Multimodal analgesia in cardiac surgery: Impact on postoperative medication consumption and cognitive function

Abstract

BACKGROUND

Patients who undergo cardiac surgery often face postoperative pain and potential cognitive issues. Multimodal analgesia may address these problems. We hypothesized that multimodal analgesia can reduce opioid use and improve cognitive recovery.

AIM

To investigate the effects of multimodal analgesia on postoperative opioid consumption and cognitive recovery in patients who underwent cardiac surgery.

METHODS

A prospective, randomized controlled trial at General Hospital from January 2020 to April 2023 recruited a total of 150 adult patients who underwent elective cardiac surgery. The patients were randomly divided into two groups. Group A had patient-controlled intravenous analgesia with sufentanil and flurbiprofen axil. Group B had flurbiprofen axil and paravertebral nerve block. Data were analyzed with appropriate statistical methods.

RESULTS

Group B had lower postoperative patient-controlled intravenous analgesia drug consumption (2.21 mL/hour vs 4.26 mL/hour, P < 0.001), shorter extubation time (2.32 hours vs 3.81 hours, P < 0.001), and intensive care unit stay (15.32 h vs 28.63 h, P < 0.001). Visual Analogue Scale pain scores were lower in group B (P < 0.001). Group B had fewer postoperative complications (no respiratory depression vs 37.9% in group A, P < 0.05), a lower postoperative cognitive dysfunction incidence (16.0% vs 28.0%, P < 0.05), and higher Barthel Index scores (P < 0.05).

CONCLUSION

Multimodal analgesia with paravertebral nerve block and flurbiprofen axil reduces opioid use and improves cognitive outcomes in patients who underwent cardiac surgery.

Key Words: Multimodal analgesia; Cardiac surgery; Postoperative medication consumption; Cognitive function; Pain management

Core Tip: In this study, 150 patients who underwent cardiac surgery were randomized into two groups. The combination of paravertebral nerve block and flurbiprofen axil in multimodal analgesia significantly reduced postoperative opioid use and enhanced cognitive function. It offered a better pain management and recovery approach.

INTRODUCTION

Cardiovascular diseases are a leading cause of morbidity and mortality worldwide, with cardiac surgery being a critical intervention for a range of conditions, including coronary artery disease, valvular heart disease, and congenital heart defects[1]. The surgical approach to cardiac surgery has evolved over time, with a shift towards minimally invasive techniques that aim to reduce trauma and accelerate recovery[2,3]. However, despite these advancements, postoperative pain remains a significant challenge for patients undergoing cardiac surgery[4].

Postoperative pain is not only a source of discomfort but also a critical factor that can delay physical recovery and lead to negative emotional responses in patients[5]. The management of postoperative pain is, therefore, a crucial aspect of postoperative care[6]. Traditionally, opioids have been the mainstay of analgesia in the postoperative period. However, their use is associated with several adverse effects, including respiratory depression, sedation, and constipation, which can prolong the hospital stay and impair the quality of recovery[7,8].

In recent years, there has been a paradigm shift towards multimodal analgesia in the management of postoperative pain[9]. Multimodal analgesia involves the use of a combination of analgesic agents with different mechanisms of action to achieve synergistic pain relief with lower doses of individual drugs, thereby minimizing side effects[10,11]. This approach has been increasingly advocated in the context of cardiac surgery, where the potential for severe pain and the need for rapid recovery make it particularly relevant[12,13].

The use of multimodal analgesia in cardiac surgery has been shown to reduce postoperative opioid consumption, which is of significant clinical importance[14]. Opioids, while effective for pain relief, can cause significant suppression of gastrointestinal motility, leading to postoperative ileus and other gastrointestinal complications. By reducing opioid requirements, multimodal analgesia can potentially decrease the incidence and severity of these complications, thereby facilitating earlier recovery and discharge[15].

Furthermore, the impact of multimodal analgesia extends beyond its effects on pain control and gastrointestinal function. Postoperative cognitive dysfunction (POCD) is a common complication following cardiac surgery, with an incidence ranging from 23% to 81%[16]. POCD is characterized by a decline in cognitive function, including memory, attention, and executive function, which can persist for weeks or even months after surgery. The etiology of POCD is complex and multifactorial, with postoperative pain and opioid use being potential contributing factors[17].

There is growing evidence to suggest that multimodal analgesia may not only improve pain control but also have a positive impact on cognitive recovery following cardiac surgery. By reducing opioid consumption and the associated cognitive side effects, multimodal analgesia may help to mitigate the risk of POCD and promote better cognitive outcomes in the postoperative period.

