Abstract
In the pain management evolution, opioid-free analgesia and multimodal analgesia strategies have emerged as feasible in many surgical settings including colorectal surgery. This was a retrospective cohort study including patients having undergone elective bowel resection between February 2012 and June 2018 aiming to evaluate whether there was reduction in opioid use after implementation of opioid-free analgesia in one medical centre. Trend analysis was conducted using Joinpoint regression employing nine-month intervals. The primary outcome for each interval was the proportion of patients receiving postoperative opioid-free analgesia, defined as forgoing all opioid analgesics after the day of surgery. This study showed a significant increasing trend in opioid-free analgesia in elective bowel resection from 0 to 42.5% over 4.5 years.
Introduction
Treatment of acute and chronic pain with opioids has been well documented, while harbouring the potential to be misused and abused. In the mid 1980s and early 1990s, literature emphasised the use of opioids to address the under-treatment of pain (Dahl 2002, National Institute of Mental Health 1998). Literature showing low addictive or abuse potential in patients with acute or chronic pain further misled prescribers to willingly increase the use of opioids. Therefore, the use of opioids increased significantly, leading to new formulations and greater pain relief (Portenoy & Foley 1986, Porter & Jick 1980). In over two decades, aggressive use of opioids has led to increases in opioid sales and mortality in both men and women. In addition, studies have not shown evidence regarding the long-term safety and efficacy of opioids in treating chronic pain, but it has been linked to hyperalgesia, disability, and other comorbidities (Jones et al 2018).
Opioids are utilised worldwide for pain relief and the excessive use in the hospital setting has led to the current state of the opioid epidemic. The epidemic is partly fuelled by dependence and abuse of prescribed opioids for postoperative pain. Up to 80% of patients undergoing surgery receive opioids for postoperative pain relief (Wunsch et al 2016). While postoperative opioid use results in pain relief, it is also associated with increased risk of long-term opioid use (Brummett et al 2017). Certain factors, such as higher total dose and longer duration prescription, are associated with greater risks of long-term abuse (Brat et al 2018, Shah et al 2017). Discharging home after surgery with large opioid doses as well as the re-prescription without review by general or community practitioners may further contribute to the above-mentioned risks. Transitional pain clinics, where patients at high risk for chronic postsurgical pain are identified early and offered coordinated and comprehensive care by the multidisciplinary team consisting of pain physicians, advanced practice nurses, psychologists, and physiotherapists, were previously shown to impact patients’ pain trajectories, preventing the transition from acute to chronic pain, and reducing suffering, disability, and health care costs (Katz et al 2015).
Opioids have played a fundamental role in postoperative pain management due to their ability to reduce pain during and following surgical intervention. However, opioids are linked to a large array of side effects such as respiratory depression, sedation, urinary retention, delirium, postoperative ileus, constipation, postoperative nausea and vomiting (PONV). In addition, postoperative opioid use is associated with increased length of hospital stay, overall cost of care, and cardiopulmonary complications (Oderda et al 2007, Overdyk et al 2016).
Enhanced recovery after surgery (ERAS) has been utilised in order to prevent opioid-related adverse events, improve patient’s outcomes, and lower health costs. It is predicated upon the use of minimally invasive surgical techniques and pain management that minimises opioid use. Alternative analgesia, such as Paracetamol (acetaminophen), nonsteroidal anti-inflammatory agents, gabapentinoids, tramadol, lidocaine, have been preferentially used to reduce dependence on opioids (Wick et al 2017). Postoperative intravenous Paracetamol (acetaminophen) reduces opioids dependence and is associated with reduced pain and lower incidence of opioid-induced PONV (Apfel et al 2013, De Oliveira et al 2015), regional analgesic techniques, such as spinal, epidural, and peripheral truncal nerve blocks with or without catheter placement, have been utilised more recently in an attempt to minimise perioperative opioid use. These analgesic techniques demonstrated shorter length of stay, earlier resumption of diet, and a significant reduction in opioid requirement and pain scores post abdominal operations (Bharti et al 2011, Ventham et al 2014). Epidural analgesia in laparoscopic colorectal surgery (CS) reduces pain levels during postoperation period (Liu et al 2014).
