**2. Systemic analgesia**

**1. Introduction**

102 Anesthesia Topics for Plastic and Reconstructive Surgery

Plastic surgery has become increasingly done over the last decades. The surgeon and patients become aware of the importance of postoperative pain control. This has occurred in part in an attempt to improve the patient experience and satisfaction. However, pain remains a major patient concern. Most patients who undergo cosmetic surgery do not report pain during the immediate postoperative period. However, most patients who underwent liposuction combined with or without other surgical procedure report pain after surgery. Pain is unpleasant sensory and emotional experience associated with tissue injury [2]. Postoperative pain is mainly derived from acute tissue manipulation during the surgical procedure. In fact, a recent study documented that 30–80% of patients undergoing outpatient surgery encountered moderate-tosevere postoperative pain. The characteristics of pain that should be evaluated are onset, loca-

tion, irradiation, type of pain, duration, and pain-related behavioral responses [2–4].

contribute to the overall value of care that is delivered to patients.

etc., are all valuable in the multimodal pain management [4–6].

**1.1. Concept of multimodal pain management**

Along with this increased awareness of the importance for pain management, a variety of newer analgesics modalities designed to reduce pain have arrived on the scene. In the era of health care reformation, it is important to consider that pain management techniques can

Treatment for each type of plastic surgery and resulted pain requires a specific approach and must be individualized to the patient. There are three main techniques for acute postoperative pain management: systemic analgesia, regional analgesia, and local/topical analgesia. Systemic analgesia can be given through intravenous injection, oral or rectal route, intramuscular, and skin patch. Regional analgesia technique can be divided into neuraxial analgesia and peripheral nerve block. Currently, pain management through intravenous injection or continuous neuraxial and peripheral nerve blocks is more controllable and safer since the invention of pain pump, which commonly use the principal of patient-controlled analgesia. Opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), mild analgesics, local anesthetics,

Nausea, vomiting, constipation, somnolence, etc., are well-known adverse effects of opioids. Although these effects may seem minor to some, they can lead to significant complications following certain types of plastic surgery, for example, face-lift hematoma following nausea and vomiting, pulmonary complications from respiratory depression, and even thromboembolic phenomena from bed rest following prolonged opioid use. In fact, a recent study documented adverse side effects in 17% of patients due to opioids. Most importantly, multimodal pain therapy including pharmaceutical agents mentioned above, long-acting local anesthetic preparations, and pain pumps may in large part replace isolated narcotic treatment of postoperative pain. This approach has been documented to increase patient satisfaction and reduce both opioid use and the incidence of nausea and vomiting in a large variety of nonfacial esthetic procedures. Although this multimodal treatment seems to have significant benefits, postoperative dosing becomes more

complex, and adverse drug interactions and drug overdose become more likely [1–10].

There are some combinations that is proven to have a good effect in multimodal analgesia, such as paracetamol and NSAIDs, paracetamol with opioids, nonselective NSAIDs or selective There are several systemic analgesic protocols to relieve postoperative pain in plastic surgery, but the IV administration of opioid and nonopioid analgesics is the most used. In the following paragraphs, each one of these managements is described, being possible for the combination of the different alternatives of analgesia.

### **2.1. Oral administration**

Postoperative pain management for ambulatory patients usually is treated with NSAIDs. This type of analgesics is the most important treatment for nociceptive pain. These kind of patients may also need a short-acting opioids such as hydrocodone, oxycodone, and acetaminophen. In immediate postoperative pain management, we prefer to use short-acting opioids rather than long-acting ones. However, if the patient is already on long-acting opioid before surgery, it is more appropriate to continue the long-acting opioid with combination of short-acting opioid for postoperative pain [3–9].

#### **2.2. Intravenous bolus injection**

Intravenous (IV) injection drugs that are commonly used as postoperative pain management are opioids (morphine and oxycodone). They are given based on patient's need, usually for every 2–4 h. This condition can become a burden for both nurse and patient when the ratio between nurse and patient is low. NSAIDs also can be given intravenously for a short period, 1–2 days [5, 7, 9, 11–13].