In this study we aimed to investigate the impact of multimodal analgesia on postoperative opioid consumption and cognitive recovery in patients undergoing cardiac surgery. We evaluated the efficacy of multimodal analgesia in reducing opioid requirements and its potential to improve cognitive function postoperatively. Our research contributed to the growing body of literature on multimodal analgesia and its role in optimizing postoperative outcomes in cardiac surgery. By elucidating the relationship between pain management strategies, opioid consumption, and cognitive recovery, our study provided valuable insights into the multifaceted impact of multimodal analgesia on patient recovery and quality of life following cardiac surgery.

MATERIALS AND METHODS

Study patients

This study was a prospective, randomized controlled trial that involved 150 adult patients who underwent elective cardiac surgery at General Hospital between January 2020 and April 2023. Employing a random number table to ensure equitable distribution, patients were allocated into two groups. The surgeries performed included aortic valve replacement, mitral valve replacement or plasty, atrial septal defect repair, and ventricular septal defect repair.

Group A, comprising 76 cases, was administered sufentanil combined with flurbiprofen axil for patient-controlled intravenous analgesia (PCIA). This group included 37 males and 39 females, aged from 18 years old to 60 years old, with body weights ranging from 34 kg to 72 kg. The patients in group A had an American Society of Anesthesiologists (ASA) physical status classification of 2 to 3 and were at a cardiac function level of 2 (Table 1).

Table 1 Baseline of the two groups.

Group	Number of cases	Gender breakdown	Age range	Weight range (kg)	American Society of Anesthesiologists classification	Cardiac function classification
Group A	76	37 males, 39 females	18-60	34-72	2-3	2
Group B	74	36 males, 38 females	18-60	39-70	2-3	2

Group B, with 74 cases, received flurbiprofen axil with paravertebral nerve block. This group consisted of 36 males and 38 females, also within the age range of 18 years old to 60 years old, with body weights from 39 kg to 70 kg. The ASA classification for these patients was also 2 to 3, and they were at a cardiac function level of 2. A comparative analysis of the general information between the two groups showed no statistically significant differences, indicating that the groups were well-matched and comparable for the objectives of the study.

Inclusion criteria

Inclusion criteria included: (1) Adults aged 18 years or older; (2) Elective cardiac open heart surgery; (3) Preoperative mini-mental state examination (MMSE) score > 24; and (4) Able to provide informed consent and cooperate with study procedures.

Exclusion criteria

Exclusion criteria included: (1) Significant psychiatric illness; (2) Known intellectual disability; (3) Severe neurological impairment; (4) Contraindications to paravertebral nerve block; (5) ASA physical status classification ≥ 4; (6) Cardiac function classification > 2; (7) History of previous cardiac surgery; (8) Substance abuse; and (9) Declined to participate or withdrew consent.

Anesthesia method

Patients were instructed to fast for 6-8 h and refrain from drinking for 4 h prior to surgery. Upon arrival, standard electrocardiograph monitoring was established, and vital signs including heart rate, oxygen saturation, blood pressure, and electrocardiograph were continuously monitored. An arterial puncture under local anesthesia was performed for invasive arterial pressure monitoring, and a central venous puncture was done for central venous pressure measurement. For group B, a paravertebral nerve block was administered at the T4-5 interspace bilaterally with 0.25% ropivacaine, 20 mL per side, under ultrasound guidance before anesthesia induction. The effectiveness of the block was assessed 15 min later using a pinprick test.

For group B, a paravertebral nerve block was administered at the T4-5 interspace bilaterally. The local anesthetic used was 0.25% ropivacaine, with 20 mL injected per side. This was carried out under ultrasound guidance before anesthesia induction. The effectiveness of the block was assessed 15 min later using a pinprick test.

Both groups underwent total intravenous anesthesia with sequential administration of midazolam 0.1 mg/kg, sufentanil 1-3 μg/kg, etomidate 0.2 mg/kg, and rocuronium 0.6mg/kg via a peripheral vein. Following induction, orotracheal intubation was performed, and mechanical ventilation was initiated with a controlled respiratory rate and tidal volume. Anesthesia was maintained with propofol, sufentanil, and rocuronium, with adjustments guided by Bispectral Index values kept between 40 and 60. Post cardiopulmonary bypass, vasoactive drugs were utilized to maintain hemodynamic stability, and arterial blood gas analysis was used to address any acid-base or electrolyte imbalances. The surgery concluded with the patients being transferred to the intensive care unit (ICU), intubated, and immediately started on PCIA.

