urinary catheter, cannula, central line or dialysis line.
- Recent antibiotics. Self-medication and antibiotics from a local pharmacy are common in Pakistan. Ask which tablets and for how long, because this predicts resistance.
- Travel and season: dengue, malaria and typhoid can all look like bacterial sepsis.
- Allergies (true penicillin allergy with rash or anaphylaxis, or just stomach upset).
Examination
- Observations and NEWS2RR, SpO₂, BP, pulse, temperature, GCS or new confusion. Calculate the score.
- Head and neckNeck stiffness, photophobia, ears, throat, teeth and gums.
- ChestCrackles, bronchial breathing, reduced air entry at a base (pneumonia, empyema).
- AbdomenTenderness, guarding, a tender liver or gallbladder (cholangitis), a tender loin (pyelonephritis).
- SkinLook everywhere: back, buttocks, perineum, feet (diabetic foot), cannula sites, wounds and pressure sores.
- JointsA hot, swollen joint is septic arthritis until proven otherwise.
- RashA non-blanching rash (press a glass against it) means meningococcal sepsis until proven otherwise.
Mimics and look-alikes
| Condition | Points towards it | Test that helps |
|---|---|---|
| Dengue shock | Day 3–7 of fever, falling platelets, rising haematocrit, leaking capillaries | CBC with haematocrit, NS1 or IgM |
| Severe malaria | Endemic area, jaundice, anaemia, low sugar, confusion | Malaria film or rapid test |
| Typhoid (enteric fever) | Fever over a week, belly pain, relative slow pulse | Blood culture |
| Pulmonary embolism | Low oxygen, clear chest, fast pulse | CT pulmonary angiogram |
| Acute pancreatitis | Epigastric pain going through to the back | Lipase |
| Adrenal crisis | Steroids stopped suddenly, low sodium, high potassium, low sugar | Cortisol |
| Heat stroke | Heat exposure, temperature above 40 °C, dry skin | Clinical |
| Drug or transfusion reaction | Started with a new drug or blood product | Clinical |
Investigations
| Test | Why | What to look for |
|---|---|---|
| Blood cultures (2 sets) | Find the organism | Take before antibiotics if it causes no delay |
| Venous gas with lactate | Perfusion | Lactate above 2 is abnormal, 4 or above is high risk |
| CBC, CRP | Infection and severity | Low platelets suggest severe sepsis, dengue or malaria |
| Urea, creatinine, electrolytes | Kidney injury | Creatinine above baseline, potassium |
| LFTs, sugar | Liver involvement, cholangitis | Raised bilirubin; sugar can be high or low |
| Clotting | DIC | Raised INR, low fibrinogen |
| Urine dipstick and culture | Urine source | Leucocytes and nitrites (less reliable in the elderly) |
| Chest X-ray | Chest source | Consolidation, effusion |
| Malaria test, dengue NS1 | Mimics | In season or endemic areas |
| Ultrasound or CT | Hidden source | Collection, blocked kidney, dilated bile duct |
The Sepsis Six
- Give oxygenTo keep SpO₂ 94–98%.
- Take blood culturesTwo sets. Plus other cultures as relevant (urine, sputum, pus, CSF if safe).
- Give IV antibioticsWithin 1 hour. Chosen by source and local policy.
- Give IV fluids500 mL bolus if BP is low or lactate is raised. Reassess after each.
- Measure lactateRepeat within 2 hours.
- Measure urine outputCatheter in shock. Hourly chart.
Antibiotics: which one?