#### **2.3. Intravenous patient-controlled analgesia (PCA-IV)**

Patient-controlled analgesia (PCA) was used since 1971. PCA is one of the pain management techniques using a programmable pump intravenous device. The machine is put at patient's bedside and connected to the IV line than contains a bag of premixed opioid solution. The patient can self-administer analgesic on demand by pressing the button connected to the PCA machine. The demand dose is already determined by the physician. The machine will lock for the amount of time before it can send another demand dose (lockout period), so it can protect the patient from overdosing. PCA device can also release the drug at a low-dose continuous infusion rate [3]. There are several advantages of PCA such as painless route to deliver opioid, give accurate analgesia, help the nursing staff in patient's pain control, and ensure the medication level compared with intermittent bolus injection or continuous IV infusion of opioid. PCA is used when the patient cannot take oral medication either in preoperative or postoperative time or has nausea that causing the patient unable to take oral medication. PCA often use to control severe pain level such as burn injuries.

*2.3.1.1. Programmed intermittent bolus (PIB)*

pointed using the PCA machine [15–19].

security systems in the PCA machine [15–19].

disturbance at night due to pain [15–19].

level in MEAC level. PCA dose is the maintenance dose [15–19].

and 4 h [15–19].

*2.3.1.2. Initial bolus dose*

*2.3.1.3. Demand dose*

*2.3.1.4. Lockout interval*

*2.3.1.5. Background infusion*

PIB is a specific dosage of drug that is programmed in PCA to give automatic bolus drug in specific intervals. PIB does not depend on demand dose or continuous infusion. PIB is usually used for epidural analgesia or peripheral nerve block analgesia. Time interval is around 15–60 min, which means every for 15–60 min. PCA machine will automatically give bolus drug in a specific dose. For all PCA method, there are basic variables, such as: (a) initial bolus dose, (b) demand dose, (c) lockout interval, (d) Background infusion, (e) Maximum dose limitation 1

Pain Management in Plastic Surgery http://dx.doi.org/10.5772/intechopen.79302 105

It is possible to give drugs titration when activated by the program (not the patient). Initial bolus dose can be used by the nurse in postanesthesia care unit (PACU) to titrate opioid dose until reach MEAC or by the nurse at ward to administer the extra dose for the breakthrough pain. Initial bolus dose is the key for the success in pain management using PCA. Without it, there is a big possibility that pain may not be resolve adequately and patient can be disap-

Demand dose is also known as incremental dose or PCA dose. It is amount of analgesia that is given to the patient when patient press the demand button. PCA dose aims to maintain opioid

To prevent opioid overdose with continuous demand, all PCA machines use lockout interval. It gives time lapse after administration of demand dose, and the machine will not respond to any demand dose, even though patient press the button, until certain time. This is one of the

Infusion with constant speed is given without considering the patient's demand. Background infusion is seldom used for patients with acute pain because of risk of overdose. Background infusion is usually administered to the patients who use opioid with large dose previously. Background infusion can be given by electrical PCA machine. Continuous infusion used as adjuvant in administration of bolus dose can increase analgesia effect for the patient, so they can sleep without any disturbance due to pain. Disadvantages from this system are that opioid could still be given without considering the sedation level and can increase the risk of respiratory depression. Routine use of background infusion is not recommended. Background infusion may be useful in patients who are tolerant toward opioid, patients who are common in using opioid and need higher dose, or patients who have sleep

Minimal analgesia can be reached with opioid titration until minimum effective analgesia concentration (MEAC) can be reached, which becomes the border between pain and analgesia. Furthermore, the dosage for causing analgesia varied among the patients and can be concluded that variability in opioid's pharmacodynamic causes differences in the dosage. Individual MEAC can be determined by level of opioid endogen in preoperative cerebrospinal fluid. Patient with higher level of opioid endogen in cerebrospinal fluid needs lower MEAC to achieve and maintain the analgesia effect [3, 5, 7, 9, 11–15] (**Figure 1**).