Postoperative pain management was standardized with PCIA for all patients. The PCIA solution for Group A was composed of sufentanil 2 μg/kg, flurbiprofen axil 200 mg, and granisetron 0.5 mg, diluted to 100 mL with 0.9% sodium chloride. The solution for Group B included flurbiprofen axil 200 mg and granisetron 0.5 mg, also diluted to 100 mL. The PCIA pump was programmed with a loading dose of 2 mL, a continuous infusion rate of 2 mL/hour, a single dose of 1.5 mL, and a lockout period of 15 min.

Observation indicators

The study focused on evaluating clinical symptom indicators for both patient groups, which included postoperative PCIA drug consumption per unit time, a measure of the amount of analgesic medication required by patients after surgery. Additionally, the time to tracheal extubation was recorded, marking a significant milestone in the immediate postoperative period that reflects the patient’s readiness to breathe without mechanical support. The duration of ICU stay was also assessed, serving as an indicator of the patient’s overall recovery and stability post-surgery.

To evaluate the efficacy of the analgesic regimens, pain scores were measured at specific intervals following tracheal extubation. These intervals included 0.5 h, 2 h, 4 h, 8 h, and 16 h post-extubation. Pain scoring was essential for quantifying the level of postoperative pain and assessing the temporal effectiveness of pain management strategies.

The study also compared the incidence of postoperative complications between the two groups. Complications such as nausea and vomiting, somnolence, atelectasis, respiratory depression, and pneumonia were closely monitored. These outcomes are critical for understanding the safety profile of the analgesic techniques and the potential side effects that patients may experience following cardiac surgery.

The incidence and scoring of POCD were assessed preoperatively and on postoperative days 3, 5, and 7. Specifically, the MMSE scale[18] was used to evaluate patient cognitive function, with a sensitivity of 87% and a specificity of 82%. The criteria for MMSE judgment are as follows: (1) For illiterate patients, a score less than 17 points; (2) For patients with elementary school education, less than 20 points; and (3) For patients with education above junior high school, less than 24 points. These scores indicate the presence of cognitive dysfunction[19]. An increase of more than 1 point in the postoperative MMSE compared with the preoperative score indicates effective treatment[20]. Additionally, the Barthel Index (BI)[21] was used to assess patients’ ability to perform daily activities, with a score of 95 or above indicating complete independence, 75-94 for mild dependence, 50-74 for moderate dependence, 21-49 for severe dependence, and 20 or below for complete dependence.

To implement blinding for outcome assessors, a two-step process was adopted. First, the data collection forms were designed in a way that concealed the group information of patients. All records related to PCIA drug consumption, tracheal extubation time, ICU stay, pain scores, and complication details were anonymized. Second, the assessors were trained to focus solely on the measured values and symptoms, without being informed about the treatment group. They were also prohibited from accessing any information that could reveal a patient’s group assignment. This ensured that the evaluation of outcomes was not influenced by knowledge of the treatment received, thus reducing potential bias.

Statistical analysis

The statistical analysis was conducted using Statistical Package for the Social Sciences software, version 25.0, to process the data. Categorical variables were expressed as percentages and analyzed using the χ² test to determine differences in proportions between the two patient groups. Continuous data, represented by the mean and range standard deviation, were compared using a t-test to assess the significance of the differences in group averages. A P value of less than 0.05 was considered to indicate a statistically significant difference, allowing the researchers to draw conclusions about the impact of the analgesic methods on the outcomes measured.

RESULTS

Comparison of treatment outcomes between the two groups

The comparative analysis of the two patient groups demonstrated that group B patients had significantly lower postoperative PCIA drug usage per unit time, shorter tracheal extubation times, and reduced ICU stay durations when compared with group A patients (Table 2). These differences were statistically significant (P < 0.05), suggesting that the treatment protocol for group B was more effective in managing postoperative pain and facilitating a quicker recovery. The shorter extubation time and ICU stay in group B indicated a more efficient recovery process and potentially a lower risk of postoperative complications.

Table 2 Clinical symptom indicators for the two groups.

