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PAIN 155 (2014) 2400–2407
www.elsevier.com/locate/pain
Early visceral pain predicts chronic pain after laparoscopic cholecystectomy Morten Rune Blichfeldt-Eckhardt a,b,⇑, Helle Ørding a, Claus Andersen b, Peter B. Licht c, Palle Toft b a
Department of Anesthesiology, Vejle Hospital, Vejle DK-7100, Denmark Department of Anesthesiology and Intensive Care, Odense University Hospital, Odense DK-5000, Denmark c Department of Thoracic Surgery, Odense University Hospital, Odense, Denmark b
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
a r t i c l e
i n f o
Article history: Received 10 July 2014 Received in revised form 18 August 2014 Accepted 11 September 2014
Keywords: Postcholecystectomy pain Postcholecystectomy syndrome Chronic postsurgery pain Visceral pain Referred pain
a b s t r a c t Chronic pain after laparoscopic cholecystectomy is related to postoperative pain during the first postoperative week, but it is unknown which components of the early pain response is important. In this prospective study, 100 consecutive patients were examined preoperatively, 1 week postoperatively, and 3, 6, and 12 months postoperatively for pain, psychological factors, and signs of hypersensitivity. Overall pain, incisional pain (somatic pain component), deep abdominal pain (visceral pain component), and shoulder pain (referred pain component) were registered on a 100-mm visual analogue scale during the first postoperative week. Nine patients developed chronic unexplained pain 12 months postoperatively. In a multivariate analysis model, cumulated visceral pain during the first week and number of preoperative biliary pain attacks were identified as independent risk factors for unexplained chronic pain 12 months postoperatively. There were no consistent signs of hypersensitivity in the referred pain area either pre- or postoperatively. There were no significant associations to any other variables examined. The risk of chronic pain after laparoscopic cholecystectomy is relatively low, but significantly related to the visceral pain response during the first postoperative week. Ó 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
1. Introduction Chronic pain after laparoscopic cholecystectomy is a common complication, with an incidence ranging between 3% and 56% [23,24,27]. The aetiology is believed to be multifactorial and include sphincter of Oddi dysfunction, bile duct stone, and other diseases; and thorough postoperative examination and treatment has been shown to significantly reduce the incidence. In many cases, however, the cause remains unknown, and visceral hyperalgesia and central sensitization have been suggested to be part of the pathophysiology [20,22]. Several risk factors have been identified, including female gender, longstanding preoperative symptoms, and psychic vulnerability [3,17,27]. As in several other types of surgery, early postoperative pain has been shown to be a significant risk factor of chronic
⇑ Corresponding author at: Department of Anesthesiology and Intensive Care, Odense University Hospital, Sdr. Boulevard 29, Odense C DK-5000, Denmark. Tel.: +45 65414721; fax: +45 66113415. E-mail address: [email protected] (M.R. BlichfeldtEckhardt).
pain [5,7,15,19,32], but little is known about this relation and it has been sparsely studied. The acute pain response after cholecystectomy consists of a somatic, a visceral, and a referred pain component [18,33]. In most subjects the somatic pain component is the worst, followed by the visceral one, and the referred pain component is the least troublesome [4]. It is unknown, which part of the acute pain response is associated with chronic pain, but the chronic postcholecystectomy pain is believed to be of visceral origin. Preoperative hyperalgesia in the referred pain area (RPA) has been discovered in subgroups of patients for cholecystectomy and has been suggested to be an indicator of central neuroplastic changes and central sensitization [2,12,31]. The overall aim of this study was to explore the association between the acute pain response after elective cholecystectomy and the development of chronic pain and, secondarily, to explore other potential risk factors for chronic postcholecystectomy pain. Specifically: 1) To study whether the intensity of the different components of the acute pain response differs between patients with and
http://dx.doi.org/10.1016/j.pain.2014.09.019 0304-3959/Ó 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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M.R. Blichfeldt-Eckhardt et al. / PAIN 155 (2014) 2400–2407
without chronic pain 12 months after cholecystectomy. The following pain components were investigated: visceral pain, somatic pain, referred pain. We hypothesized that patients who developed pain 12 months postoperatively would suffer more visceral and referred pain during the first postoperative week than patients with no pain after 12 months. 2) To test signs of hypersensitivity in RPA before, 6 months after, and 12 months after the operation. We hypothesized that patients who developed pain 12 months postoperatively would be hypersensitive in the RPA after 6 and 12 months. 3) To study the association between preoperative pain and psychological and demographic factors and the development of chronic pain 12 months after cholecystectomy. We hypothesized that female gender, psychic vulnerability, preoperative anxiety and depression, number, duration, and intensity of biliary pain attacks and other chronic pain conditions would be risk factors of chronic postcholecystectomy pain.
