Sepsis - Treatment

Question 1

What is sepsis?

Answer 1

Life-threatening organ dysfunction caused by dysregulated host response to infection, which causes injury to the body’s own tissues and organs
- inflammatory response causing hypovolemia

Question 2

How does sepsis affect the different parts of the body?

Answer 2

blood/vessels
- leakage, coagulation defects

brain/ nervous system
- altered mental state = confusion, slurred speech

lungs
- respiratory distress syndrome

liver
- reduced function

kidneys
- development of acute kidney injury (AKI) via reduction in GF and drop in urine output

heart
- septic cardiomyopathy

Question 3

What is the SOFA score?

Answer 3

Sequential Organ Failure Assessment score
- is based on six different independent scores, including respiratory, cardiovascular, hepatic, renal, coagulation, and neurological systems
- is used to check the patient’s status or the extent of organ failure and dysfunction in intensive care units (ICUs).

Question 4

What is septic shock?

Answer 4

sepsis with persisting hypotension requiring vasopressors to maintain a mean arterial pressure (MAP) ≥65mmHg, and having a serum lactate level >2mmol/l, despite adequate fluid resuscitation

Question 5

What are the sepsis red flags in adults?

RASHRNNNLR

Answer 5

Responds only to voice or pain/unresponsive

Acute confusional state

Systolic BP <90mmHg (or drop >40 from normal)

Heart rate >130 bpm

Respiratory rate >25 per minute

Needs oxygen to keep SpO2 >92%

Non-blanching rash, mottled/ashen/cyanotic

Not passed urine in last 18hr/UO <0.5ml/kg/hr

Lactate >2mmol/l

Recent chemotherapy

Question 6

What are the urgent management strategies for sepsis?

SEPSIS 6

Answer 6

give oxygen - high flow oxygen

take blood cultures - before antibiotics are give to identify organisms and best treatment

give IV antibiotics - broad spectrum initially then narrow spectrum

give rapid IV fluids (500ml over <15mins) - if hypotensive or lactate 2-4mmol/l

measure blood lactate and haemoglobin - repeat lactate measurements

measure hourly urine output - as an indicator of renal function

give vasopressors - if hypotensive during or after fluid

Question 7

What are vasopressors? What do they do?

Answer 7

are drugs that cause a rise in blood pressure to reverse circulatory failure in critically ill patients
- noradrenaline or vasopressin

• given based on weight and adjusted based on response
• given via continuous infusion in infusion pumps due to short half life and potency
• given via central IV line

Question 8

What is noradrenaline? Where does it act? When is it used?

Answer 8

NA is a hormone that is produced naturally by the body.

NA acts on alpha 1 and 2 receptors in smooth muscle of the veins and arteries.
There is some limited beta 1 activity in the heart

Use when MAP ≤ 65mmHg or >40mmHG below normal

Question 9

What is the effect of noradrenaline on the body?

Answer 9

overall effect is to constrict the vessels and increase blood pressure
- more blood is returned to the heart and cardiac output is improved.

it reduces blood flow in peripheral tissues but helps to increases perfusion of the major organs.
- can cause cyanosis of the skin because of the reduced peripheral blood flow

relative lack of beta activity means it does not stimulate the heart rate significantly, or increase oxygen requirements of the heart

Question 10

What is vasopressin?

Answer 10

vasopressin (anti-diuretic hormone) is a naturally occurring hormone.
- it is synthesised in the hypothalamus and excreted by the posterior pituitary
- it is released in response to hypertonicity i.e. dehydration

Question 11

Where does vasopressin act?

Answer 11

acts on V1 and V2 receptors

V1 - are found on vascular smooth muscle of the systemic, splanchnic, renal, and coronary circulations

V2 - are found predominantly in the distal tubule and collecting ducts of the kidney,

Question 12

What are the effects of vasopressin?

Answer 12

V1 - increase in vascular tone, and increase arterial pressure

V2 - are essential for plasma volume and osmolality control as they increase the reabsorption of water from the collecting ducts, and increase blood volume

Question 13

Why are noradrenaline and vasopressin typically given together?

Answer 13

In theory, vasopressin helps to restore the effect of noradrenaline on vascular smooth muscle.

