Postoperative Analgesia

Abstract

A failure to maintain adequate pain control is a substandard and unethical practice. Pain has disastrous effects in which poorly controlled acute postoperative pain is associated with increased morbidity and mortality, impaired quality of life, delayed recovery time, prolonged opioid usage, and higher healthcare costs. Inadequate knowledge about analgesia and pain management leads the healthcare profession to ineffective postoperative pain management. The main goal of postoperative analgesia is to reduce or eliminate pain and discomfort with a minimum of side effects. Assessment of pain severity is vital before managing it. There are many analgesic options that can be used to manage acute and chronic postoperative pain. Recently, non-opioid analgesia methods are encouraged for acute postoperative pain control due to the side effect of opioids and the advancement of recent technologies for peripheral nerve block.

1. Introduction

Pain after surgery is a common phenomenon, especially in patients who underwent general anesthesia, around half of the patients experience moderate to severe acute pain [1, 2]. The immediate experience of pain may be associated with the patient’s attitude, belief, and their personality [3].

Appropriate postoperative analgesia administration is associated with lower cardiopulmonary complications, lower mortality and morbidity, reduced hospital costs, and increased patient satisfaction [4, 5]. Standardizing multimodal analgesia combined with enhanced recovery after surgery (ERAS) are considered a quality improvement initiative in healthcare [6]. The American Pain Society introduced pain as the fifth vital sign. A failure to maintain adequate pain control is a substandard and unethical practice. The World Health Organization and the International Association for the Study of Pain have recognized pain relief as a human right [7, 8].

Unmanaged or poorly managed acute pain can lead to complications and prolonged rehabilitation. Poorly managed postoperative is associated with the development of chronic pain with a reduction in quality of life [9, 10].

Even though there are different modalities of pain management, the anesthesia type plays a great role in the decrement of postoperative pain scores. Regional anesthesia is more beneficial to control postoperative pain than general anesthesia [11]; from general anesthesia, a single controlled trial concluded that propofol anesthesia has a better analgesia outcome compared with sevoflurane anesthesia after open gastrectomy procedure in the early postoperative period [12], but a meta-analysis study concluded that there is no significant difference between propofol and inhalational anesthetics regarding postoperative pain, even though there was heterogeneity between the studies [13].

Pain management is one of the major components of ERAS protocol, and it is recommended that early and effective multimodal analgesia while decreasing opioids improves postoperative complications for colorectal surgeries [14]. Regional anesthetic techniques are the most effective methods to treat postoperative pain. A meta-analysis study suggests that epidural analgesia can no longer be considered the “gold-standard,” and another RCT study also outweighs transversus abdominis plane (TAP) block combined with opioid-sparing analgesia for laparoscopic colorectal surgery, than epidural analgesia [15, 16].

2. Pain pathophysiology acute pain

Acute pain is caused due to a response to tissue injury; during surgery, there is tissue damage and injury of small nerve fibers. The afferent nociceptors, A-delta, and C-sensory fibers (A mechano-thermal and C-polymodal) are peripheral nerve endings that normally have a high threshold for pain sensation/activation. So, noxious sensation produced by direct stimulation of A-delta and C-sensory fiber nerve endings and the inflammation due to a surgical incision will produce a peripheral sensitization enhancing the sensitivity of these nociceptors. Nociception follows four process: transduction, transmission, perception, and modulation [17]. From the damaged cells, mediators like substance P, prostaglandins, serotonin, histamine, bradykinins, and other mediators trigger the nociceptors (transduction) to send afferent impulses via the dorsal root ganglion to the spinal cord (transmission) [18]. Activation of substance P and other neurotransmitters carry the action potential to the dorsal horn of the spinal cord, from where it ascends the spinothalamic tract to the thalamus and the midbrain. From the thalamus, fibers send the nociceptive message to the somatosensory cortex, parietal lobe, frontal lobe, and the limbic system, where the third nociceptive process perception occurs [17, 19]. Finally, activation of the midbrain will result in the release of counter neuroinhibitory neurotransmitters like endorphins, serotonin, enkephalin, and dynorphin which descend to the lower central nervous system. The activation of these neurotransmitters triggers the release of endogenous opioids. Both centrally and peripherally opioid receptors are synthesized or upregulated in the sensory neurons. Binding of endogenous opioids to these receptors will reduce the excitability. From the periphery, immunocompetent cells seem to produce opioid peptides. Centrally, the opioid receptors will act as presynaptic receptors. In the dorsal horn, opioid peptides are released by the inter neurons, so the inhibition of pain transmission will occur (modulation) [20, 21, 22].