Your hospital antibiotic policy comes first, because resistance patterns differ between hospitals. Resistance (ESBL organisms, and XDR typhoid particularly in Sindh) is common in Pakistan, so cultures before the first dose matter.
| Likely source | Common first choice (adult) |
|---|---|
| Unknown source, community | Ceftriaxone plus metronidazole, or piperacillin-tazobactam, per policy |
| Unknown source, hospital-acquired or recent antibiotics | Piperacillin-tazobactam, or meropenem if resistant organisms are likely |
| Chest (community) | Ceftriaxone plus clarithromycin or azithromycin |
| Urine | Ceftriaxone (meropenem if known ESBL) |
| Abdomen or biliary | Ceftriaxone plus metronidazole, or piperacillin-tazobactam |
| Skin and soft tissue | Flucloxacillin (cefazolin or ceftriaxone if unavailable), plus clindamycin if necrotising |
| Meningitis or non-blanching rash | Ceftriaxone 2 g IV every 12 hours immediately |
| Neutropenic sepsis | Piperacillin-tazobactam within 1 hour |
| Suspected XDR typhoid | Meropenem (with azithromycin), senior advice |
Check the allergy history properly. A "penicillin allergy" that was only diarrhoea is not an allergy. A true rash or anaphylaxis is. Write which it was.
Fluids and blood pressure
- Give another 500 mL
- Reassess again
- Stop fluids
- Senior review
- Consider noradrenaline
- Septic shock
- Noradrenaline
- ICU or HDU referral now
- Which fluid: a balanced crystalloid (Ringer's lactate) or 0.9% sodium chloride. Do not use colloids or 5% dextrose for resuscitation.
- Who needs smaller boluses: elderly patients, heart failure, kidney failure on dialysis: give 250 mL and reassess.
- Noradrenaline can be started through a good peripheral cannula in a large vein while central access is arranged, if your hospital allows. Watch the site closely for leakage.
- Hydrocortisone (50 mg IV every 6 hours) is a senior decision for shock that needs ongoing noradrenaline.
Source control
Source control is half the treatment. Antibiotics will not cure pus, a blocked infected kidney, an infected line or dead tissue. Drain it, remove it or operate, ideally within 6–12 hours.
- Blocked infected kidney (stone with pyelonephritis): urgent urology for a stent or nephrostomy.
- Cholangitis: fever, jaundice, right upper quadrant pain. Needs drainage (ERCP).
- Abscess or empyema: drainage.
- Infected cannula or line: remove it and culture the tip.
- Necrotising fasciitis: theatre now. A scan must not delay surgery.
Special situations
Fever above 38 °C, or signs of sepsis, in anyone who had chemotherapy in the last 6 weeks. Treat before the blood count comes back. Piperacillin-tazobactam within 1 hour. Do not wait for the neutrophil count.
Fever with a non-blanching rash, often in a young person who becomes unwell within hours. Ceftriaxone 2 g IV immediately, before any tests. Close contacts need prophylaxis: inform public health.
Pain much worse than the skin looks, spreading quickly, dusky or blistered skin, crepitus, high fever. Often in diabetics or after injections. Call the surgeons immediately. Antibiotics alone will not save the patient.
Monitoring and handover
- Reassess at 1 hour: pulse, BP, RR, mental state, urine output, lactate.
- Write the timings: time sepsis recognised, cultures, antibiotics, each fluid bolus, lactate results.
- Review antibiotics at 48–72 hours with culture results: narrow the spectrum, switch to oral, or stop if not infection.
- Hand over: likely source, Sepsis Six timings, lactate trend, total fluid given, response, plan if worse.
Common mistakes
- Waiting for the fever, the CBC or the culture result before giving antibiotics.
- Giving 2 litres of fluid without checking the chest in between.
- Forgetting the source: antibiotics without draining the pus.
- Treating dengue shock as bacterial sepsis with large repeated boluses.
- Writing "antibiotics given" without the time.
- Labelling a stomach upset as "penicillin allergy" and then using a weaker drug.
Frequently asked questions
What is the Sepsis Six?
Give oxygen, take blood cultures, give IV antibiotics, give IV fluids, measure lactate and measure urine output, all within the first hour.
Which antibiotic should be given for sepsis of unknown source?
Follow your hospital policy. Ceftriaxone with metronidazole, or piperacillin-tazobactam 4.5 g IV every 8 hours, are common choices. Use meropenem when resistant organisms are likely.
