Guidelines Consensus Expert Consensus on Postoperative Pain Management in Adults

Expert Consensus on Postoperative Pain Management in Adults Wang Yuelan, Deng Xiaoming, Tian Yuke, Feng Yi, Mi Weidong, Yang Jianjun, Wu Xinmin, Min Su, Yue Yun, Xu Jianguo (authors/leaders), Guo Qulian, Dong Hailong, Jiang Zongbin, Xue Zhanggangyi, Postoperative Pain and Adverse Effects on the Body Pain is an unpleasant sensory and emotional experience resulting from tissue damage or potential tissue damage, or a distressing experience with sensory, emotional, cognitive, and social dimensions
.

Pain can be divided into acute pain and chronic pain based on the healing time of the damaged tissue and the duration of the pain
.

Acute pain usually lasts less than 1 month and is often associated with surgical trauma, tissue damage, or certain disease states; chronic pain is pain lasting more than 3 months and can persist after the primary disease or tissue injury has healed
.

 (1) Postoperative pain is acute nociceptive pain Postoperative pain (postoperative pain) is referred to as postoperative pain.
It is acute pain that occurs immediately after surgery and usually lasts no more than 3d~7d
.

Postoperative pain is common in invasive thoracic surgery and joint replacement surgery that requires long-term functional exercise, and sometimes pain relief may last for several weeks
.

Postoperative pain is nociceptive pain.
If postoperative pain is not adequately controlled in the initial state, it may develop into chronic post-surgical pain (CPSP), which may also be neuropathic or mixed in nature.
Sexual pain
.

Neuropathic pain is pain caused by damage to sensory nerves, leading to sensitization of peripheral and central nerves
.

Studies have shown that CPSP can occur in operations of different sizes, from inguinal hernia repair to cardiac surgery under cardiopulmonary bypass
.

CPSP is mostly moderate pain, but it can also be mild or severe pain, lasting for half a year or even decades
.

 Predisposing factors for the formation of CPSP include moderate to severe pain, irritability, depression, history of multiple surgeries before surgery; nerve damage during or after surgery; radiotherapy and chemotherapy
.

Among the most prominent factors were poor postoperative pain control and mental depression
.

 (2) Effects of postoperative pain on the body Postoperative pain is a reaction of the body after surgery (tissue damage), including a series of physiological, psychological and behavioral reactions
.

Although postoperative pain has the "good" effects of warning, braking, and conducive to wound healing, the adverse effects are more worthy of attention
.

Effective post-operative analgesia not only relieves the pain of patients, but also benefits the recovery of the disease, and has huge social and economic benefits
.

1.
Short-term adverse effects (1) Increased oxygen consumption: The excitation of the sympathetic nervous system increases the oxygen consumption of the whole body, which has adverse effects on ischemic organs
.

(2) Effects on cardiovascular function: increased heart rate, vasoconstriction, increased cardiac load, increased myocardial oxygen consumption, and increased risk of myocardial ischemia and myocardial infarction in patients with coronary heart disease
.

(3) Influence on respiratory function: the activation of nociceptors caused by surgical injury can trigger multiple noxious spinal cord reflex arcs, inhibit the excitation of the phrenic nerve and the spinal cord reflex, resulting in decreased postoperative lung function, especially in the upper abdomen and chest.
Post-surgery; Pain leads to shallow and rapid breathing, stiffness of accessory respiratory muscles leading to decreased ventilation, inability to cough forcefully, inability to clear respiratory secretions, resulting in atelectasis and other pulmonary complications
.

(4) Influence on gastrointestinal motility: lead to decreased gastrointestinal motility and delayed recovery of gastrointestinal function
.

(5) Effects on the function of the urinary system: the motility of the urethra and bladder muscles is weakened, causing urinary retention
.

(6) Effects on bones, muscles and peripheral blood vessels: increased muscle tension, muscle spasm, restricting body activities; promoting deep vein thrombosis and even pulmonary embolism
.

(7) Effects on neuroendocrine and immunity: The neuroendocrine stress response is enhanced, causing postoperative hypercoagulable state and immune inflammatory response; sympathetic nerve excitation leads to an increase in the secretion of catecholamines and catabolic hormones, and a decrease in the secretion of anabolic hormones; inhibition of Humoral and cellular immunity
.

(8) Effects on psychological and emotional aspects: It can lead to anxiety, fear, helplessness, depression, dissatisfaction, over-sensitivity, frustration, and depression; it can also cause family members to feel panic and at a loss
.

(9) Sleep disorders can have adverse psychological and behavioral effects
.

2.
Long-term adverse effects (1) Poor postoperative pain control is a risk factor for developing chronic pain
.

(2) Long-term postoperative pain (lasting more than 1 year) is a risk factor for psychological and mental changes
.

 2.
Pain assessment Pain assessment includes assessment of pain intensity, assessment of causes of pain and changes in vital signs that may be complicated by it, assessment of treatment effects and side effects, and assessment of patient satisfaction
.

Pain intensity is one of the most important assessments of acute pain
.