Group	Number of cases	Patient-controlled intravenous analgesia drug usage per unit time (mL/hour)	Extubation time (hour)	Intensive care unit stay duration (hour)
Group A	76	4.26 ± 0.67	3.81 ± 0.32	28.63 ± 4.31
Group B	74	2.21 ± 0.24	2.32 ± 0.43	15.32 ± 2.63

Comparison of Visual Analogue Scale scores

The Visual Analogue Scale scores were significantly lower in group B compared with group A at all post-extubation time points measured (0.5 h, 2 h, 4 h, 8 h, and 16 h), indicating less pain experienced by group B patients (P < 0.001 for all time points) (Table 3).

Table 3 Comparison of Visual Analogue Scale scores.

Group	0.5 h	2 h	4 h	8 h	16 h
Group A	7.82 ± 1.20	5.63 ± 1.18	5.43 ± 1.20	4.39 ± 0.85	3.96 ± 0.56
Group B	5.15 ± 1.12	4.23 ± 1.02	3.21 ± 1.05	2.42 ± 0.65	1.12 ± 0.52
t value	9.344	5.156	7.998	10.576	21.349
P value	0.001	0.001	0.001	0.001	0.001

Distribution of postoperative complications

The distribution of postoperative complications between the two patient groups revealed a notable difference in the incidence of such complications. As detailed in Table 4, group B patients exhibited a lower frequency of postoperative complications compared with group A patients across several categories.

Table 4 Distribution of postoperative complications in the two patient groups.

Group	Respiratory depression	Atelectasis	Pneumonia	Somnolence	Nausea and vomiting
Group A	34 (37.9)	36 (41.4)	4 (4.6)	9 (10.3)	12 (13.8)
Group B	0 (0)	3 (4.8)	3 (4.8)	10 (16.1)	20 (32.3)

Data are presented as n (%).

Specifically, group A, which consisted of 87 patients, had a higher number of patients experiencing respiratory depression (33 patients, 37.9%), atelectasis (36 patients, 41.4%), pneumonia (4 patients, 4.6%), somnolence (9 patients, 10.3%), and nausea with vomiting (12 patients, 13.8%). In contrast, group B, with 62 patients, had no cases of respiratory depression, fewer cases of atelectasis (3 patients, 4.8%) and pneumonia (3 patients, 4.8%), a higher rate of somnolence (10 patients, 16.1%), and a notably higher rate of nausea with vomiting (20 patients, 32.3%).

Comparison of cognitive function

The cognitive function of patients was assessed using the MMSE in both the control and training groups (Table 5). The control group showed a significant decline in MMSE scores from preoperative levels to postoperative day 3, with a score of 18.09 ± 1.56, indicating a substantial drop in cognitive function. This score improved only slightly by postoperative days 5 and 7. In contrast, the training group, which received targeted cognitive intervention, demonstrated higher MMSE scores at all postoperative time points, with significant differences observed compared with the control group (P < 0.05). The lower incidence of POCD in the training group further suggested that the intervention was effective in maintaining cognitive function.

Table 5 Comparison of postoperative cognitive dysfunction incidence and mini-mental state examination scores between the two groups (n = 50).

Group	Preoperative	Postoperative day 3	Postoperative day 5	Postoperative day 7	MMSE score preoperative	MMSE score day 3	MMSE score day 5	MMSE score day 7
Group A	0%	28%	23%	18%	28.35 ± 3.05	18.09 ± 1.56	20.14 ± 1.87	22.14 ± 2.46
Group B	0%	16%	12%	8%	28.07 ± 2.98	22.99 ± 2.32	23.08 ± 2.11	24.65 ± 3.06
P value	1.00	0.02	0.01	0.02	0.63	0.03	0.01	0.01

MMSE: Mini-mental state examination.

The ability to perform daily living activities was also evaluated using the BI (Table 6). The control group experienced a notable decrease in BI scores postoperatively, indicating a reduction in functional capacity. By the third postoperative day, the mean BI score was 48.81 ± 3.35, with a gradual recovery by days 5 and 7. Conversely, the training group preserved better functional capacity, with significantly higher BI scores at each postoperative time point (P < 0.05). These results imply that the intervention not only supported cognitive function but also aided in the preservation of patients’ ability to perform daily activities.

Table 6 Comparison of Barthel Index scores between the two groups.

