Spinal General Anaesthesia Decreases Neuroendocrine Stress Response in Laparoscopic Cholecystectomy

Transcription

1 The Journl of Interntionl Medicl Reserch 2012; 40: Spinl Generl Anesthesi Decreses Neuroendocrine Stress Response in Lproscopic Cholecystectomy P CALVO-SOTO 1, A MARTÍNEZ-CONTRERAS 2, B TRUJILLO-HERNÁNDEZ 2, FJ PERAZA-GARAY 3 AND C VÁSQUEZ 4 1 Deprtment of Anesthesi, nd 2 Reserch Units in Clinicl Epidemiology nd System of Helth, Generl Fmily Medicine nd Zone Hospitl No. 1, Mexicn Socil Security Institute, Colim, Mexico; 3 Reserch Unit, Sinlo University, Culicán, Mexico; 4 University Biomedicl Reserch Centre (CUIB), University of Colim, Colim, Mexico OBJECTIVE: A rndomized clinicl study to compre the stress response to lproscopic cholecystectomy during spinl generl nesthesi nd epidurl generl nesthesi. METHODS: Women undergoing elective lproscopic chole - cystectomy were ssigned to receive either spinl nesthesi (SA group; n = 12) or epidurl nesthesi (EA group; n = 12), in ddition to generl nesthesi. Plsm concentrtions of cortisol, drenocortico trophic hormone (ACTH), nordrenline, drenline nd totl ctecholmines were mesured pre- nd intropertively. RESULTS: Intropertive cortisol, nordrenline nd totl ctecholmine levels were significntly lower in the SA group compred with the EA group. When pre- nd intropertive vlues were compred, the SA group showed decrese in drenline, nordrenline nd totl ctecholmine levels, nd the EA group showed n increse in ACTH nd nordrenline levels. CONCLUSIONS: The type of regionl nesthesi significntly ffected the stress response: spinl nesthesi produced more fvourble endocrine response thn epidurl nesthesi. Spinl generl nesthesi my reduce postopertive morbidity in lproscopic cholecystectomy. KEY WORDS: LAPAROSCOPY; CHOLECYSTECTOMY; NEUROENDOCRINE STRESS RESPONSE; SPINAL ANAESTHESIA; CORTISOL; ADRENOCORTICOTROPHIC HORMONE; ADRENALINE; NORADRENALINE Introduction Stress-induced chnges in postopertive orgn function my be ssocited with the development of periopertive complictions. Modultion of the stress response to surgery could reduce postopertive morbidity 1 nd be key fctor in improving outcome, shortening the length of the hospitl sty s well s lowering the totl cost of ptient cre. 2 Lproscopic cholecystectomy hs gined in populrity becuse the surgicl incision required is smll compred with tht for open cholecystectomy, but surgicl stress responses remin n importnt feture of the lproscopic pproch. 3 6 Distension of the peritoneum nd incresed rteril crbon dioxide tension, due to bsorption of crbon dioxide, cn contribute to the stress 657

2 response during this procedure. 7 Lproscopic cholecystectomy is normlly performed under generl nesthesi, but regionl techniques hve been shown to ttenute the metbolic nd endocrine responses. Although there is some knowledge bout the modifying effect of epidurl nlgesic techniques on the endocrine metbolic response to lproscopic surgery, 8,9 there re limited dt on the influence of spinl nesthesi, though its effects in gynecologicl lproscopy 10 nd rthroplsty 11 hve been reported. Use of combined spinl epidurl technique without generl nesthesi hs been reported, but ws ssocited with presthesi, shoulder nd bdominl discomfort, nxiety nd hypotension. 12 Any nesthetic technique involving needle insertion into the vertebrl cnl bove the spinl cord termintion level requires gret cution nd experience. 13 Although spinl epidurl nesthesi provides benefits, thorough understnding of ssocited crdio - pulmonry chnges nd potentil complictions is necessry in order to mintin ptient sfety. 