 (1) Pain intensity scoring method 1.
Visual analogue scale (VAS) There is no mark on the patient's face, and the doctor's face is a 1-100mm scale, one end is marked with "no pain", and the other end is marked with "the most severe pain".
Pain”, the patient calibrates the corresponding position according to the intensity of the pain, and the physician determines its score
.

2.
Numerical rating scale (NRS) uses a scale of 0 to 10 to mark different levels of pain intensity, which are designated by the patient.
"0" means no pain, and "no 0" means the most severe pain.
Less than 4 is mild pain (pain does not affect sleep), 4 to 7 is moderate pain, and more than 7 is severe pain (pain causes inability to sleep or wake up from sleep)
.

 3.
Verbal Rating Scale (VRS) The words describing the intensity of pain are verbally expressed as no pain, mild pain, moderate pain, and severe pain
.

 4.
The Wong-Baker face pain rating scale consists of six facial pictograms with different expressions ranging from smiles or happiness to tears
.

This method is suitable for children, the elderly and other patients who have difficulty in communication, are unclear or cannot express accurately in words, but are easily affected by factors such as emotions, culture, education level, and environment (below), and should be used in conjunction with specific situations.

.

 (2) Evaluation of therapeutic effects The efficacy and adverse reactions of drugs or treatment methods should be regularly evaluated, with particular attention paid to changes in vital signs and unbearable side effects of patients, and adjustments should be made accordingly
.

Satisfaction should be assessed by the patient after pain treatment has ended
.

 The evaluation principles include: (1) Assess the pain intensity at rest and during exercise.
Only pain relief during exercise can ensure the maximum recovery of the patient's postoperative physical function
.

②When the pain is not under stable control, the effect of each drug and treatment intervention should be repeatedly evaluated
.

In principle, the therapeutic effect should be evaluated 5 min to 15 min after intravenous administration and 1 hour after oral administration, when the drug reaches the maximum effect; for PCA patients, it is necessary to know the number of ineffective compressions and whether to seek other analgesics
.

③ Record the treatment effect, including adverse reactions
.

④ Immediate assessment of sudden severe pain, especially changes in vital signs (such as hypotension, tachycardia, or fever), and prompt diagnosis of possible incision dehiscence, infection, deep vein thrombosis, and pulmonary embolism and treatment
.

⑤ At the end of the pain treatment, the patients' satisfaction with the medical staff's pain management and the overall pain management should be evaluated separately
.

NRS or VAS can be used, "0" is very satisfactory
.

"Ten 0" means dissatisfaction
.

 As a routine work of the postoperative analgesia treatment team, pain assessment should be carried out regularly, and if a pain relief curve can be drawn, the patient's pain and analgesic process can be better recorded
.

 3.
Management and Monitoring of Postoperative Pain and psychological, physiological function, the best patient satisfaction; ④ conducive to postoperative rehabilitation of patients
.

 (2) Management mode and operation Effective postoperative analgesia needs to be completed by a team, and an acute pain management group (acute pain service, APS) or each department is established that is hospital-wide or mainly anesthesiology, including the attending surgeon and nurses.
A multidisciplinary combined postoperative pain management team can effectively improve the quality of postoperative analgesia
.

The scope and purpose of work include: ①Treat postoperative pain, trauma and labor pain, evaluate and record analgesic effects, deal with adverse reactions and problems in analgesic treatment
.

②Promote education on the necessity of postoperative analgesia and pain assessment methods, including the training of team members and patient education
.

③ Improve the comfort and satisfaction of surgical patients
.

④Reduce postoperative complications
.

 Good postoperative pain management is an important part of ensuring the effect of postoperative analgesia, and individualized treatment should be emphasized during implementation
.

The pain treatment team must not only formulate analgesic strategies and methods, but also implement their implementation, check all functions, evaluate treatment effects and side effects, make appropriate adjustments as needed, and make forms to record postoperative analgesia methods, drug formulations, and administration.
, Pain score (VAS or NRS method), sedation score and related adverse reactions during quiet and exercise (such as coughing, turning over, limb function exercise)
.

 4.
Postoperative analgesia principles and analgesic methods Non-drug therapy, such as physiotherapy, music, distraction and other methods have different therapeutic effects.
However, the treatment of acute pain after surgery is still dominated by drug therapy
.

The goal of treatment is to achieve good pain relief and high patient satisfaction with safety and minimal side effects
.

It is worth noting that many patients are easy to tolerate pain below moderate, but difficult to tolerate side effects such as nausea, vomiting and dizziness that may be related to analgesics
.

(1) Multimodal analgesia combined with different analgesic techniques or analgesics with different mechanisms of action, acting on different targets in the pain conduction pathway, exerting an additive or synergistic effect of analgesia, and reducing the dose of each drug , the side effects are reduced accordingly, this method is called multimodal analgesia
.