In the figure above, X axis is the opioid plasma concentration and Y axis is the pain intensity from severe pain to no pain. Small circles show correlation between opioid concentration and pain intensity in an interval of increased opioid concentration. At the beginning, progressive increase of opioid concentration does not change pain intensity, but then with a little increase of opioid concentration, it can decrease pain intensity until pain is resolved. Increase of opioid concentration after this point will not give an extra effect.

#### *2.3.1. PCA variable*

PCA can be given in many methods, and the following two are the most common methods used in daily practice:


**Figure 1.** Response to opioid concentration and pain intensity [17].

### *2.3.1.1. Programmed intermittent bolus (PIB)*

PIB is a specific dosage of drug that is programmed in PCA to give automatic bolus drug in specific intervals. PIB does not depend on demand dose or continuous infusion. PIB is usually used for epidural analgesia or peripheral nerve block analgesia. Time interval is around 15–60 min, which means every for 15–60 min. PCA machine will automatically give bolus drug in a specific dose. For all PCA method, there are basic variables, such as: (a) initial bolus dose, (b) demand dose, (c) lockout interval, (d) Background infusion, (e) Maximum dose limitation 1 and 4 h [15–19].

### *2.3.1.2. Initial bolus dose*

postoperative time or has nausea that causing the patient unable to take oral medication. PCA

Minimal analgesia can be reached with opioid titration until minimum effective analgesia concentration (MEAC) can be reached, which becomes the border between pain and analgesia. Furthermore, the dosage for causing analgesia varied among the patients and can be concluded that variability in opioid's pharmacodynamic causes differences in the dosage. Individual MEAC can be determined by level of opioid endogen in preoperative cerebrospinal fluid. Patient with higher level of opioid endogen in cerebrospinal fluid needs lower

In the figure above, X axis is the opioid plasma concentration and Y axis is the pain intensity from severe pain to no pain. Small circles show correlation between opioid concentration and pain intensity in an interval of increased opioid concentration. At the beginning, progressive increase of opioid concentration does not change pain intensity, but then with a little increase of opioid concentration, it can decrease pain intensity until pain is resolved. Increase of opioid

PCA can be given in many methods, and the following two are the most common methods

• Demand dose (the dosage has been made by the anesthetist and given by patient to him/

• Continuous infusion/background infusion along with demand dose in accordance with

MEAC to achieve and maintain the analgesia effect [3, 5, 7, 9, 11–15] (**Figure 1**).

often use to control severe pain level such as burn injuries.

104 Anesthesia Topics for Plastic and Reconstructive Surgery

concentration after this point will not give an extra effect.

*2.3.1. PCA variable*

used in daily practice:

patient's need.

herself in a given period of time)

**Figure 1.** Response to opioid concentration and pain intensity [17].

It is possible to give drugs titration when activated by the program (not the patient). Initial bolus dose can be used by the nurse in postanesthesia care unit (PACU) to titrate opioid dose until reach MEAC or by the nurse at ward to administer the extra dose for the breakthrough pain. Initial bolus dose is the key for the success in pain management using PCA. Without it, there is a big possibility that pain may not be resolve adequately and patient can be disappointed using the PCA machine [15–19].

### *2.3.1.3. Demand dose*

Demand dose is also known as incremental dose or PCA dose. It is amount of analgesia that is given to the patient when patient press the demand button. PCA dose aims to maintain opioid level in MEAC level. PCA dose is the maintenance dose [15–19].

#### *2.3.1.4. Lockout interval*

To prevent opioid overdose with continuous demand, all PCA machines use lockout interval. It gives time lapse after administration of demand dose, and the machine will not respond to any demand dose, even though patient press the button, until certain time. This is one of the security systems in the PCA machine [15–19].

#### *2.3.1.5. Background infusion*

Infusion with constant speed is given without considering the patient's demand. Background infusion is seldom used for patients with acute pain because of risk of overdose. Background infusion is usually administered to the patients who use opioid with large dose previously. Background infusion can be given by electrical PCA machine. Continuous infusion used as adjuvant in administration of bolus dose can increase analgesia effect for the patient, so they can sleep without any disturbance due to pain. Disadvantages from this system are that opioid could still be given without considering the sedation level and can increase the risk of respiratory depression. Routine use of background infusion is not recommended. Background infusion may be useful in patients who are tolerant toward opioid, patients who are common in using opioid and need higher dose, or patients who have sleep disturbance at night due to pain [15–19].

