deep anaesthesia医学论文.pdf

copyright european society of anaesthesiology unauthorized reproduction of this article is prohibited copyright european society of anaesthesiology unauthorized reproduction of this article is prohibited deep anaesthesia reduces postoperative analgesic requirements after major urological procedures ioannis soumpasis fotios kanakoudis georgios vretzakis eleni arnaoutoglou georgia stamatiou and christos iatrou background and objective there is evidence from previous studies that deeper anaesthetic levels reduce postoperative pain along with analgesic requirements the aim of this study was to confi rm this observation during major urological procedures under sevofl urane anaesthesia methods seventy asa i or ii patients undergoing radical prostatectomyornephrectomywererandomlyallocatedintotwo groups the l bis group with bis bispectral index scale values kept within a range of 20 30 and the h bis group with values within the range of 50 60 sevofl urane was the main anaesthetic agent used along with inhalation of nitrous oxide and continuous remifentanil infusion postoperative analgesia wasachievedmainlythroughmorphineandketamine whichwas continuously infused by pump and intravenous parecoxib additional analgesics paracetamol parecoxib and morphine were administered in persistent continuous lasting longer than predicted and requiring repeated doses of analgesics postoperative pain the number of patients who demanded additional analgesia during the fi rst 24h was recorded as well as the number of administrations performed along with visual analogue scale vas scores at 8 and 24h results sixty patients completed the study 30 in each group vas scores at 8h were signifi cantly higher in the h bis group both at rest 1 0 4 vs 2 0 8 p 0 036 and on cough 1 0 5 vs 2 2 9 p 0 021 but at 24h were similar between the two groups four patients in the l bis group and 17 patients in the h bis group demanded additional analgesia p 0 0009 although the patients in the l bis group needed signifi cantly fewer additional doses of analgesics than those in the h bis group 0 0 2 vs 1 0 5 p 0 0008 conclusion the results show that intraoperative deep anaesthetic levels during major urological procedures achieved with high sevofl urane concentrations lead to reduced postoperative analgesic requirements eur j anaesthesiol 2010 27 801 806 keywords anaesthesia analgesia bispectral index urological procedures received 14 april 2009 revised 2 october 2009 accepted 21 january 2010 introduction effectivemanagement ofpostoperative painisassociated with early recovery and reduced cost of medical services 1 recently it was suggested that controlling anaesthetic depth affects postoperative pain levels and reduces analgesicconsumptionduringthepostoperative period 2 3although the authors of these studies do not give a specifi c explanation of this fact it has been proven that subcortical structures such as the spinal cord are among the sites of action of general anaesthetics which cause not only anaesthetic but also some analgesic effects 4 on the contrary acute pain stimulates the release of counter regulatory hormones leading to decreased insu lin sensitivity a metabolic response that seems to be related to pain intensity 5 6the subsequent hypothesis that deeper anaesthesia could attenuate this stress response and consequently infl uence postoperative pain intensityseemstobequestionedbyarecent study which is contrary to the above mentioned fi ndings 7 measurement of anaesthetic depth has been achieved in recent years by several methods such as the bispectral index scale bis auditory evoked potentials spectral edge frequency analysis and entropy bis monitoring a calculated multifactorial parameter derived from the electroencephalogram is a reliable easily readable and comprehensive method to estimate anaesthetic depth 8 bis guided anaesthesia is benefi cial to the patient as it enhances titrationand avoidsexcessiveuseofanaesthetic agents which consequently improve recovery character istics and result in faster recovery earlier orientation and less postoperative nausea and vomiting 9 12 this study was designed to investigate whether during major urological procedures a deep sevofl urane based general anaesthesia improves postoperative outcome and really leads to less pain and reduced consumption of analgesics using the bis monitor and regulating anaes thetic depth at two levels low bis 20 30 and high bis 50 60 patients and methods patients were