14 This rndomized study compred the stress response during two different regionl nesthetic techniques combined with generl nesthesi for lproscopic cholecystectomy: spinl generl nesthesi nd epidurl generl nesthesi. Ptients nd methods STUDY POPULATION Women clssified s Americn Society of Anesthesiologists grde I or II ( who were undergoing elective lproscopic cholecystectomy t the Generl Fmily Medicine nd Zone Hospitl No. 1, Mexicn Socil Security Institute, Colim, Mexico, between Jnury 2007 nd December 2008, were recruited to the study. Ptients with history of llergy, spinl surgery, crdiovsculr, metbolic or endocrine disturbnces, nd with previous or current use of medictions known to ffect sympthetic responses or hormonl secretion, were excluded from the study. Ptients were divided into two groups by computer-generted rndom lloction, to receive spinl generl nesthesi (SA group) or epidurl thorcic generl nesthesi (EA group). Neither the ptient nor the investigtor who nlysed the results ws wre of the type of nesthetic tht ws dministered. The study protocol ws pproved by the Ethics Committee of the Generl Fmily Medicine nd Zone Hospitl No. 1. All study prticipnts provided written informed consent. PREANAESTHESIA MEDICATION After collection of bsl blood smple (see Anlysis of stress response section), percutneous centrl venous ctheter ws inserted into the ntecubitl foss. All ptients were given 15 ml/kg lctted Ringer s solution to prevent hypotension, together with 75 mg diclofenc, 50 mg rnitidine, 8 mg ondnsetron nd 50 µg/kg midzolm, intrvenously, 45 min before nesthetic induction. Routine noninvsive monitoring begn before nesthesi ws initited. SPINAL ANAESTHESIA Ptients in the SA group were plced in the left lterl position nd the subrchnoid spce ws identified using routine midline pproch t either the third or fourth lumbr spce, with full septic precutions. A 27-guge Whitcre point spinl needle (Becton Dickinson, Frnklin Lkes, NJ, USA) ws dvnced until resistnce from the dur mter ws felt. Once free flow of 658

3 cerebrospinl fluid hd confirmed correct plcement, mg ( ml) of hyperbric 0.5% bupivcine mixed with 0.2 ml of 50 µg/ml fentnyl ws injected spinlly to obtin cephld spred of dequte nlgesi (defined s loss of senstion to pinprick) tht included t lest the fourth thorcic segment. 15 EPIDURAL THORACIC ANAESTHESIA Ptients in the EA group were plced in the left lterl position nd the epidurl spce ws identified t the 11th thorcic interspce, with full septic precutions. A 16-guge Tuohy needle (Becton Dickinson) ws dvnced to the epidurl spce using routine midline pproch; correct plcement ws confirmed using the loss of resistnce to ir method, nd 10 ml of 7.5 mg/ml plin ropivcine ws injected. The epidurl ctheter ws then threded into plce, the Tuohy needle ws removed nd the ctheter ws tped in position. The ptient ws then turned to the supine horizontl position nd injected epidurlly with 10 ml of 7.5 mg/ml plin ropivcine mixed with 2 ml of 50 µg/ml fentnyl. Anlgesi ws considered to be dequte if loss of senstion to pinprick included t lest the fourth thorcic segment. 15 GENERAL ANAESTHESIA AND SURGICAL TECHNIQUE After spinl or epidurl nesthesi, ll ptients received generl nesthesi ccording to the sme protocol. Before induction of nesthesi, ptients received 1 mg/kg 1% lidocine nd 3 µg/kg fentnyl, nd brethed 100% oxygen for 3 min. Anesthesi ws then induced with 5 mg/kg thiopentl. Endotrchel intubtion ws fcilitted with 0.1 mg/kg vecuronium, then ptients were given 1 minimum lveolr concentrtion (MAC) of sevoflurne (endtidl concentrtion 1 2%) in mixture of oxygen/ir with n inspired oxygen frction of 0.5. All ptients were ventilted mechniclly to give n end-tidl crbon dioxide level of mmhg. Lctted Ringer s solution ws given intrvenously t constnt rte of ml/kg per h, to mintin fluid blnce. Lproscopic cholecystectomy ws performed ccording to stndrd techniques. The intr-bdominl pressure ws mintined t < 12 mmhg during pneumo - peritoneum. Hert rte, noninvsive rteril blood pressure nd pulse oximetry were mesured intropertively using DASH 4000 monitoring system (GE Helthcre, Milwukee, WI, USA) every 5 min until