As a next step in the pain management evolution, opioid-free analgesia (OFA) and multimodal analgesia strategies have emerged as feasible in many surgical settings including CS. Currently literature does not look into the effectiveness of ERAS protocol implementation of OFA in CS and elective bowel resection; nevertheless, institutional changes have led to a paradigm shift favouring the use of OFA over more harmful options postoperatively. Hence, data were collected to review and track the use of different strategies for postoperative analgesia in elective bowel resection while monitoring patient safety, response, and recovery; we reviewed different options to the use of opioid for the management of postoperative pain, with this in mind. The primary aim of this retrospective study was to evaluate whether there was a reduction in opioid use after implementation of OFA as a safe alternative with secondary outcomes examining pain management scores in the post-anaesthesia care unit (PACU), length of stay, operative room time, estimated blood loss, opioid tolerance, type of anaesthesia, and surgery.
Methods
This was a retrospective cohort study conducted at Westchester Medical Center between February 2012 and June 2018. Patients were included if they met the following inclusion criteria: adults within the age range of 18–89 undergoing elective bowel resection. Preoperatively opioid tolerant patients (defined as taking at least 60mg of oral morphine daily or an equianalgesic dose of another opioid for at least one week) were not included. All patients underwent general anaesthesia. Intraoperative opioids were intravenous fentanyl and/or Dilaudid (hydromorphone). With regard to postoperative pain management, multimodal analgesia regimes were applied, such as regional analgesic techniques for pain management. This included low thoracic epidural catheter with 0.2% ropivacaine infusion or bilateral transversus abdominis plane/quadratus lumborum blocks with 15–20ml bupivacaine bilaterally. In addition, patient-controlled analgesia using Dilaudid (hydromorphone), 0.1–0.2mg, with 8–10min lock; intravenous Paracetamol (acetaminophen) 1g q6h until tolerating diet, or per os Paracetamol (acetaminophen) 975mg q6h; ± gabapentin 100–200mg, q12h) or with rescue dose of IV push of 0.5mg Dilaudid (hydromorphone) were applied as needed. We collected data on demographics, comorbidities, aspects of surgery, and drugs given for anaesthesia and analgesia.This study was approved by the Institutional Review Board at New York Medical College.
Mean and standard deviation was used to describe and Student’s t-test was used to compare continuous variables. Proportions (percentages) were used to describe and Pearson’s chi-squared test was used to compare categorical variables. SPSS version 25 (IBM, Inc., Armonk, New York) was used to perform the above-mentioned tests. Trend analysis was performed using Joinpoint software (Statistical Methodology and Applications Branch, Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland), employing nine-month intervals. Joinpoint regression results were expressed as detection of joinpoints across a series of intervals indicating a change in the proportion of patients receiving OFA. We considered p values <0.05 to be statistically significant.
Results
A total of 125 patients met selection criteria over a period of approximately six years. Females comprised 52.0% and mean age was 58.0 ± 15.5 years (range 19–86). Mean BMI was 29.1 ± 8.3kg/m2. The distribution by American Society of Anesthesiologists class was as follows: class 1, 0.8%; class 2, 22.4%; class 3, 69.6%; and class 4, 7.2%. Most patients were treated under the surgery service (84.0%), followed by gynaecology/obstetrics (7.2%), urology (4.0%), oncology (2.4%), medicine (1.6%), and orthopaedics (0.8%). Opioid tolerance was reported by 14 patients (11.3%). The most frequent specific surgical procedures were small bowel resection (37.6%), colon resection (31.2%), lysis of adhesions (18.4%), exploratory laparotomy (16.0%), hernia repair (15.2%), mobilisation of the splenic flexure (12.0%), rectum resection (10.4%), and bariatric surgery (10.4%). Specific indications for surgery included colorectal cancer (23.2%), diverticulitis (20.0%), other cancer (11.2%), hernia (10.4%), obesity (9.6%), ulcerative colitis (8.0%), fistula (7.2%), small bowel obstruction (4.8%), Crohn’s disease (3.2%), gastrointestinal bleeding (2.4%), and polyps (2.4%). Frequent comorbidities included hypertension (45.6%), cancer (28.8%), diabetes mellitus (20.8%), hyperlipidaemia (20.0%), gastroesophageal reflux disease (GERD, 16.8%), obesity (12.0%), and depression (10.4%). Surgical technique was laparoscopic in 46.0%, laparoscopic plus laparotomy in 2.4%, laparoscopic plus robotic in 0.8%, laparotomy in 44.0%, robotic in 5.6%, and sigmoidoscopic in 0.8%. Intraoperatively, general anaesthesia was administered in 91.2% and general anaesthesia plus regional analgesic techniques in 8.8%.