2. Methods 2.1. Design The study was a prospective observational multicenter cohort study, where patients were examined preoperatively and followed until 12 months postoperatively. 2.2. Patients Patients scheduled for elective laparoscopic cholecystectomy, who were 18 years old or above, and who could speak and read Danish, were included from April 2010 until May 2011 at 3 departments of general surgery at 3 Danish regional hospitals (Vejle Hospital, Kolding Hospital, and Nyborg Hospital). Patients were not included if they had undergone previous abdominal surgery, suffered from any disease in the central nervous system, or had peripheral sensory disturbances. The setting was ambulatory, and all patients were expected to be discharged on the day of the operation. The study was approved by the Regional Ethics Committee and The Danish Data Protection Agency. Informed written consent was obtained from all participants. 2.3. Anaesthesia, surgical, and analgesic treatment Anaesthesia, surgery, and analgesic treatment were performed according to the standards of the individual hospitals. All patients received premedication consisting of paracetamol 1 g and nonsteroidal antiinflammatory drugs (NSAIDs). General anaesthesia was induced and maintained with propofol as primary hypnotic agent. Remifentanil or alfentanil was used as primary intraoperative opioid. Orotracheal intubation was performed in all patients. All operations were conducted or supervised by experienced laparoscopic surgeons. An incision was made above or below the umbilicus, and a Veress needle was inserted into the peritoneum. CO2 was used as the insufflating gas. Intraabdominal pressure was kept at 12 mm Hg or below. Umbilical, subxiphoid, and 2 lateral trocars were introduced. At centre 3, laparoscopic cholangiography or laparoscopic ultrasound was performed. All portholes were infiltrated with bupivacaine 0.25 mg/mL or ropivacaine 2 mg/mL. The CO2 was evacuated at the end of the procedure by manual compression of the abdomen with open trocars.
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In-hospital postoperative pain was treated with paracetamol, NSAIDs, and opioids (intravenous morphine or oral oxycodone) on demand. After discharge, patients were carefully instructed in the use of paracetamol and NSAIDs as treatment for postoperative pain. Patients received 0–6 tablets of oxycodone at discharge for home use. 2.4. Quantitative sensory testing Quantitative sensory testing (QST) was done preoperatively and after 6 and 12 months. One investigator (MRBE) examined all patients who were in a relaxed supine position at room temperature between 22 °C and 24 °C. Each test was thoroughly explained and demonstrated on the nondominant forearm before testing. Test areas were the thenar of the dominating hand (for signs of general hypersensitivity), the RPA, and the similar area on the contralateral side as the control area (CA). Hair in the testing area was removed with scissors, and care was taken to avoid skin lesions that might affect the QST. 2.4.1. Thermal testing Thermal detection threshold for cold and warm stimuli and thermal pain thresholds for cold and warm stimuli were tested using an MSA Thermotester (Somedic AB, Hörby, Sweden). Thresholds were obtained with ramped stimuli (1 C/s), which were terminated when the patients pushed a button. Baseline temperature was 32 °C, and cut-off points were 6 and 50 °C. The final threshold was calculated as the mean of 3 consecutive measurements [28]. 2.4.2. Mechanical testing Brush-evoked allodynia was assessed by lightly stroking the skin using a brush (Senselab 0.5, Somedic), which was moved from outside the affected area along 8 different paths converging toward the centre. Pinprick hyperalgesia was determined in the same manner using a von Frey hair (169 g/mm2). Patients were asked to report whether the sensation of touch changed to a sensation of pain [26]. The areas of allodynia and hyperalgesia were traced on transparent plastic and the areas were calculated using graph paper. Mechanical detection thresholds were tested using modified von Frey hairs (Somedic AB) exerting forces between 5 and 178 g/mm2. Using the method of limits, the geometric mean was calculated between 5 series of ascending and descending stimuli intensities as the final threshold [28]. Mechanical pain threshold (MPT) was tested using a set of 7 custom-made weighted pinprick stimulators (flat contact area of 0.2 mm diameter) that exert forces between 8 and 512 mN (MRC Systems, Heidelberg, Germany). Again, the final threshold was the geometric mean of 5 series of ascending and descending stimuli intensities [28]. 2.4.3. Wind-up ratio Wind-up ratio was tested using a weighted pinprick stimulator of 256 mN. A single pinprick was compared with a train of 10 stimuli of the same force repeated at a 1/s rate and given within an area of 1 cm2. Alternating between a single and a train of 10 pinprick stimuli, the test was repeated 5 times at 5 different skin sites within the same body region (RPA/CA). The patient was asked to give a pain rating on a numerical rating scale between 0 and 100 for each single and train of 10 stimuli [28]. 2.4.4. Vibration Vibration detection threshold test was performed with a Vibrameter IV (Somedic AB) that was placed over the 2nd metacarpal bone on the hand, and the nearest bony prominence of RPA (rib).