extubtion. Arteril hypotension ws considered to be present when men blood pressure fell by 30% from the bsl vlue. 16 The totl doses of fentnyl nd vecuronium, nd the required MAC of sevoflurne, were recorded for ech ptient. ANALYSIS OF STRESS RESPONSE Venous blood smples were collected peripherlly from n ntecubitl vein contrlterl to the intrvenous infusion fter 15 min rest in the dmitting room (bsl) nd 30 min fter surgery hd begun (intropertive). Smples were trnsferred to precooled tubes contining 2 mm ethylene - dimine tetr-cetic cid nd 50 µl of 50 µm glutthione solution before centrifugtion t 5000 g t 4 C for 10 min. Plsm ws then stored t 80 C until nlysis. All smples from the sme ptient were nlysed together, within 3 dys of collection. Cortisol, drenocorticotrophic hormone (ACTH), nordrenline, drenline nd totl ctecholmine concentrtions were quntified in ech of the smples. Nordrenline nd drenline concentrtions were mesured using high- 659

4 performnce liquid chromtogrphy nd quntified by the electrochemicl coulometric method (Coulochem 5100A HPLC-EC detector, ESA, Bedford, MA, USA). ACTH nd cortisol were quntified using commercilly vilble rdioimmunossy kits (DetectX ; Arbor Assys, Ann Arbor, MI, USA), ccording to the mnufcturer s instructions. Inter- nd intr-ssy coefficients of vrition were 4.6 nd 4.0% for nordrenline, 4.2 nd 4.0% for drenline, 4.6 nd 2.5% for ACTH, nd 6.5 nd 2.6% for cortisol, respectively. STATISTICAL ANALYSES All dt were expressed s men ± SD. Blood pressure, hert rte, nd oxygen nd crbon dioxide sturtion were compred using the Student s t-test or Mnn Whitney U-test for equl nd different vrinces, respectively. Student s t-test or Wilcoxon signed-rnk test were used for pired comprisons of equl nd different vrinces, respectively. Percentges were compred using the χ 2 -test or the Fisher s exct test s pproprite. Sttisticl power ws clculted ccording to the following formul: z 1-β = n/2 d/s z 1-α/2 In this formul, n is smple size, d is the minimum vlue of the difference to be detected between two mens, nd S is the vrince in the control or reference group. A P-vlue < 0.05 ws considered to be sttisticlly significnt. All sttisticl nlyses were performed using SPSS softwre version 13.0 (SPSS Inc., Chicgo, IL, USA) for Windows. Results A totl of 24 women undergoing elective lproscopic cholecystectomy were recruited nd rndomized eqully to the SA group (n = 12) or the EA group (n = 12). Both groups were comprble with respect to demogrphic chrcteristics (Tble 1). The nesthetic requirements of both groups re given in Tble 2. The mounts of supplementl fentnyl nd sevoflurne MAC were significntly lower in the SA group (P = 0.01 nd P = 0.004, respectively) thn in the EA group. Figures 1 nd 2 show systolic nd distolic blood pressure, respectively, t key points during the surgicl procedure. In the SA group, systolic blood pressure ws significntly lower fter plcement in the Trendelenburg position nd distolic blood pressure ws significntly lower fter plcement in the Trendelenburg TABLE 1: Demogrphic chrcteristics of women undergoing elective lproscopic cholecystectomy under spinl generl nesthesi (SA group) or epidurl thorcic generl nesthesi (EA group) SA group EA group Chrcteristic n = 12 n = 12 Age, yers 35.2 ± ± 5.0 Weight, kg 70.4 ± ± 15.0 Height, m 1.60 ± ± 0.02 ASA grde I ASA grde II 2 2 Dt expressed s men ± SD, or of ptients. ASA, Americn Society of Anesthesiologists. No sttisticlly significnt between-group differences ذ) 0.05); Student s test - (ge, weight, height) or χ 2 -test (ASA grde). 660

