Correlation Between Changes Of Arterial Partial Carbon Dioxide Pressure Combined With Corresponding Changes Of Regional Cerebral Oxygen Saturation Variability And Delirium After Abdominal Surgery In Older Adults

Objective Perioperative neurocognitive dysfunction has become a public health problem,especially the aging population and the increasing number of surgeries.Due to significantly higher incidence of frailty and comorbidities than in young and middle-aged patients,older adults require special clinical attention.Perioperative neurocognitive impairment included preoperative mild and severe neurocognitive impairment,post-operative delirium,30-day delayed neurocognitive recovery,and post-operative mild to severe neurocognitive impairment for 12 months or longer.Among them,post-operative delirium is one of the most common complications after anesthesia in elderly patients.Post-operative delirium is usually associated with increased complications,long-term mortality,the need for additional tests and special care.Post-operative delirium affects long-term cognitive ability and quality of life,as well as prolonged hospital stay,increased treatment costs and 30-day readmission rates.Maintaining the integrity of brain function is one of the key objectives of perioperative anesthesia management,which can be achieved by optimizing the balance of cerebral oxygen supply and demand.Cerebral hypoxemia is affected by cerebral oxygen desaturation,low blood pressure and hemoglobin levels.Regional cerebral oxygen saturation（rSO₂）is a direct reflection of the oxygen content of brain tissue and reflects the oxygenation of brain tissue to a certain extent.Cerebral oxygen desaturation may be a potential pathogenesis of post-operative delirium.Therefore,the occurrence of post-operative delirium can be significantly reduced if early prediction and intervention of high-risk patients was done.Near-infrared spectroscopy is a technology for monitoring non-invasive,real-time,and continuous measurement of regional cerebral oxygen saturation.However,due to the complex nature of delirium and confounding factors in cerebral oxygenation monitoring,the correlation between intraoperative changes in rSO₂ and the occurrence of post-operative delirium remains controversial.Recent studies have applied the similar measurement of blood pressure variability to the analysis of local cerebral oxygen saturation variability to obtain the cerebral oxygen saturation variability rate.The relative change of rSO₂ based on the adjustment of partial pressure of carbon dioxide,blood pressure and cardiac output increases the clinical application of perioperative cerebral oxygen saturation.Compared with the absolute value of rSO₂,the variation rate of rSO₂ takes into account the overall change of patients over time.Meanwhile,rSO₂ variability can exclude the influence of monitoring factors that has better stability and suitable for individual evaluation.The relationship between carbon dioxide and cerebral blood flow can be used to evaluate cerebral vasomotor response,and the consequent affecting rSO₂.The reactivity of rSO₂ to carbon dioxide can be used to evaluate cerebral vascular function.However,there is no consensus on the effects of different surgical types,population heterogeneity,and study design on the degree of association.Therefore,this study aims to explore the correlation between intraoperative changes in carbon dioxide combined with consequent changes of rSO₂ variation rates and post-operative delirium in elderly patients undergoing major abdominal surgery to identify high-risk patients requiring early treatment and management.Methods Elderly patients at the Second Affiliated Hospital of Anhui Medical University who underwent elective major abdominal surgery were enrolled in this prospective study from August 2021to January 2022.Inclusion criteria including age≥60,ASA I-III level,operation time≥2 hours.The patients’informed consents were obtained at the same time.Ruling out patients combined with preoperative cognitive dysfunction,and who cannot complete cognitive and psychological tests.General conditions of patients were recorded,including age,gender,body mass index,blood pressure,heart rate,ASA Rating,pain rating,etc.,and the Cumulative Illness Rating Scale（CIRS）was used to evaluate the comorbidity of patients.Recording laboratory results including hematocrit,red and white blood