The effect of pharmacist-initiated perioperative multidisciplinary pharmaceutical care model and clinical pathway on pain management in patients undergoing orthopedic surgery: a before-after study

Poor pain control is common in perioperative orthopedic surgeries. However, there is a lack of exploration of the clinical pharmacy practice model for this population. To construct a perioperative pharmaceutical care model and clinical pathway for patients undergoing orthopedic surgeries and assess their impact on pain management. This historical before-and-after study was conducted in the Department of Orthopedics of a tertiary hospital in Guangdong Province, China. The control group was surgical patients who received routine diagnosis and treatment. The intervention group received pain management from a multidisciplinary team based on a pharmacist-initiated pharmaceutical care practice model and clinical pathways for medication management. The primary outcome measures were postoperative pain at rest (PAR) and movement-evoked pain (MEP) scores, number of breakthrough pains, and length of hospital stay. A total of 320 orthopedic surgery patients were included. Among patients with expected moderate or severe postoperative pain (82.5%), significantly lower PAR and MEP scores were observed in the intervention group 24 h after surgeries compared to the control group (p < 0.05). Compared to the control group, hospital stay in the intervention group was shortened by 2.3 days (p < 0.001). However, there were no significant differences in the control of breakthrough pain and the incidence of adverse drug reactions (p > 0.05). Multidisciplinary perioperative pain management practice models and clinical pathways initiated by pharmacists could improve outcome indicators related to pain management and support the role and value of pharmacists.


Introduction
Pain is one of the common symptoms after orthopedic surgery, and more than 50% of patients experience moderate to severe pain the first day after surgery [1][2][3]. Poorly controlled pain will affect the recovery of physical function and quality of life, increasing the risk of postoperative complications [4]. Approximately 10% of patients develop postoperative chronic pain [5]. With the in-depth implementation of a multidisciplinary team (MDT)-based enhanced recovery after surgery (ERAS) program, more and more 1 3 pharmacists are joining the surgical care team. In 2015, the Chinese Guangdong Province Pharmaceutical Association (GDPA) introduced the concept of a 'surgical pharmacist' [6,7]. Subsequently, GDPA proposed the definition of surgical pharmacy as 'a discipline that studies the characteristics of perioperative medication, seeks the most suitable medication therapy, and addresses drug-related problems for perioperative patients, to improve the clinical outcome of these patients' and calls to establish the knowledge system of surgical pharmacy [8]. Pain management is one of the main contents of surgical pharmacy practice [8,9].
Clinical pharmacists can play a role in multiple aspects, such as education, evaluation, and formulation of analgesic drug regimens, monitoring efficacy, and positively impacting postoperative pain management quality [10]. Broad participation of pharmacists in patient education before joint replacement surgery positively impacted patient satisfaction with pain control [11]. Patient-controlled analgesia (PCA) services managed by pharmacists reduced the need for breakthrough analgesic drugs in 25% of patients after surgery and are widely accepted by the MDT [12]. By providing preoperative medication counseling, pain consultation, and opioid management, pharmacists improve patient satisfaction and directly reduce the need for opioid use during hospitalization and after discharge [13][14][15].
However, clinical pharmacists' practice in perioperative pain management is still developing. In the latest survey, only 11.1% of pharmacists joined the acute pain service [16].
Most studies reported only one or more aspects of pharmacist participation in perioperative pain management. A recent study described comprehensive pharmaceutical services to patients undergoing total joint replacement during the perioperative period, such as anticoagulation, pain, and anti-infection [17]. However, it did not specifically describe the pharmacist service content and the pain management process. Currently, there is still a lack of practice models for surgical pharmacists, which may be one of the critical reasons for the insufficient participation of pharmacists in the acute pain service.
Our hospital has implemented an MDT-based acute pain management practice for patients after hepatobiliary surgery. The MDT consisted of clinical pharmacists, surgeons, and nurses. The practice delineated the postoperative pain management process and clarified the respective responsibilities of the team members. The group with pharmacist participation had better pain control than the conventional treatment group (without pharmacist participation) [18]. More research is needed to construct a surgical pain pharmacy practice model in the MDT framework in perioperative pain management.

Aim
To construct a perioperative pharmaceutical care model and clinical pathway for patients undergoing orthopedic surgeries and assess their impact on pain management.

Ethics approval
The research protocol was approved by the Ethics Committee of the Second Hospital of Guangzhou Medical University (approval date September 23, 2019, approval number 2020A25). Informed consent was obtained from all participants in the intervention group.

