Postoperative Analgesia



Pain is defined by the International Association for the Study of Pain (IASP) as ‘an unpleasant sensory and emotional experience primarily associated with actual or potential tissue damage or described in terms of such damage.’


Postoperative pain Postoperative pain management Systemic analgesia Continuous peripheral nerve blocks Day-surgery analgesia 

15.1 Physiopathology of Postoperative Pain

Pain is defined by the International Association for the Study of Pain (IASP) as ‘an unpleasant sensory and emotional experience primarily associated with actual or potential tissue damage or described in terms of such damage’.

Postoperative pain is a form of acute pain, closely related to the surgical procedure and may set in after the operation or may occur on top of an already existing chronic pain related to the disease responsible for the surgical indication.

Postoperative pain is mainly of the nociceptive type, even though, in certain particular conditions, it may present a chronic course and take the form of neuropathic pain.

Nociceptive pain or nociception is a complex mechanism whereby a nociceptive stimulus is capable of generating a pain sensation in the person on the receiving end. Four neuronal processes defining nociception can be distinguished: transduction, transmission, perception, and modulation.

The first step in the nociception process consists in the transduction of a nociceptive stimulus to an electrical stimulus, which can be transmitted to higher central nervous system structures. The primary afferents specialized in this function, called nociceptors or pain receptors, are neurons whose cell bodies reside in the ganglia of the dorsal sensory roots (dorsal root ganglia, DRG) and whose axons divide early into T-shaped branch points (T-junctions) thence giving rise to a peripheral (centrifugal) extension that runs through the peripheral nerve and a central (centripetal) extension that runs through the posterior root of the spinal cord. The nociceptive stimuli capable of causing tissue damage may be of a thermal, chemical, or mechanical type. There is a certain degree of specificity between the type of nociceptive stimulus and the type of sensory fiber activated.

The primary sensory afferents are classified on the basis of their anatomical and electrophysiological characteristics. The A-beta fibers (Aβ) are fast-conducting large-caliber myelinated fibers that are not involved in the nociceptive process. Pain transmission occurs, in fact, via amyelinic fibers (C-fibers) or poorly myelinated fibers (A-delta fibers, Aδ). Type-I A-delta fibers respond to mechanical and chemical stimuli but also to high temperatures (>50 °C). Type-II A-delta fibers respond to thermal and mechanical stimuli. C-fibers are defined as polymodal because they comprise a heterogeneous population of neurons that respond to hot, cold, and mechanical stimuli. Some of these fibers are so-called silent fibers in that they are activated only in the presence of tissue damage or inflammation. The C-fibers that innervate the viscera are known to respond to over distension of the hollow organs and are often responsible for the so-called referred pain.

The A-delta fibers, thanks to their myelin sheath, are capable of conducting the nociceptive stimulus faster than the C-fibers and are, therefore, responsible for the so-called first pain, which is acute and of brief duration. The C-fibers, by contrast, being slower, transmit the so-called second pain, which is diffuse, dull, and longer lasting.

An explanation as to what the mechanism is whereby a nociceptive stimulus is ‘transducer’ to a biological signal proved possible after the discovery of the family of ion channels defined as transient receptor potentials (TRPs) which permit the flow of sodium and calcium ions, thus giving rise to depolarization and generating an action potential. The TRPV1 channel (initially identified as the vanilloid type 1 receptor—VR1) is characterized by being activated by capsaicin and produces a burning sensation as a result of contact with temperatures >43 °C. This receptor is present on most of the nociceptive fibers activated by high temperatures. Other TRPV receptors have subsequently been identified and are responsible for the response to different temperatures: TRPV2 is activated by temperatures >52 °C; TRPV3 and TRPV4, on the other hand, are responsible for heat sensations at temperatures ranging from 25 °C to 35 °C. Similarly, there are receptors that respond to low temperatures: the TRPM8 receptor (where M stands for menthol) is activated by temperatures <25 °C, whereas TRPA1 is activated by temperatures <17 °C and also by a number of inflammation mediators. Other receptors, identified as mechanoreceptors, respond to membrane stretching and osmotic swelling, namely MDEG (mammalian degenerin) receptors and the TREK-1 (TWIC-related) potassium channel. In conditions of tissue damage and inflammation, the purinergic P2X receptors respond to changes in adenosine triphosphate (ATP) (Fig. 15.1).
Fig. 15.1

Pain transmission

Sodium and calcium channels thus play a fundamental role in the transmission of pain.

The voltage-gated sodium channels (VGSCs) most expressed on nociceptors are of three types: NaV 1.7 (sensitive to tetrodotoxin—TTX), NaV 1.8, and NaV 1.9 (resistant to TTX). Subjects suffering from erythromelalgia (paroxysmal burning pain and vasodilation of the extremities) present a mutation of the gene coding for the ion channel NaV 1.7 in such a way as to increase its activity. Conversely, the mutations that render this channel inactive are responsible for the congenital insensitivity to pain (CIP). Experimental studies in animal models have demonstrated that nerve lesions result in a redistribution of the NaV 1.8 sodium channels which are reduced on the damaged neurons and tend to increase in concentration in the healthy neurons surrounding the lesions. The concentration of NaV 1.9 channels is also significantly reduced in animal models of neuropathic pain.

The voltage-gated calcium channels (VGCCs) are the other critical elements that modulate the neuronal excitability and the transmission of the nociceptive stimulus. These channels are basically of two types. N-type VGCCs are present mainly on the terminal portion of the sensory neurons and play a key role in the release of neurotransmitters such as substance P, glutamate and calcitonin gene-related peptide (CGRP) by the primary afferents. T-type VGCCs are present both on the primary afferents and on the spinal cord postsynaptic neurons and are activated by low voltages. The activation of these channels acts in synergy with neurokinin 1 (NK1) at the level of the spinal dorsal horn via activation of the complex N-methyl-D-aspartate (NMDA) calcium/receptor channel responsible for the central sensitization process.

