Comparison of two different methods of analgesia. Postoperative course after colorectal cancer surgery

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1 129 Comparison of two different methods of analgesia. Postoperative course after colorectal cancer surgery Kęstutis Rimaitis, Irena Marchertienė, Dainius Pavalkis 1 Clinic of Anesthesia, 1 Clinic of Surgery, Kaunas University of Medicine Hospital, Lithuania Key words: general anesthesia, epidural analgesia, colorectal cancer, bupivacaine, fentanyl. Summary. Background. The purpose of our study is to compare two methods of postoperative analgesia in colorectal cancer patients after resectional operations, and to evaluate advantages and limitations of each method on the postoperative course of these patients. Methods. One hundred patients scheduled to undergo elective colorectal cancer surgery were randomized into two groups; after general anesthesia, one group received epidural analgesia (n=50) and the second one intramuscular pethidine analgesia (n=50). Visual analogue scale at rest and on coughing was used to compare intensiveness of pain between the two groups during the day of surgery and first three postoperative days. Patients mood and self-satisfaction were evaluated using self-assessment manikin scale. Side effects of both analgesia techniques were registered. All complications and postoperative hospital stay were also evaluated. Results. Visual analogue scale pain scores at rest and on coughing were significantly better in epidural analgesia group as compared to systemic intramuscular pethidine analgesia group (p<0.05). Additional analgesics were needed for 10 (20%) and 28 (56%) patients respectively to keep visual analogue scale pain scores below 5. Adverse effects such as profound sedation, nausea and vomiting were more frequent in systemic intramuscular pethidine group, but pruritus very uncommon to compare with epidural analgesia group (p<0.05). There were no significant differences between the two groups in respect to complications and postoperative hospital stay. Conclusions. Epidural analgesia has demonstrated significantly better effectiveness than intramuscular pethidine analgesia after colorectal cancer surgery with fewer adverse events. Self-assessment manikin scores showed better self-satisfaction in patients of epidural analgesia group as compared to patients in systemic pethidine group. Introduction Statistical data shows tendency of increasing number of oncological patients over the world. Every year about 1200 new cases of colorectal cancer are registered in Lithuania. Surgical operation is the only curative therapy for the patients, suffering from colorectal cancer. Modern surgical interventions became more extensive and associated with a major surgical trauma. Optimal anesthesia intraoperatively and adequate postoperative analgesia are the main purposes of anesthesiologist. Several studies (1-7) have demonstrated a significant decrease in morbidity and mortality in high-risk surgical patients undergoing epidural anesthesia and postoperative analgesia as compared to patients receiving high-dose narcotic anesthesia and parenteral narcotic analgesia. It seems, that anesthetic technique, especially postoperative analgesic technique, may be able to modify patients outcome. Epidural analgesia (EA) has been shown to improve splanchnic blood flow by sympathetic blockade that result in reduction of postoperative ileus (1-3, 8) and reduce metabolic stress response and nitrogen loss (1,8, 9,14). These effects improve healing of surgical anastomoses. EA has demonstrated some beneficial effects for the treatment of postoperative pain as compared with sys- Correspondence to K. Rimaitis, Clinic of Anesthesia, Kaunas University of Medicine Hospital, Eivenių 2, 3007 Kaunas, Lithuania. rimaitiskestutis@takas.lt