Study design and setting
This before-and-after study was conducted in the Orthopedics Department of a tertiary hospital in Guangdong Province, China. The historical control group received routine care without the participation of clinical pharmacists. The intervention group consisted of patients who received MDT pain management care. The control group underwent surgery from July 2019 to June 2020, and the intervention group underwent surgery from July 2020 to June 2021.

Study participants
Inclusion criteria were patients who (1) were 18 years and older, and (2) underwent elective or limited-term orthopedic surgeries, including removal of internal fixation of fractures, percutaneous kyphoplasty/percutaneous vertebroplasty (PKP/PVP), cervical and lumbar decompression and/or internal fixation and/or fusion, internal fixation of fractures, or knee and hip replacement. The expected level of postoperative pain was categorized as mild, moderate, and severe based on the surgery type [19]. Exclusion criteria were patients who (1) had systemic diseases that required special perioperative care, including intensive care, multiple blood transfusions, or dialysis, (2) could not be discharged for reasons not related to pain control, were transferred to another ward or hospital, died, or were discharged against the physician's advice, (3) had symptoms of moderate to severe pain not related to surgeries, or (4) could not communicate effectively with pharmacists due to language, hearing, or disease barriers.

The establishment of an MDT pharmaceutical care model for perioperative acute pain management
An MDT pharmaceutical care model for acute perioperative pain was established based on literature evaluation [9,[19][20][21] (Fig. 1). The content was based on questionnaire surveys to assess knowledge of analgesic drugs among physicians and nurses, the analysis of the past three years of analgesic drug prescription reviews, and discussions with physicians and nurses about drug-related measures to improve pain management. The model delineated responsible patient care activities of the team members.

The clinical pathway for orthopedic perioperative pain medication management
Clinical pharmacists, orthopedic surgeons, and anesthesiologists created a clinical pathway for orthopedic perioperative medication management based on guidelines, expert consensus, and medication standards [22][23][24][25]. The clinical pathway provided guidance on selecting medications based on the expected postoperative pain level and the assessment of the risk of medicines. The expected postoperative pain levels were classified as mild, moderate, or severe. The medication risk assessment [26][27][28] included contraindications and cardiovascular, gastrointestinal, or kidney risks associated with non-steroidal anti-inflammatory drugs (NSAIDs). Gastrointestinal risk assessment was based on H. pylori, alcohol abuse, a history of ulcer or epigastric pain, age ≥ 65 years, recent long-term or high-dose use of NSAIDs, and combined use of aspirin, glucocorticoids, or anticoagulants. The cardiovascular risk assessment considered hypertension (blood pressure range), coronary artery bypass, heart failure, myocardial infarction, and stroke. The evaluation of renal risk included renal function or the presence of kidney disease. The details of the clinical pathway are shown in Fig. 2.

The content of pharmacist interventions
Before starting the intervention study, pharmacists updated the pain prescription review information system and provided targeted pharmacy training to physicians and nurses. The training focused on the orientation of the pharmaceutical care model and the clinical pathway of pain medication management, the selection of multimodal analgesic regimens, the avoidance of drug interactions, and adverse drug reaction (ADR) management. Training videos were uploaded for team members to learn at any time.
The pharmacist interventions had four components: preadmission, preoperative, postoperative, and discharge management. Within 48 h of scheduled surgery, pharmacists performed a complete preadmission assessment, including pain history and evaluation (location, nature, pain, quality of life score, and breakthrough pain), past medical and medication history, risk factors for NSAIDs, and history of ADRs. The evaluation was entered into the electronic medical record system, which could be viewed on mobile phones. Preoperative interventions focused on high-risk patients. Pharmacists participated in MDT discussions to select pre-emptive, multimodal analgesia based on the type of surgery, the preadmission assessment, and the clinical pathway to meet the analgesic needs of individual patients. Patients also received preoperative education from the pharmacist within 24 h after the preadmission review. Education included the definition and harm of pain, how to describe pain, the benefits of pain medications, pain treatment methods, and addiction. Brochures were written and distributed to facilitate patients' understanding and acceptance of perioperative pain management. Postoperative interventions included monitoring pain control and adjusting analgesic regimens. Pharmacists evaluated the patient's pain within 24 h after the operation and made timely recommendations on medication changes. Pharmacists monitored the operation, analgesic effect, and ADRs for patients who were on PCA. For patients who discontinued PCA, pharmacists discussed the follow-up pain management plan with physicians according to the results of the pain assessment. Pharmacists participated in MDT ward rounds and case discussions. Furthermore, WeChat® (the largest social network in China) workgroups were created to engage in timely patient management; for example, breakthrough pain or intolerance to medications. Pharmacists also regularly monitored ADRs, such as nausea, vomiting, constipation, chest tightness, and shortness of breath. Patients were encouraged to do early rehabilitation exercises when appropriate. Discharge interventions focused on reviewing discharge prescriptions and patient education. The pharmacist checked the discharge prescription within 24-48 h before discharge. On discharge, pharmacists educated patients about how to take the medication, precautions, potential adverse reactions, and strategies for medication adherence. In addition to perioperative pain management, pharmacists also provided consultations on anticoagulation, anti-infection, and/or adjustment of antihypertensive regimens when appropriate.
Two pharmacists participated in the MDT team to provide interventions. They were trained on the pharmaceutical care model, the clinical pathway, and the components of the interventions. Furthermore, the Department of Pharmacy established a pain team (four pharmacists) to regularly assess the content and quality of the work of those two pharmacists to ensure the consistency and quality of services.

