Sepsis - severe - CUH



Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection 1.

Organ dysfunction

Organ dysfunction is an acute change in total Sequential Organ Failure Assessment (SOFA) score of 2 points or greater secondary to the infection cause. A higher SOFA score is associated with an increased probability of mortality.

  • SOFA score measures organ dysfunction in six systems, namely; Respiration, Coagulation, Hepatic, Cardiovascular, Central nervous system and Renal
  • The baseline SOFA score can be assumed to be zero in patients not known to have pre-existing organ dysfunction
  • A SOFA score >2 reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection 1

Septic shock

Septic shock is clinical sepsis with persisting ⇓BP requiring vasopressors to maintain a MAP ≥ 65 mm Hg and a serum lactate level > 2 mmol/L despite adequate volume resuscitation. With these criteria, hospital mortality is >40% 1.


Surviving sepsis Hour-1 Bundle of Care

  • Measure lactate level*
  • Obtain blood cultures before administering antibiotics
  • Administer broad-spectrum antibiotics
  • Begin rapid administration of 30mL/kg crystalloid for hypotension or lactate level ≥ 4 mmol/L
  • Apply vasopressors if hypotensive during or after fluid resuscitation to maintain MAP ≥ 65 mm Hg

* Remeasure lactate if initial lactate is elevated (> 2 mmol/L).


In patients with septic shock, an essential management step is to increase systemic and microcirculatory flow. The 2018 SSC guidelines recommend that vasopressors should be started immediately if patients remain hypotensive during or after fluid resuscitation.

Studies have reported ↑ mortality risk in patients with septic shock who had a delay in initiation of vasopressor therapy 3,4. In one study the OR of death was 1.2 per hour delay, i.e. every hour delay was associated with a 20% increased probability of death 3.

Peripheral vasopressors

Traditionally, vasopressors have been administered via a central line, due to concerns over potential adverse events associated with peripheral administration, especially extravasation (local tissue necrosis). Recent research suggest that administration of vasopressors in critically ill patients via a well-placed peripheral line is feasible and safe and that extravasation is with tissue necrosis is an uncommon complication 5-10.

Guidelines for using peripheral vasopressors:

  • Vein diameter >4mm on USS
  • Upper limb only
  • Cannula 18 or 20 gauge
  • No hand, wrist or antecubital fossa
  • Able to draw blood from cannula
  • Assess cannula fxn every 2 hours
  • 72 hours maximum use


Metaraminol (preparation guideline) predominantly stimulates α1 receptors to cause peripheral vasoconstriction and ↑BP. Indirect effects on sympathetic nerve endings cause the release of endogenous noradrenaline (NA), though stores may become depleted during prolonged use contributing to tachyphylaxis. In low doses metaraminol also has some β1 receptor agonist activity, producing a positive inotropic effect on the heart.

Metaraminol onset of action: 1–2 minutes.

Metaraminol duration of action: 20–60 minutes.

Metaraminol half-life: minutes.

Metaraminol dosing
  IV push bolus IV infusion via syringe driver
Prescribe 10mg in 20ml in 5% Dextrose
(1ml metaraminol 10mg/ml + 19ml N. saline)
20mg in 40ml in N. saline
(2ml metaraminol 10mg/ml + 38ml N. saline)
Final concentration 0.5mg/ml 0.5mg/ml
1ml/hour = 0.5mg/hr 0.5mg/hr
Dosing 1 – 2ml every 2-5min as required 0.5 – 10mg/hr (titrate to effect)


1. Initial resuscitation

  • Measure lactate level*
  • Blood cultures then antibiotics
  • Bolus of 30mL/kg crystalloid for ↓BP or lactate ≥ 4 mmol/L
  • Apply vasopressors if hypotensive during or after fluid resuscitation to maintain MAP ≥ 65 mm Hg

* Remeasure lactate if initial lactate is ↑ (> 2 mmol/L).

2. Start Peripheral vasopressor

  • Start peripheral Metaraminol as per guideline
  • Avoid Phenylephrine due to concerns over its potential to ↓ cardiac output and ↓ heart rate in patients with sepsis

3. Early escalation

If after 2 hours after initiating vasopressors, the patient still requires vasopressor support ( to maintain MAP > 65mmH), despite adequate fluid resuscitation the patient will require Central Venous Access and admission to ICU.