NA’s effectiveness may be inhibited due to receptor desensitisation with prolonged use and vasopressin is thought to help overcome this.

In addition vasopressin may inhibit the production of nitric oxide.
- as nitric oxide is a vasodilator, inhibiting it will help to increase vascular tone and increase blood pressure

Question 14

What are inotropes? What are chronotropes?

Answer 14

Inotropes increase the force of contraction

Chronotropes increase the rate of contraction

Question 15

What are inotropes used for?

Answer 15

Used to treat myocardial failure in sepsis
- adrenaline (epinephrine) or dobutamine

Question 16

What is adrenaline? Where does it act?

Answer 16

Adrenaline is a mixed alpha and beta receptor agonist
- heart, vascular tissues and lungs

Question 17

What are the effects of adrenaline (inotrope)?

Answer 17

heart
- increases the contractility of cardiac muscle via beta 1 receptors, and this then increases intracellular calcium and aids muscle contraction
- it increases heart rate
= together this increases cardiac output and oxygen delivery around the body.

vascular tissue
- cause vasoconstriction via alpha receptors, but dilation via beta 2 receptors and the overall effect depends on the dose & response of the patient.

lung
- it is a beta 2 receptor agonist causing bronchial dilation

Question 18

What are the side effects of adrenaline? When should it be used?

Answer 18

• an increase in systemic and regional lactate concentrations
• the potential to produce myocardial ischemia and promote development of arrhythmias
• reduced splanchnic blood flow

is recommended only in patients who are unresponsive to traditional agents

Question 19

What is dobutamine? When is it used?

Answer 19

a synthetic molecule which acts predominantly as aβ1 agonist, with weak β2activity, andα1activity
- overall in the blood vessels there is little effect on dilation/contraction

is used clinically for its β1 activity in cases of cardiogenic shock to increase heart contractility and cardiac output.

Question 20

What is levosimendan? How does it act? When is it used?

Answer 20

is a synthetic molecule used as an inotrope

is thought to increase the sensitivity of cardiac muscle fibres to calcium, and improve myocardial contractility without increasing consumption of ATP and oxygen
- because it does not raise intracellular calcium, there is less risk of arrhythmias

is indicated for the short­ term treatment of acutely decompensated severe chronic heart failure (ADHF) in situations where conventional therapy is not sufficient

Question 21

Why are steroids used in treating sepsis? Which is typically used?

Answer 21

sepsis is an inflammatory process, and steroids have anti-inflammatory action

hydrocortisone is typically used
- typically, 200-300mg daily, as split bolus dose or continuous infusion

Question 22

What are the adverse effects of steroids?

Answer 22

hypernatraemia
hyperglycaemia - diabetes
hypertension
muscle weakness/wasting
adrenal suppression
glaucoma and cataracts
osteoporosis and fractures
cardiovascular disease
psychiatric reactions
increased infection risk

Question 23

How should ventilated patients be managed?

Answer 23

All their basic care needs must be addressed
- eye care to avoid eyes drying out and infection
- mouth care = dry mouth can increase risk of ulcers/dental problems and infection

GI protection – if no NG feeding – risk of stress ulcers

VTE prophylaxis – immobility + effects of sepsis

Skin emollients/protection

Question 24

What are the properties of a good sedative?

Answer 24

Rapid onset
Short duration of action - so they wake up quickly
No active metabolites
No accumulation with prolonged infusion
Kinetics not affected by renal or liver impairment - no adjustments needs
Kinetics not affected by age
No kinetic interactions

Dose dependent effect
No tolerance
No ADR or interactions
Easy to administer
No abuse potential

Question 25

What drugs are used as sedatives?

Answer 25

opiates
- fentanyl
- alfentanil and remifentanil = 3 days max

anaesthetic drugs
- propofol

Question 26

Why is morphine not used as a sedative?

Answer 26

Morphine’s half-life is too long, it has active metabolites and it accumulates with renal/hepatic impairment and with prolonged use

• longer acting sedatives can delay the patient being removed from the ventilator because the drugs remain in their system for a long time and suppress their respiratory effort
• this delays recovery for the patient and needs to be avoided.