Key Points
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Due to the physiological changes and relative increase in comorbidities that accompany aging, anesthesia for the elderly population presents special considerations and the potential for complications.
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Regional anesthesia is an attractive option for elderly patients; however, type and dosing of sedatives and local anesthetics must be selected carefully. Sensitivity to sedatives increases with age, and metabolism of local anesthetics may be compromised by age-related changes in organ and tissue function.
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Both central neuraxial and peripheral nerve blocks can be administered safely in the elderly, although anatomic and physiologic considerations (e.g., ability to position the patient, decreased nerve conduction) as well as drug effects (e.g., altered rates of absorption/clearance, risk of toxicity) must be kept in mind.
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Appropriate dosing and adequate monitoring are keys to safe and effective regional anesthesia and analgesia in the elderly population.
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Keywords
- Regional anesthesia
- Central neuraxial block
- Peripheral nerve block
- Local anesthetic
- Age
- Elderly
- Pharmacology
Introduction
Life expectancy has been steadily increasing worldwide, and as a result, there is an increased proportion of the elderly population that is presenting for medical care and surgical procedures. Therefore, anesthesia for the elderly has become an increasingly important topic. Because of age-related physiologic changes that accompany aging (including a decline in organ function as well as pharmacokinetic and pharmacodynamic alterations as people age), the methods of safely administering anesthesia in this patient population need to be approached in a different fashion compared to a younger counterpart. It is therefore very important for anesthesiologists to understand these changes in order to provide safe anesthesia and analgesia to the elderly population. The elderly population is commonly assumed to consist of people 65 years of age and older. However, it must be emphasized that this is a generalization, and heterogeneity in this age group is definitely very apparent (e.g., differences in functional capacity and variable rates of organ function decline). Thus, a patient’s age is only one factor when devising plans for anesthesia.
Use of regional anesthesia in elderly patients can be safely used. This review focuses on useful and practical tips for successful regional anesthesia in the aging population. Here, different anesthetic agents used for sedation as well as the pharmacokinetic changes of local anesthetics will be discussed. In addition, the physiologic changes associated with aging will be touched upon in this review. A literature search was completed using MEDLINE© and PubMed from January 1966 through March 2015. The literature search entailed the term “elderly” in combination with the following terms: anesthesia, local anesthesia, regional anesthesia, spinal anesthesia, epidural anesthesia, and analgesia. Abstracts were selected based on relevance, and the corresponding publications were obtained. Unpublished works were not considered, and none of the corresponding authors were contacted.
Regional Anesthesia in the Elderly
One can ask: is regional anesthesia the preferred modality in this patient population, and does the choice of anesthetic influence patient outcome? Despite these questions, there are no large prospective trials that support the use of regional versus general anesthesia in improving outcomes in elderly patients. Outcome studies suggest that a difference in morbidity and mortality between general and regional anesthesia does not exist in most populations [1]. It makes intuitive sense that elderly patients benefit from regional anesthesia due to a decreased exposure to general anesthetic agents (i.e., minimal sedation) and can stay awake during surgery. Postoperative cognitive dysfunction (POCD) is a common complication following major surgery in the elderly [2, 3]. However, the effects of general anesthesia versus regional anesthesia on POCD continue to be debated. Hole et al. found a higher incidence of cognitive dysfunction in elderly patients following elective hip surgery when general anesthesia was utilized [4], which was corroborated with another future study [5]. In contrast, a study which included 262 elderly patients demonstrated that there was no difference in POCD in patients who had general anesthesia with patient-controlled analgesia compared to patients who had epidural anesthesia [1]. In a study investigating POCD in elderly patients undergoing transurethral resection of the prostate also revealed that the anesthetic method did not have a meaningful impact on cognitive dysfunction [6]. To further corroborate this, a systematic review suggests the use of intravenous versus epidural methods for postoperative analgesia in the elderly population results in no difference in perioperative cognitive function [7]. Regional anesthesia, however, may offer superior postoperative pain control in this age group [8] and can result in decreased opioid use, which may be advantageous in the elderly that are already cognitively impaired [9]. Although regional anesthesia may be a better choice in regards to cognitive function in the elderly in the immediate postoperative period, there is no evidence that avoiding general anesthesia preserves later cognitive function [10, 11]. Nonetheless, clinical observations recommend regional anesthesia in elderly patients since the use of minimal sedation for the surgical procedure allows the patient to maintain orientation and return to baseline function quickly [4, 12]. Pain has been implicated as a risk factor for developing POCD , so regional anesthesia may be of benefit in this respect [13]. Other advantages exist favoring regional anesthesia over general anesthesia. For instance, the incidence of thromboembolic events is decreased [14, 15], as are blood loss [16] and the rate of deep venous thrombosis [17] following hip surgery in the elderly population when regional anesthesia is used. However, other studies have found no difference in 28-day mortality when regional anesthesia is used compared to general anesthesia for hip surgery [1]. Additionally, provision of excellent pain control with regional anesthesia can decrease the incidence of adverse cardiac events in the postoperative period [18, 19]. Indeed, a case report demonstrating the use of regional anesthesia (brachial plexus block ) for surgery in an elderly patient with active cardiac symptoms proved successful [20], suggesting that utilizing regional anesthesia techniques may help avoid cardiovascular stress, which has ramifications because of the increased incidence of cardiovascular disease associated with the aging process. However, when perioperative hemodynamics is well controlled in patients undergoing vascular procedures of the lower extremity, there is no difference in cardiac morbidity and mortality [1, 21]. Other advantages conferred when techniques of regional anesthesia are utilized include a more rapid return of bowel function [22] as well as maintenance of the immune system postoperatively [23], which are especially important in the care of elderly patients.