2 130 Kęstutis Rimaitis, Irena Marchertienė, Dainius Pavalkis temic opioid analgesia (10-13,15), however the clinical arena has not been immune from controversy about epidural analgesia and it s effects on colorectal anastomosis (16-18). The lack of standardization has contributed to the continued confusion regarding the role of EA on postoperative outcome. Moreover, pooling patients who underwent surgical procedures in different areas of the body and anesthetized in different anesthetic technique on one single study makes the comparison of data difficult. Currently, there are only few clinical studies evaluating the influence of choice of anesthesia and analgesia on outcome after oncologic surgery (1). This study is the first attempt in our hospital to evaluate the quality of postoperative pain management and patient s outcome using two standardized analgesia techniques in one field of abdominal surgery colorectal cancer surgery. The aim of our study is to compare postoperative epidural and systemic opioid analgesia in colorectal cancer patients after resectional operations, and to evaluate advantages and limitations of each method on the postoperative course of these patients. Methods This study was conducted during a 24-month period ( ) and designed as a prospective, randomized clinical investigation. The study protocol was approved by the local Ethics Committee of our institution, and informed written consent was obtained from each patient. There were 349 colorectal cancer resections carried out in our hospital during this period and all ASA 1-3 patients (n=100) scheduled to undergo elective colorectal cancer surgery were studied. Patients, who refused to take part in this clinical study (n=36), with contraindications to EA (n=26), who underwent urgent surgery (n=54), with ASA physical status exceeding 3 (n=23) and limited ability to cooperate (n=17) were not studied. Ninety-three patients exclusion was caused by technical problems. Patients randomly were allocated into two groups: epidural - general anesthesia followed by epidural analgesia (EA group) and balanced general anesthesia followed by IM pethidine analgesia (pethidine group). The same anesthesiologist anesthetized all the patients and the same team of surgeons from colorectal surgery department performed all the operations. Approximately 1h before arrival in the operating theatre, all patients were premedicated with oral diazepam 10 mg and IV infusion of 10 ml/kg Ringer s lactate solution was given preoperatively. For patients in the EA group, following placement of routine monitors in the operating room, an epidural catheter was placed in one of T 10 L 1 interspaces, with the tip of the catheter advanced 4 5 cm into the epidural space. All catheters were tested for accidental intravascular or subarachnoid placement with 3 ml of 2% lidocaine and epinephrine 15 µg. Bupivacaine 0.25% with fentanyl 10 µg/ml was then injected through the epidural catheter in 5 ml increments till the epidural block up to T 4 was established. General anesthesia was induced the same way in both groups: with propofol mg/kg and fentanyl 2 3 µg/ kg, muscle relaxation was accomplished using pipecuronium µg/kg, and the trachea was intubated. Anesthesia was maintained with IV propofol infusion at the rate of 3 5 mg/kg/h. Fentanyl infusion at the rate of 3 5 µg/kg/h in pethidine group and epidural infusion 3 6 ml/h of bupivacaine 2.5 mg/ml with fentanyl 10 µg/ml in EA group was used to maintain analgesia until the patient was transferred out of the operating room. Ventilation was maintained with oxygen in air mixture (FiO 2 of 33%). Muscle relaxation was maintained with repeated doses of pipecuronium under clinical requirement. Infusion of fentanyl was discontinued immediately after peritoneal closure. Propofol infusion was terminated at the beginning of skin closure. Most of the patients were extubated in the operating room and transferred to post anesthesia care unit (PACU). Postoperative pain relief treatment was started in 15min after patient s admission to PACU. All patients in pethidine group received IM pethidine 0.5 mg/kg every 4 hours and all patients in EA group were given continuous infusion of 1.0 mg/ml bupivacaine with 5 µg/ml fentanyl into an epidural catheter by syringe driver in a rate of 3-6 ml/h for the first three days postoperatively. If patients asked for more analgesics and visual analogue scale (VAS) pain scores on coughing were more than 5, pethidine dose was increased to 1.0 mg/ kg in pethidine group. A bolus injection of 4 ml of the same solution (bupivacaine/fentanyl) was given in EA group and the rate of infusion was increased by 1 2 ml/h. When a sufficient level was found only unilaterally, the catheter was retracted 1 to 2 cm, and thereafter the same procedure as above was followed. If hypotension, motor blockade, or deep sedation occurred, the infusion rate was decreased by 1 to 2 ml/ h. In addition, if adequate postoperative pain relief was not obtained, rescue analgesics (ketorolac mg, diclofenac mg or tramadol mg) were administered intravenously for the patients in both groups.

