Anesthesia and memory loss
Originally published Monday, June 2, 2008 at 12:00 AM
Q. My mother recently had surgery and now is experiencing significant memory loss. The doctor said that anesthesia sometimes affects memory… How long will this last, and is there anything we can do to help her recover?
A. Surgeons and anesthesiologists call this condition postoperative cognitive decline (POCD).
There is controversy as to whether the problem is brought on by anesthesia or by surgery itself. Some commonly inhaled anesthetics like isoflurane and halothane have been linked to dementia in mouse research (Neurobiology of Aging online, March 7, 2007). Injected anesthetics such as propofol and thiopental may be less likely to cause such problems (Neurochemical Research, August 2005).
For many surgical patients, POCD disappears within a year. A small number, however, may have lasting memory problems. We don’t know of any way to reverse such cognitive decline.
Anesthesia and Postoperative Cognitive Dysfunction (POCD)
Authors: Rammes, Gerhard; Zieglgansberger, Walter; Kochs, Eberhard
Source: Central Nervous System Agents in Medicinal Chemistry(Formerly Current Medicinal, Volume 8, Number 1, March 2008 , pp. 37-47(11)
Publisher: Bentham Science Publishers
Postoperative cognitive dysfunction (POCD) describes a decline in cognitive function for weeks or months after surgery with prevalence in the elderly patient. Numerous methodological limitations make the interpretation of this clinical syndrome, based on the available literature on POCD, difficult, particularly the different definitions of POCD, the lack of control groups and the relative inconsistency in the occurrence of memory deficits. Several theories have been advanced to explain these observations, but although there is general agreement that POCD is likely to be multi-factorial, whether its occurrence is a result of the effects of surgery or general anesthesia remains unclear. This review provides a synopsis of the available clinical and preclinical data and summarizes recent research relevant to the occurrence of POCD and possible pharmacologic algorithms for its prevention and treatment. The effects of volatile and intravenous anesthetics on synaptic transmission and synaptic plasticity, which might be related to cognitive dysfunction in the postoperative period, will be discussed. Unraveling these mechanisms should provide helpful indices for the identification, synthesis and development of new chemical entities suitable for therapeutic use.
Postoperative cognitive dysfunction
C. D. Hanning
University Hospitals of Leicester and University of Leicester, Leicester, UK
Keywords: cognitive dysfunction, postoperative; measurement techniques; psychology
The target organ for anaesthetic drugs is the brain. For many years, it has been assumed that their effects do not outlast their pharmacological action, that the target organ is restored to its previous state once the agent is eliminated. There is increasing evidence that this is not true, that long term or even permanent neuronal and neurological change can follow administration of anesthetic drugs. The brain appears to be particularly vulnerable at the beginning and end of its life. Animal studies have suggested that permanent changes may be induced in developing brains,11 12 23 but this review will concentrate on changes which may occur in the ageing brain. The earliest manifestation of neuronal damage in the brain is a decline in the higher cortical functions of storage and recall of memory and cognitive processing.
The increasingly aged population has stimulated research into premature cognitive decline from all causes. A number of studies have investigated postoperative cognitive dysfunction (POCD), predominantly in the elderly, and these will be discussed together with theories on causation and the limited animal work available thus far.
One of the difficulties of human research in this area is that anaesthesia is hardly ever administered as a sole procedure but is almost invariably given to facilitate surgery. As will be discussed below, the stress response to surgery has been suggested as a possible mechanism for POCD. Thus, in all human studies, the term ‘operation’ should be understood to include both anaesthesia and surgery.
Definition and measurement
Cognition is defined as the mental processes of perception, memory, and information processing, which allows the individual to acquire knowledge, solve problems, and plan for the future. It comprises the mental processes required for everyday living and should not be confused with intelligence. Cognitive dysfunction is thus impairment of these processes.34 It is usually expressed by patients in terms of failure to perform simple cognitive tasks, for example to move to another room and, on arrival, to have forgotten the reason for the move, or to be unable to complete mental tasks, such as crosswords, that were previously easily attainable.
Causation of POCD
If it is accepted that POCD exists, it implies an effect on the brain which outlives the action of the drugs associated with anaesthesia, but, as the brain is their target organ, it does not exclude the possibility that the drugs might be responsible. Additional tasks of the ISPOCD2 studies have tested several hypotheses of the causation of POCD. The role of anaesthesia per se was examined in a randomized comparison of 364 elderly patients undergoing major, predominantly orthopedic surgery, under either GA or regional anaesthesia (RA).36 There was no difference in the frequency of POCD between the groups receiving GA and those receiving RA, suggesting that anaesthesia is not a risk factor. However, as most patients in the RA group received a sedative infusion of propofol, this conclusion may be questioned.
Hanning and colleagues18 investigated the effects, in rats, of repeated anaesthesia throughout life with pentobarbital, compared with a control group. This was a small study with an agent no longer used in human anaesthetic practice and the results should be treated with caution. There is however, some support for an effect of long-term administration of cholinergic drugs on cognitive function from other fields. For example, patients with Parkinson’s disease treated with anti-muscarinic drugs are more likely to show Alzheimer pathology at post-mortem examination;32 nicotine has been shown to be protective of nicotinic cholinergic receptors;6 49 and low level exposure to organo phosphorus esters may cause neurotoxicity.22
Greater impulsivity in behavioural task performance was noted between the elderly rats that had been subject to repeated anaesthesia throughout life and the control animals mentioned above.7 Culley and colleagues have reported long-term effects of anaesthesia on cognitive function in rats with agents commonly used in human practice.11 12
Subjects with the apolipoprotein 4 allele are known to have worse cognitive and neurological outcomes after brain injury and stroke,48 and to be at greater risk of AD.43 The role of APOE genotype was investigated in 976 patients undergoing major surgery in the ISPOCD2 studies,2 and in the smaller odour identification study mentioned above.38 In neither study was the 4 allele a risk factor for POCD. This does not rule out the possibility of a genetic propensity for POCD but suggests that other candidate genes should be sought.
I say: what about if fluoride has never been considered as the cause of Alzheimer’s for some of us? What about if fluorinated anesthetic agents precipitate this memory loss? How I wished I were rich and publish my findings ASAP and send copies to every anesthesia department in the USA… May be someone could start the research in this field… and figure out the causes of Alzheimer’s for the entire world…