Group	Preoperative	Postoperative day 3	Postoperative day 5	Postoperative day 7
Group A	96.79 ± 5.84	48.81 ± 3.35	53.13 ± 3.82	65.28 ± 5.97
Group B	97.04 ± 6.33	54.29 ± 4.06	67.74 ± 5.14	74.23 ± 6.38
P value	0.83	0.01	0.01	0.01

Adverse events

In group A, 5 patients (6.6%) had transient hypotension, 2 patients (2.6%) had minor wound infections, and 4 patients (5.3%) had urinary retention. In group B, 3 patients (4.1%) experienced transient hypotension, 1 patient (1.4%) had a minor wound infection, and 3 patient (4.1%) had urinary retention. None of these differences were statistically significant (P > 0.05).

DISCUSSION

Adult patients facing cardiac surgery frequently contend with a history of multiorgan dysfunction, notably within the respiratory system, and are often complicated by recurrent pneumonia. The extensive duration and significant trauma of cardiac surgery coupled with postoperative incisional pain can lead to restrictive ventilatory dysfunction[22]. This may exacerbate conditions such as pleural effusion, atelectasis, and pulmonary infection, thereby extending the patient’s ICU stay. Optimal postoperative analgesia not only alleviates pain but also encourages deep breathing, effective coughing, and early mobilization, which are critical for reducing atelectasis and facilitating the removal of drainage tubes[23]. Anesthesia providers, therefore, aim to minimize cardiac and hemodynamic impairments while supporting postoperative recovery through effective pain management strategies.

Multimodal analgesia offers a comprehensive approach to pain management by employing various agents and techniques that target different stages of pain processing. This method has been shown to provide superior pain relief by interrupting the generation, transmission, and perception of noxious stimuli[24]. Thoracic paravertebral block, in particular, is administered preemptively to disrupt the pain conduction pathway, reducing central sensitization and consequently the need for analgesic medication. This technique demonstrated efficacy with minimal cardiac suppression and a slight impact on hemodynamics, making it a favorable option for postoperative pain management in thoracic surgery. Compared to opioid-based analgesia, it provides clearer postoperative awakening, more effective pain control, and a lower incidence of nausea and vomiting, which are crucial for early respiratory exercise and reducing respiratory complications.

While epidural analgesia has been shown to reduce the incidence of postoperative atrial arrhythmias, myocardial ischemia, and respiratory complications as well as shortening the duration of mechanical ventilation, its use in cardiac surgery is limited due to concerns of epidural hematoma or abscess formation, especially in the context of heparinization during surgery. Bilateral paravertebral nerve block offers a safer alternative with comparable efficacy, fewer procedural complications, and a lower incidence of hypotension, respiratory depression, urinary retention, and incomplete block or block failure. The advent of ultrasound guidance has further improved the precision and success rate of paravertebral block while reducing complications. The use of local anesthetics such as 0.25% ropivacaine allows for satisfactory sensory block while preserving motor function, which is essential for postoperative coughing and clearing of secretions[25].

POCD is a common neurocognitive complication, particularly in the elderly and after major surgeries like cardiac operations[26]. The pathogenesis of POCD is complex and multifactorial, involving surgical stress, postoperative pain, inflammation, stress responses, sleep disturbances, and potential neurotoxic effects of anesthetic agents. The current study indicated that multimodal analgesia, including flurbiprofen axil with paravertebral nerve block, can reduce the incidence of POCD and improve cognitive function postoperatively. This may be attributed to the reduction in systemic inflammation and the neuroprotective effects of minimizing exposure to anesthetic agents known to cause neurotoxicity.

The findings of this study underscored the importance of the use of multimodal analgesia in patients who underwent cardiac surgery. The use of ultrasound-guided flurbiprofen axil with paravertebral nerve block provides a safe and effective analgesic regimen that can be applied to facilitate postoperative recovery in cardiac surgery. It is essential for healthcare providers to recognize the benefits of these strategies in improving patient outcomes, reducing healthcare costs, and enhancing the quality of life for patients undergoing cardiac surgery.

CONCLUSION

This prospective, randomized controlled trial involving 150 adult patients undergoing elective cardiac surgery demonstrated that multimodal analgesia, specifically the combination of paravertebral nerve block with flurbiprofen axil, led to significantly reduced postoperative opioid consumption, as evidenced by lower PCIA drug use. It also resulted in improved clinical outcomes, such as shorter extubation times, reduced ICU stays, lower Visual Analogue Scale pain scores, fewer postoperative complications, and enhanced cognitive function, as indicated by a lower incidence of POCD and higher BI scores. These findings suggested that this multimodal analgesia approach is a more effective option for pain management and recovery in patients who underwent cardiac surgery.