3 Comparison of two different methods of analgesia 131 Patients were preoperatively instructed on the use of the VAS (0 = any pain, 10 = most intensive pain can imagine) and self-assessment manikin (SAM) showing the five choices available for the evaluation of pleasure and self-satisfaction (1st = the best mood, 5 = the worst mood). Patients identified a manikin, which the best described their current state (Fig. 1). VAS pain scores at rest and VAS pain scores on coughing were obtained separately. Mood was measured using the SAM. Arterial blood pressure, pulse rate, SaO 2, breathing frequency was registered. Systolic arterial blood pressure 30% below the initial was defined as hypotension. Respiratory depression was defined as the appearance of a respiratory rate lower than 10 breaths/min and (or) SaO 2 below 90%. Sedation score was assessed on a 5 grade scale (where 0 = awake, 1 = drowsy, 2 = awakening by verbal stimulus, 3 = awakening by physical stimulus and 4 = hardly possible to awaken). Side effects, such like pruritus, nausea and vomiting (where 0 = nil, 1 = nausea only and 2 = nausea plus vomiting), and requirement of supplemental analgesics (where 0 = no analgesics, 1 = analgesics only once and 2 = analgesics more than once) were registered by the residentdoctors. Postoperative analgesia and patients evaluation was started 15 min after admission to PACU and registered every 15 min for 2 hours and every hour till 6 th postoperative hour, then patients evaluation continued every 4 hours until the end of third postoperative day. The anesthesiologist controlled all patients in EA group for the position of epidural catheter and block level once daily. Postoperative complications and patient s hospital stay were also evaluated. All data are presented as mean ± SD. Statistical analysis was performed using STATISTICA-5 software. Parametric data (age, weight, arterial blood pressure, heart rate) were compared using Student s t- test for independent samples. Non-parametric data such like VAS pain score, SAM score and sedation degree were analyzed using Man-Whitney U test. Chisquare test for sex, additional analgesics requirement, complications, nausea and vomiting analysis was appropriate. P < 0.05 was considered as statistically significant. (Modified from G. H. Hendley et al. (12)) Fig. 1. Self - Assessment Manikin (SAM) showing five choices available for the evaluation of mood and pleasure Table 1. Demographic patients data Demographic criteria Pethidin group n (%) EA group n (%) P mean ± SD mean ± SD Female 26 (52%) 25 (50%) 0.84 Male 24 (48%) 25 (50%) 0.84 Age (years) 67±11 65± Weight (kg) 70±11 74± Height (cm) 167±8 169± ASA 1 6 (12%) 5 (10%) 0.75 ASA 2 32 (64%) 32 (64%) 1.0 ASA 3 12 (24%) 13 (26%) 0.82

4 132 Kęstutis Rimaitis, Irena Marchertienė, Dainius Pavalkis Table 2. Type and duration of surgery Surgery Pethidin group EA group P Anterior rectal resection 20 (40%) 21 (42%) 0.84 Total proctectomy 4 (8%) 6 (12%) 0.51 Abdomino-perineal resection 4 (8%) 6 (12%) 0.51 Sigmoid colectomy 3 (6%) 3 (6%) 1.0 Left hemicolectomy 4 (8%) 5 (10%) 0.73 Right hemicolectomy 9 (18%) 5 (10%) 0.25 hemicolectomy* 6 (12%) 4 (8%) 0.51 Duration of surgery (min.) 141±45 144± Number of operations n (%), duration of surgery (mean ± SD). *Extended operations large bowel resections with simultaneously performed gynecological or other operations caused by invasion of malignant process or another disease. Results The patient characteristics are given in Table 1. There were no statistically significant differences between the two groups in respect to sex, age, body weight and height, and ASA physical statement. Colorectal carcinoma was complicated by partial ileus, anemia, metastatic carcinoma or both to 28 (56%) patients in pethidine group and to 25 (50%) in EA group (p=0.69). Surgical operations and duration of surgery are shown in Table 2. There were no significant differences between the two groups in respect to surgical procedure or duration of surgery. Single dose of pethidine 0.72±0.1 mg/kg was administered every 4 hours for the patients in pethidine group. Bupivacaine 1mg/ml and fentanyl 5µg/ml epidural infusion at a rate of 4.1±0.7 ml/h was administered to the patients of EA group. All the patients in both groups had sufficient pain relief during the period of study, but VAS pain scores in EA group were better as compared to pethidine group with statistical significance (p<0.05) during all period of study. The average VAS pain scores at rest and on coughing are shown in Fig. 2. Rescue analgesics single doses during the day of surgery were needed 8 (16%) patients in pethidine group and 9 (18%) patients in EA group to keep VAS pain score below 5, but repeated doses of rescue analgesics needed 20 (40%) patients in pethidine group to compare with 1(2%) patient in EA group and these differences were statistically significant (p < 0.05). Patients pleasure and self-satisfaction were different between the two groups with statistical significance (p <0.05) and are shown in Fig. 3. There were no cases of severe hypotension that needed vasoactive drugs in both groups. The values of systolic and diastolic blood pressure and pulse rate were lower in EA group but SaO 2 values in EA group were better as compared to pethidine group with statistical significance during all period of study and are shown in Table 3. Sedation level during the day of surgery was deeper (1.8 ± 0.9) and nausea more often (16 patients, 32%) occurred in pethidine group as compared to EA group (1.0 ± 0.7; 3 patients (6%), respectively). These differences were statistically significant (p< 0.05) during 1 st postoperative day too. There were no sedation and nausea differences between the two groups during the 2 nd and 3 rd postoperative days. The incidence of severe nausea and vomiting was similar in both groups (Table 4). Respiratory depression (SaO 2 < 90%) occurred similar in both groups (p=0.46): for 5 patients in pethidine group and for 3 patients in EA group on the day of surgery, and for two patients in pethidine group and one patient in EA group on the 2 nd postoperative night. In all cases, adequate spontaneous breathing was re-attained by awakening the patient. Mild pruritus occurred in 3 (6%) patients of pethidine group as compared with 20 (40%) patients in EA group and this difference was statistically significant (p < 0.05). Postoperative complications occurred to 9 (18%) patients in pethidine group as compared with 12 (24%) patients in EA group and there were no statistically significant differences (p=0.62) between the two groups (Table 5). The epidural catheter was retracted 1.5 cm to one patient in EA group, who had sufficient block level only unilaterally. Another patient in EA group had ac-

5 Comparison of two different methods of analgesia VAS Pain score (at rest) p<0.05 VAS 6 4 Pethidine group EA group Day of surgery 1-st day 2-nd day 3-rd day Time after surgery VAS pain score (on coughing) p< VAS Pethidine group EA group Day of surgery 1-st day 2-nd day 3-rd day Time after surgery Fig.2. VAS pain scores VAS pain scores (mean ± SEM) when resting and on coughing were statistically significantly lower (p< 0.05) in the EA group than in Pethidine group during all period of evaluation cidental withdrawal of epidural catheter in the morning of 3 rd postoperative day and systemic analgesia was started. Two patients had repeated surgery on the 5 th and 6 th postoperative days, when developed clinical symptoms of peritonitis but any patient died in EA group during period of study. Unfortunately, one patient died from unexpected massive pulmonary thrombi embolism on the 6 th postoperative day in pethidine group. Hospital stay in pethidine group was 10 ± 4 days postoperatively as compared with 11 ± 5 days in EA group. There were no significant differences between two groups in respect to postoperative hospital stay (p=0.27). Discussion Systemic intermittent parenteral IM opioid analgesia in pethidine group was chosen in accordance to

6 134 Kęstutis Rimaitis, Irena Marchertienė, Dainius Pavalkis 5 p < SAM score , Pethidine group EA group Day of surgery 1-st day 2-nd day 3-rd day Time after surgery Fig. 3. Mood and self-satisfaction of the patients Self-Assessment Manikin (SAM) scores presented as mean ± SEM. Self-satisfaction evaluation using SAM showed better results in EA group as compared to Pethidine group with statistical significance (p<0.05). Table 3. Hemodynamic parameters of the patients Hemodynamic parameters Day of 1-st day 2-nd day 3-rd day surgery after surgery after surgery after surgery Pethidine EA Pethidine EA Pethidine EA Pethidine EA group group group group group group group group Systolic ABP (mmhg) 137±20* 116±15 132±15* 121±13 133±13* 124±13 132±13* 125±13 Diastolic ABP (mmhg) 81±11* 69±10 78±8* 71±9 79±8* 73±9 80±8* 73±9 Heart rate 78±12* 70±12 80±10* 75±10 81±9* 75±8 80±8* 76±8 SaO 2 (%) 94.7±2.1* 96.2± ±1.4* 96± ±1.4* 96.3± ±1* 96.4±1.5 *Marks a statistically significant difference between the two groups (p<0.05) Values are presented as mean ± SD Table 4. Comparison of side effects in both groups Day of 1-st day 2-nd day 3-rd day Side effect surgery after surgery after surgery after surgery Pethidine EA Pethidine EA Pethidine EA Pethidine EA group group group group group group group group Sedation score 1,8±0,9* 1,0±0,7 0,9±0,8* 0,4±0,6 0,5±0,6 0,3±0,6 0,3±0,5 0,3±0,5 Nausea 16 (32%)* 3 (6%) 13 (26%)* 4 (8%) 7 (14%) 2 (4%) 3 (6%) 4 (8%) Nausea and vomiting 9 (18%) 9 (18%) 6 (12%) 5 (10% 1 (2%) 2 (4%) 3 (6%) 1 (2%) Respiratory depression 5 (10%) 3 (6%) 2 (4%) 1 (2%) *Marks a statistically significant difference between the two groups (p<0.05). Sedation values are presented as mean ± SD, respiratory depression, nausea and vomiting as N (%).