Extravasation of peripheral vasopressors Mx

Extravasation Treatment with Phentolamine

  1. On suspecting extravasation, the infusion must be stopped
  2. The prescriber must be contacted immediately in order to assess the site and initiate treatment
  3. The IV catheter is left in place and any residual medication is aspirated through the catheter. The IV catheter is then removed
  4. The extent of the extravasation is marked with a pen to provide a baseline for monitoring
  5. 1 vial of 5 mg of Phentolamine administered as follows:
    1. 10 ml of normal saline is added to the vial to reconstitute phentolamine powder to a final concentration of 0.5 mg/ml
    2. After full dissolution, the contents of the vial are loaded into one 10 ml syringe
    3. 25 or 27 gauge needles are used for each injection, and the needle should be changed after each injection. Therefore, 5 needles are needed
    4. Inject the 10 ml of phentolamine subcutaneously into the affected area as 5 separate 2 ml clockwise injections around the leading edge of the extravasation marked by the pen
    5. At the judgment of the attending or fellow in the ICU, 2.5 cm of nitroglycerin paste may be applied to the area of extravasation
  6. A medication occurrence must be filled out and sent to the proper departments for review

Blood products

  • Once tissue hypoperfusion improved (and no significant coronary artery disease or acute haemorrhage), transfuse with red blood cells to a target a haemoglobin of 7.0 - 9.0 g/dL
  • Do not use FFP to correct lab. clotting abnormalities, unless there is bleeding or planned invasive procedures
  • Do not use antithrombin therapy
  • Administer platelets when counts are less than 5000/mm3 (5 x 109/L), regardless of bleeding
  • Transfuse platelets when counts are 5000 to 30,000/mm3 (5-30 x 109/L) and there is significant bleeding risk
  • Higher platelet counts (= 50,000/mm3 [50 x 109/L]) are required for surgery or invasive procedures


  • Avoid high Tidal Volumes with high plateau pressures
  • Goal = reduce TV over 1-2 hours to 6 ml per kg (lean) body wt with end-inspiratory plateau pressures <30 cm H2O
  • If necessary, minimize plateau pressures and tidal volumes, by allowing PaCO2 to increase above normal
  • Set a minimum PEEP to prevent lung collapse at end expiration
  • To prevent ventilator-associated pneumonia maintain mechanically ventilated patients in a semi-recumbent position (head up 45°), unless contraindicated

Glucose control

  • Maintain blood glucose < 8.3mmol/L following initial stabilization - (insulin ± glucose infusion)

Recombinant human activated protein C (rhAPC)

rhAPC is recommended in patients at high risk of death (APACHE II ≥ 25, sepsis-induced multiple organ failure, septic shock, or sepsis-induced acute respiratory distress syndrome) and with no absolute contraindication related to bleeding risk or relative contraindication that outweighs the potential benefit of rhAPC.


  • Treat patients who still require vasopressors despite fluid replacement with hydrocortisone (200-300 mg/day)
  • Or
  • Perform 250-microgram ACTH Stimulation Test and discontinue steroids in responders

Renal replacement

  • Intermittent haemodialysis and CVVH are considered equivalent
  • CVVH offers easier management in haemodynamically unstable patients
  • Do not use bicarbonate therapy to improve haemodynamics (e.g. "lactic acidosis")


  • Use either low-dose unfractionated heparin or LMWH

Stress ulcer prophylaxis.

  • With H2 receptor inhibitors


  1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8): 801-10
  2. National Sepsis Report 2018
  3. Beck V, Chateau D, Bryson GL, Pisipati A, Zanotti S, Parrillo JE, Kumar A, Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Timing of vasopressor initiation and mortality in septic shock: a cohort study. Crit Care. 2014;18(3):R97
  4. Bai X, Yu W, Ji W, Lin Z, Tan S, Duan K, Dong Y, Xu L, Li N. Early versus delayed administration of norepinephrine in patients with septic shock. Crit Care. 2014;18(5):532
  5. Cardenas-Garcia, J., Schaub, K. F., Belchikov, Y. G., Narasimhan, M., Koenig, S. J., & Mayo, P. H. (2015). Safety of peripheral intravenous administration of vasoactive medication. Journal of hospital medicine10(9), 581–585.
  6. Tian DH, Smyth C, Keijzers G, Macdonald SP, Peake S, Udy A, Delaney A. Safety of peripheral administration of vasopressor medications: A systematic review. Emerg Med Australas. 2020 Apr;32(2):220-227. doi: 10.1111/1742-6723.13406. Epub 2019 Nov 7. PMID: 31698544
  7. Lewis T, Merchan C, Altshuler D, Papadopoulos J. Safety of the Peripheral Administration of Vasopressor Agents. J Intensive Care Med. 2019 Jan;34(1):26-33. doi: 10.1177/0885066616686035. Epub 2017 Jan 11. PMID: 28073314
  8. Emergency Care Institute New South Wales. Peripheral Vasopressors. Available at:
  9. Loubani OM, Green RS. A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters. Journal of critical care. 2015;30(3):653 e9-17
  10. Safety of peripheral intravenous administration of vasoactive medication. J Hosp Med. 2015 Sep ;10(9):581-5. doi: 10.1002/jhm.2394. Epub 2015 May 26

Content by Dr Arina Kruis 24/01/2021. Last review Dr ÍOS 9/02/23.