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Risk-based targeting of adjuvant pregabalin treatment in laparoscopic cholecystectomy: a randomized, controlled trial

  • Hanna von Plato EMAIL logo , Kristiina Mattila , Satu Poikola , Eliisa Löyttyniemi , Katri Hamunen and Vesa Kontinen
Published/Copyright: January 31, 2019
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Scandinavian Journal of Pain
From the journal Scandinavian Journal of Pain Volume 19 Issue 2

Abstract

Background and aims

Pain is the most common reason for delayed discharge after day-case laparoscopic cholecystectomy. This study investigates a simple five-item questionnaire in evaluating the risk of postoperative pain in day-case cholecystectomy and the efficacy and safety of single-dose preoperative pregabalin on patients with multiple risk factors for pain. There are no previous studies on targeting adjuvant pain treatment based on the individual risk factors like the preoperative state of anxiety, acute or chronic pain, and the expectation of pain in day-case surgery.

Methods

One hundred and thirty patients scheduled for day-case laparoscopic cholecystectomy were evaluated with a five-item questionnaire assessing the risk for postoperative pain. The patients with multiple risk factors (n=60) were randomized to receive either pregabalin 150 mg or placebo, 1 h before surgery. The primary outcome was abdominal pain intensity on numerical rating scale (NRS) 1 h after surgery. Pain, analgesic consumption and adverse effects during first three postoperative days, and the length of hospital stay were also recorded.

Results

Pregabalin 150 mg given as an adjuvant analgesic preoperatively did not decrease postoperative abdominal pain or opioid consumption in the first hour after surgery compared to placebo in a preselected group of patients with multiple risk factors for postoperative pain (p=0.31). Preoperative anxiety assessed with a scale of 0–10 had a positive association with postoperative pain (p=0.045).

Conclusions and implications

This was the first trial on systematically selecting patients with a high-risk factor profile for postoperative pain as a target for a preventive adjuvant analgesic intervention. Although numerous previous studies have identified various risk factors, including those used in the current trial, it seems to be challenging to use these risk factors as predictive tools for targeting adjuvant analgesics in day-case surgery. Preoperative anxiety has a positive association with postoperative pain in day-case laparoscopic cholecystectomy, and this should be taken into account when treating these patients.

Keywords: postoperative pain; day-case cholecystectomy; risk of postoperative pain

1 Introduction

Postoperative pain is the most common reason for failure of planned discharge in day-case surgery [1], and a known risk factor for chronic pain [2], [3], [4]. Although the intensity of postoperative pain depends on the procedure, marked variation exists in pain intensity between individual patients.

Previous studies have identified risk factors for postoperative pain and high analgesic consumption, including young age, gender, chronic pain, preoperative acute pain, preoperative anxiety, catastrophizing and psychological distress [5], [6], [7], [8], [9], [10]. In addition, the expectation of pain has an effect on the pain experienced [11], [12]. However, information is lacking on how these risk factors could be systematically preoperatively evaluated to improve the management of pain.

Earlier, Pan et al. showed that three simple preoperative questions on anxiety, anticipated pain, and anticipated need of analgesic predict postoperative pain after cesarean section [13]. In another study, these three questions were successfully used to assess the risk of postoperative pain and target two multimodal anesthetic techniques [14].

Laparoscopic cholecystectomy is a common day-case procedure, but some patients suffer from severe postoperative pain that prevents discharge on the day of surgery [1]. Gabapentinoids have been used in the treatment of acute postsurgical pain, to decrease opioid consumption and adverse effects and to improve postoperative analgesia [15], [16]. Gabapentin is absorbed slowly after oral administration, with maximum plasma concentrations attained within 3–4 h. Orally administered pregabalin is absorbed more rapidly, with maximum plasma concentrations attained within 1 h [17]. Studies on gabapentinoids in day-case cholecystectomy show conflicting results. While they seem to decrease pain intensity, they may also cause more adverse effects than placebo [18], [19], [20], [21]. Recent systematic reviews conclude that the effect of perioperative gabapentinoids has been less impressive than previously reported [22], [23]. According to a recent review, there is only low-quality evidence to support the use of analgesics for the prevention and treatment of pain following laparoscopic cholecystectomy [24].

