Using a diagram, explain the effect of PaO2, PaCO2 and MAP (Mean Arterial Pressure) on cerebral blood flow (CBF). (60 % of marks) Outline the effects of propofol and ketamine on CBF and cerebral metabolic requirement for oxygen (CMRO2). (40% of marks)
This question was well answered. It is a structured question that guides candidates through
exactly what is required. Well drawn graphs were a particularly effective means of scoring
It is perhaps presumptious of the author to present the doodles below as "well drawn graphs", but they are offered here nonetheless.
- 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 in excess of the increase in metabolic rate (
- Therefore, ketamine decreases SjvO2
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.