7 Comparison of two different methods of analgesia 135 Table 5. Complications Complications Pethidine group N (%) EA group N (%) Wound infection 3 (6%) 5 (10%) Intraabdomnal abscess 1 (2%) 3 (6%) Anastomotic leak 3 (6%) Chest infection 2 (4%) 1 (2%)* Cardiac arrhythmias 2 (4%) Pulmonary embolism 1 (2%) Acute renal failure 1 (2%)* Urinary tract infection 1 (2%) * Subsequent complications to the same patients with intraabdominal abscess. Patient died from massive pulmonary thrombi embolism. recommendations of International association for the study of pain for the treatment of acute postoperative pain. Our choice to use bupivacaine 1.0 mg/ml and fentanyl 5 µg/ml mixture epidurally in EA group was determined by several studies (10,11,19-22), that demonstrated fewer side effects to compare with bupivacaine and morphine mixture or opioid and local anesthetics alone (22). Continuous epidural infusion showed excellent analgesia after colorectal cancer surgery as compared with parenteral IM analgesia (23,24). VAS pain scores were significantly lower, both at rest and on coughing in EA group and it s no wonder that rescue analgesics in pethidine group patients were needed more often (52%). Lower, but normotensive arterial blood pressure and heart rate values in EA group reflects sympathetic blockade and suppressed stress response (1-7). These effects reduce the incidence of myocardial ischemia and dysrhythmias (1,2,8,10-13). Epidural administration of local anesthetics modifies perioperative hypercoagulable state and reduces the risk of deep venous thrombosis with resultant pulmonary embolism (25-27). EA reduces incidence and severity of hypoxemia in the early postoperative period perhaps because of improved pulmonary function or reduced sedation (1,2,19,20). Our study showed, that systemic opioids caused more profound sedation and worse SaO 2 values on the day of surgery and 1 st postoperative day. Moreover, the nausea and vomiting occurred more often in pethidine group with clinical significance to compare with EA on the early postoperative period. Mood and self-satisfaction of the patients were better in EA group and depended on better quality of analgesia and the lower incidence of adverse events (1,2,10-12,20). Epidural administration of fentanyl is associated with increased patient complains on pruritus (19,20) as compared with systemic opioids and this difference was clinically significant. Surgical complications depend on many factors including age of the patient, extensiveness of surgical trauma, surgical technique, course of main disease, radiotherapy, antibiotic prophylaxis and coexisting diseases of the patient. Finally, the study design also can influence the outcome (1,4,5,7,12,21,24,25). We failed to demonstrate, that postoperative complications depend on the choice of anesthesia and analgesia (1-7,16-19,20,25). Colorectal carcinoma was complicated by partial ileus, anemia, metastatic carcinoma or both to 28 (56%) patients in pethidine group and to 25 (50%) in EA group. This, might be, was an important factor and with factors mentioned above influenced our failure to demonstrate differences in postoperative morbidity between the two groups. Patient hospital stay was also similar in both groups. There were no clear criteria for patient discharge from the hospital in our clinic and this was the lack of our study design to demonstrate differences in respect to hospital stay postoperatively between the two kinds of analgesia (1,2,4,5,7,16, 25-28) after colorectal cancer surgery. Conclusions 1. Continuous epidural analgesia using bupivacaine and fentanyl mixture has demonstrated significantly better effectiveness than intermittent intramuscular opioid analgesia using pethidine after colorectal cancer surgery with fewer adverse events. 2. Self-assessment Manikin scores showed better self-satisfaction in patients of epidural analgesia group as compared to patients in systemic pethidine group.