Day surgery and less traumatic surgery are mostly analgesic with a single drug or method; multimodal analgesia is the basis for postoperative analgesia, especially for moderate and above surgical analgesia.
The commonly used methods include ultrasound-guided analgesia.
of peripheral nerve block combined with wound local anesthetic infiltration; peripheral nerve block and/or wound local anesthetic infiltration + acetaminophen; peripheral nerve block and/or wound local anesthetic infiltration + NSAIDs or opioids or Other drugs; systemic (intravenous or oral) acetaminophen and/or combinations of NSAIDs and opioids and other drugs
.

Drugs with different mechanisms of action should be used in combination, including opioids, tramadol, NSAIDs, etc.

.

Preoperative use of pregabalin or gabapentin, specific COX-2 inhibitors, α2-adrenergic receptor agonists, and ketamine, etc.
, may also reduce postoperative pain and opioid-saving and inhibit central or peripheral pain sensitization role
.

Whether preoperative use of NSAIDs can prevent central sensitization remains to be demonstrated
.

The use of magnesium sulfate before surgery, adding epinephrine to local anesthetics, and alkalizing local anesthetics can enhance postoperative pain relief or reduce the amount of postoperative opioids, but their efficacy and appropriate dose compatibility have not yet been determined
.

(2) Local administration of local anesthetics Local administration of local anesthetics includes three methods: local infiltration of incisions, peripheral nerve block and intraspinal administration
.

In the early postoperative period, for patients without anticoagulant and antithrombotic drugs and no bleeding tendency, if epidural anesthesia is used during operation, epidural analgesia can be extended after operation
.

Epidural analgesia has exact effect, prevents excessive stress response after operation more completely, and also helps to prevent cardiac ischemia (thoracic spinal nerve block) or the formation of deep vein thrombosis of lower extremities.
Epidural analgesia is often combined with local anesthetics.
The method of high fat-soluble opioids (such as fentanyl or sufentanil) has an analgesic effect of spinal nerve analgesia, but rarely causes side effects of cranial nerves above the foramen magnum
.

Spinal analgesia should not be used in patients receiving antithrombotic drugs in the early postoperative period
.

Postoperative incision local infiltration can significantly reduce the use of postoperative analgesics, but it depends on the cooperation of the surgeon
.

Ultrasound-guided peripheral nerve block alone or in combination with systemic NSAIDs or opioids is one of the main methods of postoperative analgesia for limbs and body parts
.

(3) Systemic administration 1.
Oral administration is suitable for the control of postoperative mild and moderate pain in patients with conscious, non-gastrointestinal surgery and postoperative gastrointestinal function; other methods (such as intravenous) can be used for analgesia After that, oral analgesia is used as a continuation; it can be used as part of multimodal analgesia
.

Oral administration has the advantages of non-invasiveness, convenient use, and patients can take it by themselves.
However, due to the liver-intestinal "first-pass effect" and some drugs can bind to gastrointestinal receptors, the bioavailability varies
.

The onset of action of the drug is slow.
When adjusting the dose, not only the peak blood time of the drug, but also the plasma protein binding rate and tissue volume of distribution should be considered
.

Oral administration is contraindicated in patients with swallowing dysfunction (eg, after neck surgery) and intestinal obstruction
.

Use with caution in patients with severe postoperative nausea, vomiting and constipation
.

2.
Subcutaneous injection, intramuscular injection, pleural or peritoneal intramuscular injection is faster than oral administration, but the side effects such as injection pain and large dosage of single injection are obvious, and repeated administration is prone to occur.
Analgesia blind spot, not recommended for postoperative analgesia
.

Although subcutaneous administration has the inconvenience of injection pain, it can be administered for a longer time by implanting a catheter
.

The analgesic effect of pleural and peritoneal administration is not reliable, and local anesthetic poisoning is prone to occur, so it is not recommended for routine use
.

 3.
Intravenous injection (1) Single or intermittent intravenous injection is suitable for outpatient surgery and short surgery, but the peak-to-trough ratio of drug plasma concentration is large, and the analgesic effect is unstable.
Those who need continuous pain after operation should be administered on time
.

Drugs that irritate the veins can cause complications such as phlebitis
.

Commonly used drugs include acetaminophen, NSAIDs, tramadol, and injections of opioids (including agonists and agonist antagonists)
.

 (2) Continuous intravenous administration: Continuous administration after dilution with isotonic saline or glucose solution
.

Generally, the loading dose is given first, and opioids are preferably injected in small doses and titrated to an appropriate dose.
After the analgesic effect is achieved, it is maintained or intermittently administered at a maintenance dose or according to the duration of action of the drug
.

Because the pain threshold will change after surgery, the effect of constant drug infusion is not easy to predict, and the use of patient-controlled methods is more advocated
.

4.
Patient controlled analgesia (PCA) PCA has the advantages of rapid onset of action, no analgesic blind spot, relatively stable blood concentration, timely control of burst pain through pulse dose, individualized medication, and high patient satisfaction.
, is the most commonly used and ideal method for postoperative analgesia, suitable for moderate to severe pain after surgery
.

 (1) Loading dose is a commonly used parameter of PCA: given immediately after surgery, the drug needs to take effect quickly, and opioids are best given in small fractions to achieve the purpose of titrating the dose
.