5 TABLE 2: Anesthetic requirements of women undergoing elective lproscopic cholecystectomy under spinl generl nesthesi (SA group) or epidurl thorcic generl nesthesi (EA group) SA group EA group Sttisticl Anesthetic drug n = 12 n = 12 significnce Fentnyl, µg ± ± = 0.01 ذ Vecuronium, mg 5.54 ± ± 1.30 NS % Sevoflurne, ± ± = ذ Dt expressed s men ± SD. Student s test ). ذ) NS, not sttisticlly significnt position nd during gllbldder mnipultion, compred with mesurements in the EA group (P < 0.05). There were no sttisticlly significnt differences in hert rte, oxygen sturtion or end-tidl crbon dioxide between the SA nd EA groups (dt not shown). Crdiovsculr chnges were miniml: three ptients in the SA group received ephedrine for hypotension, wheres no ptient in the EA group developed hypotension. No nesthetic or surgicl complictions occurred in ny of the ptients. Men pre- nd intropertive stress response hormone levels in the two groups re given in Tble 3. There ws no difference in the plsm cortisol concentrtion between the two groups before surgery, but the intropertive cortisol concentrtion in the EA group ws significntly higher thn tht in the SA group (P < 0.05). Intropertive plsm ACTH concentrtions incresed Systolic blood pressure (mmhg) SA group EA group 0 Mediction Insuffltion Trendelenburg Mnip Extubtion FIGURE 1: Systolic blood pressure before nd fter nesthetic drug tretment, insuffltion, plcement in the Trendelenburg position, during gllbldder mnipultion (Mnip) nd extubtion in women undergoing elective lproscopic cholecystectomy under spinl generl nesthesi (SA group; = 12) or epidurl thorcic generl nesthesi (EA group; = 12). Dt expressed s men ± SD; test -ص 0.05, Mnn Whitney < ذ 661

6 Distolic blood pressure (mmhg) SA group EA group 10 0 Mediction Insuffltion Trendelenburg Mnip FIGURE 2: Distolic blood pressure before nd fter nesthetic drug tretment, insuffltion, plcement in the Trendelenburg position, during gllbldder mnipultion (Mnip) nd extubtion in women undergoing elective lproscopic cholecystectomy under spinl generl nesthesi (SA group; = 12) or epidurl thorcic generl nesthesi (EA group; = 12). Dt expressed s men ± SD; test -ص 0.05, Mnn Whitney < ذ Extubtion TABLE 3: - nd intropertive stress response hormone levels in women undergoing elective lproscopic cholecystectomy under spinl generl nesthesi (SA group; n = 12) or epidurl thorcic generl nesthesi (EA group; n = 12) Stress hormone opertive level Intropertive level Cortisol, ng/ml SA group 8.7 ± ± 8.7 EA group 12.8 ± ± 7.2 Adrenocorticotrophic hormone, pg/ml SA group 17.7 ± ± 72.8 EA group 34.6 ± ± b Adrenline, pg/ml SA group 66.1 ± ± 15.2 b EA group ± ± Nordrenline, pg/ml SA group ± ± b EA group ± ± 339.2,b Totl ctecholmines, pg/ml SA group ± ± 208 b EA group ± ± Dt expressed s men ± SD. < 0.05 compred with preopertive level for ذ ; test - b < 0.05 compred with SA group, unpired Student s ذ sme group, pired Student s. test - 662

7 compred with preopertive levels in both groups, but this increse ws only sttisticlly significnt in the EA group (P < 0.05). There were significnt intropertive decreses in plsm drenline, nordrenline nd totl ctecholmines compred with preopertive concentrtions in the SA group (P < 0.05 for ll comprisons; Tble 3). In the EA group, intropertive plsm nordrenline concentrtions were incresed compred with preopertive levels (P < 0.05). Intropertive nordrenline nd ctecholmine concentrtions were significntly lower in the SA group thn in the EA group, despite comprble preopertive concentrtions (P < 0.05). Power clcultions performed fter completion of the study generted sttisticl power of 83.09% nd indicted tht 36 ws the minimum number of ptients required to chieve sttisticl power of 90%. There were lrge intergroup differences in the percentge of chnge in ech vrible (27 78%), nd smll intrgroup vrince (5 11%). Discussion Despite being less invsive procedure thn open cholecystectomy, the surgicl stress response remins n importnt feture of the lproscopic pproch. 3 6 The incisions, tissue mnipultion nd pneumo peritoneum involved in lproscopic cholecystectomy result in n intense stimulus to the nervous system, with subsequent increse in ctecholmine nd corticosteroid requirements. 