How much fluid should be given in sepsis?
500 mL of crystalloid over 15 minutes, then reassess. Repeat while the patient responds, up to about 30 mL/kg in the first 3 hours. Use smaller boluses in heart or kidney failure.
Can a patient be septic without a fever?
Yes. Elderly, diabetic and immunosuppressed patients, and those who have taken paracetamol, may have a normal or low temperature.
What lactate level is dangerous in sepsis?
Above 2 mmol/L shows poor perfusion. 4 mmol/L or more is high risk and needs senior review and close monitoring.
Test yourself
Exam-style questions on this guide, from our two question banks. Choose an answer to see why each option is right or wrong.
1. A 54-year-old woman with pneumonia has received 2 litres of crystalloid. BP is 82/48 (MAP 59) and lactate is 5 mmol/L. What is the most appropriate next step?
Answer: Start noradrenaline and involve ICU. This is septic shock: hypotension needing vasopressors to keep MAP 65 mmHg or more, with lactate above 2 mmol/L despite fluids. Noradrenaline is the first-line vasopressor; it can be started peripherally through a good cannula while central access is arranged.
- Wait for the repeat lactate in 2 hours: Septic shock needs action now.
- Add a second antibiotic and observe: Antibiotics are needed, but the BP still needs support.
- IV hydrocortisone alone: Steroids are considered for refractory shock, not instead of a vasopressor.
- A further 2 litres of fluid as fast as possible: After adequate fluid, persistent hypotension needs a vasopressor; more fluid risks overload.
2. A 47-year-old man had chemotherapy 10 days ago. He now has a temperature of 38.4 °C. BP and pulse are normal. The blood count has not been reported yet. What is the best next step?
Answer: Cultures, then IV piperacillin-tazobactam within 1 hour. Fever after recent chemotherapy is treated as neutropenic sepsis until proven otherwise. Antibiotics (piperacillin-tazobactam, or per local policy) within 1 hour of arrival, without waiting for the count.
- Chest X-ray first, then decide: Investigations follow the first antibiotic dose.
- Wait for the neutrophil count before antibiotics: Neutropenic sepsis can kill within hours; treatment is not delayed for the count.
- Paracetamol and repeat temperature in 4 hours: This delays treatment of possible neutropenic sepsis.
- Oral co-amoxiclav and review tomorrow: Oral treatment at home is only for selected low-risk patients after assessment.
3. A 38-year-old woman has fever, rigors and right loin pain. She has had IV antibiotics. Ultrasound shows a dilated right kidney with a stone in the ureter. What else is needed urgently?
Answer: Urological drainage of the kidney. An infected, obstructed kidney is a urological emergency. Source control (ureteric stent or percutaneous nephrostomy) is needed within hours, alongside antibiotics.
- Repeat ultrasound in 48 hours: An infected obstructed kidney is an emergency.
- Double the antibiotic dose: Antibiotics alone fail when infected urine cannot drain.
- Tamsulosin and observation: Medical expulsive therapy is not for an infected, obstructed kidney.
- Lithotripsy today: Stone treatment waits until the infection is controlled.
4. According to Sepsis-3, sepsis is defined as:
Answer: Infection + organ dysfunction. Sepsis-3: life-threatening organ dysfunction caused by a dysregulated host response to infection — acute increase in SOFA score ≥ 2. qSOFA (RR ≥ 22, altered mentation, SBP ≤ 100) is a bedside prompt (not diagnostic). Septic shock: vasopressor requirement to maintain MAP ≥ 65 and lactate > 2 mmol/L despite adequate fluids. Bacteraemia is not required.
- Infection with SIRS ≥ 2: SIRS criteria are the older definition.
- Positive blood culture: A positive culture is not required, nor is it sufficient.
- Fever with tachycardia alone: Fever with tachycardia is non-specific.
5. A 60-year-old woman with pyelonephritis has BP 82/50 mmHg after 30 mL/kg of crystalloid, lactate 4.6 mmol/L and confusion. What should be started next to reach a MAP of 65 mmHg?