recruited at the department of anaesthe sia g gennimatas general hospital thessaloniki greece during the period from january 2006 to january 2007 the study protocol was approved by the hospital s ethics committee and written informed consent was obtained by all patients enrolled in the study after a full explanation of the methods purposes and associated original article from the g gennimatas general hospital of thessaloniki thessaloniki is fk anaesthesiology clinic university hospital of larissa larissa gv gs anaesthesiology clinic university hospital of ioannina ioannina ea and anaesthesiology clinic university hospital of alexandroupolis alexandroupolis ci greece correspondence to ioannis soumpasis md 37 stratigi str 54352 thessaloniki greece tel 30 6974073077 e mail siwannis 0265 0215 2010 copyright european society of anaesthesiologydoi 10 1097 eja 0b013e328337cbf4 copyright european society of anaesthesiology unauthorized reproduction of this article is prohibited copyright european society of anaesthesiology unauthorized reproduction of this article is prohibited potential risks patients aged 18 70 years diagnosed with prostate or renal cancer and undergoing radical prosta tectomies or nephrectomies respectively were eligible for the study exclusion criteria were asa status greater than iii bmi higher than 30kgm 2 neurological or psychiatric disorders severe cardiac renal or liver dis ease alcohol or drug addiction recent within 7 days operation under general anaesthesia and known allergies or contraindications to the protocol drugs as well as chronic pain syndromes or previous history of opioid use patients were randomly assigned into two groups the l bis group in which bis values should remain intraoperatively between 20 and 30 and the h bis group in which bis values should remain between 50 and 60 randomization was based on computer gener ated codes maintained in sequentially numbered opaque envelopes which were opened just before induction of anaesthesia allpatientswerepremedicatedwithdiazepam 0 08mgkg 1per os 1h prior to admission tothe operating theatre upon arrival in the operating room a 16 gauge peripheral catheter was placed for administrating fl uids and medication whereas another 20 gauge catheter was inserted under local anaesthesia into the right radial artery to provide invasive arterial blood pressure monitor ing standard asa monitoring was implemented includ ing heart rate and ecg peripheral pulse oximetry and respiratorygasmonitoring includingmeasurementofthe expired concentration of carbon dioxide nitrous oxide and sevofl urane as well as body temperature monitoring probe inserted into the nasopharynx every patient had a four point bis sensor attached to his her forehead according to the manufacturer s instructions after proper cleaning of the skin with an alcohol swab and was connected to the bis monitor bisxp aspect medical systems norwood massachusetts usa a train of four monitor innervator 272 fischer abbott laboratories ltd uk as the main anaesthetic agent the concentration of sevofl urane was titrated in order to achieve before the surgery started and consequently maintain bis values within the range set by the protocol 20 30 in the l bis group and 50 60 in the h bisgroup maintaining ineverycase less than 2 mac the end tidal concentration of sevofl urane was recorded at 10 min intervals beginning right after induc tion until the end of surgery and a mean value was calculated afterwards remifentanil infusion was also titrated in order to maintain mean arterial pressure map within 25 of the baseline values recorded before induction and heart rate hr higher than 45beatsmin 1 or up to a 25 increase from the baseline in cases of tachycardia or hypertension an additional bolus dose of 1mgkg 1remifentanil was administrated and if the symptoms were not treated properly the infusion rate was increased until signs returned to within limits in cases of hypotension or bradycardia the infusion rate was decreased until the symptoms were reversed and small bolus doses of phenylephrine 100mg or atropine 0 5mg respectively were administered in severe cases map 25 of the baseline or hr 3 any time during the 24h period accord ing to a protocol used by the urology clinic paracetamol 15mgkg 1followed by parecoxib 40mg i v if pain did not decline within 15 20min for persistent pain additional incremental doses of morphine were adminis teredwithin5 10minafterthepatient srequest persons assessing pain and administering