7 The present study found tht the type of regionl nesthesi significntly ffected the stress response during lproscopic cholecystectomy. There ws no within-group chnge in the men intropertive cortisol concentrtion in the SA group in the present study, but there ws slight but nonsignificnt increse in the EA group: finding tht is consistent with other reports. 7,9,11,14,17,18 The incresed ACTH levels in the EA group in the present study my be due to trnsitory immunosuppression induced by surgicl stress, with suprnorml ctivtion of the ACTH cortisol xis nd loss of the norml pituitry drenocorticl negtive feedbck mechnisms. 19 Another possible cuse of the ACTH increse is the stimulting effect of cytokines (tumour necrosis fctor-α nd interleukin-6) on the hypothlmic pituitry drenl xis. 20 Adrenline, nordrenline nd totl ctecholmine concentrtions significntly decresed during surgery in the SA group in the present study, in ccordnce with the findings of nother study. 14 Chnges in circulting drenline levels reflect drenl medull ctivity, wheres chnges in nordrenline reflect sympthetic nervous system ctivity. A decrese in both ctecholmines my, therefore, be due to complete blockge of the drenl medull innervtion vi the T6 L2 spinl nerves, 21 nd blockge of the thorcolumbr sympthetic nervous system by the high spinl nesthesi. 14 Ptients in the SA group required lower doses of opioid nlgesics nd hlogented nesthetics thn those in the EA group, in the present study. These results re consistent with those of Eldor, 22 who reported tht the combintion of regionl nd generl nesthesi llowed for the locl nesthesi dose to be reduced, voiding the use of vrious intrvenous drugs nd moving towrd chieving idel nesthesi. Other studies hve demonstrted the dvntges of the spinl nesthetic technique, gin reporting decrese in locl, inhled nd nrcotic nesthesi requirements. 23,24 Ptients in the SA group in the present study showed sttisticlly nd cliniclly 663

8 significnt decreses in blood pressure t key points relted to importnt hemodynmic chnges: fter plcement in the Trendelenburg position nd during gllbldder mnipultion. These decreses my be due to the phrenic nd sympthetic efferent nerves being directly bthed by nesthetics during spinl nesthesi, leding to complete block with greter relxtion, less pin nd less stress. 7 Arteril hypotension ws only observed in three ptients in the SA group. This indictes tht preopertive dministrtion of 15 ml/kg lctted Ringer s solution ws sufficient to prevent the hypotension tht cn be secondry to sympthetic blockde in regionl nesthesi, prticulrly in spinl block. 25 This study ws limited by its smll size. Power clcultions performed fter study completion indicted tht minimum number of 36 ptients ws required, rther thn the 24 who were studied. Tht this study generted sttisticlly significnt results my be explined by the lrge intergroup differences, the smll intrgroup vrince nd the quntittive nture of the prmeters studied. Further studies of the effects of different regionl nesthetic techniques on stress responses during the erly nd lte postopertive periods re required. In ddition, it is necessry to determine the reltionship between the stimulting effects of tumour necrosis fctor-α nd interleukin-6 on ACTH hormone secretion, with the loss of norml pituitry drenocorticl negtive feedbck mechnisms due to the trnsitory immunosuppression tht is induced by surgicl stress. In conclusion, the present study showed tht the type of regionl nesthesi significntly ffected the stress response: spinl nesthesi produced more fvourble endocrine response thn epidurl nesthesi. This suggests tht spinl generl nesthesi my be ssocited with lower rte of postopertive morbidity in lproscopic cholecystectomy. Conflicts of interest The uthors hd no conflicts of interest to declre in reltion to this rticle. Received for publiction 4 