The control group
The control group received routine perioperative pain management without the participation of clinical pharmacists. Physicians and nurses administered drugs based on experience, mainly on-demand, without standard medication risk assessment, pain education, and analgesic clinical pathway. During this period, pharmacists only provided essential prescription reviews remotely (intercepting unreasonable prescriptions according to instructions and guidelines without considering the actual pain conditions of patients).

Main outcome measures
Pain assessment was performed using the numeric rating scale (NRS) score. Primary outcome indicators were pain at rest scores (PAR) immediately (when the patient woke up), 24 h, 48 h, and 72 h after surgeries, movement-evoked pain scores (MEP) [29][30][31][32], breakthrough pain, and length of hospital stay. Secondary outcome measures were analgesic ADRs. The severity of ADR was classified into grades 1-5 according to the Common Terminology Criteria for Adverse Events (CTCAE 4.0) [33].

Data collection
The breakthrough pain and ADRs in the control group were extracted from medical and nursing records. In contrast, these data were recorded by pharmacists for the intervention group. The following baseline data were collected: age, sex, expected postoperative pain level, surgical site, anesthesia method, American Society of Anesthesiologists (ASA) classification, and disease information. The ASA grading system was used to assess the preoperative comorbid conditions of a patient and assigned a class ranging from 1 to 6 [34].

Sample size calculation
According to previous studies, patients with the lowest acute pain relief had a 35% reduction in the mean NRS score [35]. Most patients had moderate to severe postoperative orthopedic pain [1,2,36]. The sample size calculation was based on the following assumptions [2,35,36]: the average NRS score of 5 on the first postoperative day, the minimum clinically important difference in pain scores of 1.75 points, α = 0.05, 1-β = 0.9, the standard deviation of the control group of 2.5, the standard deviation of the intervention group of 1.09, and a dropout rate of 20%. The control and intervention groups required a minimum of 36 and 44 patients, respectively.

Statistical analysis
For baseline data and outcome indicators, the Kolmogorov-Simonov test was used to determine the use of parametric or nonparametric tests. Measurement data corresponding to the normal distribution are expressed as mean ± standard deviation (SD). Independent samples t-tests were used to compare the groups. For groups that did not conform to the normal distribution, comparisons were made using a nonparametric test (Mann-Whitney U test). Enumeration data are expressed as the number of cases or rate (%), and the χ 2 test was used to compare groups. p < 0.05 was considered statistically significant. Data were analyzed using SPSS version 26.

Results
A total of 320 patients were included, 158 in the control group and 162 in the intervention group (Supplemental Fig. 1). There were no significant differences in the baseline demographic and clinical characteristics of the patients between the two groups (p > 0.05) ( Table 1).

Primary outcomes
The postoperative pain scores and the length of hospital stay in the two groups are shown in Table 2 Table 3 shows the pain scores and length of hospital stay between the two groups based on the expected levels of postoperative pain. There were no significant differences in pain scores and hospitalization time between the two groups of patients with expected mild postoperative pain (p > 0.05). However, compared to the control group, the intervention group had significantly lower mean PAR

Secondary outcomes
The occurrence of ADR of analgesic drugs between groups is shown in Table 4. Eight patients (4.9%) had ADR in the intervention group compared to six (3.8%) in the control group. However, the difference was not statistically significant (p = 0.948). All ADRs were transient and rated as CTCAE grade 1-2.