Once the electrical stimulus has been generated, for it to be perceived, it has to be transmitted via an intact conduction system from the periphery to the central nervous system. The primary afferents described above enter the central nervous system via the dorsal horns of the spinal cord, which are functionally subdivided into laminae that receive inputs from various types of fibers. The A-delta fibers and part of the C-fibers terminate in the external part of lamina I and lamina II, thus forming the substantia gelatinosa. Other C-fibers terminate in the internal part of lamina II, whereas the deeper laminae from III to V mainly receive fibers that do not conduct nociceptive stimuli, such as the A-beta fibers. Lamina V also receives part of the A-delta fibers. Supraspinal projections depart from laminae I and V leading to the thalamus, amygdala, and basal nuclei which, in turn, transmit information to the cerebral cortex.

The transmission then occurs in three steps: (1) from the periphery to the spinal cord; (2) from the spinal cord to the thalamus; and (3) from the thalamus to the cerebral cortex. The first-order sensory neuron transmits the electrical impulse from the periphery to the spinal cord, entering via the posterior horn. It then synapses with the second-order neuron, and the impulse travels up via the spinal pathways towards the thalamus, where, together with a third order neuron, the information is transmitted to the sensory cortex where it generates the pain sensation.

The transmission of the pain impulse at the spinal level occurs via two ascending pathways to the brain, namely the neospinothalamic and paleospinothalamic tracts.

The second-order neurons of the neospinothalamic bundle are endowed with long axons that rapidly crossover to the opposite side of the spinal cord and terminate at the thalamic level in the ventrobasal complex and partly in areas of the reticular formation. The paleospinothalamic tract, on the other hand, as the name suggests, is phylogenetically a much more ancient structure, that mainly transmits information coming from the C-fibers and part of the information coming from the A-delta fibers. At the level of the brain, we distinguish between the areas where this pain pathway terminates: the reticular nuclei, the tectal area, and the periaqueductal gray area.

The information is transmitted from the thalamic nuclei to the sensitivity areas (parietal lobes), cognitive areas (temporal lobes), and emotivity areas (frontal lobes) of the brain. The fourth and last fundamental process in nociception is modulation of the nociceptive impulses which enables their intensity to be physiologically controlled. In conditions of stress or immediate danger, the human body is known to resist much more easily to pain stimuli. There exists, in fact, a so-called analgesic system consisting in three main structures: the periaqueductal gray area (PAG), the nucleus raphe magnus, and the complex of inhibitory neurons situated at the level of the spinal dorsal horns. Electrical stimulation or microinjections of morphine at the level of the PAG give rise to a substantial antinociceptive reaction. The PAG sends inputs to the rostral ventromedial medulla (RVM), from which depart, in turn, descending projections that cross the dorsolateral funiculus and go on to reach the spinal cord. At the level of the medulla, these neurons synapse with primary afferents or second-order neurons, modulating their nociceptive inputs. The main neurotransmitters involved in this ‘descending inhibitory system’ are serotonin and noradrenaline. The other basic system involved in the nociception modulation mechanism is the system of endorphins produced by pro-opiomelanocortin which interacts with the opioidergic receptors present in the central and peripheral nervous systems.

15.2 Postoperative Pain Management

The treatment of postoperative pain is one of the indispensable aspects of any correct anesthesiological management and, to all intents and purposes, must be regarded as a patient’s ‘right.’ It has been abundantly demonstrated that inadequate postoperative pain relief significantly increases the perioperative morbidity, the duration of the hospital stay and the costs, particularly in the case of major surgery or in patients at high anesthesiological risk (ASA > 3). Pain generates a series of alterations of the body’s homoeostasis: it increases metabolic demands, tachycardia, blood pressure, respiratory effects (increased incidence of postoperative lung infections); it also causes increased fluid retention, reduced limb mobility (with a consequent increased risk of deep vein thrombosis), reduced gastrointestinal motility, and immunological effects. Therefore, adequate postoperative analgesia is a priority in the postoperative management of surgical patients.

Pain, then, figures as the fifth vital parameter in the postoperative period, alongside heart rate, blood pressure, respiratory rate and diuresis.

For the purposes of accurately assessing postoperative pain, it is advisable to use an instrument that is simple, repeatable, and common to all those involved in the pain evaluation process (anesthetists, surgeons, nurses, and patients). The visual analog scale (VAS) is the most commonly used rating scale in the strictly scientific setting, but in day-to-day clinical practice, it may be more practical to use an 11-score numerical rating scale (NRS), where 0 denotes no pain and ten stands for the maximum pain imaginable. In some subjects, such as the elderly, it may be necessary to adopt a verbal scale, whereas for children a visual scale is advisable, with graphic representation of facial expressions reflecting the different intensities of the pain experience. It is advisable to assess both resting pain and pain in motion.

The variety of operations performed on the upper limbs means that the approach to postoperative pain is correspondingly extremely varied. The pain intensity ranges from mild to moderate pain, as in the case of minor operations on the hand (trigger finger, carpal tunnel syndrome), to severe pain, such as that resulting from major shoulder surgery. The analgesic techniques to be used range therefore from systemic analgesia (intravenous or oral) to regional anesthesia techniques (continuous peripheral blocks). The possibilities of interacting with the nociceptive system are multiple and range from those involving the periphery to those involving the central nervous system (Fig. 15.2).
Fig. 15.2

Analgesic drugs and sites of action

15.3 Systemic Analgesia

There are two fundamental types of approaches to the receptors directly involved in the nociceptive process, namely direct administration of the drug in the immediate vicinity of the receptors (central or perineural approaches) and indirect administration systemically whereby the drugs reach their action site via the bloodstream. In systemic analgesia, the intravenous route is the one most commonly used in the postoperative setting, in that it bypasses the gastrointestinal absorption process necessarily involved in oral administration. Nevertheless, in particular circumstances, alternative administration routes may also be opted for. For example, in day surgery, the oral route is a first choice solution for pain treatment at home. In minor pediatric surgery, the rectal route (paracetamol) is a widely used therapeutic approach.

