Concentration Variation Of Minimum Alveolar Concentration-awake In Patients With End Stage Renal Disease

Objective:End stage renal disease（ESRD）,characterized by glomerular,tubular,and parenchymal disturbances,leads to metabolic abnormalities collectively known as uremia.With an increasingly prevalent multi-symptom illness complex,ESRD has been shown to co-exist with abnormal brain function,characterized by personality changes,neuropsychological deficits,and other neurological symptoms.According to the accepted cause of uremic encephalopathy,it is suggested that neurotransmission and structures in the brain are altered through several mechanisms including toxic accumulation of metabolic byproducts,hypercoagulability,immunological disturbances,and tubular acid-base disequilibrium,among others.The focus of development in the field of renal replacement therapy has centered around adequate removal of urea and other associated toxins.However,ESRD treatment involving hemodialysis and peritoneal dialysis may also contribute to neurological disorders due to the insufficient elimination of toxic substances,fluctuation of extracellular fluid volume,and exposure to bio-incompatible materials.Accumulating evidence has suggested that inhaled anesthetics exert their effects by acting on ion channels and receptors expressed on the neuronal cell membrane and altering synaptic transmission in the central nervous system.For patients with ESRD,pathophysiological alternations in the brain may affect sensitivity to inhaled anesthetics.The minimum alveolar concentration（MAC）for achieving a 50%probability of no response to a verbal command(MAC_awake)provides one measure of hypnotic potency.Sevoflurane,one of the most common clinically used volatile anesthetics for general anesthesia and sedation,is believed to act through multiple receptor targets to inhibit excitatory ion channels and potentiate inhibitory ion channels.Accordingly,we designed this study to determine whether the MAC_awake of sevoflurane in patients with ESRD undergoing surgical treatment is different from that in patients with normal renal function.In addition,serum neuron-specific enolase（NSE）,a biochemical marker rapidly released into the circulation by damaged nerve cells,as well as blood gas and renal function,were analyzed during the measurement of MACawake.Methods This study was approved by the Ethics Committee for Clinical Trials of the Second Affiliated Hospital of Anhui Medical University.Written informed consent was obtained from 60 patients undergoing elective surgery requiring general anesthesia.Thirty patients with ESRD scheduled for parathyroidectomy were included in this study（ESRD group）.Patients were currently undergoing hemodialysis at a frequency of three times per week or daily peritoneal dialysis,and no patients exhibited signs of overt uremic encephalopathy.An additional 30 patients scheduled for general anesthesia with normal renal function and American Society of Anesthesiologists physical status I or II served as controls（control group）.All patients were between 18 and 65 years of age.Each patient fasted for 8 h,and did not receive any sedative or analgesic drugs before anesthesia.Investigations involving patients with ESRD were performed the day after hemodialysis or peritoneal dialysis.After priming the circuit for 1 min,all patients took three maximum breaths of 8%sevoflurane in 100%oxygen at a flow rate of 6L/min via a tight-fitting facemask delivered through a semi-closed circuit system.After loss of consciousness,the sevoflurane dial concentration was reduced to a predetermined end-expiry concentration.MAC_awake testing for each group was performed by the Dixon up and down sequential-allocation technique.The response of a patient determined the concentration of sevoflurane administered to the following patients in each group.The first patient’s predetermined end-expired concentration of sevoflurane in both groups was 1.0%.This and subsequent steps were maintained for 15min to allow adequate time for alveolar and brain sevoflurane partial pressures to equilibrate.A designated observer,who was blinded to the aim and design of the study,then asked the patient in a normal tone to open his/her eyes,repeating the request not more than three times.If the patient responded appropriately,the end-expired sevoflurane concentration in the next patient would be increased by 0.2%and,again,maintained for 15 min.If the response was negative,the end-expired sevoflurane concentration given to the next patient was decreased by an equivalent amount.The process of assessing the response was continued until seven crossovers of a negative response in the pre-patient with a positive response in the next patient had occurred.The corresponding end-expired sevoflurane concentration to a midway point between the negative response and the positive response was defined as the value of MAC_awake of sevoflurane for one crossover,and the mean value of seven crossovers in each group was defined as the group’s MAC_awake for sevoflurane.Up and down sequences were analyzed using the probit test,which enabled MAC_awake with 95%confidence interval of the mean to be derived.Heart rate（HR）and mean arterial pressure（MAP）were manually recorded before induction and immediately before the MAC_awake measurement.An appointed anesthesiologist who was blinded to the patient group recorded the data.When MAC_awake had been determined,samples of arterial blood were collected for analysis of blood gas tensions and measurements of renal biochemistry.Serum NSE levels were measured using an immuno-luminometric assay.After the above measurements had been completed,anesthesia was deepened to a level appropriate for tracheal intubation and the surgical procedure.Results Thirty patients provided written informed consent and met the inclusion criteria in each group;21 patients were sequentially selected until seven crossovers were obtained.One case was excluded from the ESRD group because of hyperkalemia.Thus,41 patients were included in the final analysis with 20 in the ESRD group and 21 in the control group.As a result of chronic renal failure and secondary hyperparathyroidism,patients with ESRD exhibited significantly higher levels of blood urea nitrogen（BUN）,creatinine（Cr）,uric acid（UA）and Ca²⁺as well as lower levels of hematocrit and hemoglobin values compared to the control patients.Due to the regular dialytic therapy and sufficient ventilation,no acid-base,glucose,electrolyte abnormalities,hypoxia or hypercapnia were noted.There was a significant higher level of NSE in patients with ESRD.The MAC_awake of sevoflurane in patients with ESRD was 0.56%（SD=0.10%）,which was significantly less than that observed in the control group（0.67%[SD=0.08%];P=0.031）.Similar results were obtained using probit analysis with values of0.59%（95%confidence interval,0.50%to 0.66%）and 0.71%（95%confidence interval,0.63%to 0.80%）,for the ESRD and control groups respectively,and the relative median potency was 0.82（95%confidence interval,0.47 to 0.99）.There was also a difference in the MAC_awake of the two groups,since the confidence interval of relative median potency did not include 1.Multivariable logistic analysis suggested that the odds of being awake was 0.016 times higher（95%CI 0.0003 to 0.9411）for ESRD patients compared to those in control group when controlling for age,body weight,and gender.There was no serious hemodynamic instability except in one patient with ESRD who had a fall in MAP below 60 mm Hg,which was successfully managed with 40μg phenylephrine and fluid therapy.Conclusion Our study demonstrated that patients with ESRD exhibit a somewhat lower MAC_awake of sevoflurane compared to patients with normal renal function.Our findings may be useful in avoiding excessive depth of anesthesia in patients with ESRD.Additional studies should be performed to elucidate the mechanisms of the reduction of MAC_awake in this population.