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Vibration threshold was determined as the mean of 3 series of ascending and descending stimulus intensities. 2.4.5. Pressure Pressure pain threshold (PPT) was performed with an Algometer II (Somedic AB) with a probe area of 1 cm2 and determined as the mean response of 3 independent measurements, each applied as a slowly increasing ramp of 50 kPa/s [28]. 2.5. Psychological evaluation and evaluation of preoperative pain Preoperatively, the Hospital Anxiety and Depression Scale was used to screen for preoperative depression and anxiety symptoms. Cut-off was P11 for probable anxiety and depression [37]. Psychic vulnerability was measured on the Psychic Vulnerability Scale [1], a psychometrical, statistically evaluated rating scale of 22 generic questions concerning symptoms in Danish citizens. Maximum score was 12; cut-off between 2 and 3 dichotomizes people into psychologically vulnerable or not [6,16,17]. Furthermore, patients were interviewed about preoperative pain, both concerning biliary pain attacks and other existing pain conditions. Patients were asked about pain intensity during worst experienced pain attack, the average pain intensity of pain attacks, the average duration of pain attacks, and the average number of attacks per month. Pain intensity during the pain attacks was registered on a visual analogue scale (VAS; 0 = no pain, 100 mm = worst pain imaginable). Furthermore, worst biliary pain attack was characterized by the McGill Pain Questionnaire [11,25]. 2.6. Postoperative pain assessment Before surgery the patients were instructed to use a 100-mm VAS to register overall pain and the following 3 pain components: Incisional pain (somatic pain component) was defined as a superficial pain, wound pain, or pain located in the abdominal wall, a pain that one can ‘‘touch.’’ Intraabdominal pain (visceral pain component) was defined as pain inside the abdomen, which may be deep, dull, and more difficult to localize, and may resemble a biliary pain attack. Shoulder pain (referred pain component) was defined as a sensation of pain in the shoulder [4]. Pain assessment was based on self-reported registrations starting at 8 PM at the day of the operation and during the following 7 days. Patients registered maximum and average pain covering the preceding 24 hours. Each patient was supplied with a questionnaire consisting of VASscore forms for the entire postoperative week, which the patients mailed back after completion. 2.7. Follow-up Three, 6, and 12 months after surgery, a structured questionnaire was mailed to all 100 patients. If the questionnaire was not returned within 2 weeks, another questionnaire was sent and patients were reminded by telephone to complete and return the questionnaire. Patients reporting abdominal pain 3 months after surgery were seen in the office for an interview and further investigations. The following examinations were done until a diagnosis was reached: Physical examination (abdominal palpation, including port sites, evaluation of back pain due to facet joint syndrome), liver function tests, transabdominal ultrasound scanning, gastroscopy, and magnetic resonance cholangiopancreatography. If no diagnosis was reached, the pain was defined as unexplained pain. Six and 12 months after surgery, all patients who still reported pain were examined with QST and psychological tests as described above. A sample of pain-free patients was examined in the same way.