3. Pain assessment

Before an administration of analgesics, it is better to assess the pain to understand the severity of the pain. There are different options for pain assessment.

3.1 Numeric rating scale (NRS)

It is the most popular pain assessment scale which is simple to use and widely used for research purposes, and the patient is ordered to indicate the number that is ordered from 0 to 10 which best reflects the intensity of their pain. 0 indicates no pain and 10 indicates the worst pain [23].

It is further categorized for the sake of intervention 0 = no pain, 1–3 mild pain, 4–6 moderate pain, and 7–10 = severe pain. The numeric rating scale (NRS) can be administered verbally (therefore also by telephone) or graphically for self-completion.

3.2 Visual analog scale (VAS)

Visual analog scale (VAS) has a sensory component and is considered a reliable measurement of pain [24]. It is subjective and measured by using a ruler, and the score is determined by measuring the distance (mm) on the 10-cm line between the “no pain” and the patient’s mark, providing a range of scores from 0 to 100. As with the NRS, categories may be imposed on this (no pain 0–4 mm; mild pain 5–44 mm; moderate pain 45–74 mm; and severe pain 75–100 mm), but this is arbitrary and does not necessarily reflect patients’ meanings.

There are also other types of pain assessment tools such as Defense and Veterans Pain Rating Scale (DVPRS), adult Non-Verbal Pain Scale (NVPS), pain, assessment in Advanced Dementia Scale (PAINAD), Behavioral Pain Scale (BPS), Critical Care Pain Observation Tool (CPOT), and the rater can use the convenient method of assessment and can categorize the pain intensity as mild, moderate, and severe for the sake of analgesia administration.

4. WHO analgesic ladder

The WHO analgesic ladder was primarily proposed for cancer pain and other chronic pain management, but it can be applied for postoperative pain management too. Analgesia administration is based on the severity of the pain from mild to severe pain, but the revised 2021 WHO analgesic ladder includes invasive and minimally invasive treatments for patients with no pain relief/persistent pain despite managing with strong opioids. The invasive or minimally invasive procedures include epidural analgesia, intrathecal administration of analgesic and local anesthetic drugs with or without pumps, neurosurgical procedures (e.g. lumbar percutaneous adhesiolysis and cordotomy), neuromodulation strategies (e.g. brain stimulators and spinal cord stimulation), nerve blocks, ablative procedures (e.g. alcoholization, radiofrequency, microwave, cryoablation ablations, laser-induced thermotherapy, irreversible electroporation and electrochemotherapy), cementoplasty, and palliation radiotherapy [25] (Figure 1).

Figure 1.

Transition from the original three-step WHO analgesic ladder (A) to the revised four-step form [25].

5. Postoperative analgesia/postoperative pain management

Postoperative analgesia administration is depending on the severity of the pain, and it is a wastage and disastrous to administer strong opioids for mild pain and is wrong and unethical to not to manage pain while the patients are crying due to severe pain. Pain management after having surgery depends on many factors such as type of surgery, site of surgery severity of the pain, the impact of the pain on the life quality, the medical status of the patient, and the intake of other medications [8, 24, 26].

When we describe postoperative analgesia, primitive analgesia will be remembered. Primitive analgesia is a treatment that prevents the establishment of altered sensory processing that amplifies postoperative pain. The effective preemptive analgesic technique requires a multimodal approach of nociceptive input, increasing the threshold for nociception and decreasing nociceptor receptor activation. Primitive analgesics are safe and effective and have superior pain control with a decreased VAS score of pain [27].

5.1 Multimodal analgesia

Multimodal analgesia was developed for the management of postoperative pain, and the concept is clear and reasonable. It is an administration of two or more drugs that have a different mechanism of action that maximizes pain control and minimizes the side effects of a single drug [28]. Opioids, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), local anesthetics, regional anesthesia, peripheral nerve block (PNB), local/wound site infiltration, N-methyl-d-aspartate receptor antagonists, anticonvulsants, alpha ₂ agonists, etc., are commonly used multimodal analgesia drugs/techniques [29, 30, 31, 32].

MMA generally involves optimizing non-opioid pharmacologic and nonpharmacologic interventions and reserving opioid use to treat breakthrough pain. A review of articles regarding MMA generalizes the implementation of MMA that should involve different stakeholders. The article concluded that health system benefits can also be realized from the implementation of an effective MMA, as fewer opioid-related side effects can improve patient recovery and lead to faster discharge and improved utilization of resources [33].