Among outcomes, two deaths occurred (1.6%). Continuous and categorical patient characteristics and outcomes for all patients and by interval subgroups are shown in Tables 1 and 2, respectively. PACU numeric rating scale (NRS, 0–10) pain at postoperative interval 1 was 4.58 ± 2.45, compared with 4.09 ± 2.65 at interval 2 and 3.51 ± 2.82 at interval 3. Mean hospital length of stay was 11.2 ± 15.5 days. Mean operative time was 325.1 ± 133.6min. Mean estimated blood loss was 242.5 ± 333.8ml. NRS scores did not significantly differ between open and laparoscopic approaches at postoperative intervals 1 and 3 (Table 3). Nonetheless, NRS score was lower in patients undergoing bowel resection by open approach in postoperative interval 2. OFA rates did not significantly differ between the two approaches.
Continuous patient characteristics and outcomes for all patients and by interval subgroups
ASA: American Society of Anesthesiologists; BMI: body mass index; N: number; OR time: operating time; PACU: post-anaesthesia care unit; SD: standard deviation.
In univariate comparison of continuous variables between the intervals 1–3 and 5–9, age, ASA score, PACU NRS scores, hospital length of stay, and estimated blood loss did not yield a statistically significant difference. Nonetheless, BMI was significantly higher in the interval 1–3, whereas OR time was significantly longer in the interval 5–9.
*Statistically significant difference.
Categorical patient characteristics by interval subgroups
In univariate comparison of categorical variables between the intervals 1–3 and 5–9, the rates of opioid tolerance, diagnostic laparoscopy, exploratory laparotomy, and lysis of adhesions did not yield a statistically significant difference. Nonetheless, gender distribution was found to be statistically significantly different.
*Statistically significant difference.
NRS scores and opioid-free analgesia rates stratified by surgical approach
PACU: post-anaesthesia care unit; SD: standard deviation.
Surgical approaches were compared in terms of pain outcomes to identify whether surgical approach was a confounding factor. Although NRS scores did not significantly differ between open and laparoscopic approaches at postoperative intervals 1 and 3, it was significantly lower at interval 2. Opioid-free analgesia rates did not differ either.
Trend analysis was conducted using nine-month intervals, beginning in February 2012 (Figure 1). The proportion of patients receiving OFA during interval 1 was 20%, falling steadily to 0% at interval 4. The OFA proportion then rose back to 20% at interval 6, declined to 10% at interval 7, then rebounded to 15.4% at interval 8, and rose further to 42.9% at interval 9. Joinpoint regression found that the slope of the line between intervals 1 and 4 (segment 0) was not different statistically from zero. However, modelling detected a joinpoint at interval 4 marking the beginning of segment 1. The slope of segment 1 was positive and statistically different from zero, with an average per cent change of 42.6 with a 95% confidence interval of 1.8–99.8 and a p value of 0.043. Thus, since interval 4, there has been a positive increasing trend of use of OFA in this patient population. This change coincides with the arrival of an anaesthesiologist co-author who implemented a new analgesics usage.
Trends in probability of OFA across nine-month intervals: a Joinpoint chart. ^Indicates that the Annual Per cent Change (APC) is significantly different from zero at the alpha = 0.05 level. Final Selected Model: 1 Joinpoint
Statistical comparisons were made between patients appearing in intervals 1–3 and 5–9. Among statistically significant between-group differences, BMI was higher for intervals 1–3 (p = 0.017) and OR time was longer in intervals 5–9 (p = 0.036). In intervals 1–3, patients were more likely to be female (p = 0.047) and more likely to have experienced opioid tolerance (p < 0.001). Mobilisation of the splenic flexure (p = 0.001) and rectum resection (p = 0.016) were more likely in intervals 5–9, while small bowel resection was more frequent in intervals 1–3 (p = 0.003). Obesity as a surgical indication (p = 0.013) and as a comorbidity (p = 0.002) was more common in intervals 1–3. GERD was a comorbidity among more patients in intervals 1–3 (p = 0.032), while kidney disease was more prevalent in intervals 5–9 (p = 0.048). General plus regional intraoperative analgesia was given to more patients in intervals 5–9 (p = 0.006).