The dose of postoperative analgesia should be able to avoid postoperative analgesia blank period without affecting postoperative wakefulness and removal of the tracheal tube
.

Long-acting analgesics can also be used before surgery, which can reduce postoperative pain and reduce the amount of opioids
.

 Continuous dose or background dose: The goal is to achieve stable, sustained analgesia
.

Intravenous PCA does not advocate the use of fentanyl and other drugs with high lipid solubility and strong accumulation effect, and it is best not to use background doses to achieve satisfactory analgesic effects and reduce possible side effects; single injection dose (bolus dose): Also known as a shock dose, a fast-acting drug can be used
.

Generally, the shock dose is equivalent to 1/10 to 1/15 of the daily dose; lockout time: ensure that the second dose can be given only after the first shock dose reaches the maximum effect to avoid drug poisoning
.

Some analgesic pumps have a 1-hour limit (such as morphine 10mg-12mg), a 4-hour limit,
etc.

 Whether the analgesic effect of PCA is good is evaluated by whether it is safe and achieves the minimum side effects and the maximum analgesic effect
.

Evaluation indicators include: VAS 0-1 at calm, sedation score 0-1, no obvious motor block
.

The side effects were slight or no, the ratio of effective compressions/total compressions of the PCA pump was close to 1, there was no sleep disturbance, and the patients' satisfaction was high
.

 (2) Common administration routes of PCA: According to different administration routes, it is divided into intravenous PCA (PCIA), epidural PCA (PCEA), subcutaneous PCA (PCSA) and peripheral nerve block PCA (PCNA)
.

 (3) PCIA: The main analgesics used are opioids (morphine, oxycodone, sufentanil, hydrocodone, fentanyl, butorphanol, dezocine, etc.
), tramadol or Flurbiprofen axetil, ketorolac,
etc.

The relative potency ratio of opioid analgesic intensity is as follows: meperidine 100mg≈tramadol 100mg≈morphine 10mg≈alfentanil 1mg≈fentanyl 0.
1mg≈sufentanil 0.
01mg≈oxycodone 10mg≈ Butorphanol 2mg≈Dezocine 10mg
.

The recommended regimen of commonly used PICA drugs is shown in Table 1
.

 Table 1.
Recommended regimens of commonly used PCIA drugs Drug loading (titration) dose/single injection /h Sufentanil 1µg ~3µg2µg ~4µg5min~10min1µg /h ~2µg /h Oxycodone 1mg~3mg1mg~2mg5min~10min0~1mg/h Tramadol 1.
5mg/kg ~3mg/kg, administered 30min before surgery 20mg~30mg6min~10min10mg/h~15mg/h Butorphanol0.
25mg~1mg0.
2mg~0.
5mg10min~15min0.
1mg/h~0.
2mg/h Dezocine 2mg~5mg1mg~3mg10min~15min30mg/48h~50mg/ 48h Flurbiprofen axetil 25mg~75mg50mg——200mg/24h~250mg/24h Note: All the above loading doses should be injected slowly (more than 1min) into NSAIDs.
The analgesic effect of the drug has a capping effect, and overdose should not be administered
.

However, opioids should be administered individually and given in different loading doses (for non-opioid addicts, the loading dose of morphine should be 1 mg to 4 mg/time).
After administration, the maximum effect should be observed for 5 min to 20 min, and repeated as appropriate.
This amount to NRS score <4 points
.

 (4) PCEA: suitable for moderate and severe postoperative pain
.

Local anesthetics such as low-concentration ropivacaine or bupivacaine combined with fentanyl, morphine, butorphanol and other drugs are often used (see Table 2)
.

Sufentanil 0.
3μg/ml～0.
6μg/ml and 0.
0625%～0.
125% ropivacaine or 0.
05%～0.
1% bupivacaine peripheral nerve block can achieve analgesia and have little impact on motor function, which is more suitable For labor analgesia and lower extremity surgery requiring functional exercise
.

(5) PCSA: suitable for patients with difficult venipuncture
.

Drugs may remain subcutaneously, such as opioids bioavailability is about 80% of intravenous administration
.

The onset of PCSA is slower than that of intravenous administration, and the analgesic effect is similar to that of PCIA.
If an indwelling catheter is used, it should be noted that catheter blockage or infection may occur
.

Commonly used drugs are morphine, tramadol, oxycodone, ketamine and buprenorphine
.

Meperidine is a tissue irritant and should not be used in PCSA
.

(6) PCNA: The indwelling catheter for nerve plexus or nerve trunk adopts PCA for continuous administration
.

Commonly used local anesthetics and dosage are shown in Table 2
.

 Table 2.
Local Anesthetics and Opioid Formulations for Post-epidural Analgesia ~0.
2%, or chloroprocaine 0.
8%~1.
4% (the above drugs can be added with sufentanil 0.
4µg/ml~0.
8µg/ml, fentanyl 2µg/ml~4µg/ml or morphine 20µg/ml ~40µg/ml) PCEA regimen with an initial dose of 6ml~10ml, maintenance dose of 4ml/h~6ml/h, shock dose of 2ml~4ml, lock-in time of 20min~30min, maximum dose of 12ml/h (4) Commonly used drug combinations so far, No drug alone is effective in stopping severe pain without side effects
.

