MCQ 1: Induction agents in anesthesia

 IV induction agents in anesthesia MCQ - 1

1. Which of the following statements about etomidate are true? 

1. The standard induction dose of etomidate is 0.3 mg/kg
2. Etomidate owes its anaesthetic activity to its action as an NMDA receptor antagonist
3. Etomidate is not suitable for use in major trauma since it raises intracranial pressure
4. Etomidate reversibly blocks the activity of the adrenocortical hormone 11β-hydroxylase
5. Etomidate has intrinsic analgesic activity equivalent to 5–10 mg of intravenous morphine

2. Which of the following statements about propofol are true?

1. Propofol is contraindicated in patients with an allergy to eggs
2. Excitatory movements seen on induction with propofol are due to epileptiform EEG activity
3. Propofol is 75% protein-bound in plasma
4. Propofol causes more cardiovascular changes than thiopental when used in equi-analgesic doses
5. Pain on injection of propofol can be reduced by injecting into a fast-flowing intravenous drip

3. You are asked to provide anaesthesia for a pregnant woman undergoing emergency appendicectomy. Of the following drugs administered to the woman, which is the least likely to accumulate in the fetus?

1. Bupivacaine 
2. Pethidine
3. Thiopental 
4. Diamorphine
5. Diazepam

4. Which of the following combinations correctly describes a neurotransmitter (stated first) matched with the receptor at which it is an agonist (stated second)?

1. α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionate(AMPA)andN-methyl- D-aspartate (NMDA)
2. Substance P and neurokinin 1
3. Glutamate and γ-aminobutyric acid A (GABAA)
4. Glycine and NMDA
5. Kainate and glutamate

5. Which of the following statements about a sedative drug are true?

1. Zopiclone is a benzodiazepine
2. Plasma concentrations of zopiclone may be increased by concurrent administration of clarithromycin
3. Zopiclone is suitable for long-term use as a night sedative
4. Zopiclone is available as an intravenous formulation
5. Zopiclone has active metabolites

6. You are asked to anaesthetise a patient for emergency laparotomy. The patient has an ASA score of III with a known significant history of ischaemic disease. Which ONE of the following statements about rapid sequence induction of anaesthesia in shocked patients is best supported?

1. Etomidate causes less cardiovascular depression than other IV induction agents and is preferred for induction of anaesthesia in trauma
2. A low pulse oximeter reading during induction of anaesthesia reliably suggests inadequate oxygenation
3. Hypotension during induction should be diagnosed by palpating the pulse if an arterial line is not available
4. If the patient cannot be intubated after two attempts with optimal head/neck positioning, he/she should be ventilated until spontaneous ventilation returns and then woken from anaesthesia
5. Opioid drugs should not be used, as they cause a prolonged period of apnoea in shocked patients

7. A 69-year-old male who is a poorly controlled asthmatic falls off a balcony and sustains pelvic trauma. His blood pressure is 60/40mmHg and heart rate is 122/minute. There is no neurological injury and the CT scan of his head is normal. He is scheduled for internal fixation of his pelvis. The most appropriate induction agent would be?

1. Etomidate.
2. Thiopentone.
3. Propofol.
4. Ketamine.
5. Inhalational induction with sevoflurane

8. A 29 years of female with porphyria presents for an emergency laparotomy for a ruptured ectopic pregnancy. Her heart rate is 92/minute and blood pressure is 110/60mmHg. Which one of the following anaesthetic drugs is most unsafe in this patient?

1. Isoflurane.
2. Thiopentone.
3. Propofol.
4. Ketamine.
5. Suxamethonium.

9. A 33-year-old female is due to undergo an emergency laparotomy for a ruptured ectopic pregnancy. She has had a previous general anaesthesic when she was told she might suffer from a possible allergy to an anaesthetic agent. She suffers from hay fever and has a history of allergic reactions to multiple medications including antibiotics and NSAIDs. Her previous anaesthetic notes are not available. Which one of the following is most appropriate for intravenous induction of anaesthesia?