#### *2.3.1.6. Maximum dose limitation*

Some machine may have time limit 1 or 4 h. This program limits patient interval either 1 or 4 h to get total cumulative dose. Usage of the interval 1 or 4 h is controversial. Prolimitation said that the limitation could give better security, while the contra side said there is no evidence that shows this limitation could give better security. In the other hand, if patient needs demand dose or PCA dose in large amount until it reaches the limitation for 1 or 4 h, may be they really need that much dose to resolve the pain; thus, it is not necessary to reach that need. The usual maximum dose for morphine is 10 mg in 1 h or 30 mg in 4 h. Keep in mind that PCA is used as maintenance therapies and pain should be under controlled before PCA is started. Disadvantages of this system are that opioid could still be given without considering the sedation level and can increase the risk of respiratory depression [15–19] (**Figure 2**).

brain. Knowledge about all of the above will become essential to choose the right opioid that can be used in the PCA system. Parenteral opioid has three characters when binding with micro-opioid pure agonist, agonist-antagonist, and partial agonist. Character of pure agonist is the mainstay in acute pain management because can give full binding to microreceptor, and there is no maximal limit of analgesia (more opioid titration will give better effect in resolving pain.) However, there is a clinical maximal limitation that can give adverse effects such as sedation, respiratory depression, and often limit extra dose before reaching adequate level of analgesia. microagonist opioids are also effective in equianalgesic dose (i.e., 10 mg

Pain Management in Plastic Surgery http://dx.doi.org/10.5772/intechopen.79302 107

There are no significant differences in adverse effects due to opioids, even though patient can develop nausea, vomiting, or pruritus with one opioid, but not with other opioid drugs. All µ agonist decrease intestine movement, that contribute in ileus paralytic after surgery

Agonist-antagonist opioids activate κ receptor and antagonist toward microreceptor. Even though they are used with maximal effect limitation toward respiratory depression, it can give a wider safety margin, and this effect can happen with very large dose comparing it with microagonist. The most important thing is that agonist-antagonist has maximal limit of analgesic effect, so this group cannot make better analgesia compared with microagonist. Furthermore, agonist-antagonist drugs will induce acute withdrawal response in patients who receive microagonist opioids before. Due to activation of σ receptor, this group often induces psychotomimetic adverse effects. These type of opioids are uncommon to be used in PCA IV

All opioids have been used successfully for PCA intravenous analgesia, with morphine as the most substance to be studied. Whatever opioid is chosen for intravenous PCA, knowledge about pharmacology is needed to control variable dose in PCA machine. Key component for effective PCA therapy is the right titration to get analgesia. Loading dose of morphine is 2–4 mg (or equianalgesic dose for alternative opioid) given every 5–10 min in postanesthesia care unit (PACU) until pain score ≤4 from 10 or if respiratory rate <12 times per minute, which will give limitation for the next opioid administration. It should become a consideration to use multimodal therapy to achieve optimal analgesia and to decrease the use of opioid and

will decrease the possibility of adverse effect and respiratory depression (**Table 1**).

Morphine 1 mg/ml 1–2 mg 6–10 0–2 mg/h Fentanyl 10–20 μg/ml 20–50 µg 5–10 0–60 µg/h Sufentanil 1–4 μg/ml 4–6 µg 1–10 0–8 µg/h Hydromorphone 0.1–0.2 mg/ml 0.2–0.4 6–10 0–0.4 mg/h Tramadol 10–20 mg/ml 10–20 mg 6–10 0–20 mg/h Oxycodone 1–2 mg/ml 1–2 mg 5–10 0–2 mg/h

Continuous infusion is not recommended in early design.

**Table 1.** Common PCA regimen.

**Opioid Concentration Demand dose Lockout (min) Continuous basal**

morphine = 2 mg hydromorphone = 100 mg meperidine) [15–19].

[15, 16, 18, 20].

[15, 17, 18].