8 136 Kęstutis Rimaitis, Irena Marchertienė, Dainius Pavalkis Skirtingų skausmo malšinimo metodų veiksmingumo įvertinimas bei jų įtaka pooperacinei eigai po storosios žarnos vėžio rezekcinių operacijų Kęstutis Rimaitis, Irena Marchertienė, Dainius Pavalkis 1 Kauno medicinos universiteto klinikų Anesteziologijos klinika, 1 Chirurgijos klinika Raktažodžiai: bendroji anestezija, epidurinė analgezija, storosios žarnos vėžys, fentanilis, bupivakainas. Santrauka. Tyrimo tikslas. Palyginti du skirtingus skausmo malšinimo metodus po rezekcinių storosios žarnos vėžio operacijų ir įvertinti jų veiksmingumą, privalumus bei trūkumus, jų įtaką pooperacinei eigai bei hospitalizavimo trukmei. Tyrimo medžiaga ir metodai. Ištirta 100 ligonių, kuriems Kauno medicinos universiteto klinikų Chirurgijos klinikoje m. atliktos storosios žarnos rezekcijos dėl vėžio. Tiriamieji atsitiktiniu būdu suskirstyti į dvi grupes po 50 ligonių: epidurinės analgezijos bei sisteminio skausmo malšinimo petidinu į raumenis grupes. Operacijos metu bendrosios anestezijos indukcija ir jos palaikymas atlikti pagal standartizuotą protokolą abiejų grupių ligoniams. Po operacijos epidurinės analgezijos grupės ligoniams tęsta bupivakaino 1 mg/ml ir fentanilio 5 µg/ml epidurinė infuzija 3 6 ml/val. greičiu, o petidino grupės ligoniams 0,5 1,0 mg/kg petidino injekcijos į raumenis keturių valandų intervalais. Skausmo intensyvumas vertintas pagal vizualią analoginę skalę atskirai ramybės būklės ir kosulio metu. Ligonių pasitenkinimas ir nuotaika vertinta pagal G. H. Hendley ir bendradarbių modifikuotą skalę. Abiejose tiriamųjų grupėse registruoti visi nepageidaujami reiškiniai, komplikacijos ir ligonių hospitalizavimo trukmė. Rezultatai. Registruojant pagal vizualią analoginę skalę, skausmo intensyvumo balai tiek ramybės būklės tiek kosulio metu statistiškai reikšmingai (p<0,05) buvo mažesni epidurinio skausmo malšinimo grupėje negu petidino. Papildomų analgetikų, kad vizualios analoginės skalės skausmo balai nesiektų 5, reikėjo tik 10 (20 proc.) ligonių epidurinės analgezijos grupės lyginant su 28 (56 proc.) ligoniais iš petidino grupės. Nepageidaujami analgetikų reiškiniai pykinimas ir gilesnė sedacija dažnesnė petidino grupės ligoniams, tačiau niežuliu dažniau skundėsi epidurinės analgezijos grupės ligoniai (p<0,05). Komplikacijų dažnis ir ligonių hospitalizavimo trukmė po operacijos nesiskyrė abiejų grupių tiriamųjų. Išvados. Epidurinis skausmo malšinimas po operacijos yra veiksmingesnis, rečiau pasireiškia nepageidaujamų reiškinių lyginant su sisteminiu skausmo malšinimu. Ligonių nuotaika ir pasitenkinimo laipsnis, skiriant epidurinę analgeziją pooperaciniu laikotarpiu, yra geresnis negu taikant skausmo malšinimą petidinu į raumenis. Adresas susirašinėjimui: K. Rimaitis, KMUK Anesteziologijos klinika, Eivenių 2, 3007 Kaunas El. paštas: rimaitiskestutis@takas.lt References 1. Liu S, Carpenter RL, Neal JM. Epidural anesthesia and analgesia. Their role in postoperative outcome. Rev Anesthesiology 1995;82: Buggy DJ, Smith G. Epidural anaesthesia and analgesia: better outcome after major surgery? B M J 1999;319(28): Murayi P, Joris J, Lamy M. General anesthesia vs perimedullary anesthesia+general anesthesia. Rev Med Liege 1999;54(7): Yeager M, Glass DD, Neff RK, Brinck-Johnson T. Epidural anesthesia and analgesia in high risk surgical patients. Anesthesiology 1987;66: De Leon-Casasola OA, Parker BM, Lema MJ, Groth RI, Orsini-Fuentes J. Epidural analgesia versus intravenous patient - controlled analgesia. Differences in the postoperative course of cancer patients. Reg Anesth 1994;19(5): Hasoda R, Hattori M, Shimada Y. Favorable effects of epidural analgesia on hemodynamics, oxygenation and metabolic variables in the immediate post-anesthetic period. Acta