15.3.1 Non-opioid Analgesics

The management of mild-to-moderate postoperative pain is based fundamentally on the use of non-opioid analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 inhibitors (coxibs), and paracetamol. These drugs may also be used in the management of moderate-to-severe pain in combination with opioids in a multimodal analgesia regimen. The use of two or more analgesic drugs which act at different points along the pain transmission and modulation pathway makes it possible to reduce the dosage of the individual drugs and consequently to limit the incidence of their side effects. The interaction between the two drugs chosen or between two or more antalgic techniques may be of the additive or synergistic type. The multimodal approach improves the postoperative outcome and speeds up the discharge both of hospital inpatients (reducing the number of days’ stay in hospital) and of patients operated on in the day-surgery setting. This phenomenon is part and parcel of the broader concept of fast track surgery, which assigns a new role to the anesthetist, no longer confined to the operating room, but as the main figure in perioperative medical care. As introduced by Kepler in the 1990s, a perioperative multimodal program that guarantees reduced morbidity and early discharge capability comprises: correct preoperative patient information, a reduced response to stress, adequate pain relief, early enteral nutrition, and early physiotherapy and mobilization.

15.3.2 NSAIDs and Coxibs

NSAIDs exert an anti-inflammatory and analgesic action by means of the non-selective inhibition of the central and peripheral cyclooxygenases, thus reducing the level of prostaglandins. This lack of selectivity underlies the known side effects associated with these drugs at the gastrointestinal, renal, and platelet levels. The prostaglandins perform a series of important physiological functions for the homoeostasis of the body: protection of the gastric mucosa and of renal tubule function, intrarenal vasodilation, bronchodilation, production of prostacyclines that induce vasodilation, and of thromboxanes that induce platelet aggregation and vasospasm. These physiological functions are controlled mainly by the so-called constitutive isoenzyme COX-1, whereas the COX-2 isoenzyme is thought to be involved mainly in inflammatory and pain processes as a result of tissue damage and which, at the level of the spinal cord, may contribute to the process of central sensitization. For these reasons, in the past decade, selective COX-2 inhibitors (coxibs) have come onto the market which guarantee good analgesic efficacy with none of the unwanted gastrointestinal side effects associated with the NSAIDs. In the postoperative period, coxibs have been used successfully in both oral and intravenous formulations. Coxibs significantly reduce postoperative pain and opioid intake and increase the measure of patient satisfaction. Despite these drugs having an opioid-sparing effect, no reduction in the opioid-related incidence of side effects has been observed. The preoperative administration of celecoxib or parecoxib (pre-emptive analgesia) offers no advantage in terms of postoperative pain and perioperative opioid intake when compared to administration at the end of surgery. At the renal level, the side effects of coxibs are similar to those of NSAIDs, since the COX-2s also participate in maintaining an adequate renal blood flow. At the platelet level, on the other hand, the coxibs do not interfere with platelet agreeability and therefore do not increase postoperative bleeding. When used chronically, some coxibs (rofecoxib) have caused cardiovascular alterations and specifically an increased incidence of myocardial infarction and for this reason have been withdrawn from the market. However, the short-term use of parecoxib and valdecoxib postoperatively after non-cardiac surgery does not increase the risk of cardiovascular side effects. At the respiratory level, it has been demonstrated that coxibs, unlike NSAIDs, do not induce bronchospasm in patients sensitive to aspirin. In arthroscopic shoulder surgery, the addition of etoricoxib 120 mg per os to subacromial analgesia with bupivacaine significantly reduces the level of postoperative pain for up to 7 days after the operation and reduces the patient’s hospital stay.

15.3.3 Paracetamol

Paracetamol is a centrally acting drug endowed with analgesic and antipyretic activity. Unlike the NSAIDs, it does not interfere with peripheral cyclooxygenase activity and therefore does not have either the classic side effects of the NSAIDS related to COX-1 inhibition nor any of the pronounced anti-inflammatory activity related to COX-2 inhibition. Although it has been available on the market for more than a century, its actual mechanism of action is still a subject of study. Recent studies have led researchers to postulate a possible potentiation of the descending inhibitory serotoninergic system, a possible interaction with the endocannabinoid system (paracetamol being metabolized to the compound AM404, which is an inhibitor of the cellular reuptake of anandamide and therefore an indirect activator of cannabinoid CBI receptors) and the possible inhibition of substance P-mediated hyperalgesia and therefore an interaction with the nitric oxide synthase system.

The recent introduction of a ready-to-use intravenous formulation has given this molecule a new lease of life for the management of postoperative pain. The ideal dosage is 1 g every 6 h, to be administered in an approximately 15 min infusion. At this dosage, the intravenous formulation crosses the blood–brain barrier rapidly and affords a good level of rapid, predictable analgesia. A number of authors have proposed an initial priming dose of 2 g, which has proved more efficacious than the 1 g dose, but is not currently recommended in everyday clinical practice. Paracetamol has an approximately 20 % opioid-sparing effect on morphine and therefore has not been found to significantly reduce the incidence of opioid-related side effects but may significantly increase patient satisfaction.

The risk of hepatotoxicity is negligible at the doses recommended. Retrospective studies have shown that the mean dose taken by patients presenting acute paracetamol-induced hepatotoxicity is approximately 24 g, that is, far higher than the 4 g per day recommended for intravenous administration. Even in patients suffering from alcoholic liver disease, the administration of 4 g of paracetamol a day for three consecutive days does not give rise to any significant increase in transaminases. The hepatotoxic effects are therefore to be regarded as being exclusively related to accidental overdoses or to voluntary overdoses for the purposes of committing suicide.

15.3.4 Opioids

Opioids are the mainstay of postoperative systemic analgesia for surgery causing moderate-to-severe pain. They exert their analgesic efficacy by interacting with the mu opioidergic receptors present at the level of the central and peripheral nervous systems, and belonging to the G-protein-coupled receptor family.

There is no evidence of any analgesic superiority of one opioid over another, if used at the appropriate dosage. The conversion tables of equianalgesic doses used in order to identify the right dose of a drug compared with another of the same category are partly flawed by the degree of inter-individual pharmacokinetic and pharmacodynamic variability. These tables are often based on studies conducted on single administrations of a drug and fail to take proper account of repeated exposure in the course of time to the same molecule.

