7.7 Hypotensive Drugs

Question 1

When would you decrease the blood pressure to induce hypotension intraoperatively?

Answer 1

Induced hypotension is the deliberate lowering of blood pressure by more
than 30% of its resting value. Its use is highly controversial and is associated
with dramatic consequences due to organ ischaemia and dysfunction of all
vital organs.

Anaesthetic indications
* Nil
* Might be used in the preservation of blood in patients who are Jehovah’s
Witnesses

surgical indications
* Types of surgery where the procedure might be hindered by bleeding,
e.g. middle ear and neurosurgery

Question 2

How would you decrease blood pressure during anaesthesia?

Answer 2

Mechanisms that decrease any of the above contributing factors can
decrease blood pressure.

1. Non pharmacological
   * Head-up positioning
   * Use of intermittent positive pressure ventilation and preventing hypercarbia
2. Pharmacological

Question 3

How do you calculate BP

Answer 3

BP = Stroke volume (SV) × Heart rate (HR) × Systemic vascular resistance (SVR)

Question 4

Pharmacological methods to reduce BP

Answer 4

1. • Drugs with effect on heart rate
     ° Beta blockers
2. • Drugs with effect on venous return
     ° Neuraxial blockade
     ° Venodilators
3. • Drugs with effect on myocardial contractility
     ° Inhalational agents
4. • Drugs with effect on SVR
     ° Vasodilators
     ° Inhalational and intravenous anaesthetic agents
     ° Neuraxial blockade

Question 5

What drugs are commonly used for hypotensive anaesthesia?

Answer 5

1. 𝛃 adrenoceptor blockers
2. Vasodilators
3. 𝛂 adrenoceptor blockers
4. Ganglion-blocking drugs

Question 6

𝛃 adrenoceptor blockers

Answer 6

Decreases heart rate and also inhibits the renin angiotensin system
1. * Esmolol—selective β1 antagonist

2. • Labetolol—most commonly used α and β antagonist (1:7)
     resulting in decreased SVR without reflex tachycardia

Question 7

Vasodilators

Answer 7

1. • Glyceryl trinitrate (GTN)
     ° Venodilator via cyclic GMP pathway resulting in decreased intracellular Ca2+

° Decreases venous return and stroke volume

2. • Sodium nitroprusside
     ° Similar action to GTN but causes both arterial and venous dilatation,
     giving rise to hypotension and reflex tachycardia
3. • Hydralazine
     ° Similar action to GTN and also a weak α inhibitory effect

° Causes more arteriolar dilatation than venous
causes reflex tachycardia

Question 8

𝛂 adrenoceptor blockers

Answer 8

• Phentolamine

° Nonselective α antagonist with weak β agonist action

Question 9

Ganglion-blocking drugs

Answer 9

• Trimetaphan

° Antagonists at acetyl choline nicotinic receptors at the autonomic ganglia

° Direct vasodilator effects on peripheral vessels

Question 10

What are the problems with hypotensive anaesthesia?

Answer 10

1. • Need for invasive arterial monitoring
2. • CNS
     ° Impaired cerebral perfusion, depending on associated comorbidities
     ° Need for cerebral function monitors in ‘at-risk’ patients
3. • CVS
     ° Hypotension can be useful by decreasing oxygen consumption, but
     in patients with ischaemic heart disease, it is detrimental because the
     coronary perfusion is pressure-dependent.

° ECG monitoring is not helpful.

4. • Renal
     ° Induced hypotension can impair renal perfusion
     especially in ‘at-risk’ patients.

Question 11

Alternative answer: Drugs to treat hypertension can also be classified as

Answer 11

centrally acting drugs
* Methyl dopa
* Clonidine
* Dexmedetomidine

Ganglion-blocking agents
* Trimetaphan

Adrenergic neuron blockade
* Guanethidine

Drugs affecting renin-angiotensin-aldosterone system
* ACE inhibitors
* Angiotensin II receptor blockers

𝛃 blockers
* Atenolol and others

Diuretics
* Loop diuretics
* Thiazides

Vasodilators
* GTN
* Sodium nitroprusside
* Potassium channel activators—nicorandil
* Calcium channel blockers—verapamil, nifedipine, diltiazem

Question 12

What level of mean arterial pressure (MAP) are you satisfied with intraoperatively in a patient who is normotensive?

Answer 12

Safe level of hypotension is no lower than about
two-thirds of the resting blood pressure before inducing hypotension.

This number is obtained by various cerebral perfusion and EEG studies.

The cerebral blood flow decreases to 60% normal with two-thirds MAP, with
clinical manifestations of yawning, and inability to concentrate and carry out
simple commands.

With further decrease in MAP and cerebral blood flow,
the slowing and flattening of EEG occurs with ischaemic irreversible brain
damage ensuing.

Do not forget that the blood pressure decreases 2 mmHg for every 2.5 cm
height above the point of measurement. So, mean arterial pressure in brain
in a reclining or sitting patient under anaesthesia is about 12–16 mmHg
lower than that measured at the upper arm.

Question 13

Discuss sodium nitroprusside.

Preparation

Dose

Onset

Answer 13

It is a vasodilator available as a reddish-brown powder that is reconstituted
in 5% dextrose. The reconstituted solution is covered in an aluminium foil as
it turns dark brown or blue on exposure to sunlight due to the production of
cyanide ions.

Dose: 0.5–6 μg/kg/min and titrated to effect

Onset: 3 minutes and the effects are short-lived

Question 14

Discuss sodium nitroprusside.

PD

Answer 14

Pharmacodynamics:

CVS:
Arteriolar and venous dilatation,
decreased preload and reflex tachycardia

RS:
Inhibition of hypoxic pulmonary vasoconstriction and
increase of shunt

Cerebral:
Cerebral vasodilatation and increased ICP

others:
* Tachyphylaxis

• Toxicity due to thiocyanate (less toxic) and mainly cyanide ions,

which bind to cytochrome oxidase and impair aerobic metabolism,
causing a metabolic acidosis and histotoxic hypoxia.

Treat cyanide toxicity with oxygen, chelating agents, sodium thiosulphate
(provide additional sulphydryl groups to aid conversion of cyanide to
thiocyanate) and

nitrites (converts oxyhaemoglobin to methaemoglobin and
cyanide ions bind more avidly to methaemoglobin than cytochrome oxidase).

Question 15

Discuss sodium nitroprusside.

MOA

Answer 15

Mechanism of action:
Vasodilatation happens due to the production of No,

which activates the enzyme guanylate cyclase,

leading to increased levels of intracellular cyclic GMP.

This increases the uptake of Ca2+ into the endoplasmic reticulum,

hence the cytoplasmic calcium concentration falls, resulting in vasodilatation.

Question 16

What are the advantages of remifentanil in mastoidectomy?

Answer 16

Intraoperative

• Controlled ventilation without neuromuscular blocking agents,
  thus permitting unimpeded facial nerve monitoring.
• Remifentanil provides a titratable degree of hypotension
  while maintaining a stable heart rate and provides superior operating conditions.
• Provides excellent analgesia and reduces the need for intraoperative morphine.

Question 17

What are the advantages of remifentanil in mastoidectomy?

Answer 17

Postoperative

• Prevents airway irritation and coughing and provides smooth emergence.
• Rapid clearance of remifentanil due to metabolism by nonspecific plasma
  esterases results in a uniform and predictable onset and duration of
  action despite changes in the duration of infusion.
• Better recovery profiles – lesser pain, shivering, and PONV