Multimodal analgesia is the most common form of postoperative analgesia
.

 1.
Analgesia combined with local anesthetic incision infiltration, ultrasound-guided regional block or peripheral nerve block can be used alone for postoperative analgesia, but strong analgesia is not complete, and can be combined with systemic analgesics (NSAIDs, Combined application of tramadol or opioids), systemic medication on the basis of topical medication, the patient's need for analgesics is significantly reduced, and the incidence of adverse drug reactions is low
.

2.
The combination of analgesic drugs mainly includes ① the combination of opioids or tramadol and acetaminophen
.

The daily dose of acetaminophen is 1.
5g ~ 2.
0g, which can save 20% ~ 40% of opioids in major surgery
.

②The combination of acetaminophen and NSAIDs, each using 1/2 of the conventional dose, can exert an additive or synergistic effect on analgesia
.

③ Combination of opioids or tramadol and NSAIDs, the use of conventional doses of NSAIDs after major surgery can save 20% to 50% of opioids, especially good analgesia can be achieved when the patient is awake
.

Preoperative use of COX-2 inhibitors (eg, oral celecoxib or intravenous parecoxib), which can have higher concentrations in the cerebrospinal fluid, exert anti-inflammatory, suppressive central and peripheral sensitization effects, and may reduce postoperative The incidence of pain transformation into chronic pain
.

Studies have shown that preoperative, intraoperative and postoperative continuous infusion of flurbiprofen axetil can also penetrate the blood-brain barrier to exert anti-inflammatory and inhibit central sensitization effects.
The role of other non-selective NSAIDs before surgery has not been determined.

.

④ Opioids, especially high fat-soluble fentanyl or sufentanil combined with local anesthetics for PCEA
.

⑤ Ketamine (especially D-ketamine), tramadol, gabapentin, pregabalin, and α2-adrenergic receptor agonist clonidine epidural administration or low-dose dexmedetomidine and other preoperative applications can also be used.
Reduce postoperative pain and reduce postoperative opioid consumption
.

Occasionally, multitargeted analgesia can be administered with three drugs with different mechanisms of action
.

 3.
Implement a multimodal analgesia regimen according to the expected pain intensity after different types of surgery (Table 3)
.

 Table 3.
Expected pain intensity after different types of surgery and postoperative multimodal analgesia plan (eg chest: thoracic paravertebral nerve block, abdomen: transversus abdominis plane block), or combined with NSAIDs or opioids PCEA (2) acetaminophen + NSAIDs drugs and local anesthetic incision infiltration (or ultrasound-guided peripheral Nerve block) (3) Combination of NSAIDs (except contraindications) and opioids (or tramadol) (4) Epidural local anesthetic combined with high fat-soluble opioids PCEA Moderate pain in knee joint and lower limbs Surgery Shoulder and back surgery Hysterectomy Maxillofacial surgery (5) Ultrasound-guided peripheral nerve block (eg, brachial plexus block in the upper extremity or total knee femoral nerve block in the lower extremity or adductor canal block) or local block with local anesthetic Incompatibility (6) (1) + acetaminophen or NSAIDs (7) Epidural local anesthetic combined with high fat-soluble opioids PCEA (8) NSAIDs combined with opioids for PCIA mild pain inguinal hernia repair Laparoscopic surgery for varicose veins (1) Local anesthetic infiltration and/or peripheral nerve block, or systemic acetaminophen or NSAIDs or tramadol (2) (1) + low-dose opioids ( 3) Paracetamol + NSAIDs 5.
Commonly used analgesics (1) Opioid analgesics are narcotic analgesics, which are the most commonly used drugs for the treatment of moderate to severe acute and chronic pain
.

It exerts analgesic effect by activating opioid receptors in the peripheral and central nervous system (spinal cord and brain)
.

Currently confirmed opioid receptors include mu, kappa, delta and orphanin four types, among which mu, kappa and delta receptors are closely related to postoperative analgesia
.

 There are various types of opioids, which can be divided into strong opioids and weak opioids according to the intensity of analgesia
.

The World Health Organization (WHO) three-step principle for the treatment of cancer pain divides opioids into second-step (weak opioids) or third-step drugs (strong opioids)
.

Second-step drugs include codeine, dihydrocodeine, etc.
, which are mainly used for mild to moderate acute pain analgesia
.

Strong opioids, including morphine, fentanyl, pethidine, sufentanil, oxycodone, and hydromorphone, are mainly used for the treatment of moderate and severe postoperative pain
.

Agonist-antagonists and partial agonists, such as butorphanol, dezocine, pentazocine, nalbuphine, and buprenorphine, are mainly used for the treatment of moderate postoperative pain and can also be used as multimodal sedatives.
Pain components are used in severe pain treatment
.