September 2011 Accepted subject to revision 8 October 2011 Revised ccepted 14 Mrch 2012 Copyright 2012 Field House Publishing LLP References 1 Mrn E, Annett MG, Mrn R, et l: Neuroendocrine stress response in lproscopic surgery for benign ovrin cyst. Cn J Anesth 2004; 51: Mrn E, Annet MG, Meo F, et l: Sevoflurne improves the neuroendocrine stress response during lproscopic pelvic surgery. Cn J Anesth 2003; 50: Schuer PR, Sirinek KR: The lproscopic pproch reduces the endocrine response to elective cholecystectomy. Am Surg 1995; 61: Kryinnkis AJ, Mkri GG, Mntzioc A, et l: Systemic stress response fter lproscopic or open cholecystectomy: rndomized tril. Br J Surg 1997; 84: Dexter SP, Griffith JP, Grnt PJ, et l: Activtion of cogultion nd fibrinolysis in open nd lproscopic cholecystectomy. Surg Endosc 1996; 10: Donld RA, Perry EG, Wittert GA, et l: The plsm ACTH, AVP, CRH nd ctecholmine responses to conventionl nd lproscopic cholecystectomy. Clin Endocrinol (Oxf) 1993; 38: Aono H, Tked A, Trver SD: Stress responses in three different nesthetic techniques for crbon dioxide lproscopic cholecystectomy. J Clin Anesth 1998; 10: Kehlet H: The endocrine metbolic response to postopertive pin. Act Anesthesiol Scnd Suppl 1982; 74: Tsuji H, Asoh T, Tkeuchi Y, et l: Attenution of drenocorticl response to upper bdominl surgery with epidurl blockde. Br J Surg 1983; 70: Vghdi H, Solylo MA, Henderson CL, et l: 664

9 Selective spinl nesthesi for outptient lproscopy. II: epinephrine nd spinl cord function. Cn J Anesth 2001; 48: Dvis FM, Lurenson VG, Lewis J, et l: Metbolic response to totl hip rthroplsty under hypobric subrchnoid or generl nesthesi. Br J Anesth 1987; 59: Vn Zundert AA, Stultiens G, Jkimowicz JJ, et l: Lproscopic cholecystectomy under segmentl thorcic spinl nesthesi: fesibility study. Br J Anesth 2007; 98: Joshi GP: Anesthesi for lproscopic surgery. Cn J Anesth 2002; 49(suppl 1): R45 R Pflug AE, Hlter JB: Effect of spinl nesthesi on drenergic tone nd the neuroendocrine responses to surgicl stress in humns. Anesthesiology 1981; 55: Villegs Mez GM, Mrrón Peñ M, Cñs Hinojos G, et l: Técnics nestésics en cirugí lproscópic mbultori. Rev Mex Anestesiol 1995; 18: [in Spnish, English bstrct]. 16 Vughn RW, Wise L: opertive rteril blood gs mesurement in obese ptients: effect of position on gs exchnge. Ann Surg 1975; 182: Møller IW, Hjortsø E, Krntz T, et l: The modifying effect of spinl nesthesi on intrnd postopertive drenocorticl nd hyperglycemic response to surgery. Act Anesthesiol Scnd 1984; 28: Cb F, Echevrrí M, Guerrero JM, et l: Comprison of chnges in plsm concentrtions of ACTH nd bet-endorphin in cholecystectomy under generl nesthesi nd generl plus epidurl nesthesi. Rev Esp Anestesiol Renim 1995; 42: [in Spnish, English bstrct]. 19 Scrborough DE: Cytokine modultion of pituitry hormone secretion. Ann N Y Acd Sci 1990; 594: Nito Y, Tmi S, Shingu K, et l: Responses of plsm drenocorticotropic hormone, cortisol, nd cytokines during nd fter upper bdominl surgery. Anesthesiology 1992; 77: Bonic JJ: Autonomic innervtion of the viscer in reltion to nerve block. Anesthesiology 1968; 29: Eldor J: Combined spinl epidurl generl nesthesi. Med Hypotheses 1995; 45: Zorić S, Stmenković D, Stevnović S, et l: Combined spinl epidurl nd generl nesthesi in bdominl surgery. Med Arh 2003; 57(4 suppl 1): [in Bosnin, English bstrct]. 24 Mlenkovi V, Zori S, Rndelovi T: Advntge of combined spinl, epidurl nd generl nesthesi in comprison to generl nesthesi in bdominl surgery. Srp Arh Celok Lek 2003; 131: [in Serbin, English bstrct]. 25 Cunninghm AJ, Brull SJ: Lproscopic cholecystectomy: nesthetic implictions. Anesth Anlg 1993; 76: Author s ddress for correspondence Dr Clemente Vásquez University Biomedicl Reserch Centre (CUIB), University of Colim, Avenid 25 de Julio 965, Coloni Vills de Sn Sebstián, CP 28040, Colim, Mexico. E-mil: clemvs@ucol.mx 665