#### **2.4. Opioid for IV-PCA**

Knowledge about pharmacology is the basic to use PCA effectively. A physician should understand not only indication and contraindication, but also pharmacodynamic and pharmacokinetic of opioid, including absorption, distribution, biotransformation, and elimination from many types of opioid. Besides that, a doctor needs to understand specific physiologic response that can be happened when a drug binds to specific receptor inside or outside the

**Figure 2.** Comparison between plasma drug concentration and their administration. Plasma drug concentration after small frequent dose PCA administration compared with large dose intramuscular or intravenous administration every 2-4 hours and continuous infusion intravenous. Ideally, plasma drug concentration is constant in analgesia range without any surge of plasma drug concentration that lead to over sedation and respiratory depression or low level of drugs that cause inadequate analgesia. Small but frequent dose could be reached by PCA.

brain. Knowledge about all of the above will become essential to choose the right opioid that can be used in the PCA system. Parenteral opioid has three characters when binding with micro-opioid pure agonist, agonist-antagonist, and partial agonist. Character of pure agonist is the mainstay in acute pain management because can give full binding to microreceptor, and there is no maximal limit of analgesia (more opioid titration will give better effect in resolving pain.) However, there is a clinical maximal limitation that can give adverse effects such as sedation, respiratory depression, and often limit extra dose before reaching adequate level of analgesia. microagonist opioids are also effective in equianalgesic dose (i.e., 10 mg morphine = 2 mg hydromorphone = 100 mg meperidine) [15–19].

There are no significant differences in adverse effects due to opioids, even though patient can develop nausea, vomiting, or pruritus with one opioid, but not with other opioid drugs. All µ agonist decrease intestine movement, that contribute in ileus paralytic after surgery [15, 16, 18, 20].

Agonist-antagonist opioids activate κ receptor and antagonist toward microreceptor. Even though they are used with maximal effect limitation toward respiratory depression, it can give a wider safety margin, and this effect can happen with very large dose comparing it with microagonist. The most important thing is that agonist-antagonist has maximal limit of analgesic effect, so this group cannot make better analgesia compared with microagonist. Furthermore, agonist-antagonist drugs will induce acute withdrawal response in patients who receive microagonist opioids before. Due to activation of σ receptor, this group often induces psychotomimetic adverse effects. These type of opioids are uncommon to be used in PCA IV [15, 17, 18].

All opioids have been used successfully for PCA intravenous analgesia, with morphine as the most substance to be studied. Whatever opioid is chosen for intravenous PCA, knowledge about pharmacology is needed to control variable dose in PCA machine. Key component for effective PCA therapy is the right titration to get analgesia. Loading dose of morphine is 2–4 mg (or equianalgesic dose for alternative opioid) given every 5–10 min in postanesthesia care unit (PACU) until pain score ≤4 from 10 or if respiratory rate <12 times per minute, which will give limitation for the next opioid administration. It should become a consideration to use multimodal therapy to achieve optimal analgesia and to decrease the use of opioid and will decrease the possibility of adverse effect and respiratory depression (**Table 1**).


**Table 1.** Common PCA regimen.

*2.3.1.6. Maximum dose limitation*

106 Anesthesia Topics for Plastic and Reconstructive Surgery

depression [15–19] (**Figure 2**).

**2.4. Opioid for IV-PCA**

Some machine may have time limit 1 or 4 h. This program limits patient interval either 1 or 4 h to get total cumulative dose. Usage of the interval 1 or 4 h is controversial. Prolimitation said that the limitation could give better security, while the contra side said there is no evidence that shows this limitation could give better security. In the other hand, if patient needs demand dose or PCA dose in large amount until it reaches the limitation for 1 or 4 h, may be they really need that much dose to resolve the pain; thus, it is not necessary to reach that need. The usual maximum dose for morphine is 10 mg in 1 h or 30 mg in 4 h. Keep in mind that PCA is used as maintenance therapies and pain should be under controlled before PCA is started. Disadvantages of this system are that opioid could still be given without considering the sedation level and can increase the risk of respiratory