Nevertheless, for reasons of pharmacokinetics, metabolism and elimination, a number of opioids are to be preferred to others in certain special types of patients. For example, since morphine is a strongly hydrophilic drug, it is particularly indicated in obese subjects. Fentanyl, in turn, thanks to its prevalently hepatic metabolism, would appear to be particularly indicated in subjects with renal insufficiency. In any event, in these specific categories, such as the elderly, the obese, patients suffering from obstructive sleep apnoea (OSA), and patients with renal or hepatic insufficiency, the doses must be carefully calibrated for each subject on an individual basis.

In particular, in the immediate postoperative period, it is always advisable to perform the titration of the opioid until an adequate level of analgesia is obtained, usually estimated as a VAS value of less than 4.

The use of opioids is burdened, to various extents, with unwanted side effects unavoidably related to the pharmacological action of these substances. The most feared adverse event is unquestionably respiratory depression, but, in the postoperative setting, the most frequent unwanted side effects are nausea and vomiting, constipation, itching, sedation, and possibly hemodynamic effects (bradycardia, hypotension, arrhythmias).

For surgeries that give rise to mild-to-moderate pain, the so-called weak opioids can be used, such as tramadol or codeine. These opioids are also available in combination with paracetamol, in fixed-dose oral formulations.

15.3.5 Tramadol

Tramadol is defined as an atypical opioid on account of its combined effect on opioidergic receptors and on monoaminergic transmission. Tramadol has an effect on mu receptors, which is 6,000-fold less than that of morphine and an inhibitory effect on serotonin and noradrenaline reuptake that potentiates the descending inhibitory pathway.

Tramadol is available as a racemic mixture: The (+) enantiomer mainly has an effect on serotonin, while the (−) enantiomer mainly affects noradrenaline.

Tramadol is subject to a cytochrome-dependent hepatic metabolism, related to CYP2D6, that produces tramadol’s main analgesic metabolite MI, which is 200 times more potent than the molecule from which it derives. This is responsible for the profound inter-individual variability of the response to the drug. Subjects who are so-called poor metabolizers have significantly lower blood concentrations of MI compared to the so-called extensive metabolizers, whether homo- or heterozygous, who therefore fail to obtain adequate pain relief. Moreover, the perioperative use of 5-HT3 receptor inhibitors, such as ondansetron, for antiemetic treatment may reduce its efficacy.

Unlike the other opioids, tramadol presents the advantage of carrying only a minimal risk of respiratory depression and having less of an impact on gastrointestinal motility. However, its use is burdened by a certain incidence of postoperative nausea and vomiting. When compared to the NSAIDs, particularly in patients potentially at risk, it presents the advantage of having no effects on the gastric mucosa or on platelet function.

15.3.6 Codeine

Codeine, too, is subject to metabolism on the part of cytochrome CYP2D6. At the hepatic level, approximately 10 % of the drug is demethylated to morphine. In extensive metabolizers, the morphine blood concentration, as a result of the oral administration of codeine, is approximately 50 % greater than that of normal subjects. Therefore, in addition to an altered renal clearance, also a genetic modification of the metabolism may be responsible for the side effects observed after the administration of codeine. There are more than 100 allelic variants of the cytochrome CYP2D6 gene. In the Caucasian population, there are at least 10 % of poor metabolizers and 5 % of extensive metabolizers. The latter, in particular, are at high risk of side effects due to elevated blood concentrations of morphine.

In cases of major surgery of the upper extremity (fractures, shoulder prostheses) causing severe pain, in which it is decided to implement systemic analgesic therapy, the most commonly used pure opioid agonists are morphine, fentanyl, and sufentanil.

15.3.7 Morphine

Morphine still remains today the most widely used drug in the postoperative period. Its metabolism is mainly via the liver which, by glucuronidation, produces two main metabolites—M3G and M6G. The M6G metabolite is also a mu opioidergic receptor agonist that crosses the blood–brain barrier more slowly than morphine, but possesses an analgesic potency superior to that of the drug from which it derives. The M3G metabolite, on the other hand, has no analgesic effect but is responsible for the neuroexcitatory effects of morphine, such as hyperalgesia, allodynia, and myoclonus. The accumulation of morphine metabolites in patients with renal insufficiency is responsible for side effects such as sedation and respiratory depression.

The genetic polymorphism of the mu opioidergic receptor may be responsible for the variability of the individual responses to morphine. In particular, the nucleotide A118G that codes for the mu receptor has been identified. Whereas homozygous subjects (AA) respond well to morphine, heterozygous subjects (AG) or homozygous subjects for the G variant of the allele (GG)—particularly frequent in the Asian and Caucasian populations—show an increased intake of opioids in patient-controlled analgesia (PCA). Other polymorphisms concern genes that code for enzymes participating in the metabolism of morphine (UGT2B7) or for the glycoprotein for transporting the drug across the blood–brain barrier (MDRI).

15.3.8 Fentanyl

Fentanyl is structurally related to pethidine. It is a strongly lipophilic drug, metabolized mainly at the hepatic level. Less than 10 % is excreted via the kidneys, which makes it particularly suitable for subjects with renal insufficiency. Furthermore, the absence of active metabolites constitutes another important advantage over morphine in postoperative pain management. The polymorphism of the mu A304G opioidergic receptor may affect the analgesic response to fentanyl.

15.3.9 Sufentanil

Sufentanil is a synthetic lipophilic opioid, which is from five to ten times more potent than fentanyl. It has a pharmacological profile similar to that of fentanyl, with a mainly hepatic metabolism.