5.2 Lidocaine infusion

Lidocaine is an amide local anesthetic agent which can be used for various pain management techniques; beyond this, it can be used for cardiac arrhythmia management. Infiltration of lidocaine is commonly known; but apart from infiltration, continuous perioperative lidocaine infusion has a clear advantage in patients undergoing abdominal surgery, provides significant pain relief, reduces postoperative opioid consumption, decreases opioid-induced side effects including postoperative nausea and vomiting, and promotes the faster return of bowel function, which decreases the length of hospital stay [34].

Lidocaine has a potent anti-inflammatory effect which is more potent than other known anti-inflammatory drugs and decreases circulating inflammatory cytokines. Lidocaine infusion is also used to treat chronic pain neuropathic pain by relieving the mechanical effect of allodynia and hyperalgesia, and it found to relieve pain caused by diabetic neuropathy [35, 36].

To achieve steady-state concentrations of 3 mg/mL, an infusion rate of 30 mg/kg/minute or 1.8 mg/kg/hour would be required. The weight-based lidocaine regimens used in the studies reviewed, which ranged from 1.33 to 3 mg/kg/hour, should have achieved adequate plasma concentrations in the range of 2–5 mg/ml. The optimum dose, timing, and duration of infusion of lidocaine also need to be established [34, 37].

5.3 Acetaminophen/Paracetamol

Paracetamol is a commonly used postoperative analgesic that can decrease opioid consumption by 20–30%. Its mechanism of action is not well known but believed that it may act through cyclooxygenase inhibition, serotonergic activation, and/or cannabinoid pathways, and it can easily cross the blood-brain barrier [38]. For postoperative pain management, it can be applied and effective for mild to moderate pain either combined with other analgesic techniques or alone. A systematic review and meta-analysis showed that an administration of prophylactic intravenous (IV) acetaminophen reduces postoperative nausea and vomiting through its direct effect of reduction in postsurgical pain but not due to decrement in opioid consumption [39].

Both oral and intravenous (IV) prophylactic acetaminophen before the surgical incision were found to be equally efficacious, and no superiority was found in the IV acetaminophen regarding immediate postoperative pain, postoperative nausea, vomiting reduction, and length of hospital stay according to a randomized placebo-controlled trial study [40]. A single dose of paracetamol is also effective to treat pain for about 50 % of patients for the first 4 hours with minimal side effects, but the use of postoperative IV acetaminophen does not affect the reduction of hypoxemia over 48 hours [41, 42].

The therapeutic window of acetaminophen is low, so administration beyond 4 g in a single day for a fit adult is not recommended, and a small amount of paracetamol overdose can result in liver damage. A single dose of 40–60 mg/kg rectal paracetamol is safe for children [43].

5.4 Nonsteroidal anti-inflammatory drugs (NSAIDs)

According to a review, NSAIDs have been shown to increase patient satisfaction, decrease opioid requirements, and decrease opioid-induced side effects. They have no increased incidence of adverse effects during the acute postoperative period. NSAIDs and COX-2 inhibitors, however, should use cautiously for colorectal surgical patients, and they were found to cause an anastomotic leak [44].

5.5 Regional analgesia/anesthesia

Regional anesthesia is a technique with an administration of a local anesthetic agent with or without adjuvants near the nerve roots so that the patient can get better analgesia. It includes both epidural and intrathecal analgesia/anesthesia and can be applied as a single injection or continuous catheter technique, and the latter is more advantageous than a single injection, because the analgesic agent can be added when the patients complain pain [45].

A level 1 evidence study showed that regional blocks have improved analgesia at rest and reduced incidence of postoperative ileus, pulmonary complications, surgical stress response, negative nitrogen balance, and other analgesic requirements [11]. Beyond analgesic purpose, malignant surgical procedures which underwent regional anesthesia are proposed to lower the recurrence of cancer after surgery compared with general anesthesia and opioid analgesia, and they are also used as a preventive measure for deep venous thrombosis [46, 47].

A meta-analysis of 141 RCTs where most of them were after major orthopedic surgery concluded that neuraxia blockade reduces the risk of deep venous thrombosis by 44%, pulmonary embolism by 55%, blood transfusion requirements by 50%, pneumonia by 39%, respiratory depression by 59%, and myocardial infarction by 30%. The mortality rate with a single dose of neuraxia also decreased by 30% [48].