2.8. Statistical analysis Parametric data are presented in means and compared with the Student’s t-test; nonparametric data are presented as medians and compared using the Mann-Whitney U-test or Wilcoxon’s signed-rank test where relevant. Ratios were compared using Fisher’s exact test. To prevent mass significance, daily pain scores for each pain component were cumulated into 1 total pain score for each pain component. For final determination of risk factors, a multivariate logistic regression model was used with stepwise selection of independent variables. A P-value
PAIN 155 (2014) 2400–2407
www.elsevier.com/locate/pain
Early visceral pain predicts chronic pain after laparoscopic cholecystectomy Morten Rune Blichfeldt-Eckhardt a,b,⇑, Helle Ørding a, Claus Andersen b, Peter B. Licht c, Palle Toft b a
Department of Anesthesiology, Vejle Hospital, Vejle DK-7100, Denmark Department of Anesthesiology and Intensive Care, Odense University Hospital, Odense DK-5000, Denmark c Department of Thoracic Surgery, Odense University Hospital, Odense, Denmark b
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
a r t i c l e
i n f o
Article history: Received 10 July 2014 Received in revised form 18 August 2014 Accepted 11 September 2014
Keywords: Postcholecystectomy pain Postcholecystectomy syndrome Chronic postsurgery pain Visceral pain Referred pain
a b s t r a c t Chronic pain after laparoscopic cholecystectomy is related to postoperative pain during the first postoperative week, but it is unknown which components of the early pain response is important. In this prospective study, 100 consecutive patients were examined preoperatively, 1 week postoperatively, and 3, 6, and 12 months postoperatively for pain, psychological factors, and signs of hypersensitivity. Overall pain, incisional pain (somatic pain component), deep abdominal pain (visceral pain component), and shoulder pain (referred pain component) were registered on a 100-mm visual analogue scale during the first postoperative week. Nine patients developed chronic unexplained pain 12 months postoperatively. In a multivariate analysis model, cumulated visceral pain during the first week and number of preoperative biliary pain attacks were identified as independent risk factors for unexplained chronic pain 12 months postoperatively. There were no consistent signs of hypersensitivity in the referred pain area either pre- or postoperatively. There were no significant associations to any other variables examined. The risk of chronic pain after laparoscopic cholecystectomy is relatively low, but significantly related to the visceral pain response during the first postoperative week. Ó 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
1. Introduction Chronic pain after laparoscopic cholecystectomy is a common complication, with an incidence ranging between 3% and 56% [23,24,27]. The aetiology is believed to be multifactorial and include sphincter of Oddi dysfunction, bile duct stone, and other diseases; and thorough postoperative examination and treatment has been shown to significantly reduce the incidence. In many cases, however, the cause remains unknown, and visceral hyperalgesia and central sensitization have been suggested to be part of the pathophysiology [20,22]. Several risk factors have been identified, including female gender, longstanding preoperative symptoms, and psychic vulnerability [3,17,27]. As in several other types of surgery, early postoperative pain has been shown to be a significant risk factor of chronic
⇑ Corresponding author at: Department of Anesthesiology and Intensive Care, Odense University Hospital, Sdr. Boulevard 29, Odense C DK-5000, Denmark. Tel.: +45 65414721; fax: +45 66113415. E-mail address: [email protected] (M.R. BlichfeldtEckhardt).
pain [5,7,15,19,32], but little is known about this relation and it has been sparsely studied. The acute pain response after cholecystectomy consists of a somatic, a visceral, and a referred pain component [18,33]. In most subjects the somatic pain component is the worst, followed by the visceral one, and the referred pain component is the least troublesome [4]. It is unknown, which part of the acute pain response is associated with chronic pain, but the chronic postcholecystectomy pain is believed to be of visceral origin. Preoperative hyperalgesia in the referred pain area (RPA) has been discovered in subgroups of patients for cholecystectomy and has been suggested to be an indicator of central neuroplastic changes and central sensitization [2,12,31]. The overall aim of this study was to explore the association between the acute pain response after elective cholecystectomy and the development of chronic pain and, secondarily, to explore other potential risk factors for chronic postcholecystectomy pain. Specifically: 1) To study whether the intensity of the different components of the acute pain response differs between patients with and
http://dx.doi.org/10.1016/j.pain.2014.09.019 0304-3959/Ó 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Ò
M.R. Blichfeldt-Eckhardt et al. / PAIN 155 (2014) 2400–2407
without chronic pain 12 months after cholecystectomy. The following pain components were investigated: visceral pain, somatic pain, referred pain. We hypothesized that patients who developed pain 12 months postoperatively would suffer more visceral and referred pain during the first postoperative week than patients with no pain after 12 months. 2) To test signs of hypersensitivity in RPA before, 6 months after, and 12 months after the operation. We hypothesized that patients who developed pain 12 months postoperatively would be hypersensitive in the RPA after 6 and 12 months. 3) To study the association between preoperative pain and psychological and demographic factors and the development of chronic pain 12 months after cholecystectomy. We hypothesized that female gender, psychic vulnerability, preoperative anxiety and depression, number, duration, and intensity of biliary pain attacks and other chronic pain conditions would be risk factors of chronic postcholecystectomy pain.