1. Thiopentone.
2. Propofol.
3. Etomidate.
4. Ketamine.
5. Methohexitone.

10. A 76-year-old female underwent a hemi-arthroplasty under general anaesthesia. A lumbar plexus block was performed at induction to provide postoperative analgesia. During the intra-operative period she required a transfusion of 2 units of blood. In the recovery room she is confused, disorientated and agitated. Her pain appears to be adequately controlled. Her vital parameters in recovery are shown in Table 2. 40% oxygen has been administered via a face mask.

Vital parameters are:

HR - 86

BP - 168/88

R/R - 14

SpO2 - 97%

Temp - 36.9 c

Despite all measures it is difficult to control her agitation. The following is the most appropriate pharmacological treatment in this patient:

1. Midazolam 2mg I.V.
2. Haloperidol 0.5-1mg I.V.
3. Titrated doses of diazepam.
4. Ketamine 0.25mg/kg I.V.
5. Propofol 50-100mg I.V.

Answers:

1. (1,4)

2. (4.5)

3. 1

4. 2

5. (2,5)

6. 3

7. 4

8. 2

9. 3

10. 2

Explanations:

1. Etomidate is an imidazole derivative and an ester, which is presented as 0.2% solution in water and ethylene glycol or at the same concentration in a lipid emulsion. It is chiral with two enantiomers, of which only the R(+) isomer is biologically active. It is highly lipid-soluble and 75% protein-bound, making it sensitive to factors which change protein binding. The effect of a bolus of etomidate is terminated by redistribution of drug to peripheral tissues, and it is rapidly metabolised in the liver and by plasma esterases to inactive products. It works by enhancing the binding of GABA to GABAA receptors, and it has no intrinsic analgesic activity.

The standard dose for induction of anaesthesia is 0.3 mg/kg, producing anaesthesia in one arm-brain time. It has very little effect on the cardiovascular system, causing a very slight reduction in SVR, blood pressure and heart rate while preserving cardiac output. Indeed, the cardiovascular stability is so good that it has been recommended for use in hypovolaemic patients or those with poor cardiac function. Epileptiform activity is frequently seen on EEG and there is more excitatory muscle movement than is seen with barbiturates. It reduces cerebral blood flow, cerebral metabolic rate and intracranial pressure. It reduces tidal volume and respiratory rate, but to a much lesser degree than barbiturates.

Etomidate causes minimal histamine release and hypersensitivity is rare, but it does cause pain on injection and it seems to have a higher incidence of postoperative nausea and vomiting than other induction agents. It can also trigger a porphyric crisis in susceptible individuals. Most importantly, it blocks the function of the adrenocortical enzymes 11β-hydroxylase and 17α-hydroxylase, reducing corticosteroid and minera- locorticoid synthesis. This effect lasts for 3–6 hours after a bolus dose, but this is of little clinical significance in otherwise fit patients. However, when given as an infusion it causes profound adrenocortical blockade and has been shown to increase mortality; it is no longer licensed for use by infusion.

2. Propofol (2,6-di-isopropyl phenol) is an alkylated phenol. It is presented as a white emulsion at concentrations of 1% or 2% with soya bean oil (10%), purified egg phos- phatide (1.2%) and glycerol (2.25%); the solution has a pH of 6.5–8.0 and is stable at room temperature and not light-sensitive. The soya bean oil and egg components are denatured by processing and there is no evidence that propofol should be avoided in patients with allergies to eggs or soya.

Its pKa is 11 and so it is almost entirely un-ionised in solution; in the plasma it is 98% protein-bound. It causes dose-dependent depression of cortical activity, with the EEG showing alpha waves followed by delta waves as anaesthesia deepens. Excitatory movements are seen relatively commonly although there are no epileptiform features on the EEG; indeed, propofol has good anticonvulsant activity and can be used to treat status epilepticus.