additional analgesics both on the pacu nurse and the ward anaesthesia resident were unaware of the protocol ensuring the double blindness of the study the parameters recorded were total intraoperative con sumption of remifentanil calculated as mg 1kg 1h 1 the averagevalueoftheexpiredconcentrationofsevofl urane the time interval from discontinuation of sevofl urane until the bis value reached 90 bis90 and the number of patients who required analgesics on the pacu we also recorded the vas score at rest and on coughing at 8 and 24h the number of patients receiving additional analgesics during the fi rst 24h and the total amount of all analgesics administered on both the pacu and the ward statistics all statistical analyses were conducted using a pc based statistical program graphpad prism4 graphpad soft ware san diego california usa calculation of power and sample size was based on initial observations 10 cases in each group of the frequency of administration of additional analgesics during the fi rst 24h l bis group 0 2 0 5 h bis group 1 1 1 0 in order to fi nd a statistically signifi cant difference with a 0 05 and b 0 10 power 0 9 a sample size of 25 patients in each group proved to be suffi cient data are presented as the median lower and upper quartiles unless otherwise stated continuous normallydistributeddata passedthe kolmogorov smirnov test were compared using the unpaired student s t test continuous nonnormally dis tributed data were compared using the mann whitney test binominal data were compared using fisher s exact test p values less than 0 05 were considered to be statistically signifi cant results seventy patients were included in the study and 10 of them were subsequently excluded owing to protocol violations three patients because they were re operated within 24h from the primary operation two patients because they were transferred to icu because of surgical complications four patients whose pumps were acciden tally removed and one patient because the surgical time was relatively short changed surgical plan sixty patients remained in total 30 in each group fig 1 there were no signifi cant differences between the two groups in regard to demographic characteristics duration of anaesthesia and the volume of administered crystal loids colloids or blood the type of surgery did not differ between the two groups as an equal number of patients underwent either one of the two types of operations in each group table 1 deeper anaesthesia reduces postoperative pain803 fig 1 70 patients included 35 patients randomized to l bis group 35 patients randomized to h bis group 5 patients were excluded 2 patients were re operated accidental removal of i v pump in 2 patients 1 patient transferred to icu due to surgical complications 5 patients were excluded 1 patient was re operated accidental removal of i v pump from 2 patients 1 patient transferred to icu due to significant bleeding operation time was relatively short in 1 patient 60 patients completed the study 30 patients to l bis group 30 patients to h bis group flowchart european journal of anaesthesiology2010 vol 27 no 9 copyright european society of anaesthesiology unauthorized reproduction of this article is prohibited copyright european society of anaesthesiology unauthorized reproduction of this article is prohibited the end tidal concentration of sevofl urane was signifi cantlyhigher inpatients inthel bisgroup 3 2 2 5 3 7 vs 0 9 0 6 2 p 0 0001 as was the remifentanil consumption 6 75 4 85 9 45 vs 5 84 3 15 9 11 p 0 021 reaching bis90 was signifi cantly prolonged in the l bis group 25 14 35 vs 10 5 17 p 0 0001 table 1 there was no signifi cant difference between the two groups in regard to the number of patients who needed additional analgesia in the pacu fi ve patients in the l bis group and 10 patients in the h bis group table 2 vas scores at 8h were signifi cantly higher in the h bis group both at rest 1 0 4 vs 2 0 8 p 0 036 and on coughing 1 0 5 vs 2 2 9 p 0 021 whereas at 24h no signifi cant differences were observed between the groups table 2 in the l bis group only four patients demanded additional analgesia during the fi rst 24h whereas in the h bis group 17 patients asked for additional analgesics p 0 0009 finally patients in the h bis group demanded signifi cantly more repeated doses of analgesics during the 24h than those in the l bis group 0 0 2 vs 1 0 5 p 0 0008 table 2 fig 2 discussion the results of the present study are similar to those of previous