 1.
Application of opioids Strong pure opioid receptor agonists have strong analgesic effects, no organ toxicity, and no capping effect.
The principles of maximum analgesia and no unbearable adverse reactions should be followed when using them
.

Since the analgesic effects and adverse reactions of opioids are dose-dependent and receptor-dependent, multimodal analgesia is advocated to achieve the effect of saving opioids and reducing side effects
.

 2.
The common side effects of opioids and most of the side effects of dealing with opioids are dose-dependent.
Most side effects except constipation can be tolerated in the short term (1 to 2 weeks), but for short-term postoperative pain, it is necessary to prevent and treat them.
side effects
.

The principles for dealing with side effects are as follows: (1) discontinue the drug or reduce the dosage of opioids; (2) treat side effects; (3) switch to other opioids; (4) change the route of administration
.

(1) Nausea and vomiting: Nausea and vomiting are the most common and uncomfortable adverse reactions after surgery, and should be actively prevented
.

 (2) Respiratory depression: Opioids can cause slow breathing
.

After a larger dose is administered after surgery, if the dose is not adjusted in time, or it is used for the elderly, patients with chronic obstructive pulmonary disease and combined use of sedatives, respiratory depression is prone to occur
.

Respiratory frequency ≤8 times/min, SpO2<90% when breathing air, or shallow breathing should be regarded as respiratory depression and treatment should be given immediately
.

Treatment methods include immediate discontinuation of opioids, oxygen inhalation, strong pain stimulation, establishment of artificial airway or mechanical ventilation if necessary, and intravenous naloxone (0.
1 mg to 0.
2 mg each time, depending on the degree of respiratory depression, until the respiratory rate is reached).
>8 times/min or SpO2>90% when breathing air, the maintenance dose is 5μg/(kg·h)～10μg/(kg·h)
.

 (3) Tolerance, physical dependence and mental dependence: tolerance refers to the The efficacy of the drug is reduced during administration, which is often manifested by the shortening of the action time of analgesics
.

In addition to constipation and mydriasis, which are side effects for a long time (more than 6 months), other adverse reactions of opioids such as nausea, vomiting, Itching, etc.
are all tolerable side effects in a short time (3 to 14 days)
.

In patients whose body is dependent on regular drug administration, drug withdrawal or sudden dose reduction leads to drug withdrawal reactions, which are manifested as anxiety, irritability, tremor, skin Flushing, generalized joint pain, sweating, catarrh symptoms, fever, nausea and vomiting, abdominal pain and diarrhea, etc.

Sedatives
and clonidine or dexmedetomidine acting on α2-adrenergic receptors are the main symptomatic drugs
.

Dependence is the most difficult to treat, and it is a mandatory drug-seeking willingness and behavior, and the use of drugs is regarded as the first need, with or without physical symptoms
.

 (4) Pruritus: the effect of the second-generation antihistamine loratadine Long time, mild sedative effect, more commonly used
.

Small doses of propofol (40mg~50mg), small doses of naloxone or μ receptor agonist antagonists butorphanol, dezocine, nalbuphine, etc.
Dansetron is also commonly used to treat pruritus
.

 (5) Muscle stiffness, myoclonus and convulsions: muscle stiffness is mainly chest wall and abdominal wall muscle stiffness, seen in rapid intravenous opioids and long-term morphine treatment, especially high-dose long-term treatment can be eliminated
by
the use of the central relaxant baclofen or opioid antagonists
.

Myoclonus is usually mild and self-limiting, with more frequent seizures in drowsiness and light sleep states, and occasional persistent generalized seizures in a convulsive state
.

Opioid receptor antagonists have antagonistic effects on convulsions caused by opioids, but they have spasmodic effects on the metabolite of pethidine, norpetidine itself, so the therapeutic effect on convulsions caused by pethidine is weak
.

 (6) Sedation and cognitive dysfunction: mild sedation often occurs
.

Inability to wake up or coma should be regarded as excessive sedation and alert for the occurrence of airway obstruction or respiratory depression
.

Long-term high-dose use of opioids may lead to cognitive decline and occasional delirium.
Droperidol 1 mg to 1.
25 mg can be given for treatment
.

 (7) Miosis: Mu-receptor and κ-receptor agonists excite parasympathetic nuclei of the ophthalmic nerve, and patients with long-term use of opioids may tolerate it, but if the dose is increased, it can still manifest as miosis
.

It should be distinguished from changes in pupil size caused by hypercapnia and hypoxemia
.

 (8) Hypothermia: Opioids can induce vasodilation and change the hypothalamic thermoregulation mechanism to cause cooling
.

Meperidine, tramadol, butorphanol, dezocine, nalbuphine, dexmedetomidine, etc.
can inhibit or reduce the chills after general anesthesia
.

 (9) Immunosuppression: strong opioids can cause immunosuppression, and severe pain can also lead to immunosuppression, but tramadol, opioid partial agonists and agonist antagonists have little effect on immune function
.

 (10) Constipation, tolerance and mental dependence: long-term use of opioids can cause such side effects, but it is difficult for patients with postoperative analgesia to appear
.