Propofol causes a reduction in systemic vascular resistance and central venous pres- sure by vasodilation, and also reduces myocardial contractility. This reduces blood pressure, and the heart rate is usually unchanged. These cardiovascular effects are more pronounced than those produced by barbiturates at equi-anaesthetic doses. More respiratory depression is seen with propofol than with barbiturates (apnoea is universal) and propofol supresses the response to laryngoscopy more than thiopental does.

One of the problems with propofol is pain on injection. This is increased by injection into a small vein, rapid injection, lower temperature of the propofol and the use of an IV carrier infusion to dilute the propofol as it enters the vein. Adding 2 mL of 1% lidocaine to a 20 mL syringe of propofol or giving the same dose prior to propofol administration is effective at attenuating this symptom.

3. The placenta forms a barrier to the transfer of drugs between the mother and the fetus but it is not particularly discriminating and most drugs will cross it to a certain degree. Factors which increase the rate of transfer include increasing lipid-solubility, decreasing maternal protein binding, decreasing molecular weight, increased materno- fetal concentration gradient and placental blood flow.

Feto-maternal (F/M) concentration ratios describe the relative distribution of the drug across the placenta. Certain drugs may accumulate in the fetal tissue (i.e. have F/M ratios > 1) for several reasons. Highly lipid-soluble drugs such as thiopental cross the placenta easily, and can accumulate as the pH is lower in the fetus, causing differ- ential rates of protein binding. Pethidine and diamorphine are both metabolised in the fetus to less lipid-soluble products (norpethidine and morphine, respectively) which remain on the fetal side of the placenta. The elimination half-lives of these drugs are also longer in the fetus because of immature hepatic metabolism, further prolonging their presence in the fetus. Diazepam is also metabolised to less lipid-soluble products, and can have an F/M ratio of 2 an hour after maternal administration.

Local anaesthetic agents are weak bases which are largely un-ionised at physiolog- ical pH, and hence cross the placenta readily. Bupivacaine has a higher degree of protein binding than other local anaesthetics (e.g. lidocaine), meaning that its rate of transfer is relatively low. If the fetus is markedly acidotic, increased ionisation in the fetus can cause ‘ion trapping’ and drug accumulation within the fetus. However, this is not clinically significant at normal pH values because the pKa of the drug (8.1) is well above the physiologically observed range.

4. Glutamate is an excitatory amino acid neurotransmitter that may act at the NMDA, AMPA, kainate or metabotropic glutamate receptor. These synapses are involved in transmission of nociception, central sensitisation and the ‘wind-up’ phenomenon. Kainate is an exogenous molecule derived from red algae and found to stimulate the kainate receptor. AMPA is an artificial glutamate analogue. Neither AMPA nor kainate are neurotransmitters. The agonism of NMDA receptors by glutamate is antagonised by the drug ketamine. Substance P and neurokinin A are also involved in pain pathways and are peptide neurotransmitters that both stimulate neurokinin-1 receptors. Glycine is an inhibitory neurotransmitter confined to the central nervous system and acts at glycine recptors. It is also a co-agonist with glutamate at the NMDA receptor but is not an agonist when acting alone.

Gamma-aminobutyric acid A (GABAA) and GABAB are receptors at which GABA is an agonist, not glutamate. The β subunit of GABAA is potentiated by thiobarbiturates. The α subunit of GABAA appears to be the binding site of benzodiazepines. The GABAA receptor is a ligand-gated ionotropic Cl– channel. The GABAB receptor is metabotropic.

5. Zopiclone is not structurally a benzodiazepine but it acts via the benzodiazepine site on the GABAA receptor. It is a cyclopyrolone derivative. Zopiclone is metabolised by the CYP3A4 isoenzymes, and they are inhibited by drugs such as clarithromycin, leading to increased plasma concentrations and adverse reac- tions. Zopiclone was developed in an attempt to overcome dependence associ- ated with benzodiazepines but has been found to cause dependence and is unsuitable for long-term use. Metabolites of zopiclone are weakly active at the GABAA receptor. 