ones which demonstrated that deep anaesthesia results in less postoperative pain and reduced consump tion of analgesics 2 3 our fi ndings have shown that a signifi cantlydecreasednumberofpatientsinthe l bis group needed further treatment for pain during the fi rst 24h as well as fewer repeated doses of analgesics vas scores at 24h were similar between the two groups suggesting an effective overall postoperative pain man agement although it was achieved with more analgesics in the h bis group during recent years several methods for assessing anaes thetic depth have been introduced such as auditory evoked potentials spectral edge frequency analysis entropy as well as bis bis a 0 100 dimensionless 804soumpasis et al table 1patients characteristics and surgical data l bis grouph bis group signifi cance patient s 3030 age years 62 42 73 60 29 75 ns weight kg 78 65 110 80 60 115 ns height cm 170 155 184 173 155 185 ns bmi kgm 2 27 1 26 6 30 26 7 25 30 ns duration min 125 80 195 128 95 205 ns bis90 min 25 14 35 10 5 17 0 0001 crystalloids ml 2200 345 6800 2500 355 6500 ns colloids ml 1000 640 3000 1000 653 3100 ns blood ml 240 0 1310 190 0 2000 ns remifentanil consumption mgkg 1h 1 6 75 4 85 9 45 5 84 3 15 9 11 0 021 sevofl urane end tidal concentration 3 2 2 5 3 7 0 9 0 6 2 0 0001 type of surgery prostatectomies1615ns nephrectomies1415ns bis bispectral index scale table 2postoperative visual analogue scale scores and additional analgesia demands l bis grouph bis group signifi cance patients3030 vas score 8h postoperative at rest1 0 4 2 0 8 0 036 on coughing1 0 5 2 2 9 0 021 24h postoperative at rest0 0 2 1 0 2 ns on coughing0 0 3 1 1 4 ns additional analgesia in pacu number of patients510ns morphine mg 0 0 2 0 0 5 ns additional analgesia number of patients417 0 0009 repeated administrations0 0 2 1 0 5 0 0008 bis bispectral index scale ns not signifi cant pacu postanaesthesia care unit vas visual analogue scale fig 2 4 3 2 additional analgesia times 1 0 l bish bis postoperative additional analgesia in l bispectral index scale and h bispectral index scale groups european journal of anaesthesiology2010 vol 27 no 9 copyright european society of anaesthesiology unauthorized reproduction of this article is prohibited copyright european society of anaesthesiology unauthorized reproduction of this article is prohibited numbered scale based on the electroencephalogram is considered to be a reliable and concise method for monitoring anaesthetic depth without the need for specifi c eeg interpretation and helps to provide ideal intraoperative conditions by avoiding extreme fl uctu ations in anaesthetic depth 8adding bis to standard monitoring helps to reduce signifi cantly the consumption of volatile anaesthetics and propofol while improving the outcome with less postoperative nausea and vomiting as well as earlier orientation of the patients 9 12in addition other studies suggest that deep anaesthesia is correlated with less postoperative pain and a reduced need for analgesics raising the question of whether deeper anaes thetic levels should be used as a norm in order to mini mize pain and analgesic consumption 2 3 15 as expected higher concentrations of sevofl urane were neededto achieve a deeperanaesthetic levelin the l bis group resulting in a signifi cant difference in the end tidal sevofl uraneconcentrationfromtheh bisgroup remifentanil was used as the intraoperative analgesic becauseitspharmacokineticandpharmacodynamic characteristics allow rapid emergence from anaesthesia without prolonged sedation but its lack of preemptive analgesic effects allows the accurate estimation of analge siaproducedbytheanalgesic regimenadministratedpost operatively 16 18 thesignifi cantlyhigheramountsofremi fentanil that were used by patients in the l bis group comparedwiththoseintheh bisgroup 6 75 4 85 9 45 vs 5 84 3 15 9 11 might be a limitation of our study the increased dosage of remifentanil in the l bis group could only be attributed to achieving the deep sedation levels bis 20 30 by using it as an adjuvant to the sevofl urane action remifentanil as an opioid itself could also induce postoperative hyperalgesia owing to acute opioid tolerance which could consequently affect post operative pain and the demand for analgesics evidence shows that this seems to develop when high infusion rates 0 4mg 1kg 1min 1 of remifentanil are administered forlongerthan3h 19lowerratesoflessthan 0 2mg 1kg 1min 1 actually 0 17mg 1kg 1min 1or about 10 2mg 1kg 1h 1 which a