Aims of this study were to investigate a simple five-item questionnaire in evaluating the risk of postoperative pain in day-case cholecystectomy, and to assess the efficacy and safety of single-dose preoperative pregabalin in a high-risk group of patients. The hypothesis was that pregabalin 150 mg administered preoperatively to patients with more risk factors would decrease 1-h postoperative pain intensity compared to placebo.

2 Materials and methods

2.1 Study design and participants

This study was approved by the local Ethics Committee, and written informed consent was obtained from all participants. The trial was registered prior to patient enrolment in the EU Clinical Trials Register (www.clinicaltrialsregister.eu) (2015-004515-20 PAIKIPAIN, Principal Investigator: Vesa Kontinen MD, DmedSci, Date of registration: 30.12.2015). This manuscript adheres to the applicable CONSORT guidelines [25].

This was a double-blind, placebo-controlled, multi-arm parallel clinical study. Between March and September 2016 all patients scheduled for an elective, day-case laparoscopic cholecystectomy were assessed for eligibility. Adult patients over 18 years but under 70 years, with an ASA-classification under three, weight over 50 kg, BMI under 40 kg/m2, who were not pregnant or breast feeding, with no allergies or significant adverse effects for medications used in the protocol, and able to use the NRS scale and to communicate in the Finnish language were included. Data on demographics, underlying illnesses including depression and anxiety disorder, chronic and acute pain, and prior surgery and medications were collected. The study was performed in the Day-Surgery Department of Jorvi Hospital, Helsinki University Hospital, Finland.

2.2 Risk assessment for postoperative pain

Patients were allocated to a study group or a follow-up group based on a preoperative five-item questionnaire assessing the risk for postoperative pain (Table 1). The questions were designed based on previous studies on predictive factors [5], [6], [7], [8], [11], [12], [13], 26].

Table 1:

Preoperative questionnaire and scoring for the risk of postoperative pain.

1. Have you experienced severe pain after an operation before? Yes/no
2. Do you have, or have you had before, pain for 6 months or longer? Yes/no
3. Based on your previous experiences, do you assume that you need more pain medication that is commonly needed after this operation? Yes/no
4. How strong do you assume the pain after the operation will be on a scale from 0 to 10? 0–10
5. How anxious have you felt during the past week on a scale of 0–10? 0–10
 YES in questions number 1, 2 and 3→high risk

 Score more than 4 in both questions 4 AND 5→high risk

 YES in one of the questions 1–3 combined to score of 4 or more in either question 4 or question 5→high risk

A preoperative nurse presented the questions in a telephone interview. The rating was based on a pilot test with 40 ambulatory cholecystectomy patients. The correlation between the risk assessment questions and postoperative pain were evaluated. For detailed information about the questions and the rating, see Table 1. Patients with many risk factors were allocated to the high-risk group until a total of 60 patients was reached. Patients with less risk factors formed the low-risk follow-up group. Altogether 130 patients were recruited.

2.3 Trial medication

The high-risk group was randomized to receive pregabalin 150 mg (n=30) or placebo (n=30) 1 h before surgery. Two group 1:1 block randomization was conducted using block sizes of six and performed by a surgeon in Jorvi Hospital who did not otherwise participate in the study, using a computer-generated allocation list. Group allocations and the study medication were concealed in sequentially numbered opaque envelopes. Study medication was prepared in the Central Pharmacy of Helsinki University Hospital. Pregabalin and placebo capsules appeared identical. Study personnel, including the anesthesiologist, surgeon, and nurses performing follow-up outcome assessments, as well as study participants were blinded to group allocation concerning the placebo and pregabalin groups. The patients were blinded to group allocation concerning all groups.