Opioid Dose Determinants

There is a great deal of inter-individual variability with regard to the amount of opioid drug necessary for adequate postoperative analgesia. A number of factors, however, have been identified as indicators of a greater or lesser opioid requirement. It is well known that age, more than body weight, contributes to a patient’s postoperative analgesic needs. With advancing age, the mean dosages are reduced to a half or a quarter of those for younger subjects, the reasons for this reduced opioid requirement are changes in the pharmacokinetic parameters (metabolism) and in the percentage penetration at the cerebral level. In the immediate postoperative period, women present significantly higher pain levels than men, surgical procedures being equal, as well as a significantly greater opioid intake. Obviously, as mentioned previously, genetic factors may significantly modify the opioid requirement postoperatively.

In the light of these observations, administration modes must be used that can be modulated on the basis of the individual patient’s specific requests. Titration of the opioid at the end of surgery is undoubtedly the first step for an appropriate use of opioids in the management of postoperative pain. The choice of a suitable intravenous infusion modality is equally important in order to guarantee adequate analgesia.

15.3.10 Modes of Administration: Patient-Controlled Analgesia

Patient-controlled analgesia (PCA) is a pain relief modality which permits the patient to self-administer small doses of analgesic drugs on the basis of his or her effective needs. Worldwide it constitutes one of the most commonly used postoperative pain treatment modalities. PCA fulfills two fundamental requirements for effective opioid therapy: It enables the dose to be individualized by titrating the right amount to ensure adequate pain relief and avoids the so-called ‘peak and valley’ phenomenon in which phases of excessive analgesic cover alternate with phases of acute pain.

For the use of intravenous PCA to be effective, it is necessary to administer a priming dose that stabilizes the intensity of the patient’s pain at a predefined acceptable level, corresponding to a VAS rating of less than 4. This stabilization is obtained by titrating the intravenously administered opioid in the immediate postoperative period before discharging the patient from the surgical unit or the recovery room.

The pumps for PCA are programmed by setting a number of basic parameters: the bolus dose (how many milliliters of solution injected in the device are released per bolus delivered), the lock-out time (the time interval between two doses—the doses required are not delivered until the predetermined time interval has elapsed) and the maximum dosage that can be delivered per hour or over a 4-h period.

PCA pumps are also capable of delivering a continuous basal infusion, when programmed to do so. It has been demonstrated, however, that this mode of use (infusion + boluses) does not improve the quality of the postoperative analgesia and increases the risk of side effects. Continuous basal infusion is not recommended in that it bypasses the negative feedback mechanism on which the safety of the PCA system rests. The most feared unwanted side effect of opioids is respiratory depression. When implementing PCA, the use of appropriate doses of opioids at predetermined intervals means that, in the case of an overdose, sedation is manifested before respiratory depression. In this situation, the patient will be so sedated as not to require a subsequent dose. For this reason, it is important that the patient should be the only person managing the PCA pump, and that he or she should understand the mode of use in advance and be informed, together with the family, of the possible complications deriving from an inappropriate use of drugs such as opioids.

There is no evidence in the literature that any given type of programming is more effective than another. Morphine is certainly the opioid most commonly used, at a bolus dose of 1 mg with lock-out intervals of 6 min. The bolus dose should be sufficient to afford a certain degree of analgesia, but should not be so large as to risk generating side effects due to an acute overdose. Similarly, the lock-out interval should be long enough to allow the patient to avail himself to the full of the beneficial effects of the single dose delivered before receiving the next, but not so long as to risk gaps in the analgesic cover. On the basis of the periodic review of the PCA pump and the relationship between the doses required and those effectively received by the patient, the programming of the system can be appropriately modulated in the course of postoperative antalgic therapy.

Intravenous analgesia with PCA affords a superior level of analgesia and greater patient satisfaction when compared to the conventional use of opioids via the parenteral route. There is, however, no evidence of a reduction in the intake of opioid analgesics, nor of any reduction in the incidence of side effects related to these drugs.

The electronic pumps for PCA are available in hospital versions, to be attached to stands, and in versions for use at home which are small and portable so as not to encumber the patient’s movements.

One of the problems associated with the use of these devices is the possibility of a pump programming error. An error in the concentration of the drug or in the programming of the boluses may even have very serious consequences. Available on the market today are particularly sophisticated PCA pumps, designed to comply with the strict acknowledged standards for reducing errors. The CADD Solis Smart Pump uses the CADD Solis Medication Safety Software which allows up to 500 different protocols to be programmed directly by the computer and catalogued in specific libraries. The infusion history can be called up directly on the computer with graphics both in PDF and in Excel. The infusion profiles are extremely flexible with absolute and relative limits that can be programmed by the user. Despite its very considerable potential, the structure of the work menus is extremely simple so as to simplify the work of the users (Fig. 15.3).
Fig. 15.3

Electronic pump for patient-controlled analgesia (CADD Solis Smart Pump)

Another system designed to avoid programming errors is transdermal PCA by means of the fentanyl iontophoretic transdermal system (IONSYSTM). The application of a small amount of energy, by means of a battery applied to a patch containing fentanyl, permits the administration of predetermined 40 mcg boluses at 10 min intervals (maximum 6 doses per h) up to a total of 80 administrations. This system has proved effective in different types of surgery—abdominal, pelvic, and orthopedic. What is more, the degree of patient satisfaction has proved distinctly superior with this transdermal system when compared to the traditional intravenous PCA system with morphine. However, the system is not yet available for clinical use.

