Mohammed T. Abou-Saleh

ANAESTHETICS AND MENTAL STATE 747Table 137.2Other studies of general anaesthesia and postoperative cognitive dysfunctionReferenceAge (n)Type ofsurgeryType ofpsychometrictestsTiming of postoperativetestsResultsLong-termchange?Comments32 >60 (1218patients,plus 321communitycontrols)Major noncardiacsurgery (ifpreoperativeMini-MentalStatus was 24or more)33 48–88 (112) Transurethralresection ofprostateEUBT (see textfor details)Choice reactiontime7 days3 months16 25–83 (40) Cholecystectomy Mini-Mental, digit 1, 2, 3, 4 days,symbol/span, trail 1 monthmaking34 Two groups:young,mean age50; oldmean age69 (n=85)Orthopaedic, 17 Questionsgynaecological (orientation/and general concentration),surgery plus objectlearning testPostoperative cognitivedysfunction (definedafter comparisonswith untreated controls)in 25.8% at 7days and 9.9% at 3months (controls3.4%, 2.8%)1, 2, 3 days Increased variability inchoice reaction time,day 1 onlyChanges on day 1 only:digit symbol (all), trailmaking (old only)2 days Memory deficits (youngand old). Orientationand concentrationdeficits (old only)YesNot testedNoNot testedAge, duration of anaesthesia,less education,and respiratory andother complications(but not hypoxaemia)correlated withdysfunction at 7 daysAge was only risk factorcorrelating with cognitivedysfunction at 3monthsIncreased variability associatedwith previouslow CAPE (CliftonAssessment Procedurefor the Elderly),extent of surgery,postoperative pain/sedationConcluded there was nomajor difference inrate of recoverybetween young andelderly groupsCorrelation betweenpostoperative deficitsand poor preoperativecognitivefunctioncontinuous pulse oximetry before surgery, throughout the day ofsurgery, and for the next three nights. Blood pressure wasrecorded by oscillometry during the operation and every 30 minfor the rest of the operative day and night. Patients receivedgeneral anaesthesia but no restriction was placed on anaesthetic orsurgical technique, which conformed to local practice in the studycenters. However, to avoid the cerebral vasoconstrictor effects ofhypocapnia, capnography was a requirement during surgery, sothat normocapnia could be maintained.Analysis of the data from ISPOCD1 32 showed that 25.8%patients had POCD 7 days after surgery and that 9.9% of allpatients still had evidence of POCD on the repeat neuropsychologicaltests carried out at 3 months (corresponding values forcontrols were 3.4% and 2.8%). Contrary to expectations, norelationship was found between hypoxaemia and/or hypotensionand the development of early or late POCD. Indeed, despiteanalyses of the effects of more than 25 other clinical parameters,only age showed a statistically significant correlation with latePOCD. Age was also positively correlated with early POCD, aswere duration of anaesthesia, a lesser level of education, a secondoperation, postoperative infections and respiratory complications.The overall conclusion of the ISPOCD1 investigators 32 was thattheir study had demonstrated a measurable degree of postoperativecognitive change in a minority of older patients 3months after surgery (in about 10% of patients vs. about 3% ofnon-operated controls) and that the risk increased with age.However, the expected relationship between hypoxaemia and/orhypotension and POCD did not emerge in the study. It was alsodisappointing that, despite a large number of statistical analyses,the study failed to find any specific risk factors that were amenableto therapeutic or preventive intervention. In addition, the hopethat the study would give better insight into the pathophysiologyof POCD was not fulfilled.Because the ISPOCD1 study did not provide the expectedanswers in regard to the prevention or treatment of POCD,ISPOCD2 is now under way, coordinated from Copenhagen byJ. T. Moller and L. S. Rasmussen. I am very grateful to DrChristopher Hanning, a member of the ISPOCD2 steeringcommittee, for the following information. ISPOCD2 comprisesa linked group of multicentre projects which will ask a dozenmajor research questions in a variety of patient populations. Amajor task of ISPOCD2 will be to follow up patients for aprolonged period, to see whether the 3 month postoperativeneuropsychological changes persist, and to test whether thesechanges produce measurable effects on Activities of Daily Livingand Quality of Life. Other research tasks addressed by ISPOCD2include: an investigation of the effects of outpatient anaesthesia; acomparison of the effects of regional anaesthesia with those ofgeneral anaesthesia; a comparison of POCD incidence in patientsaged 40–60 years and in older patients; a test of the hypothesisthat there might be a genetic predisposition to POCD related tothe apolipoprotein E allele, which is known to have an associationwith the development of Alzheimer’s disease; a correlation ofblood levels of benzodiazepines and their metabolites with thedevelopment of POCD; an examination of the role of cholinergicand other neurotransmitters in POCD, using an animal model andpositron emission tomography (PET) in humans; the study ofpossible protected effects of ondansetron; a study of structuralcerebral changes by both MRI and SPET scanning; correlationsof POCD with neurone specific enolase and protein S100; and theinvestigation of the relationship between POCD and ‘‘stress’’,particularly prolonged hypercortisolaemia.