The low-risk follow-up group of 70 patients received standardized and otherwise similar treatment to the study group but without the intervention.

2.4 Anesthesia and postoperative analgesia

Anesthesia and postoperative analgesics during hospital stay were standardized according to PROSPECT guidelines [27]. Anesthesia was induced with fentanyl 0.05 mg and propofol 2–3 mg/kg, followed by total intravenous anesthesia (TIVA) with propofol and remifentanil infusions. All patients were intubated and the depth of anesthesia was monitored. Dexamethasone 5 mg i.v. was given as an analgesic adjuvant and prophylactic antiemetic. Ropivacaine 7.5 mg/mL 20 mL was injected to the trocar incisions. Ketoprofen 100 mg i.v. and fentanyl 0.05 mg i.v. were administered at the end of surgery. Postoperative analgesics were given as needed in the following order if the pain intensity on NRS exceeded 3: paracetamol 1 g p.o. or i.v., tramadol 50 mg p.o., fentanyl in 0.05 mg i.v. doses up to a total dose of 0.15 mg. If pain intensity still exceeded NRS 3, oxycodone in doses of 3 mg i.v. was given as needed.

2.5 Outcomes

The primary outcome was abdominal pain intensity at rest 1 h after extubation on NRS. Secondary outcomes were abdominal pain and shoulder pain intensity on NRS at rest at 15 and 30 min, and then every hour, consumption of opioids and adverse effects (drowsiness, dizziness, nausea, vomiting and headache) during the hospital stay. The adverse effects were evaluated with a scale of 0–3 at 15 and 30 min, and then every hour during the hospital stay. Abdominal pain and shoulder pain, adverse effects, consumption of analgesics during the first three postoperative days measured once a day on an electronic questionnaire, overall satisfaction and the length of hospital stay were recorded. Opioid consumption was reported as morphine equivalents [28]. Follow-up during the first three postoperative days was performed using an electronic questionnaire, a similar questionnaire has demonstrated to be suitable for the follow-up of day-case surgery patients [29]. Patients who were unable to use e-mail answered on paper forms.

2.6 Statistical analysis

Pain measured with NRS 60 min after the surgery was chosen as the primary outcome variable. The study group size was decided based on a power calculation where the standard deviation of pain on NRS was estimated to be 40% of the mean value (sigma 0.4), and the aim was to be able to detect clinically meaningful change (reduction of 30% or more) in pain. When alpha error was set to be below 0.05 and the power was set to be 0.8 or higher, at least 28 patients were needed in both intervention groups.

Descriptive statistics are shown with means and standard deviation (SD) when the variable is normally distributed and with median and range otherwise. Categorical variables are summarized with counts and percentage.

To study whether mean change over time differed between the groups in following variables (NRS, abdominal pain), a hierarchical linear mixed model (HLMM) was used, including one within-factor (time with five time-points), one between-factor (group), and their interaction. The time factor was handled as categorical to be able to estimate all possible shapes of mean changes over time. Compound symmetry covariance structure was used for time. We also studied in a separate model whether the five preoperative questions for evaluating the risk of postoperative pain, age, gender, body mass index, dyspepsia, a diagnosis of depression, or the surgeon performing the operation had an effect on the results.

Differences in abdominal pain, nausea, vomiting, headache and sleepiness between the groups were evaluated at different time-points with Fisher’s exact test.

Opioid consumption in morphine equivalents and time spent in hospital were compared between the groups with one-way analysis of variance.

Normality assumption was checked visually together with Shapiro-Wilk’s test. Equality of variances was tested with Levene’s test. All statistical tests were performed as two-sided, with significance level set at 0.05. The analyses were performed using SAS System, version 9.4 for Windows (SAS Institute Inc., Cary, NC, USA).

