# Hemodynamics and Vasopressors in Septic Shock — SCCM/ESICM 2021

## Mean Arterial Pressure Target

The SSC **recommends** an initial target **MAP of 65 mmHg** over higher MAP targets for adults with septic shock on vasopressors (Strong recommendation, Moderate quality of evidence).

- The SEPSISPAM trial demonstrated no mortality benefit for targeting MAP 80-85 mmHg versus 65-70 mmHg.
- Higher MAP targets were associated with **increased incidence of atrial fibrillation**.
- A MAP of 65 mmHg is appropriate as an initial target; individualisation may be considered for patients with pre-existing chronic hypertension, where a slightly higher target may improve renal perfusion.

## Vasopressor Selection Hierarchy

### First-Line: Norepinephrine

The SSC **recommends** using **norepinephrine as the first-line vasopressor** over other vasopressors for adults with septic shock (Strong recommendation, Moderate quality of evidence).

- Norepinephrine provides potent alpha-1 adrenergic vasoconstriction with moderate beta-1 cardiac stimulation.
- Superior to dopamine: meta-analyses demonstrate lower mortality and fewer arrhythmias compared with dopamine.
- Starting dose: typically **0.1-0.5 mcg/kg/min**, titrated to MAP >= 65 mmHg.
- In settings where norepinephrine is not available, **epinephrine or dopamine** may be used as alternatives, but efforts should be made to improve norepinephrine availability.

### Second-Line: Add Vasopressin

The SSC **suggests** adding **vasopressin** instead of escalating the dose of norepinephrine for adults with septic shock on norepinephrine with inadequate MAP (Weak recommendation, Moderate quality of evidence).

- Fixed dose: **0.03 units/min** (not titrated).
- Vasopressin is typically started when norepinephrine dose is in the range of **0.25-0.5 mcg/kg/min**.
- Higher vasopressin doses may be associated with adverse effects including **cardiac ischaemia, digital ischaemia, and mesenteric ischaemia**.
- The VASST trial demonstrated that vasopressin added to norepinephrine was safe and may reduce norepinephrine requirements.

### Third-Line: Add Epinephrine

The SSC **suggests** adding **epinephrine** for adults with septic shock and inadequate MAP despite norepinephrine and vasopressin (Weak recommendation, Low quality of evidence).

- Epinephrine provides additional alpha-1 and beta-1 adrenergic stimulation.
- Dose: typically **0.01-0.5 mcg/kg/min**, titrated to MAP target.
- Caution: epinephrine may increase **heart rate, risk of arrhythmias, and transient lactic acidosis** (aerobic glycolysis in skeletal muscle).
- Serial lactate measurements may be unreliable for guiding resuscitation when epinephrine is being administered.

### Agents to Avoid or Use with Caution

- The SSC **suggests against** using **terlipressin** in adults with septic shock (Weak recommendation, Low quality of evidence).
- The SSC **suggests against** using **dopamine** except in highly selected patients (e.g., patients with absolute or relative bradycardia and low risk of tachyarrhythmias) (Weak recommendation, High quality of evidence).
  - Dopamine is associated with higher mortality and more arrhythmias than norepinephrine in septic shock.
- **Phenylephrine** is not recommended as a first-line agent; it provides pure alpha-1 stimulation without inotropy and may reduce cardiac output.

## Vasopressor Escalation Algorithm

```
Septic shock: MAP < 65 mmHg despite initial fluid resuscitation
  --> Start norepinephrine (first-line)
      --> Titrate 0.1-0.5 mcg/kg/min to MAP >= 65 mmHg
      --> May start via peripheral IV if central access not yet available
          --> Transition to central line as soon as feasible
      --> MAP target met? --> Continue current dose
      --> MAP not met and norepinephrine 0.25-0.5 mcg/kg/min?
          --> Add vasopressin 0.03 units/min (fixed dose, no titration)
          --> MAP target met? --> Continue current regimen
          --> MAP still not met?
              --> Add epinephrine 0.01-0.5 mcg/kg/min
              --> Reassess volume status, source control, adrenal function
              --> Consider echocardiography to evaluate cardiac function
              --> Consider corticosteroids (see below)
```

## Inotropic Support

The SSC **suggests** using **dobutamine** in patients with sepsis-induced myocardial dysfunction manifesting as persistent hypoperfusion despite adequate volume status and arterial blood pressure (Weak recommendation, Low quality of evidence).

- Dobutamine dose: **2-20 mcg/kg/min**, titrated to clinical response.
- Consider when cardiac output is low despite adequate vasopressor support.
- Echocardiographic assessment should guide the decision to initiate inotropic therapy.
- Avoid targeting supranormal oxygen delivery.

## Corticosteroids

The SSC **suggests** using **IV corticosteroids** for adults with septic shock who have an ongoing requirement for vasopressor therapy (Weak recommendation, Moderate quality of evidence).

- This represents a **change from the 2016 guideline**, which suggested against routine use of IV hydrocortisone.
- **Drug:** Hydrocortisone.
- **Dose:** 200 mg/day IV, administered as:
  - **50 mg IV every 6 hours**, OR
  - **Continuous IV infusion of 200 mg over 24 hours**
- **When to initiate:** Typically when norepinephrine (or epinephrine) dose is >= **0.25 mcg/kg/min** for at least **4 hours** after vasopressor initiation.
- Meta-analyses demonstrate corticosteroids **shorten the duration of shock** and may reduce ICU length of stay.
- **Mortality effect:** Overall mortality benefit remains unclear; some meta-analyses show trends toward reduced mortality, but this is not consistently statistically significant.
- **Duration:** Continue until vasopressor therapy is no longer required, then taper. Typical duration is 5-7 days with gradual taper.

### Against Vitamin C

The SSC **suggests against** IV vitamin C for adults with sepsis or septic shock (Weak recommendation, Low quality of evidence).

- The VITAMINS and LOVIT trials did not demonstrate a clear benefit for IV vitamin C alone or in combination with hydrocortisone and thiamine.

## Fluid Type for Ongoing Resuscitation

### Crystalloids as First-Line

The SSC **recommends** using crystalloids as first-line fluid for resuscitation of adults with sepsis and septic shock (Strong recommendation, Moderate quality of evidence).

### Against Starches

The SSC **recommends against** using **hydroxyethyl starches (HES)** for acute resuscitation in adults with sepsis or septic shock (Strong recommendation, High quality of evidence).

- HES is associated with increased mortality and increased need for renal replacement therapy.

### Against Gelatins

The SSC **suggests against** using **gelatins** for resuscitation (Weak recommendation, Moderate quality of evidence).

## Limitations

- The optimal MAP target may need individualisation, particularly in patients with pre-existing chronic hypertension; the 65 mmHg target is an initial recommendation, not an absolute ceiling.
- Vasopressin dosing is fixed at 0.03 units/min; evidence for higher doses is limited and associated with ischaemic complications.
- The corticosteroid mortality benefit remains debated; the primary established benefit is shock reversal and reduced vasopressor duration.
- The vasopressor escalation sequence (norepinephrine --> vasopressin --> epinephrine) is based on indirect comparisons and expert consensus, not head-to-head escalation RCTs.
- Peripheral vasopressor initiation evidence is limited to short durations (< 6 hours) and proximal peripheral IV sites.