Discussion
This retrospective study of 125 patients who underwent bowel resection found that perioperative multimodal analgesia is a viable alternative to postoperative opioid use. We found that the trends of surgeries managed receiving OFA after interval 4 (segment 1) increased. This can be explained by the increasing popularity of IV Paracetamol (acetaminophen) additionally to the arrival an anaesthesiologist co-author who initiated regional analgesia and acute pain service and implemented a new analgesics usage policy favouring nonopioid agents. Besides, we found that during the first three intervals at PACU NRS, pain trends used to decrease; in this case, it can be explained by the use of opioid or multimodal analgesia trying to improve postoperative pain management; in addition, we found that between interval 1 and 3, patients were more likely to be female and to have experienced opioid tolerance resulting in decreased trends of opioid free therapy due to adaptation in which exposure to the drug induces changes that result in diminution of one or more of the opioid’s effects over time.
Literature regarding the prevalence and efficacy of OFA following CS is relatively new. Despite this, Meyer et al (2018) reported that postoperative opioid use was significantly lower in ERAS group. Moreover, the reduction in opioid intake was even greater postoperatively. The authors concluded that intra and postoperative opioid use can be significantly decreased without compromising pain management. Cata et al (2017) reported that multimodal analgesia approach providing adequate pain relief beyond the duration of hospitalisation is needed not only to avoid the development of postsurgical persistent pain, but also to decrease the exposure of patients to opioids reducing the opioids related adverse events like increased constipation, decreased bowel motility, ileus, PONV, sedation, and delirium, and decreasing the cost associated with them (Kamdar et al 2017).Unfortunately, excessive use of opioids in the management of acute pain is known to lead to an increase in the rates of opioid use disorder. This phenomenon was named opioid epidemic and declared as a major public health concern (Hurley 2017). Data suggest that those who receive an opioid prescription for the management of acute after surgery are 44% more likely to become long-term opioid users. Therefore, implementation of OFA according to the guidelines for safe and effective postoperative pain management is important (Alam et al 2012). Moreover, initiation and development of PROSPECT guidelines led to the implementation of procedure-specific pain management, thereby, decreasing the risks of the above-mentioned consequences (Joshi et al 2013, 2019).
This study has several limitations. First, this was a retrospective study which by its nature entails selection bias and our second limitation was a small sample size. Also, colorectal procedures were performed by general surgeons who could have influence in findings like operating time. Another limitation was the evaluation of pain score and follow-up over time.
In conclusion, OFA in patients undergoing emergency or elective CS is a valid alternative; this study has shown increasing trend in the use of OFA, and we think that the risks associated to opioids use, abuse, or misuse are higher up than the fear of inadequate analgesia when you use appropriate multimodal analgesia techniques. Overtime, in CS patients, further prospective studies with evaluation of pain score are needed to support these findings.
Summary
Opioids are commonly used worldwide for postoperative pain relief and the excessive use in the hospital setting, especially in patients undergoing bowel resection, has shown to lead to postoperative paralytic ileus and in some cases dependence. The aim of this retrospective cohort study was to evaluate whether any changes in the use of opioids occurred in a cohort of adults undergoing elective bowel resection at a single centre. Between 2012 and 2018, 125 patients with the mean age of 58.0 ± 15.5 years and mean BMI of 29.1 ± 8.3kg/m2 were included (male – 48%; female – 52%). The study span was divided into equal intervals and trend analysis evaluating changes in the proportion of patients receiving OFA over time was carried out. The main finding was that a statistically significant increase in the proportion of patients receiving OFA was observed starting with interval 4. This time point coincided with the arrival of a new anaesthesiologist and widespread implementation of multimodal analgesia. When perioperative variables were compared between two time intervals (interval 1–4 versus interval 4–9), significantly increased rate of regional intraoperative analgesia use was found starting with interval 4. This study confirmed that OFA is a viable alternative to opioids in patients undergoing elective bowel resections.
No competing interests declared