3 Results

Total of 157 patients were assessed for eligibility and 130 patients were included (Fig. 1). Sixty patients in the study group were randomized to receive pregabalin 150 mg or placebo 1 h preoperatively. Seventy patients in the follow-up group received no intervention. The operation was converted to laparotomy in three cases and these patients were excluded from the study. Twenty-nine patients in the pregabalin group, 30 patients in the placebo group, and 68 patients in the follow-up group, thus a total of 127 patients were included in the analysis. There was no missing outcome data during the hospital follow-up. Patients’ median age was 48 (19–68) years and 77% were women. No significant differences were present between the groups in baseline characteristics (Table 2).

Fig. 1: CONSORT flow diagram. CONSORT indicates for Consolidated Standards of Reporting Trials. Pre op=preoperative; p.o.=orally.
Fig. 1:

CONSORT flow diagram. CONSORT indicates for Consolidated Standards of Reporting Trials. Pre op=preoperative; p.o.=orally.

Table 2:

Baseline characteristics of the study groups and the follow-up group.

Pregabalin (n=29) Placebo (n=30) Follow-up (n=68) p-Value
Age (years) 46 (23–66) 46 (23–64) 49 (19–68) 0.58
Height (cm) 169 (154–186) 168 (156–186) 168 (156–192) 0.82
Weight (kg) 85 (51–117) 79 (58–108) 80 (50–114) 0.31
BMI (kg/m2) 28 (19–38) 27 (19–38) 27 (20–38) 0.39
ASA PS (1/2/3) 15/9/5 9/19/2 28/36/4 0.08
Female 23 (79%) 24 (80%) 51 (75%) 0.89
Depression 3 (10%) 3 (10%) 0 0.30
Prior abdominal surgery 12 (40%) 18 (60%) 28 (40%) 0.29

  1. Values are expressed as median with range or as absolute number and percentage of patients. Total number of patients included is 127. BMI=body mass index; ASA PS=American Society of Anesthesiologists Physical Status.

3.1 Postoperative pain, opioid consumption and adverse effects during hospital stay

Pregabalin 150 mg given orally to a preselected patient group with a high risk of postoperative pain an hour before laparoscopic cholecystectomy did not decrease abdominal pain intensity 1 h after surgery compared to placebo (p=0.31) (Table 3). The majority of the patients did not experience severe pain, defined as NRS≥6. However, despite pain treatment with i.v. opioids given repeatedly as needed, 46 out of 127 patients (36%) had severe pain (NRS≥6) at some time-point during the 3 h of postoperative care. Of these patients, 9 (31%) were in the pregabalin group, 16 (53%) in the placebo group, and 21 (31%) in the follow-up group.

Table 3:

Abdominal pain in recovery room on NRS.

Pregabalin (n=29) Placebo (n=30) Follow-up (n=68) p-Value
15 min 4.2 (2.5) 4.5 (2.7) 3.5 (2.6) 0.12
30 min 3.8 (2.5) 4.5 (2.6) 3.6 (2.3) 0.14
1 h 3.5 (2.2) 4.0 (2.2) 3.3 (2.1) 0.31
2 h 2.8 (2.2) 2.8 (2.3) 2.3 (1.8) 0.56
3 h 2.6 (1.9) 2.4 (1.8) 1.8 (1.2) 0.31
4 h 2.1 (1.9) 2.9 (2.8) 1.8 (1.4) 0.16

  1. Values are expressed as mean (standard deviation). NRS=Numerical Rating Scale; min=minutes. The p-value describes group differences between the three groups at each timepoint.

Data on abdominal pain in the recovery room are presented in Table 3. Five patients had to stay in hospital until the next day because of pain. Shoulder pain intensity was low throughout the follow-up. There were no significant differences between the groups. Opioid consumption expressed as i.v. morphine equivalents [median (range)] during the first hour was 8.8 (5.0–10.0) mg in the pregabalin group, 10.0 (5.0–10.0) mg in the placebo group and 5.0 (0–10.0) mg in the follow-up group (p=0.07). The total opioid consumption during hospital stay was 10.0 (5.0–15.0) mg in the pregabalin group, 10.0 (5.0–15.0) mg in the placebo group and 10.0 (0–15.0) mg in the follow-up group (p=0.14). For detailed information, see Table 4.

