Question 16

College Answer

Graphical depictions of the effect of Mean Arterial Pressure, oxygen tension and carbon dioxide tension on cerebral blood flow were common and in general accurate. Mention of factors that affected, and regulation of, the MAP vs CBF graph was expected in order to pass this question well. 
The effect of propofol and ketamine on the CBF was well answered. Propofol and ketamine have an opposite effect on cerebral haemodynamic and metabolic rate. Propofol produces a dose dependent reduction in CBF with proportionate reduction in CMRO2, and thus a minimal change in cerebral venous O2 Sat. Propofol doesn’t affect the autoregulatory curve of CBF and the PaCO2 response. Ketamine produce a dose dependent increase in CBF and a mild increase in CMRO2. 

Recommended sources: Guyton Textbook of Medical Physiology Chp 61; Goodman and Gilman 
The pharmacological basis of therapeutics 11th edition pgs 350-352. 

Discussion

With any luck, this graph is "in general accurate". It attempts to bring all of the factors onto one graphical field, mindful of the fact that they are only related by the fact that they are measured in mmHg

• PaCO₂: increased PaCO₂ leads to increased CBF 
  • At a PaCO₂ of around 70 mmHg, the CBF is basically doubled (Kety & Schmidt, 1947) 
• PaO₂:  PaO₂ falling below 50 mmHg leads to exponentially increased CBF.
  • At a PaO₂ of around 20 mmHg, CBF may increase up to 700% (Jóhannsson and Siesjö, 1975),
• MAP: CBF is stable over a range of MAP between 50 and 150 mmHg.
  • As MAP decreases below around 60 mmHg, CBF cannot be maintained
  • As MPA increases beyond around 150 mmHg, cerebral autoregulation fails and CBF increases in proportion to the increase in pressure 

• Effects of propofol on cerebral blood flow and CMRO₂: 
  • Propofol produces a dose-dependent decrease in CMRO₂.
  • As CMRO₂ is closely tied to the autoregulation of blood flow, it also decreases CBF
  • The relationship between CBF and CMRO₂ changes is linear
  • Thus, because both oxygen consumption and oxygen delivery are decreased together, the total oxygen extraction ratio remains stable, and there is no change in the SjvO₂ (Oshima et al, 2002).
• Effects of ketamine on cerebral blood flow and CMRO₂:
  • Ketamine certainly increases CBF
  • Ketamine supposedly also increased CMRO₂. 
  • The increase in CBF is said to be uncoupled from the increase in metabolic rate, but in spite of that, they are sufficiently well matched, such that with ketamine the SjvO₂ remains stable (Bhaire et al, 2019; Mayberg et al, 1995)

It would be uncontroversial to say that propofol decreases, and ketamine increases, cerebral blood flow. The question on the effects of propofol and ketamine on cerebral metabolism is more delicate, mainly because most  textbooks will still tell you that ketamine increases CMRO₂. For example, this is what you will find in the 23rd edition of Katzung (p. 456). However, modern human data (eg. Långsjö et al, 2003) suggests that this is not a real effect, and that ketamine either has no effect on cerebral metabolic rate, or only a mild and regional effect (mainly increasing CMRO₂ in the frontal lobe and limbic system).  Unfortunately, question writers base these questions on textbooks (often, textbooks from their own distant youth), which means you really have to give the wrong answer here to score any marks. As always, the basic principle remains: don't start an argument with the examiner.

Busija, David W., and Donald D. Heistad. Factors involved in the physiological regulation of the cerebral circulation. Springer Berlin Heidelberg, 1984.

Kety, Seymour S., and Carl F. Schmidt. "The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men." The Journal of clinical investigation 27.4 (1948): 484-492.

Jóhannsson, Halldór, and Bo K. Siesjö. "Cerebral blood flow and oxygen consumption in the rat in hypoxic hypoxia." Acta physiologica Scandinavica 93.2 (1975): 269-276.

Oshima, T., F. Karasawa, and T. Satoh. "Effects of propofol on cerebral blood flow and the metabolic rate of oxygen in humans." Acta anaesthesiologica scandinavica 46.7 (2002): 831-835.

Schwedler, Margaret, David J. Miletich, and Ronald F. Albrecht. "Cerebral blood flow and metabolism following ketamine administration." Canadian Anaesthetists’ Society Journal 29.3 (1982): 222-226.

Takeshita, Hiroshi, Yoshiaki Okuda, and Atuo Sari. "The effects of ketamine on cerebral circulation and metabolism in man." Anesthesiology: The Journal of the American Society of Anesthesiologists 36.1 (1972): 69-75.

Slupe, Andrew M., and Jeffrey R. Kirsch. "Effects of anesthesia on cerebral blood flow, metabolism, and neuroprotection." Journal of Cerebral Blood Flow & Metabolism 38.12 (2018): 2192-2208.

Långsjö, Jaakko W., et al. "Effects of subanesthetic doses of ketamine on regional cerebral blood flow, oxygen consumption, and blood volume in humans." Anesthesiology: The Journal of the American Society of Anesthesiologists 99.3 (2003): 614-623.

Bhaire, Vishwanatha S., et al. "Effect of combination of ketamine and propofol (ketofol) on cerebral oxygenation in neurosurgical patients: a randomized double-blinded controlled trial." Anesthesia, essays and researches 13.4 (2019): 643.

Mayberg, Teresa S., et al. "Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anesthesia in patients undergoing craniotomy." Anesthesia & Analgesia 81.1 (1995): 84-89.