cell counts,hemoglobin,sodium and potassium levels,creatinine,blood glucose,albumin concentration.Blood gas analysis was detected to record p H,arterial oxygen partial pressure,arterial carbon dioxide partial pressure and lactic acid concentration.All patients were fast for 8 hours,and did not take any sedative and analgesic drugs before surgery.Vital signs,rSO₂ and anesthesia depth were monitored after entry.Anesthesia tracheal intubation was performed after right radial artery puncture and internal jugular vein catheterization.The time points including before anesthesia induction（T₀）,5 minutes after intubation（T₁）,and 5 minutes after the adjustment of tidal volume and ventilation frequency to achieve arterial carbon dioxide partial pressure（Pa CO₂）of 25-30mm Hg before cuticle resection（T₂）.Then the tidal volume was halved and the respiratory rate was reduced until Pa CO₂ of 45-50mm Hg was maintained for 5 minutes（T₃）.Intraoperative Pa CO₂ was maintained at 35-45mm Hg until the end of suture（T₄）,and the Pa CO₂ was adjusted again for 5 minutes（T₅）after25-30mm Hg and 5 minutes（T₆）after 45-50mm Hg.The patient would be eliminated if the time from the adjustment of mechanical ventilation parameters to the target Pa CO2 was above 5 minutes,or the whole intervention period was above 20 minutes.Hemodynamic parameters,rSO₂ and blood gas analysis parameters of patients were continuously measured and recorded.Using rSO₂ at T₀ as the baseline,the absolute value of rSO₂ before and after adjustment of carbon dioxide was recorded.The variation rate of rSO₂ in response to CO₂（TΔrSO₂%）was calculated using the similar measurement of blood pressure variability through the testing time.The formula was implant into the near-infrared spectroscopy.The main outcome of the study was the occurrence of post-operative delirium.Patients’general condition,TΔrSO₂%,rSO₂ at different time points during the operation were compared between the group with and without delirium.Results Among the 139 participants initially included,35 were excluded and 3 lost follow up.A total of 101 subjects were finally analyzed that 69（68.3%）were males and 32（31.7%）were females,both aged 73（66.5,78.0）years.After the operation,16 patients（15.8%）developed delirium.Compared with the non-delirium group,there were significant differences in age,CIRS,use of vasopressors and preoperative albumin levels than that in delirium group（P<0.05）.There were no significant differences in intraoperative MAP and HR between the two groups,but the delirium group had lower p H and Pa O₂ at T₄,T₅ and T₆,and higher lactate levels（P<0.05）.rSO₂ was 69.0（63.2,75.2）,70.7±7.3,68.2±7.5,72.1±8.0,69.9±7.8,67.4±7.2,71.7±8.1 at each time point,respectively.The average carbonate intervention period was 17.2.2±1.1 min,with 16.9±1.2min and 17.3±1.0min respectively.The test time had no significant difference（P=0.158）.Excluding the effect of carbon dioxide on rSO₂,the absolute value of rSO₂ was（63.2±6.0）in delirium group which was significantly lower than that in non-delirium group（70.9±7.1）（P<0.05）.TΔrSO₂%6.62（5.31,9.36）,the change rate of post-operative response to carbon dioxide in delirium group was lower than that before operation（-11,11）,and there was no significant change in TΔrSO₂%7（6,9）in non-delirium group,which was statistically significant between the two groups（P<0.05）.Univariate analysis showed that Age（P=0.028）,CIRS（P=0.002）,vasopressor use（P=0.037）,preoperative albumin level（P=0.038）,length of hospital stays（P=0.018）,rSO₂ at T₁（P=0.003）,rSO₂ at T₄（P<0.001）and post-operative TΔrSO₂%（P=0.002）were significantly associated with post-operative delirium.However,multivariate analysis found that CIRS（OR=1.89,95%CI:1.10-3.25,P=0.021）,preoperative albumin levels（OR=0.67,95%CI:0.48-0.94,P=0.022）,absolute value of rSO₂ at the end of surgery（OR=0.61,95%CI:0.41-0.89,P=0.010）and TΔrSO₂%（OR=0.80,95%CI:0.66-0.98,P=0.028）was independently associated with post-operative delirium in elderly patients undergoing elective major abdominal surgery.Conclusion This study confirmed that the reduction of absolute value of rSO₂ during surgery and the decrease of reactivity to carbon dioxide after surgery（TΔrSO₂%）were independently associated with the occurrence of post-operative delirium in elderly patients undergoing selective major abdominal surgery.The test method in this study can provide a new predictive means to identify high-risk patients.