Table 4:

Postoperative opioid consumption.

Pregabalin (n=29) Placebo (n=29) Follow-up (n=68) p-Value
1 h 8.8 (5.0–10.0) 10.0 (5.0–10.0) 5.0 (0–10.0) 0.07
2 h 0 (0–5.0) 1.1 (0–5.0) 0 (0–5.0) 0.63
3 h 0 (0–0) 0 (0–0) 0 (0–0) 0.87
Total 10.0 (5.0–15.0) 10.0 (5.0–15.0) 10.0 (0–15.0) 0.14

  1. Opioid consumption is expressed as i.v. morphine equivalents median (range). The p-value describes group differences between the three groups at each timepoint.

Paracetamol 1 g orally was given to 102 patients. Twenty-five patients did not need any analgesics during the hospital stay. Tramadol 50 mg orally was given to 58 patients.

Patients in the pregabalin group did not experience more adverse effects, including nausea, vomiting, dizziness, drowsiness, or headache, during the hospital stay than those in the placebo or follow-up group. One hour after the operation 6/29 (21%) of the patients in the placebo group, 3/30 (10%) in the pregabalin group and 15/69 (22%) in the follow-up group had nausea, but no vomiting was reported. Dizziness was reported by 5/29 (17%), 9/30 (30%) and 17/69 (25%), headache by 1/29 (3%), 1/30 (3%) and 0/69 (0%), and dizziness by 18/29 (62%), 24/30 (80%), and 46/69 (67%) of the patients in the placebo group, pregabalin group and follow-up group respectively. Administration of pregabalin did not lead to prolonged hospital stay. Mean duration of hospitalization was 275 (SD 69) min in the pregabalin group, 250 (SD 61) min in the placebo group, and 266 (SD 70) min in the follow-up group, (p=0.44).

3.2 Evaluation of risk of postoperative pain

The question about anxiety: “How anxious have you felt during the past week on a scale of 0–10?” predicted higher postoperative pain intensity in a linear manner. Anxiety was positively associated with the postoperative abdominal pain intensity during 4 h in the recovery room (p=0.04). Chronic pain, former experiences of severe pain after surgery, expectation of high intensity of postoperative pain, and expectation of large amount of pain medication needed, did not correlate with postoperative pain in this sample of patients. Previous or ongoing chronic pain was experienced by 10/29 patients in the pregabalin group, 16/30 patients in the placebo group, and 3/68 patients in the control group, thus, in total by 29/127 patients, (23%).

3.3 Expectation of postoperative pain

The question “How strong do you assume the pain after surgery will be on a scale from 0 to 10?” did not predict higher postoperative pain intensity. The expected intensity of postoperative pain (NRS) was 6.9 (SD 3.7) in the pregabalin group, 6.8 (SD 3.6) in the placebo group and 5.9 (SD 1.1) in the control group. All of these figures were higher than the actual postoperative pain levels (Fig. 2).

Fig. 2: Preoperative expectation of postoperative pain according to the question “How strong do you assume the pain after the operation will be on a scale from 0 to 10?” and the postoperative pain experienced at 1 h in different groups on NRS. NRS=Numerical Rating Scale.
Fig. 2:

Preoperative expectation of postoperative pain according to the question “How strong do you assume the pain after the operation will be on a scale from 0 to 10?” and the postoperative pain experienced at 1 h in different groups on NRS. NRS=Numerical Rating Scale.

3.4 Other predictive factors for postoperative pain

In the whole study group, the patients with a diagnosed depression had higher postoperative pain intensity. Fourteen surgeons performed the operations during the study period. Patients of two of the surgeons had significantly higher pain intensity than the patients of the other 12 surgeons (p=0.001).