Knowledge about pharmacology is the basic to use PCA effectively. A physician should understand not only indication and contraindication, but also pharmacodynamic and pharmacokinetic of opioid, including absorption, distribution, biotransformation, and elimination from many types of opioid. Besides that, a doctor needs to understand specific physiologic response that can be happened when a drug binds to specific receptor inside or outside the

**Figure 2.** Comparison between plasma drug concentration and their administration. Plasma drug concentration after small frequent dose PCA administration compared with large dose intramuscular or intravenous administration every 2-4 hours and continuous infusion intravenous. Ideally, plasma drug concentration is constant in analgesia range without any surge of plasma drug concentration that lead to over sedation and respiratory depression or low level of

drugs that cause inadequate analgesia. Small but frequent dose could be reached by PCA.

*2.4.1. Initial dose and adjusted dose*

**3. Regional analgesia**

describe some procedures.

**3.1. Central neuraxial analgesia**

*3.1.1. Patient-controlled epidural analgesia (PCEA)*

There is no ideal dose in IV-PCA. Deciding dose for PCA depends on patient and expected postoperative pain. The key component of effective PCA therapy is initial titration to achieve pain-free condition or minimal pain before starting the IV-PCA program. One consideration is that multimodal therapy approach must start early to optimize the analgesia and decrease the need of opioid, so can decrease the adverse effect and respiratory depression. Pain management with PCA will fail if initial analgesia cannot be achieved. This condition will disappoint the patient who still feels pain even though the machine has been started. Patient will be frustrated and refuse to use PCA. Keep in mind that basic principle of PCA is to maintain

Pain Management in Plastic Surgery http://dx.doi.org/10.5772/intechopen.79302 109

Analgesia with regional techniques has been fashionable due to its advantages: effective, safe, economical, and easy to perform. There are numerous techniques of perioperative analgesic blocks, which have benefited with the advent of ultrasound. The following paragraphs

Epidural analgesia is a safe and effective method to handle pain in any patient. It can be used for babies, children, adult, elderly in a short period (hours until days) or long period (weeks until months). Epidural analgesia can give superior regional analgesia compared with conventional systemic route (IV or oral) with minimum systemic side effect (nausea, sedation, or constipation). Drugs in epidural space are distributed through three main routes: (1) diffusion process through dura to cerebrospinal fluid, then to spinal cord or nerve root, (2) through uptake in epidural space blood vessel into systemic circulation, and (3) fat uptake of drug in epidural space where it can enter cerebrospinal fluid or systemic circulation. Epidural analgesia insertion can be combined with PCA machine to reduce pain with patient as the controller, which is known as patient-controlled epidural analgesia (PCEA). PCEA is an effective method to control pain with analgesia and local anesthesia through a catheter inside the epidural space connected with a pain pump that delivers small dose of drugs directly to the epidural space. Unlike systemic administration, drugs that are injected into the epidural space are potent because it is close to the opioid and alpha agonist receptors in dorsal horn. Due to small dose, the side effects are minimum such as nausea, sedation, and respiratory depression. Usage of this method is usually seen in obstetric surgery and postsurgery pain management for lower abdomen, thoracic, and cancer pain or chronic pain management. Currently, there are two main methods in PCEA usage such as demand

the analgesia in optimal range for the patient [15, 17, 18] (**Figure 3**).

**Figure 3.** Simplified algorithm of IV-PCA management for basic setting of IV-PCA with morphine.

#### *2.4.1. Initial dose and adjusted dose*

There is no ideal dose in IV-PCA. Deciding dose for PCA depends on patient and expected postoperative pain. The key component of effective PCA therapy is initial titration to achieve pain-free condition or minimal pain before starting the IV-PCA program. One consideration is that multimodal therapy approach must start early to optimize the analgesia and decrease the need of opioid, so can decrease the adverse effect and respiratory depression. Pain management with PCA will fail if initial analgesia cannot be achieved. This condition will disappoint the patient who still feels pain even though the machine has been started. Patient will be frustrated and refuse to use PCA. Keep in mind that basic principle of PCA is to maintain the analgesia in optimal range for the patient [15, 17, 18] (**Figure 3**).