Answer: Noradrenaline infusion. Septic shock is sepsis with vasopressor need to keep MAP ≥ 65 mmHg and lactate > 2 mmol/L despite adequate fluid. Surviving Sepsis Campaign: 30 mL/kg crystalloid in the first 3 hours, cultures before antibiotics (without delaying them), broad-spectrum antibiotics within 1 hour, and noradrenaline as the first-line vasopressor (can start peripherally while central access is arranged). Vasopressin is added if MAP stays low; hydrocortisone 200 mg/day if vasopressor needs keep rising. Source control (e.g. relieving an obstructed kidney) is part of resuscitation.
- Dopamine infusion: Dopamine causes more arrhythmias and is second-line.
- IV hydrocortisone alone: Hydrocortisone is added for refractory shock, not given alone.
- Further 3 L fluid bolus: More fluid causes overload once the patient is unresponsive to fluid.
6. A girl with meningococcal septicaemia has fever, a spreading purpuric rash and becomes profoundly hypotensive. Autopsy shows bilateral adrenal haemorrhage. What is this?
Answer: Waterhouse–Friderichsen syndrome. Meningococcal endotoxin (lipo-oligosaccharide) causes septic shock and DIC with bilateral adrenal haemorrhage and acute adrenal failure. Treat urgently with IV antibiotics (benzylpenicillin or ceftriaxone), fluids and steroids if needed. Contacts receive prophylaxis (rifampicin or ciprofloxacin).
- Sheehan's syndrome: Pituitary necrosis after postpartum haemorrhage.
- Addison's disease from tuberculosis: Chronic, not acute septic.
- Conn's syndrome: Aldosterone excess.
- Cushing's syndrome: Cortisol excess.
7. A neutropenic patient on chemotherapy develops fever and hypotension. Blood cultures grow Pseudomonas aeruginosa. Which bacterial component is chiefly responsible for his septic shock?
Answer: Lipopolysaccharide. Gram-negative bacteria have lipopolysaccharide in the outer membrane. Its lipid A component is endotoxin, which activates macrophages through TLR4 and triggers a cytokine storm (TNF, IL-1), causing fever, vasodilatation and shock.
- Exotoxin A: Pseudomonas exotoxin A inhibits protein synthesis (EF-2), causing tissue damage, but endotoxin drives septic shock.
- Peptidoglycan: Present in both Gram-positive and Gram-negative bacteria; thick in Gram-positives.
- Alginate capsule: Helps biofilms in cystic fibrosis; not the cause of shock.
- Pili: Help attachment.
References and dose sources
- NICE NG51: Sepsis, recognition, diagnosis and early management
- Surviving Sepsis Campaign adult guidelines 2021
- NICE NG253 — suspected sepsis in over 16s
- NICE CG151 — neutropenic sepsis
- NICE NG240 — meningococcal disease
- Ceftriaxone dosing: Drugs.com: Ceftriaxone dosage (see also our ceftriaxone dose page)
- Piperacillin-tazobactam dosing: Drugs.com: Piperacillin/tazobactam dosage (see also our piperacillin-tazobactam dose page)
- Metronidazole dosing: Drugs.com: Metronidazole dosage (see also our metronidazole dose page)
- Meropenem dosing: Drugs.com: Meropenem dosage (see also our meropenem dose page)
- Vancomycin dosing: Drugs.com: Vancomycin dosage (see also our vancomycin dose page)
- Clindamycin dosing: Drugs.com: Clindamycin dosage (see also our clindamycin dose page)
- Noradrenaline (norepinephrine) dosing: Drugs.com: Norepinephrine dosage (see also our noradrenaline (norepinephrine) dose page)
- Hydrocortisone dosing: Drugs.com: Hydrocortisone dosage (see also our hydrocortisone dose page)
International guidance is linked where it reflects good practice. Where your hospital’s protocol differs, follow your hospital.