Statement of key findings
This study described the pharmacy-initiated perioperative pain MDT service model and clinical pathways for medication management. Pharmacist participation improved postoperative pain control in orthopedic surgery patients. Among patients with expected moderate or severe postoperative pain, the intervention groups had lower PAR or MEP scores 24 h after surgeries compared to the control group. The mean NRS scores were ≤ 3, which were rated as mild pain [37,38]. Among patients with expected severe postoperative pain, the postoperative MEP scores in the intervention group were significantly lower than those of the control group, with an average reduction of 2.1 points (41% reduction). The average hospital stay was also reduced by 3.3 days in the intervention group. The degree of pain relief exceeded the clinically meaningful level of pain reduction of 30% in patients with acute postoperative pain [39].

Strengths and weaknesses
Our study established standard analgesic drug management and perioperative clinical medication pathways through multidisciplinary collaboration to improve the quality of surgical pharmacy practice. Surgical pharmacy practice should permeate the multidisciplinary cooperative diagnosis and treatment links, such as improving the overall medication management, strengthening the monitoring of the effectiveness and safety of pain medications for postoperative patients, and improving patients' medication adherence in the perioperative period. Our study has several limitations. First, the before and after study design may introduce bias, which could be minimized by adopting strict inclusion and exclusion criteria when selecting patients [40]. Second, pain assessment is subjective and can result in potential biases. Standardized training on pain assessment can reduce bias. Finally, the research plan for this project has a comparison of economic benefits. However, in the middle of the project implementation, the ongoing reform of China's medical insurance and the centralized drug procurement system [41] led to a drastic reduction in the price of a variety of pain relief drugs, with a range of more than 60%, so the economic benefits could not be analyzed according to the original plan.

Interpretation
Perioperative pain management requires a well-trained multidisciplinary team [42,43], in which the clinical pharmacist is a member [44]. Several studies have reported positive outcomes of pharmacists' interventions in acute pain management [45][46][47]. Another US study described having a clinical pain pharmacist in transitional perioperative pain management. The patients were referred to the pain pharmacist before elective surgery. The pharmacist worked with the patients to develop an individualized perioperative analgesic plan and provided education on surgery. The study demonstrates that pain management pharmacy specialists contribute to positive patient pain management outcomes and surgical provider satisfaction [48]. Our research also supported the participation of pharmacists in surgical pain management and further explored the integrated practice model of pain pharmacists. The practice model delineates the roles of team members and the work content and process of pharmacists. The model provides a reference for standardizing the management of perioperative pain in surgical pharmacy practice. Different orthopedic surgeries may have different expected levels of postoperative pain, and patients may have insufficient analgesia based on the pain level [2]. To provide adequate pain control, we created hierarchical pain management clinical pathways. The results showed that pharmacist interventions significantly impacted pain control, especially in patients with expected moderate or severe postoperative pain.
Patients who have undergone orthopedic surgery should start functional exercise as soon as possible. Pain management during exercise is a critical and essential factor to discharge success [23,39]. Based on the MEP score, postoperative pain management could guide medical personnel to perform a comprehensive pain assessment, take active analgesic measures, and encourage patients to participate more actively in self-pain control [49]. MEP is 25-226% more intense than PAR in the first three days after surgery, and adequate pain control is essential [49]. In our study, pharmacists effectively reduced MEP scores for three days after surgeries in patients who underwent expected severe pain surgeries. Pain control allowed for accelerated rehabilitation. The average hospitalization cost in the orthopedics department of our hospital is $386 per person per day. Patients in the intervention group had 2.3 days less of hospital stays than those in the control group. This would lead to a total decrease in hospitalization costs of $142,333.2 in the intervention group. Although many factors contributed to cost savings, the participation of surgical pharmacists in effectively assisting patients with managing pain after surgery is a crucial factor. We plan to conduct future pharmacoeconomic studies of the surgical pharmacists' perioperative pain management services.
There were no significant differences in the number and frequency of breakthrough pain between the two groups. There were no significant differences in the incidence of ADRs between the groups, which may be related to the similar types of analgesic drugs used (mainly NSAIDs). The small-sample study may contribute to these nonsignificant findings.

Further research
Many patients may have persistent pain after discharge and even develop chronic postoperative pain [50], in which pharmacists can play a role and even open pharmacist clinics [51,52]. More research is needed on pharmacist intervention methods and their effects on post-discharge orthopedic surgery patients.

Conclusion
The MDT orthopedic perioperative pharmaceutical care model and clinical pathway initiated by pharmacists positively impacted pain control and length of hospital stays. Efforts should be directed to establish standardized practice and medication management clinical pathways.