Clinical Emergencies in Experimental Neurology

Question 1

Do CRFs have to be associated with a hospital?

Answer 1

CRFs do not have to be based in a co-located hospital but they must be associated with a local hospital.

Question 2

Why must CRFs be associated with a local hospital?

Answer 2

In case of emergency scenarios in which participants need immediate transfer to a hospital.

Question 3

What must hospitals be aware of regarding clinical trials?

Answer 3

They must be aware of the clinical research unit, the research which is taking place and that trial participants can be referred to them at any time. They are often informed through governance procedures.

Question 4

What is in place in case of emergency scenarios in a clinical trial?

Answer 4

1. All staff working on a trial must have Advanced Life Support, Immediate Life Support and emergency scenario training.
2. Emergency equipment must be regularly checked to be in date and well stocked.
3. There must be arrangements for resus and stabilisation.
4. There must be someone to contact out-of-hours in case of emergency.
5. There must be a dedicated individual(s) who can unblind participants if required in an emergency.

Question 5

What is in place to reduce the risk of emergencies occurring?

Answer 5

1. All drugs must have undergone pre-clinical testing.
2. All drugs will have an IB (or SNPC for drug repurposing trials) which outlines what side effects may occur and their prevalence.
3. The trial protocol will outline procedures (including observations, medications, infusion rate etc).
4. Phase I trials may have a staggered recruitment and treatment process.
5. The DSMB review safety data and decide if amendments must be made to the protocol.
6. If required, pre-medications may be given to participants.

Question 6

What is an Adverse Event (AE)?

Answer 6

Any experience by the patient which occurs during the trial period.

Question 7

What is an Adverse Reaction (AR)?

Answer 7

An experience by the patient which has a likely association to the intervention.

Question 8

What is a Serious Adverse Event/Reaction (SAE/SAR)?

Answer 8

An event which:
- results in death
- is life-threatening
- requires hospitalisation or prolongation of existing hospitalisation
- results in persistent or significant disability or incapacity
- consists of a congenital anomaly or birth defect.

Question 9

Are SAE/SARs the same for all clinical trials?

Answer 9

No, the exact definition of serious will be outlined in the trial protocol. For example, death may be an AE in trials for cancer medications in patients with terminal cancer.

Question 10

What is a Suspected Unexpected Serious Adverse Reaction (SUSAR)?

Answer 10

A serious reaction which is not expected based on the preclinical data or from the disease the participants have.

Question 11

What should you do in a SAE, SAR or SUSAR?

Answer 11

All must be reported within 24 hours. The precise reporting pathway guidelines in the protocol should be followed but the Sponsor and PIs at all sites must be informed.

Question 12

What happens following the reporting of events?

Answer 12

There should be an investigation to determine the relatedness and severity of the events.

Question 13

What is the most common type of emergency as a result of reacting to a drug?

Answer 13

Shock.

Question 14

What types of shock may trial participants experience?

Answer 14

1. Anaphylactic shock (severe allergy)
2. Cardiogenic shock (heart unable to pump enough blood)
3. Hypovolemic shock (a reduction in blood volume)
4. Septic shock (severe infection)
5. Neurogenic shock (damage to the nervous system)

Question 15

What is the equation for calculating blood pressure?

Answer 15

BP = HR x SV x TPR

Question 16

What are the 4 types of drug hypersensitivity reactions?

Answer 16

1. Type 1 - Drug-specific IgE and mast cell reaction. Occurs immediately (within half an hour, if not 10 minutes).
2. Type II - Antibody-mediated (typically IgG) cell destruction.
3. Type III - IgG-drug immune complex deposition and complement activation.
4. Type IV - T-cell mediated.

Question 17

What approach is taken to deteriorating or critically ill patients?

Answer 17

ABCDE approach.
A = airway
B = breathing
C = circulation
D = disability
E = expose
Patients should be assessed and the problem in each system treated before moving onto the next system. Both the patients and the treatments should be re-assessed.

Question 18

What emergency considerations are particularly important for neurological trials?

Answer 18

Participants who have received neuroactive substances may have disability without a reduced level of consciousness. Acute onset flaccid paralysis may be due to peripheral, NMJ, muscle or CNS damage.

Question 19

How do you assess AIRWAY?

Answer 19

Look for obstructions, secretions or swelling of the lips.
Feel for air movement.
Listen for speaking, stridor or snoring.
Treat with airway manoeuvres, airway suction, adrenaline 0.5mg 1:1000 IM.

Question 20

How do you assess BREATHING?

Answer 20

Look for chest movement, cyanosis.
Feel for expansion of the chest, check the trachea is central.
Listen to breath sounds, check for added sounds such as wheeze.
Measure RR, O2 sats, blood gas, perform chest x-ray.
Treat with high flow O2, bag valve mask, salbutamol 2.5-5mg nebulised.

Question 21

How do you assess CIRCULATION?

Answer 21

Look at the skin colour - cyanosed, pale, pink or mottled.
Feel for the quality and regularity of pulse, temperature of skin.
Listen to heart sounds, check for added sounds.
Measure HR, BP, temperature, capillary refill time, urine output, perform ECG.
Treat with IV cannula, bloods, fluid challenge of 250-500mls, CPR, MONA.

Question 22

How do you assess DISABILITY?

Answer 22

Look for pupils equal and reactive to light.
Feel for sensation, power.
Check for alertness, verbalisation, pain, responsiveness.
Measure blood glucose.
Treat with naloxone 400mcg, glucose, glucagon 1mg.

Question 23

How do you EXPOSE?

Answer 23

Fully expose the patient to look for rashes, injuries, bleeding.
Feel the abdomen and for bone deformities.
Treat by compressing any bleeding and splinting injured limbs.