Anaesth Scand 1993;37: Frank E, Sood OMP, Torjman M, Mulholland SG, Gomella LG. Postoperative epidural analgesia following radical retropubic prostatectomy: outcome assessment. J Surg Oncology 1998;67: R Hasoda, M Hattori, Y Shimada. Favorable effects of epidural analgesia on hemodynamics, oxygenation and metabolic variables in the immediate post-anesthetic period. Acta Anaesth Scand 1993;37: F Carli, M Phil, D Halliday. Continuous epidural blockade arrests the postoperative decrease in muscle protein fractional synthetic rate in surgical patients. Anesthesiology 1997;86: De Leon-Casasola OA, Parker BM, Lema MJ, Harrison P, Massey J. Postoperative epidural bupivacaine-morphine therapy. Experience with 4227 surgical cancer patients. Anesthesiology 1994;81: Scott DA, Beilby DSN, McClymont C. Postoperative anal-

9 Comparison of two different methods of analgesia 137 gesia using epidural infusions of fentanyl with bupivacaine. A prospective analysis of 1014 patients. Anesthesiology 1995;83: Handley GH, Silbert BS, Mooney PH, Schweitzer SA, Allen NB. Combined general and epidural anesthesia versus general anesthesia for major abdominal surgery: postanesthesia recovery characteristics. Reg Anesth 1997;22(5): Bredtman RD, Herden HN, Teichmann W, et al. Epidural analgesia in colonic surgery: Results of randomized prospective study. Br J Surg 1990;77: Scott NB, James K, Murphy M, Kehlet H. Continuous thoracic epidural analgesia versus combined spinal/thoracic epidural analgesia on pain, pulmonary function and the metabolic response following colonic resection. Acta Anaesth Scand 1996;40: Woolf CJ, Chong M-S. Pre-emptive analgesia: treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993;77: Ryan P, Schweitzer SA, Woods RJ. Effect of epidural and general anaesthesia compared with general anaesthesia alone in large bowel anastomoses. Eur J Surg 1992;158: Sala C, Garcķa-Granero E, Molina MJ, Garcķa JV, Lledo S. Effect of epidural anesthesia on colorectal anastomosis. A tonometric assessment. Dis Colon Rectum 1997;40(8): Worsley MH, Wishart HY, Peebles-Brown DA, Aitkenhead AR. High spinal nerve block for large bowel anastomosis. A prospective study. Br J Anaesth 1988;60: Gedney JA, Liu EHC. Side effects of epidural infusions of opioid bupivacaine mixtures. Anaesthesia 1998;53: White MJ, Berghousen EJ, Dumont SW, et al. Side effects during continuous epidural infusion of morphine and fentanyl. Can J Anaesth 1992;39: Sjöström S, Bläss J. Postoperative analgesia with bupivacaine and low-dose fentanyl a comparison of two concentrations. Acta Anaesth Scand 1998;42: George KA, Chisakuta AM, Gamble JA, Browne GA. Thoracic epidural infusion for pain relief following abdominal aortic surgery; bupivacaine, fentanyl or a micture of both? Anaesthesia 1992;47: Cox CR, Serpell MG, Bannister J, Coventry DM, Williams DR. A comparison of epidural infusions of fentanyl or pethidine with bupivacaine in the management of postoperative pain. Anaesthesia 1996;51: George KA, Wright PM, Chisakuta A. Continuous thoracic epidural fentanyl for post-thoracotomy pain relief: with or without bupivacaine? Anaesthesia 1991;46: Tuman KJ, McCarthy RJ, March R, DeLaria GA, Patel RV, Ivankovich AD. Effects of anesthesia on coagulation and outcome after major vascular surgery. Anesth Analg 1991;73: Steele S, Slaughter T, Greenberg C, Reves J. Epidural anesthesia and analgesia: implications for perioperative coagulability. Anesth Analg 1991;73: Modig J, Borg T, Karlström G, Maripuu E, Sahlstedt B. Thromboembolism after total hip replacement: Role of epidural and general anesthesia. Anesth Analg 1983;62: De Leon-Casasola OA, Lema MJ. Postoperative pulmonary complications. Anaesthesiology 1993;79:1149. Received 2 December 2002, accepted 23 January 2003