15.3.11 Elastomeric Pumps

Elastomeric pumps consist of a PVC tubing connected up to a reservoir, the elasticity of which ensures that, once filled, it tends to empty progressively as a function of its own elastic spring-back characteristics (Fig. 15.4). These pumps are available with various capacities (60–300 ml) and different flow rates (0.5–12 ml/h). The reservoir is protected by an external shell, which prevents it from suffering damage with loss of the analgesic-containing solution. Obviously, this system fails to comply with any of the PCA principles, inasmuch as the infusion, once initiated, proceeds without any regard for the effective analgesic needs of the patient. The decision to use these devices is based mainly on considerations of an economic nature. Therefore, to avoid unwanted side effects, in the devices with a fixed infusion rate, there is a tendency to deliver under doses of the analgesic drug scheduled for the treatment period. To overcome this limitation, variable flow elastomeric pumps have been designed (multirate infusor systems) which, while maintaining the simplicity principle (they do not require electricity, have no alarm system, cost less than electronic pumps, and are single-use disposable, light and practical to use), they permit easier modulation of postoperative analgesic treatment. These pumps enable the flow rate of the analgesic solution to be varied from a minimum of 0.5 ml/h to a maximum of 7.5 ml/h. A further therapeutic possibility is offered by the availability of elastomeric pumps equipped with a control module for the self-administration of boluses within predetermined dose limits set at the patient’s request. These devices permit the administration of simple, economic PCA, but with none of the complex technology associated with the latest electronic PCA pumps.
Fig. 15.4

Elastomeric pump

15.4 Continuous Peripheral Nerve Blocks

Continuous peripheral nerve blocks (CPNBs) prolong the duration of postoperative analgesia beyond the maximum period of analgesic cover guaranteed by peripheral blocks with single-shot injection of local anesthetic. Their use has increased over the years for the management of moderate-to-severe pain of the upper and lower limbs.

The first continuous peripheral nerve block for upper limb surgery was described in 1946 by Paul Ansbro, who infused 220 ml of 1 % procaine in repeated boluses for an operation lasting approximately 4 h, positioning a non-cutting needle laterally to the subclavian artery, with a supraclavicular approach.

Since then, continuous peripheral nerve blocks for analgesia of the upper limb have evolved and have been used both in traditional surgery and in the day-surgery setting.

It has been amply demonstrated that, when compared to systemic analgesia with opioids, CPNBs afford better analgesia and a lower incidence of nausea, vomiting itching, and sedation (Table 15.1).
Table 15.1

Continuous peripheral nerve block versus systemic analgesia with opioids



Catheter positioning




Borgeat 1997

Major shoulder surgery


0.15 % Bupivacaine

Nicomorphine i.v.

Reduced VAS at 12 and 18 h less vomiting and itching

Borgeat 1998

Major shoulder surgery


0.2 % Ropivacaine

Micomorphine i.v.

Greater patient satisfaction reduced VAS less nausea and itching

Lehtipalo 1999



0.25 % Bupivacaine

Morphine i.v.

Reduced VAS at 12 and 24 h no difference in side effects or opioid intake

Borgeat 2000

Major shoulder surgery


0.2 % Ropivacaine

Nicomorphine i.v.

Greater patient satisfaction reduced VAS at 12 and 24 h less nausea and itching

Klein 2000

Open rotator cuff repair


0.2 % Ropivacaine

Morphine i.v.

Reduced VAS at 12 and 24 h less morphine intake

Ilfeld 2002

Elbow day surgery


0.2 % Ropivacaine

Oxycodone p.o.

Reduced VAS at 24 and 48 h less nausea and sedation

Ilfeld 2003

Shoulder day surgery


0.2 % Ropivacaine

Oxycodone p.o.

Reduced VAS at 24 and 48 h less nausea, sedation and itching less opioid intake

The ideal local anesthetic concentration to be used, however, still remains a controversial issue. Various long-acting local anesthetics have been used at different concentrations (Table 15.2). There are no significant differences between the use of 0.2 % ropivacaine and 0.125 % levobupivacaine infusions. Nevertheless, in a recent study, Borgeat et al. have demonstrated that it is possible to use 0.3 % ropivacaine at an infusion rate of 14 ml/h in interscalene CPNB, significantly reducing the intake of opioids (compared to 0.2 % ropivacaine) without increasing the intensity of the motor block or the incidence of side effects.
Table 15.2

Continuous peripheral nerve blocks for upper limb surgery: comparison between different local anesthetic concentrations



Catheter positioning



Casati 2003

Open shoulder surgery


a 0.125 % Levobupivacaine

Similar analgesia. Lesser volume infused in the first 24 h (a versus b)

b 0.2 % Ropivacaine

Eroglu 2004

Open shoulder surgery


a 0.15 % Bupivacaine

No significant difference between a and b (analgesia, opioid intake, total volume infused, side effects)

b 0.15 % Ropivacaine

Borghi 2006

Open shoulder surgery


a 0.25 % Levobupivacaine

No significant difference between a and c (analgesia, opioid intake, motor block intensity)

b 0.25 % Ropivacaine

c 0.4 % Ropivacaine

Borgeat 2010

Rotator cuff repair


a 0.3 % Ropivacaine

Less opioid intake (a versus b). Better quality sleep (a versus b). No difference in motor block. Intensity or side effects

b 0.2 % Ropivacaine

Shoulder arthroprosthetic surgery is one of the main indications for the placement of a catheter for interscalene continuous infusion; 0.2 % ropivacaine can be used at an infusion rate of 8 ml/h for the first 40–72 h postoperatively. The analgesia obtained with the perineural infusion can be supplemented with NSAIDs, paracetamol or PCA with morphine, if necessary. Even so-called minor shoulder arthroscopic procedures may benefit from a continuous block. The use of a 0.2 % ropivacaine infusion via the interscalene route significantly reduces pain due to movement in the first 24 h.

In traumatized patients, continuous peripheral nerve blocks are an excellent analgesic aid for limb fractures. In the case of injuries to the forearm or hand, a catheter can be placed at the axillary or infraclavicular level, whereas for shoulder, humerus, or elbow injuries an interscalene or supraclavicular approach will be necessary. Obviously, the execution of an axillary block will be possible only in patients in whom the injury does not prevent the abduction of the injured limb and, in any event, maintaining a catheter in that site always presents distinct management problems.

In an attempt to enable patients operated on in the day-surgery setting to be discharged early, some authors have proposed CPNB also for the management of postoperative pain at home after shoulder or elbow surgery.

The continuous infusion can be done with an elastomeric system or with a pump for regional PCA.

In continuous infusions, the anesthetist must bear in mind the toxic potential of local anesthetic agents. It has recently been demonstrated by Bleckner et al. that even prolonged infusions of 0.2 % ropivacaine at a rate of 6–14 ml/h lasting more than 120 h in traumatized patients (supraclavicular or infraclavicular block) do not give rise either to dangerous increases in blood concentrations of free ropivacaine (more than 0.6 mg/L) or to local anesthetic systemic toxicity phenomena.