2. Methods 2.1. Design The study was a prospective observational multicenter cohort study, where patients were examined preoperatively and followed until 12 months postoperatively. 2.2. Patients Patients scheduled for elective laparoscopic cholecystectomy, who were 18 years old or above, and who could speak and read Danish, were included from April 2010 until May 2011 at 3 departments of general surgery at 3 Danish regional hospitals (Vejle Hospital, Kolding Hospital, and Nyborg Hospital). Patients were not included if they had undergone previous abdominal surgery, suffered from any disease in the central nervous system, or had peripheral sensory disturbances. The setting was ambulatory, and all patients were expected to be discharged on the day of the operation. The study was approved by the Regional Ethics Committee and The Danish Data Protection Agency. Informed written consent was obtained from all participants. 2.3. Anaesthesia, surgical, and analgesic treatment Anaesthesia, surgery, and analgesic treatment were performed according to the standards of the individual hospitals. All patients received premedication consisting of paracetamol 1 g and nonsteroidal antiinflammatory drugs (NSAIDs). General anaesthesia was induced and maintained with propofol as primary hypnotic agent. Remifentanil or alfentanil was used as primary intraoperative opioid. Orotracheal intubation was performed in all patients. All operations were conducted or supervised by experienced laparoscopic surgeons. An incision was made above or below the umbilicus, and a Veress needle was inserted into the peritoneum. CO2 was used as the insufflating gas. Intraabdominal pressure was kept at 12 mm Hg or below. Umbilical, subxiphoid, and 2 lateral trocars were introduced. At centre 3, laparoscopic cholangiography or laparoscopic ultrasound was performed. All portholes were infiltrated with bupivacaine 0.25 mg/mL or ropivacaine 2 mg/mL. The CO2 was evacuated at the end of the procedure by manual compression of the abdomen with open trocars.
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In-hospital postoperative pain was treated with paracetamol, NSAIDs, and opioids (intravenous morphine or oral oxycodone) on demand. After discharge, patients were carefully instructed in the use of paracetamol and NSAIDs as treatment for postoperative pain. Patients received 0–6 tablets of oxycodone at discharge for home use. 2.4. Quantitative sensory testing Quantitative sensory testing (QST) was done preoperatively and after 6 and 12 months. One investigator (MRBE) examined all patients who were in a relaxed supine position at room temperature between 22 °C and 24 °C. Each test was thoroughly explained and demonstrated on the nondominant forearm before testing. Test areas were the thenar of the dominating hand (for signs of general hypersensitivity), the RPA, and the similar area on the contralateral side as the control area (CA). Hair in the testing area was removed with scissors, and care was taken to avoid skin lesions that might affect the QST. 2.4.1. Thermal testing Thermal detection threshold for cold and warm stimuli and thermal pain thresholds for cold and warm stimuli were tested using an MSA Thermotester (Somedic AB, Hörby, Sweden). Thresholds were obtained with ramped stimuli (1 C/s), which were terminated when the patients pushed a button. Baseline temperature was 32 °C, and cut-off points were 6 and 50 °C. The final threshold was calculated as the mean of 3 consecutive measurements [28]. 2.4.2. Mechanical testing Brush-evoked allodynia was assessed by lightly stroking the skin using a brush (Senselab 0.5, Somedic), which was moved from outside the affected area along 8 different paths converging toward the centre. Pinprick hyperalgesia was determined in the same manner using a von Frey hair (169 g/mm2). Patients were asked to report whether the sensation of touch changed to a sensation of pain [26]. The areas of allodynia and hyperalgesia were traced on transparent plastic and the areas were calculated using graph paper. Mechanical detection thresholds were tested using modified von Frey hairs (Somedic AB) exerting forces between 5 and 178 g/mm2. Using the method of limits, the geometric mean was calculated between 5 series of ascending and descending stimuli intensities as the final threshold [28]. Mechanical pain threshold (MPT) was tested using a set of 7 custom-made weighted pinprick stimulators (flat contact area of 0.2 mm diameter) that exert forces between 8 and 512 mN (MRC Systems, Heidelberg, Germany). Again, the final threshold was the geometric mean of 5 series of ascending and descending stimuli intensities [28]. 2.4.3. Wind-up ratio Wind-up ratio was tested using a weighted pinprick stimulator of 256 mN. A single pinprick was compared with a train of 10 stimuli of the same force repeated at a 1/s rate and given within an area of 1 cm2. Alternating between a single and a train of 10 pinprick stimuli, the test was repeated 5 times at 5 different skin sites within the same body region (RPA/CA). The patient was asked to give a pain rating on a numerical rating scale between 0 and 100 for each single and train of 10 stimuli [28]. 2.4.4. Vibration Vibration detection threshold test was performed with a Vibrameter IV (Somedic AB) that was placed over the 2nd metacarpal bone on the hand, and the nearest bony prominence of RPA (rib).