3.5 Pain, adverse effects and analgesics after discharge

Altogether 111 of the 127 patients (87%) answered the postoperative electronic questionnaire during the three postoperative days. The highest abdominal pain intensities during day one were 3.4 (SD 2.5), 4.0 (SD 2.5), and 2.9 (SD 1.6), during day two 2.7 (SD 1.9), 3.5 (SD 2.1), and 2.3 (SD 1.0), during day three 2.2 (SD 1.8), 2.6 (SD 2.0), and 1.5 (SD 1.3) in the pregabalin, placebo, and follow-up group, respectively (p=0.067).

Patients in the pregabalin group did not experience more adverse effects, including nausea, vomiting, dizziness, drowsiness, or headache, during the first three postoperative days than those in the placebo or follow-up group.

One month after surgery 84 of the 127 patients (66%) answered the electronic questionnaire. Intensity of abdominal pain on NRS was 0.3 (SD 0.6) in the pregabalin group, 0 (SD 0.7) in the placebo group and 0.1 (SD 0.4) in the control group (p=0.067).

3.6 Overall satisfaction with pain treatment during hospital stay and at home

The satisfaction with pain treatment on a scale of 0–10 at the time of discharge was 9.0 (SD 1.3), 9.2 (SD 1.6), and 9.4 (SD 1.1) and on the third postoperative day 7.6 (SD 2.4), 8.1 (SD 1.8), and 8.5 (SD 2.0) in the pregabalin, placebo and follow-up group, respectively (p=0.073).

4 Discussion

We found that preoperative pregabalin 150 mg did not decrease pain intensity after laparoscopic day-case cholecystectomy compared with placebo when it was targeted to patients who according to a short systematic preoperative risk assessment had more risk factors for postoperative pain. Despite opioid treatment, 36% of the cholecystectomy patients experienced severe (NRS≥6) postoperative pain during the first hours. Preoperative state of anxiety had a positive correlation with postoperative pain intensity.

This is the first trial on the effect of a preventive adjuvant analgesic targeted to a preselected group of patients based on individual risk factors in day-case surgery. We applied three predictive questions formerly validated in two cesarean section studies [13], [14] and combined one question on chronic pain and one on intensive pain after earlier surgery. In previous clinical studies investigating preoperative risk assessment in day-case surgery, time-consuming and complicated questionnaires have been found to be problematic [11], [30]. In our trial, it was possible to conveniently accomplish the risk evaluation by a simple survey conducted via a preoperative phone call made by a nurse.

Preoperative anxiety had a positive correlation with postoperative pain, consistent with previous studies on cesarean section patients [13], [14]. However, contrary to these studies, expectation of either postoperative pain intensity or amount of analgesic needed did not correlate with postoperative pain. This shows that the predictive model developed in the cesarean section trials cannot be directly applied to other patient groups. In the present study, the questions on chronic pain and preoperative acute pain in the operated area did not predict acute postoperative pain, nor did the question about previous intensive pain experienced after surgery. The occurrence of chronic pain was 53% in the placebo group and only 34% in the pregabalin group. Chronic pain before surgery is one of the most important predictors of pain problems after surgery. This may well have contributed to the observation that 53% of the patients in the placebo-group had intensive pain >6/10, and only 31% in the pregabalin group – during the 3 h of observation after surgery. Acute preoperative pain at the surgical site was not common, only 4 out of 127 patients (3%) had pain intensity over NRS 3, which may have an effect on the predictive ability of this question. Although numerous previous studies have identified various risk factors for more severe postoperative pain and higher analgesic consumption [5], [6], [7], [8], [11], [12], including those used in the current trial, it is challenging to use these risk factors as predictive tools in high-volume clinical practice.

Our trial showed that there is a group of patients experiencing severe pain during the first postoperative hours after laparoscopic cholecystectomy, even when multimodal analgesia is used and opioids are given as needed. A similar finding has been reported in an earlier trial of day-case hallux valgus surgery [31]. This emphasizes the need for preventive pain management based on individual risk assessment of the surgical patient, as stated also by the American Pain Society in the guideline on management of postoperative pain [3]. It is noteworthy that intensive acute post-surgical pain is a risk factor for chronic pain [4], the risk of chronic pain after surgery varying somewhere between 15% and 60% depending on the procedure and patient risk factors [3], [32], [33], [34].