15.4.1 Subacromial or Intra-articular Infiltration

Since major shoulder surgery is associated with severe pain, there is often a need for high doses of opioids for prolonged periods. For the purposes of reducing the use of these drugs, various different analgesic techniques have been studied, in addition to CPNB. The intra-articular or subacromial approach is particularly easy to use. The surgeon himself, at the end of the surgical procedure, may inject 20–50 ml of local anesthetic in a single administration or may insert an indwelling catheter. This technique was successfully used early in this decade as an alternative to the interscalene block on account of its simplicity and reduced risks. The first studies were conducted in minor surgery (shoulder arthroscopy) and yielded positive results. More recent studies, conducted in major shoulder surgery (open surgery or rotator cuff repair), have failed to show significant advantages compared to placebo, and therefore, the technique has witnessed something of a decline in recent years. Furthermore, attention has recently been drawn to the possibility of direct toxicity of intra-articularly administered local anesthetics on chondrocytes. Fredrickson et al., in a recent meta-analysis of analgesic techniques for shoulder surgery, conclude that, in the light of the latest results, this technique can no longer be recommended.

15.5 Day Surgery: Analgesia at Home

Pain is the main cause of readmission to hospital after surgical operations in the day-surgery setting. Up to one-third of patients undergoing surgery in the day-surgery regimen complain of moderate-to-severe pain within 24 h of the operation. Orthopedic surgery, in particular, is associated with a higher incidence of severe postoperative pain than the other surgical specialties. In recent years, we have witnessed a substantial rise in orthopedic surgical procedures performed in the day-surgery setting, as reflected by the numerous difficulties encountered in the management of postoperative pain at home.

The therapeutic options for postoperative pain management in the orthopedic day-surgery setting consist basically in three techniques: oral analgesics, intra-arterial analgesics, or local anesthetics, or CPNBs.

The ideal analgesic treatment for the management of day-surgery postoperative pain must be not only effective but also safe and simple for patients to use autonomously at home. From this point of view, oral analgesia is certainly the most commonly used therapy, particularly NSAIDs, paracetamol and tramadol. Unfortunately, all too often there is as lack of any methodical outcome assessment. One of the main reasons for the inadequate treatment of postoperative pain in day surgery is failure to detect the pain, at rest or due to movement, at the time the patient is discharged and allowed to go home. This leads to an underestimate of the extent of the postoperative pain accompanying a given surgical procedure and, consequently, failure to provide an adequate antalgic treatment. It is therefore necessary to ensure the availability of simple assessment instruments (diary cards) to be filled in by the patient and handed into the facility delivering the medical care at the first check-up visit.

In a study conducted in 120 patients undergoing ambulatory hand surgery, Rawal et al. demonstrated that the postoperative pain lasts for up to 2–3 days after the surgery and that paracetamol (1 g every 6 h) presents an excellent analgesic and tolerability profile, whereas tramadol (100 mg every 6 h), despite being the most effective drug, is associated with a higher incidence of unwanted side effects.

Since home treatment needs to guarantee maximum compliance with the therapy prescribed, and the compliance is related to the simplicity of the dosage regimen, an easy solution may be to use fixed drug combinations to be administered orally, which, with a single administration, meet the needs of a multimodal approach. In hand surgery, the fixed combination of paracetamol + tramadol (325 + 37.5 mg) has been used successfully, with analgesic efficacy equal to tramadol 50 mg and a lower incidence of gastrointestinal and central nervous system side effects. In day surgery, even more than in hospital inpatients, the tolerability profile of an analgesic acquires greater importance, inasmuch as the drug is taken in the home setting. Postoperative nausea and vomiting (PONV) are a major problem in day surgery, where approximately one-third of patients manifest these side effects after being discharged, regardless of the anesthetic and/or antalgic treatment opted for.

In the field of upper extremity surgery, the main limitation of a number of operations in the day-surgery setting is precisely the difficulty encountered in the management of postoperative pain at home, particularly as relating to shoulder surgery. Alongside systemic analgesia, more sophisticated techniques have also been proposed, for which thorough assessment of the patient’s cognitive capacities and adequate preoperative information are absolutely mandatory. Continuous peripheral nerve blocks have been proposed by some authors for the postoperative management of arthroscopic shoulder surgeries. Fredrickson, in more than one study, has demonstrated the efficacy and safety of CPNBs in ambulatory surgery, making it possible to significantly reduce home consumption of opioids. The interscalene use of 0.2 % ropivacaine significantly reduces movement-induced pain in the first 24 h after arthroscopic shoulder surgery. A continuous interscalene block with a posterior approach using 0.2 % ropivacaine has been employed for orthopedic day surgery on the shoulder, with an improvement in pain relief, a reduced opioid intake, better quality sleep, and enhanced patient satisfaction compared to the single-shot block.

Rawal et al. have evaluated the efficacy and safety of patient-controlled regional analgesia (PCRA) at home, using the axillary block in patients undergoing hand surgery (0.125 % ropivacaine or 0.125 % bupivacaine—10 ml boluses). This self-administration approach has proved effective and safe in the domiciliary management of postoperative pain. Adequate patient selection, telephone follow-up and 24 h anesthesia availability are deemed indispensable.

The use of CPNBs in day surgery, however, still remains a controversial issue inasmuch as the postoperative pain as a result of ambulatorial surgery is usually regarded as being of a mild-to-moderate level of intensity and therefore well controlled with oral systemic analgesia in most patients. It would therefore not appear to be appropriate to use invasive and expensive techniques when not strictly necessary, given the availability of simple, low-cost alternative therapies.