(2) Paracetamol and NSAIDs 1.
Paracetamol alone is effective for mild to moderate pain, and combined with opioids or tramadol or NSAIDs, it can exert an additive or analgesic effect.
synergistic effect
.

The usual dose is 6 mg/kg to 10 mg/kg orally every 6 hours, the maximum dose should not exceed 3000 mg/day, and the daily dose of combined administration or compound preparation should not exceed 1500 mg, otherwise it may cause severe liver damage and acute renal tubular necrosis
.

 2.
Non-selective NSAIDs and selective COX-2 inhibitors These drugs have antipyretic, analgesic, anti-inflammatory, and anti-rheumatic effects, and the main mechanism of action is to inhibit the production of cyclooxygenase (COX) and prostaglandins (PGs).
synthetic
.

The selectivity of COX-1 and COX-2 action is one of the main reasons for their different pharmacological effects and adverse reactions
.

There are reports that non-selective NSAIDs with two mechanisms have complementary pharmacological effects
.

The oral dosage forms of these drugs can generally be used for analgesia of mild or moderate postoperative pain in patients who can be orally, or as a component of multimodal analgesia before and after surgery
.

The oral drugs used for postoperative analgesia in China mainly include ibuprofen, diclofenac, meloxicam, celecoxib and lornoxicam; the injection drugs include flurbiprofen axetil, parecoxib, Ketorolac, lornoxicam, diclofenac,
etc.

The doses and effects of commonly used oral and injectable NSAIDs are shown in Table 4 and Table 5
.

 Table 4.
Commonly used oral NSAIDs drugs per dose (mg) times/day maximum daily dose (mg) ibuprofen 400~6002~32400~3600 Diclofenac 25~502~375~150 Meloxicam 7.
5~1517.
5 ~15 Celecoxib 100~2001~2200~400 Lornoxicam 8324 Table 5.
Commonly used injection of NSAIDs drug dose range (mg) Intravenous onset time (min) Maintenance time (h) Usage and dosage Fluoride ratio Profen axetil 50~200158IV: 50mg each time, 3~4 times/day, the daily dose does not exceed 200mg parecoxib 40~807~1312 IM/IV: 40mg for the first dose, 40mg/12h thereafter, continuous use for no more than 3 days Ketorolac 30~120504~6IM/IV: The first dose is 30mg, then 15mg/6h~30mg/6h, the maximum dose is 120mg/day, and the continuous use does not exceed 2 days.
Lornoxicam 8~24203~6IV: 8mg/time, 2~3 times/day, the daily dose does not exceed 24mg.
Non-selective NSAIDs inhibit the production of all prostaglandins in the body.
While inhibiting inflammatory prostaglandins to exert antipyretic, analgesic and anti-inflammatory effects, it also inhibits important protection of physiological functions.
prostaglandins, which can cause blood (platelets), digestive tract, kidney and cardiovascular side effects, other side effects include allergic reactions and liver damage
.

The above-mentioned adverse reactions of selective COX-2 inhibitors can be alleviated to varying degrees, but they may also aggravate myocardial ischemia, which should be regarded as relative or absolute contraindications to patients undergoing cardiac surgery and patients at risk of stroke
.

(1) Effects on platelet function: There are only COX-1 receptors on platelets, and aspirin is a highly selective COX-1 receptor inhibitor, which leads to changes in platelet function and may aggravate intraoperative bleeding tendency
.

Other NSAIDs drugs cause reversible changes in platelets, which can be recovered after 1d-2d of drug withdrawal before surgery
.

(2) Effects on the digestive tract: The incidence of digestive tract damage of non-selective NSAIDs is higher than that of selective COX-2 inhibitors, but the risk of short-term use of such drugs within 3 to 5 days after surgery has not yet been determined.

.

It has been reported that long-term use of non-selective NSAIDs may affect intestinal healing and even increase the incidence of intestinal fistulas
.

(3) Effects on kidneys: All non-selective NSAIDs and selective COX-2 inhibitors affect renal function, and short-term use in patients with prerenal or renal parenchymal damage such as dehydration and hypovolemia may lead to renal failure
.

(4) Cardiovascular effects: Both non-selective NSAIDs and selective COX-2 inhibitors may increase cardiovascular risk through COX-2, and these drugs are contraindicated for postoperative analgesia after coronary artery bypass grafting
.

In conclusion, the adverse reactions caused by the long-term use of these drugs are not only related to the characteristics of the drugs, but also related to the dose, time of use, and risk factors for the use of NSAIDs (see Table 6)
.

In principle, such drugs should be carefully considered for patients with risk factors
.

