**2. PCA: principles and pharmacological aspects**

The principle of intravenous PCA was first described by Austin et al. in 1980, after he admin‐ istrated small increasing doses of meperidine and measured the plasma levels, demonstrating the dose‐related analgesic effect in patients [13].

Despite being associated with the idea of pump with intravenous opioids, there are several routes of administration, drugs, and equipment that can be used in this mode of analgesia. It is essential that, for the PCA recommendation, individual pain pattern and intensity be considered.

The patients must be previously and duly enlightened on the technical procedure and their consent should be obtained. As desirable characteristics of PCA, we can highlight the ade‐ quate pain relief according to individual requirements, the tolerance and safety profile of drugs administered, the high level of patients' satisfaction and minimal complications related to technological aspects [12].

emotions [1]. The painful experience involves interpretation of biological aspects of pain and

In surgical procedures, moderate to severe pain can be observed in up to 40% of cases [3], representing an important source of complications as well as morbidity and mortality in the postoperative period [4]. Postoperative pain can limit mobility and respiratory function,

Moreover, the lack of adequate pain control in acute situations can lead to chronic pain, with deleterious effects for the patient and health‐related quality of life [7]. Despite these findings, between 50% to 75% of those submitted to major surgery do not receive enough analgesic medication, increasing the risk of complications and length of stay and costs for the health

Morphine was isolated by a German pharmacist Friedrich Wilhem Sertürner in 1806 and, after that, opioids have become widely used in clinical practice for pain control. Later in 1844, parenteral administration of morphine has started after the introduction of glass syringe [2]. In 1963, Roe demonstrated that administration of small doses of intravenous morphine allowed a better pain control compared to intramuscular injections [9]. Sechzer, in 1968, was the first to evaluate the quality of analgesia after administration of small doses of opioids *per* patient request, performing the first patient‐controlled analgesia (PCA). Due to complex logistic to meet the requests of many patients, which would require numerous nursing staff, Sechzer and other doctors began to develop equipment prototypes for anal‐ gesic administration with reduced costs. The first PCA pump available for marketing was named "Cardiff Palliator" and it was developed in the Welsh National School of Medicine

Since then, several drugs and routes of administration have been used in PCA, with differences in analgesic efficacy, tolerability profile, adverse effects, and procedure‐related complications

The principle of intravenous PCA was first described by Austin et al. in 1980, after he admin‐ istrated small increasing doses of meperidine and measured the plasma levels, demonstrating

Despite being associated with the idea of pump with intravenous opioids, there are several routes of administration, drugs, and equipment that can be used in this mode of analgesia. It is essential that, for the PCA recommendation, individual pain pattern and intensity be

The patients must be previously and duly enlightened on the technical procedure and their consent should be obtained. As desirable characteristics of PCA, we can highlight the ade‐ quate pain relief according to individual requirements, the tolerance and safety profile of

increasing the incidence of atelectasis, pneumonia and thromboembolic events [5, 6].

its interaction with social and cultural characteristics [2].

48 Pain Relief - From Analgesics to Alternative Therapies

system [8].

in 1973 [10, 11].

considered.

as well as patient satisfaction [12].

**2. PCA: principles and pharmacological aspects**

the dose‐related analgesic effect in patients [13].

In order to understand the effectiveness of PCA, we need to understand the concept of "minimal effective analgesic concentration (MEAC)." The MEAC is defined as the smallest concentration at which the pain is relieved [13].

Considering the existence of individuals' variability, the MEAC cannot be determined from the plasma levels of opioids. It is known that the plasma concentration is a function related to the dose, dosage intervals, gender and age of the patient. It can be calculated based on pharmacokinetic concepts such as volume of distribution and distribution and elimination rates. However, in clinical situations, the plasma levels are not able to predict the pattern of analgesic response [14]. Tamsen et al. showed that the MEAC has a direct correlation with preoperative concentrations of endogenous opioids and substance P in the cerebral spinal fluid. Obviously, the achievement of these measurements is restricted in clinical practice [15].

For the PCA effectiveness, the MEAC should be achieved by titration, which means that the drug is administered as a *bolus* of small doses until the establishment of an adequate analgesia pattern is obtained. Considering the acute postoperative pain, this can be done in the post‐ anesthetic recovery room, before patient discharge. From this reference dose, the equipment is regulated in order to maintain the plasma concentration of analgesic levels of MEAC or slightly above it, looking for adequate pain control with minimal adverse effects. The goal of this approach is to prevent the occurrence of sharp peaks and troughs in plasma concentra‐ tions in a standard that seeks the lowest level of oscillation of concentrations, ideally as close to a continuous infusion [16].

Regardless of the route or administered drug, the two main types of PCA are: the demand dosing (the fixed dose which is self‐administered intermittently) and continuous infusion associated with demand dosing (the constant‐rate fixed background infusion is supplemented by patient demand dosing), whereas the principles of a fixed infusion administration as well as principles of variation of the infusion rates managed by a period of time are considered [17].

Some basic principles and technical parameters are common to several modalities. They are initial loading dose, demand dose, interval lockout, and background infusion rate.

The initial dose usually is not administered by the patient, since the goal of first administration is to promote adequate pain control or prevent the early pain manifestation. This approach allows the establishment of the demand dose, also called PCA dose or *bolus* dose, which will be administered by the patient when he shoots the demand button.

The lockout interval is a set period in which the equipment does not perform a new infusion of demand. During the interval lockout, if the patient triggers the button, he/she will not receive the medication. Normally, the equipment has a sound signal connected to the drive, regard‐ less of the infusion, so that the patient does not know whether his/her requests were effective. The lockout interval has the primary function of security by preventing the administration of an overdose of analgesic drugs. The background infusion rate is a given infusion rate in a continuous manner, independent of the patient's wish (also called continuous infusion). The 1‐h and/or 4‐h limits, depending on the equipment configuration, it has the function to limit the total cumulative dose in the period of 1 or 4 h in order to reduce the adverse effects and ensure the patient safety [11, 18].

Considering the advances in the development of drug delivery systems, the use of infusion pumps for patient‐controlled analgesia (PCA) and analgesia epidural catheter with opioids are considered the most powerful strategies to control of postoperative pain. However, there are doubts about the advantages and limitations of these different forms of PCA.

The basal opioid administration doses may be administered concurrently with the adminis‐ tration of opioids by PCA techniques. However, the basal administration increases the risk of respiratory depression without providing necessarily an additional analgesia pattern [19].

PCA different modalities can minimize the occurrence of gaps in analgesic administration, supplying analgesic dosage immediately after the system activation, providing more uniform analgesia and eliminating painful waiting periods between the patient's request and drug administration.