Preoperative pregabalin targeted to patients who according to the preoperative assessment had more risk factors for postoperative pain, did not decrease pain, but it also did not increase side-effects or prolong hospital stay in our study. It is though noteworthy, that pregabalin can increase the risk of respiratory depression and negative cognitive effects when combined to opioids. This should be considered in postoperative use especially in day-case surgery [35]. Previous studies of Balaban, Agarwal and Zhang and the meta-analysis of Li found that preoperative pregabalin decreased postoperative pain and opioid consumption after laparoscopic cholecystectomy [17], [18], [19], [20]. However, two meta-analyses of Fabritius suggest that firm evidence for the use of gabapentinoids in postoperative pain management in general is lacking [21], [22]. It is noteworthy that in these studies and the meta-analyses gabapentinoids have been given based on the type of surgery, not based on the patients individual risk factors for postoperative pain.

4.1 Strengths and limitations

A limitation of this trial is, that the preoperative risk questionnaire used has not been formerly tested or evaluated. This trial has two clear strengths. First, it was designed to reflect a clinical situation of day-case laparoscopic cholecystectomy. Second, risk assessment performed via telephone interview and collection of follow-up data using an electronic questionnaire proved to be feasible and easy to perform.

4.2 Conclusions

This was the first attempt to systematically select patients with a high-risk factor profile for postoperative pain as a target for a preventive adjuvant analgesic intervention. Preoperative pregabalin 150 mg administered to this target population did not decrease postoperative pain intensity compared to placebo. The simple question on anxiety rated on a scale of 0–10 had a positive correlation with postoperative pain. Chronic pain, previous severe pain after surgery, and expectation of pain or amount of analgesic needed did not correlate with postoperative pain.

Corresponding author: Hanna von Plato, MD, Consultant, Helsinki University Hospital, Jorvi Hospital, P. O. Box 800, 00029 HUS, Helsinki, Finland, Phone: +358 50 428 4471, Fax: +358 9 471 85907

  1. Authors’ statements

  2. Research funding: The study has been supported by state funding for university-level health research, project code TYH3052014.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Informed consent: Informed consent has been obtained from all individuals included in this study.

  5. Ethical approval: The study was performed in accordance with the tenets of the Helsinki Declaration, and was approved by the Regional Committee for Medical Ethics in Helsinki, Finland.

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Received: 2018-10-25
Revised: 2018-12-04
Accepted: 2018-12-18
Published Online: 2019-01-31
Published in Print: 2019-04-24

©2019 Scandinavian Association for the Study of Pain. Published by Walter de Gruyter GmbH, Berlin/Boston. All rights reserved.