 Table 6.
Risk factors for the use of COX inhibitors (1) Age > 65 years (male prone) (2) Underlying diseases of the original vulnerable organs: upper gastrointestinal ulcer, history of bleeding; ischemic heart disease or brain History of vascular disease (contraindicated in the perioperative period of coronary artery bypass grafting, with caution in the history of stroke or cerebral ischemic attack); renal dysfunction; bleeding, coagulation disorders and use of anticoagulants (use of selective COX-2 inhibitors is not contraindicated) (3) Concomitant use of corticosteroids or angiotensin-converting enzyme inhibitors and diuretics (4) Long-term, high-dose use (5) NSAIDs such as hypertension, hyperglycemia, hyperlipidemia, smoking, and alcoholism There is a "cap" effect, so overdose should not be overdose; slow intravenous infusion is not easy to achieve effective blood concentration, and a loading dose should be given before the maintenance dose; flurbiprofen axetil, ketorolac, etc.
can be combined with opioids.
Combined pump administration to maintain effective drug concentration; except for a few drugs such as acetaminophen, the plasma protein binding rate of NSAIDs drugs is high, so the two drugs cannot be used at the same time; but among similar drugs, one drug is ineffective, Maybe another drug still works better
.

 The main indications of NSAIDs for postoperative analgesia are: ① analgesia after small and medium operations or as a supplement to local analgesia; ② combined with opioids or tramadol or multimodal analgesia for major surgical analgesia It has a significant effect of saving opioids; ③ After discontinuation of PCA, the analgesia of residual pain in major surgery; ④ The selective COX-2 inhibitor celecoxib before surgery can enhance postoperative analgesia and reduce pain The effect of morphine, domestic research shows that intravenous parecoxib also has the same effect; domestic research also shows that preoperative, intraoperative and postoperative continuous administration of flurbiprofen axetil can also quickly penetrate the blood-brain barrier
.

The role of other NSAIDs remains unproven
.

(3) Tramadol (Tramadol) Tramadol is a central analgesic with two isomers: (+)-tramadol and (-)-tramadol
.

The former and its metabolite (+)-0-nortramadol (M1) are agonists of μ-opioid receptors, both of which inhibit the reuptake of central serotonin and norepinephrine, respectively, and increase the response to spinal cord.
Inhibition of pain transmission
.

The synergistic effect of the two isomers enhances the analgesic effect
.

 Tramadol is available in oral dosage forms such as tablets, capsules, and extended-release formulations and in dosage forms for intramuscular, intravenous, or subcutaneous injection
.

For postoperative analgesia, equal doses of tramadol and pethidine have almost the same effect, and have a synergistic effect when combined with acetaminophen and NSAIDs
.

 When used for postoperative analgesia, the recommended dose of tramadol is 1.
5 mg/kg to 3 mg/kg intravenously 30 minutes before the end of the operation, and the dose of patient-controlled analgesia is 300 mg to 400 mg every 24 hours after surgery, and the impulse dose is not less than 20 mg to 20 mg.
30mg, locking time 5min ~ 6min
.

The purpose of intraoperative loading dose is to reduce the plasma concentration at the end of the operation, thereby reducing postoperative complications such as nausea and vomiting
.

Its main side effects are nausea, vomiting, dizziness, drowsiness, sweating and dry mouth, and the incidence of constipation and physical dependence is lower than that of opioids
.

In addition, the analgesic dose of tramadol also has the effect of preventing and treating postoperative chills
.

 (4) Local anesthetics Local anesthetics are used for postoperative analgesia mainly through three types: intraspinal medication, peripheral nerve block and local infiltration
.

Although local anesthetics are mixed with many drugs for clinical analgesia, with the exception of glucocorticoids, which have not been clinically adopted or recommended due to their uncertainty in the intensity of action and duration of analgesia (see "Specialists in Postoperative Analgesia after Day Surgery" for details).
consensus")
.

 Local anesthetics commonly used for postoperative analgesia are: bupivacaine, levobupivacaine, ropivacaine, and chloroprocaine
.

Bupivacaine has a long duration of action and low price, and is widely used for postoperative analgesia, but overdose can easily lead to central nervous system and cardiac toxicity
.

The pharmacological properties of levobupivacaine are similar to that of bupivacaine, and the cardiotoxicity is lower than that of bupivacaine
.

The distinguishing feature of ropivacaine is "kinesthetic dissociation", that is, low drug concentrations (0.
0625% to 0.
15%) that produce effective analgesia have relatively weak motor blockade effects, and are less toxic than bupivacaine and Levobucaine
.

Chloroprocaine has a rapid onset of action, and there is a certain "kinesthetic dissociation" phenomenon at low concentrations.
When used for subarachnoid anesthesia, it should not contain a preservative (binitrite), and the dose should be less than 60 mg
.

(5) Other ketamines are NMDA receptor antagonists, and gabapentin and pregabalin are α2 and δ receptor blockers
.

Preoperative intravenous injection of low-dose ketamine (0.
2 mg/kg to 0.
5 mg/kg) or oral pregabalin (150 mg) and gabapentin (900 mg to 1200 mg) have important effects on postoperative analgesia and prevention of central and peripheral sensitization.
At the same time, the amount of opioids can be reduced
.

The analgesic effect of D-ketamine is twice that of the racemate, and the side effects such as drowsiness, dreams, delirium, and vomiting are significantly lower than those of racemic or L-ketamine
.