5.6 Peripheral nerve blocks

Peripheral nerve blocks (PNBs) are a type of regional anesthesia. The local anesthetic is injected near a specific nerve or bundle of nerves that can block sensations of pain from a specific area of the body. PNBs usually last longer than local infiltration anesthesia. They are most commonly practiced for surgery on the arms and hands, the legs and feet, or the face. Beyond upper and lower extremity blocks, abdominal field/truncal blocks can be performed solely or as a part of multimodal analgesia [49, 50]. Peripheral nerve blocks are practiced with blind landmark technique, using a nerve stimulator, or ultrasound-guided technique either a single injection or continuous using a catheter. Technological advances, such as real-time ultrasonography, allow more accurate identification of plexuses and peripheral nerves, resulting in the improvement of block success [51, 52].

A meta-analysis of RCTs to determine the analgesic efficacy of postoperative peripheral catheter analgesia is compared with opioid-based analgesia. Catheter-based analgesia provided a statistically and clinically superior postoperative pain control compared with opioids with decreased side effects [53].

Although PNBs are overall safe when performed correctly, there are rare but serious risks associated with them. Risks include block failure, bleeding, infection, damage to surrounding structures, transient/permanent nerve injury, inadvertent intravascular injury, and intravascular uptake of local anesthetic resulting in systemic toxicity.

5.7 Wound site infiltration

Wound site infiltration has a good option for postoperative pain management as part of multimodal analgesia, and it has comparable result with ultrasound-guided transversus abdominis plane block for lower abdominal surgeries [54]. A systematic review regarding wound infiltration analgesia showed that it has better pain relief if it is used correctly, and in adequate doses, wound infiltration analgesia can be used in a multimodal analgesic regime without major complications, with low cost in a single injection [55, 56].

5.8 Miscellaneous

Other drugs and techniques are also used to treat postoperative pain regarding the severity of pain. Antidepressants, anticonvulsants, NMDA receptor blockers, alpha 2 agonists, corticosteroids, cannabinoids, GABA agonists, neuroimmunomodulators, etc., can be used to treat pain majorly as an adjuvant but can also use as a primary treatment for a specific type of pain [57].

Alpha 2 agonists (dexmedetomidine and clonidine): they were found to reduce postoperative opioid consumption and increase the duration of nerve block, but they cause hemodynamic instability (hypotension) and sedation [58, 59].

Dexamethasone: it is associated with a decrease in pain scores during mobilization postoperatively. As part of multimodal analgesia, high-dose dexamethasone (more than 0.2 mg/kg) was found to have an opioid-sparing effect. It has also been shown to delay the time to first postoperative analgesic intake when used in conjunction with peripheral nerve blocks [60, 61].

Ketamine: it is NMDA receptor blocker that decreases postoperative opioid consumption at 24 and 48 hr. Along with decreasing pain intensity, it reduces opioid consumption by decreasing central excitability and possibly modulates opioid receptors. It is also effective when used as a sole agent, or in conjunction with opioids, NSAIDs, and paracetamol; surprisingly, it has the potential to decrease pain scores from weeks to months [29, 62, 63].

Ketamine was found beneficial for painful procedures, including, upper abdominal, thoracic, and major orthopedic surgeries. Its analgesic effect was independent of the type of intraoperative opioid administered, timing of ketamine administration, and its dosage of administration [64].

5.9 Non-opioid analgesia

Non-opioid analgesics play an important role in treating postoperative pain as monotherapy or combined with weak/strong opioids. Non-opioid analgesics are usually indicated to treat mild to moderate pain with fewer side effects compared with opioids because opioids have many deleterious effects. But peripheral nerve blocks and regional blocks can be considered as non-opioid analgesics and can be used to treat severe pain. Short-term effects seen in the perioperative period include postoperative nausea and vomiting, and gastrointestinal dysfunctions like ileus, pruritus, urinary retention, somnolence, and respiratory depression [43, 65].

5.10 Nonpharmacological

During the postoperative period, nonpharmacologic methods of pain management can increase the effect of analgesics. They can be applied when there is no availability of analgesics and when the analgesic drugs are perceived to cause deleterious effects. Exercise, aromatherapy, therapeutic touch, positioning, music, reflexology, hypnosis, acupuncture, acupressure, transcutaneous electrical nerve stimulation (TENS), prayer, relaxation hot application, cold application, meditation, imagination, biofeedback, distraction, massage, etc. [66].

6. Conclusion

Due to inadequate pain management having deleterious effects, optimal and multidisciplinary pain management protocol is recommended, especially to accomplish fast recovery after surgery. Recently, there are many choices for pain management that are used to decrease the side effects of opioids. Even though there are many options, the management of pain should be based on the pain severity.