  1. Bleckner LL, Bina S, Kwon KH, McKnight G, Drogavich A, Buckenmaier CC (2010) Serum ropivacaine concentrations and systemic local anesthetic toxicity in trauma patients receiving long-term continuous peripheral nerve block catheters. Anesth Analg 110(2):630–634PubMedCrossRefGoogle Scholar
  2. Borgeat A, Aguirre J, Marquardt M, Mrdjen J, Blumenthal S (2010) Continuous interscalene analgesia with ropivacaine 0.2% versus ropivacaine 0.3% after open rotator cuff repair: the effects on postoperative analgesia and motor function. Anesth Analg 111(6):1543–1547PubMedCrossRefGoogle Scholar
  3. Borghi B, Facchini F, Agnoletti V, Adduci A, Lambertini A, Marini E et al (2006) Pain relief and motor function during continuous interscalene analgesia after open shoulder surgery: a prospective, randomized, double-blind comparison between levobupivacaine 0.25%, and ropivacaine 0.25 or 0.4%. Eur J Anaesthesiol 23(12):1005–1009PubMedCrossRefGoogle Scholar
  4. Casati A, Borghi B, Fanelli G, Montone N, Rotini R, Fraschini G et al (2003) Interscalene brachial plexus anesthesia and analgesia for open shoulder surgery: a randomized, double-blinded comparison between levobupivacaine and ropivacaine. Anesth Analg 96(1):253–259PubMedGoogle Scholar
  5. Coluzzi F, Bragazzi L, Di Bussolo E, Pizza G, Mattia C (2011) Determinants of patient satisfaction in postoperative pain management following hand ambulatory day-surgery. Minerva Med 102(3):177–186PubMedGoogle Scholar
  6. Dayer P, Desmeules J, Collart L (1997) Pharmacologie du tramadol. Drugs 53(Suppl. 2):18–24PubMedCrossRefGoogle Scholar
  7. Eroglu A, Uzunlar H, Sener M, Akinturk Y, Erciyes N (2004) A clinical comparison of equal concentration and volume of ropivacaine and bupivacaine for interscalene brachial plexus anesthesia and analgesia in shoulder surgery. Reg Anesth Pain Med 29(6):539–543PubMedGoogle Scholar
  8. Fredrickson MJ, Ball CM, Dagleish AJ (2010) Analgesic effectiveness of a continuous versus single-injection interscalene block for minor arthroscopic shoulder surgery. Reg Anesth Pain Med 35(1):28–33PubMedCrossRefGoogle Scholar
  9. Fredrickson MJ, Ball CM, Dagleish AJ (2008) Successful continuous interscalene analgesia for ambulatory shoulder surgery in a private practice setting. Reg Anesth Pain Med 33(2):122–128PubMedGoogle Scholar
  10. Fredrickson MJ, Krishnan S, Chen CY (2010) Postoperative analgesia for shoulder surgery: a critical appraisal and review of current techniques. Anesthesia 65:608–624CrossRefGoogle Scholar
  11. Grass AJ (2005) Patient controlled analgesia. Anesth Analg 101:S44–S61PubMedCrossRefGoogle Scholar
  12. Ilfeld BM, Enneking FK (2005) Continuous peripheral nerve blocks at home: a review. Anesth Analg 100:1822–1833PubMedCrossRefGoogle Scholar
  13. Ilfeld BM, Morey TE, Enneking FK (2002) Continuous infraclavicular brachial plexus block for postoperative pain control at home: a randomized, double-blinded, placebo-controlled study. Anesthesiology 96:1297–1304PubMedCrossRefGoogle Scholar
  14. Mariano ER, Afra R, Loland VJ, Sandhu NS, Bellars RH, Bishop ML et al (2009) Continuous interscalene brachial plexus block via an ultrasound-guided posterior approach: a randomized, triple-masked, placebo-controlled study. Anesth Analg 108(5):1688–1694PubMedCrossRefGoogle Scholar
  15. Mattia C, Coluzzi F, Sonnino D, Anker-Møller E (2010) Efficacy and safety of fentanyl HCl iontophoretic transdermal system compared with morphine intravenous patient-controlled analgesia for post-operative pain management for patient subgroups. Eur J Anaesthesiol 27(5):433–440PubMedCrossRefGoogle Scholar
  16. Mattia C, Coluzzi F (2009) What anesthesiologists should know about paracetamol (acetaminophen). Minerva Anestesiol 75(11):644–653PubMedGoogle Scholar
  17. Rawal N, Allvin R, Amilon A, Ohlsson T, Hallén J (2001) Postoperative analgesia at home after ambulatory hand surgery: a controlled comparison of tramadol, metamizol, and paracetamol. Anesth Analg 92(2):347–351PubMedCrossRefGoogle Scholar
  18. Rawal N, Allvin R, Axelsson K et al (2002) Patient-controlled regional analgesia (PCRA) at home: controlled comparison between bupivacaine and ropivacaine brachial plexus analgesia. Anesthesiology 96:1290–1296PubMedCrossRefGoogle Scholar
  19. Richman JM, Liu SS, Wong R et al (2006) Does continuous peripheral nerve block provide superior pain control to opioids? A meta-analysis. Anesth Analg 102:248–257PubMedCrossRefGoogle Scholar
  20. Russon K, Sardesai AM, Ridgway S, Whitear J, Sildown D, Boswell S et al (2006) Postoperative shoulder surgery initiative (POSSI): an interim report of major shoulder surgery as a day case procedure. Br J Anaesth 97(6):869–873PubMedCrossRefGoogle Scholar
  21. Scott LJ, Perry CM (2000) Tramadol, a review of its use in perioperative pain. Drugs, 60(1):139–176Google Scholar
  22. Toivonen J, Pitko VM, Rosenberg PH (2007) Etoricoxib pre-medication combined with intra-operative subacromial block for pain after arthroscopic acromioplasty. Acta Anaesthesiol Scand 51(3):316–321PubMedCrossRefGoogle Scholar
  23. Trompeter A, Camilleri G, Narang K, Hauf W, Venn R (2010) Analgesia requirements after interscalene block for shoulder arthroscopy: the 5 days following surgery. Arch Orthop Trauma Surg 130(3):417–421PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  1. 1.Department of Medico-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and MedicineSapienza UniversityRomeItaly

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