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 was patients who received MDT pain management care. Witten informed consent was obtained from patients enrolled in the intervention group. The control group was patients who underwent surgery from July 2019 to June 2020, and the intervention group was patients who 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 the 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 [16]. 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, transfer to another ward or hospital, death, or discharged without physician’s advice, 3) with 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 [17, 18] (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 [19–22]. The clinical path 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 [23–25]included contraindications and cardiovascular, gastrointestinal, or kidney risks associated with non-steroidal anti-inflammatory drugs (NSAIDs). Gastrointestinal risk assessment was based on the presence of 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 renal risk assessment included renal function or the presence of kidney diseases. 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 ADR management. Training videos were uploaded for team members to learn at any time.
The pharmacist interventions in the intervention study had five components: pre-admission, preoperative, intraoperative, postoperative, and discharge management. Within 48 hours of scheduled surgery, pharmacists performed a complete pre-admission 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 a mobile phone. 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 pre-admission assessment, and the clinical pathway to meet the analgesic needs of individual patients. Patients also received preoperative education from the pharmacist within 24 hours after the pre-admission 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 hours after the operation and made timely recommendations on medication changes. harmacists 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 media 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 reviewed the discharge prescription within 24–48 hours before hospital discharge. On the day of 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 and were trained on the pharmaceutical care model, the clinical pathway, and the components of the interventions. In addition, 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. The primary outcome indicators were pain at rest scores (PAR) immediately (when the patient just woke up), 24 hours, 48 hours, and 72 hours after surgeries, and movement-evoked pain scores (MEP) [26–29], breakthrough pain, and length of hospital stay. Secondary outcome measures were ADRs from analgesics. The severity of ADR was classified into grades 1–5 according to the Common Terminology Criteria for Adverse Events (CTCAE 4.0) [30].
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 basic disease information. The ASA grading system was used to assess the preoperative comorbid conditions of a patient and assigned a class ranging from 1–6.
Sample size calculation
According to previous studies, patients with the lowest acute pain relief had a 35% reduction in the mean NRS score [31]. Most patients had moderate to severe postoperative orthopedic pain [1, 2, 32]. The sample size calculation was based on the following assumptions: 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 [2, 31, 32], the standard deviation of the intervention group of 1.09 [33], and a dropout rate of 20%. The control and intervention groups required a minimum of 36 and 44 patients, respectively.
Statistical analysis
For the baseline data and outcome indicators, the Kolmogorov-Simonov test was used to determine the use of parametric or nonparametric tests. The measurement data conformed to the normal distribution are expressed as mean ± standard deviation (SD), and two independent samplest-test was used to compare 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 χ2 test was used to compare groups. P < 0.05 was considered statistically significant. Data were analyzed using SPSS version 26.