Articles in the same Issue

  1. Frontmatter
  2. Editorial comment
  3. Systemic inflammation firmly documented in chronic pain patients by measurement of increased levels of many of 92 inflammation-related proteins in blood – normalizing as the pain condition improves with CBT-based multimodal rehabilitation at Uppsala Pain Center
  4. Systematic review
  5. Transcutaneous electric nerve stimulation (TENS) for acute low back pain: systematic review
  6. Clinical pain research
  7. Detection of systemic inflammation in severely impaired chronic pain patients and effects of a multimodal pain rehabilitation program
  8. Chronic Widespread Pain in a tertiary pain clinic: classification overlap and use of a patient generated quality of life instrument
  9. Symptom reduction and improved function in chronic CRPS type 1 after 12-week integrated, interdisciplinary therapy
  10. Chronic pain after bilateral thoracotomy in lung transplant patients
  11. Reference values of conditioned pain modulation
  12. Risk severity moderated effectiveness of pain treatment in adolescents
  13. Pain assessment in hospitalized spinal cord injured patients – a controlled cross-sectional study
  14. Risk-based targeting of adjuvant pregabalin treatment in laparoscopic cholecystectomy: a randomized, controlled trial
  15. The impact of comorbid pain and depression in the United States: results from a nationally representative survey
  16. Observational study
  17. The utility/futility of medications for neuropathic pain – an observational study
  18. Posttraumatic stress and autobiographical memory in chronic pain patients
  19. Prescribed opioid analgesic use developments in three Nordic countries, 2006–2017
  20. Characteristics of women with chronic pelvic pain referred to physiotherapy treatment after multidisciplinary assessment: a cross-sectional study
  21. The Oslo University Hospital Pain Registry: development of a digital chronic pain registry and baseline data from 1,712 patients
  22. Investigating the prevalence of anxiety and depression in people living with patellofemoral pain in the UK: the Dep-Pf Study
  23. Original experimental
  24. Interpretation bias in the face of pain: a discriminatory fear conditioning approach
  25. Taboo gesticulations as a response to pain
  26. Gender bias in assessment of future work ability among pain patients – an experimental vignette study of medical students’ assessment
  27. Muscle stretching – the potential role of endogenous pain inhibitory modulation on stretch tolerance
  28. Letter to the Editor
  29. Clinical registries are essential tools for ensuring quality and improving outcomes in pain medicine
  30. Fibromyalgia in biblical times
https://doi.org/10.1515/sjpain-2018-0330
Keywords for this article
postoperative pain; day-case cholecystectomy; risk of postoperative pain

Articles in the same Issue

  1. Frontmatter
  2. Editorial comment
  3. Systemic inflammation firmly documented in chronic pain patients by measurement of increased levels of many of 92 inflammation-related proteins in blood – normalizing as the pain condition improves with CBT-based multimodal rehabilitation at Uppsala Pain Center
  4. Systematic review
  5. Transcutaneous electric nerve stimulation (TENS) for acute low back pain: systematic review
  6. Clinical pain research
  7. Detection of systemic inflammation in severely impaired chronic pain patients and effects of a multimodal pain rehabilitation program
  8. Chronic Widespread Pain in a tertiary pain clinic: classification overlap and use of a patient generated quality of life instrument
  9. Symptom reduction and improved function in chronic CRPS type 1 after 12-week integrated, interdisciplinary therapy
  10. Chronic pain after bilateral thoracotomy in lung transplant patients
  11. Reference values of conditioned pain modulation
  12. Risk severity moderated effectiveness of pain treatment in adolescents
  13. Pain assessment in hospitalized spinal cord injured patients – a controlled cross-sectional study
  14. Risk-based targeting of adjuvant pregabalin treatment in laparoscopic cholecystectomy: a randomized, controlled trial
  15. The impact of comorbid pain and depression in the United States: results from a nationally representative survey
  16. Observational study
  17. The utility/futility of medications for neuropathic pain – an observational study
  18. Posttraumatic stress and autobiographical memory in chronic pain patients
  19. Prescribed opioid analgesic use developments in three Nordic countries, 2006–2017
  20. Characteristics of women with chronic pelvic pain referred to physiotherapy treatment after multidisciplinary assessment: a cross-sectional study
  21. The Oslo University Hospital Pain Registry: development of a digital chronic pain registry and baseline data from 1,712 patients
  22. Investigating the prevalence of anxiety and depression in people living with patellofemoral pain in the UK: the Dep-Pf Study
  23. Original experimental
  24. Interpretation bias in the face of pain: a discriminatory fear conditioning approach
  25. Taboo gesticulations as a response to pain
  26. Gender bias in assessment of future work ability among pain patients – an experimental vignette study of medical students’ assessment
  27. Muscle stretching – the potential role of endogenous pain inhibitory modulation on stretch tolerance
  28. Letter to the Editor
  29. Clinical registries are essential tools for ensuring quality and improving outcomes in pain medicine
  30. Fibromyalgia in biblical times
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