6. Induction in shock is only justified where immediate surgery or ventilation is required and cannot be delayed for adequate resuscitation. Ideally an arterial line should be sited prior to induction in hypotensive patients. When this is not possible, setting an automated non-invasive blood pressure machine to ‘stat’ mode is an acceptable alter- native, although keeping a finger on the pulse may give an earlier indication of a falling blood pressure.

The choice of induction agent in shocked patients is not clear-cut. Etomidate has the advantage of cardiostability, but it has a slow onset and a single dose suppresses adrenocortical function; the resultant fall in cortisol and aldosterone is significant in the context of shock. Thiopental has a rapid action but a long duration and more cardiodepressant activity than other agents. Propofol inhibits airway reflexes and this may facilitate laryngoscopy at a lower induction dose. Ketamine should be considered in cases of cardiovascular collapse because of its sympathomimetic activity.

The dose of agent should be judicious, and the use of an opioid allows intubation at a lower dose with less cardiac effect than an opioid-free technique, and also decreases the risk of awareness. Short-acting opioids such as alfentanyl or remifentanyl have a similar duration of action to suxamethonium, and naloxone can be used to reverse opioid activity if required.

Patients are usually woken after failed intubation, but in this situation this is rarely appropriate. Priority must be given to maintenance of oxygenation, and the patient should be ventilated via bag and mask or LMA/ProSeal LMA. If oxygenation fails, cricoid pressure should be reduced and if necessary ventilation should proceed via cricothyrotomy.

Pulse oximeters can be misleading in hypotensive patients, and a low reading may be due to poor peripheral perfusion rather than failure of adequate oxygenation and ventilation.

7. The patient has fallen off a balcony and has probably suffered a major haemorrhage due to major pelvic trauma. He is in shock and is wheezy. Propofol and thiopentone should not be used here as they can worsen his hypotension and may lead to cardiac arrest at induction. Whilst etomidate is more cardiostable, ketamine is a better choice as it would help maintain his blood pressure and is also a bronchodilator. Inhalational induction is not appropriate for this situation.

Further reading

1. Pai A, Heining M. Ketamine. British Journal of Anaesthesia CEACCP 2007; 7: 59-63

2. Bell RF, Dhai JB, Moore RA, Kalso E. Peri-operative ketamine for acute postoperative pain, a quantitative and qualitative review (Cochrane review). Acta Anaesthesiol Scand 2005; 49: 1405-28.

8. This patient has porphyria, which restricts the choices of drugs which can be used in an emergency. Barbiturates (thiopentone, methohexitone) are definitely unsafe. Judicious use of propofol (along with boluses or infusion of vasopressors) would be the preferred drug for induction. As this patient requires rapid sequence induction and there is no contraindication for using suxamethonium, it can be used. Ketamine is probably safe and is unlikely to provoke acute porphyria. Similarly volatile agents such as isoflurane have been used safely in patients with porphyria.

9. Taking into consideration the history of this patient it would be most appropriate to use etomidate, which is an intravenous anaesthetic agent with the lowest incidence of allergic reactions.

10. The most likely diagnosis is postoperative delirium (POD). The incidence in elderly patients with hip fracture is high, ranging from 16-62% with an average of 35%. The primary treatment is identification and correction of any underlying causes such as pain, hypoxia and dehydration. Pharmacological treatment may be necessary when agitation puts the patient and staff at risk of harm.

Haloperidol is the drug of choice for treating POD. It is administered at a dose of 0.5-1mg I.V. every 5-10 minutes until the agitation is controlled. It has a long half-life of up to 72 hours; it is therefore essential to titrate the dose carefully to avoid over sedation. Benzodiazepines such as midazolam and diazepam can result in sedation, respiratory depression and hypoxia, which may aggravate agitation. In patients undergoing cardiac surgery, ketamine has been shown to reduce the incidence of POD when administered at a dose of 0.5mg/kg at induction.

Further reading.

1. Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. British Journal of Anaesthesia 2009; 103 (Suppl. I): i41- 6.