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Vibration threshold was determined as the mean of 3 series of ascending and descending stimulus intensities. 2.4.5. Pressure Pressure pain threshold (PPT) was performed with an Algometer II (Somedic AB) with a probe area of 1 cm2 and determined as the mean response of 3 independent measurements, each applied as a slowly increasing ramp of 50 kPa/s [28]. 2.5. Psychological evaluation and evaluation of preoperative pain Preoperatively, the Hospital Anxiety and Depression Scale was used to screen for preoperative depression and anxiety symptoms. Cut-off was P11 for probable anxiety and depression [37]. Psychic vulnerability was measured on the Psychic Vulnerability Scale [1], a psychometrical, statistically evaluated rating scale of 22 generic questions concerning symptoms in Danish citizens. Maximum score was 12; cut-off between 2 and 3 dichotomizes people into psychologically vulnerable or not [6,16,17]. Furthermore, patients were interviewed about preoperative pain, both concerning biliary pain attacks and other existing pain conditions. Patients were asked about pain intensity during worst experienced pain attack, the average pain intensity of pain attacks, the average duration of pain attacks, and the average number of attacks per month. Pain intensity during the pain attacks was registered on a visual analogue scale (VAS; 0 = no pain, 100 mm = worst pain imaginable). Furthermore, worst biliary pain attack was characterized by the McGill Pain Questionnaire [11,25]. 2.6. Postoperative pain assessment Before surgery the patients were instructed to use a 100-mm VAS to register overall pain and the following 3 pain components: Incisional pain (somatic pain component) was defined as a superficial pain, wound pain, or pain located in the abdominal wall, a pain that one can ‘‘touch.’’ Intraabdominal pain (visceral pain component) was defined as pain inside the abdomen, which may be deep, dull, and more difficult to localize, and may resemble a biliary pain attack. Shoulder pain (referred pain component) was defined as a sensation of pain in the shoulder [4]. Pain assessment was based on self-reported registrations starting at 8 PM at the day of the operation and during the following 7 days. Patients registered maximum and average pain covering the preceding 24 hours. Each patient was supplied with a questionnaire consisting of VASscore forms for the entire postoperative week, which the patients mailed back after completion. 2.7. Follow-up Three, 6, and 12 months after surgery, a structured questionnaire was mailed to all 100 patients. If the questionnaire was not returned within 2 weeks, another questionnaire was sent and patients were reminded by telephone to complete and return the questionnaire. Patients reporting abdominal pain 3 months after surgery were seen in the office for an interview and further investigations. The following examinations were done until a diagnosis was reached: Physical examination (abdominal palpation, including port sites, evaluation of back pain due to facet joint syndrome), liver function tests, transabdominal ultrasound scanning, gastroscopy, and magnetic resonance cholangiopancreatography. If no diagnosis was reached, the pain was defined as unexplained pain. Six and 12 months after surgery, all patients who still reported pain were examined with QST and psychological tests as described above. A sample of pain-free patients was examined in the same way.
2.8. Statistical analysis Parametric data are presented in means and compared with the Student’s t-test; nonparametric data are presented as medians and compared using the Mann-Whitney U-test or Wilcoxon’s signed-rank test where relevant. Ratios were compared using Fisher’s exact test. To prevent mass significance, daily pain scores for each pain component were cumulated into 1 total pain score for each pain component. For final determination of risk factors, a multivariate logistic regression model was used with stepwise selection of independent variables. A P-value