Despite these potential benefits of utilizing regional anesthesia techniques, a clear improvement in patient outcomes over general anesthesia cannot be established, possibly because there are few clinical situations where one technique can fully establish unequivocal advantages over the other, in part because there are multiple factors that come into play. The type of surgery, duration of procedure, and invasiveness of the operation are important factors to consider. From a patient perspective, important factors include existing comorbidities and baseline cognitive function (including preexisting neurologic disease ). Finally, the underlying skill and expertise not only of the anesthesiologist but also of the surgeon are important provider factors which can affect outcomes. For instance, a regional anesthetic that is poorly executed can be more deleterious for an elderly patient than a well-conducted general anesthetic [24]. Therefore, it would be best practice to optimize the conditions of the patient during the perioperative period, with an emphasis on quality of anesthetic administered rather than the type of anesthetic (regional versus general) which may be the more important factor rather than choice in type of anesthetic. For additional discussion of this topic, please refer to Chaps. 2 and 4.
Sedation for Regional Anesthesia
When preparing patients for a regional anesthesia procedure, sedation is an important aspect of the process. Elderly patients exhibit enhanced sensitivity to most centrally acting agents (sedatives and opioids), thus paying particular attention to dosing and appropriate titration of these medications is of utmost importance to obtain the most benefit with the least side effect profile.
In the elderly, the ideal sedative agents should have a quick onset, be short acting, be easily administered, and have a high safety margin with minimal side effects. Long-acting benzodiazepines should be avoided [25]. Effective agents used for sedation include propofol, dexmedetomidine, midazolam, fentanyl, remifentanil, or a combination of two or more of these drugs (with appropriate dose reductions for each one used). Ketamine can be used either by itself or can be used in combination with midazolam, propofol, fentanyl, or remifentanil, and can also be very useful in the elderly. Regardless of which agents are chosen for sedation, the anesthesiologist must remain cognizant of the physiological changes associated with aging (which can affect the pharmacokinetics and pharmacodynamics of the agents). For instance, spinal anesthesia induces a sedative effect in elderly patients (in the absence of exogenous sedative agents) [26, 27], and given the physiologic changes associated with aging, significantly reduced quantities of sedative agents are prudent in this patient population when this anesthetic technique is used. Indeed, deep and profound sedation can be a frequent occurrence in this patient population [28].
Benzodiazepines
Midazolam
Midazolam is a short-acting water-soluble benzodiazepine, making it an excellent choice for sedation in elderly patients undergoing regional anesthesia procedures. In the elderly, midazolam has both a reduced clearance as well as an increased potency [29, 30]. Intravenous bolus injection doses should be reduced by as much as 75 % in this patient population [31]. The Canadian Compendium of Pharmaceuticals and Specialties (CPS) recommendation for an initial dose is 1–1.5 mg of midazolam, with the total dose not exceeding 3.5 mg or 0.07 mg/kg [32].
Lorazepam
Lorazepam is a short-acting benzodiazepine (t 1/2 ~8–12 h, with no active metabolites) and is one of the few sedative agents which can be administered sublingually with good effect. Although lorazepam has enhanced central nervous system effects in the elderly, its disposition is minimally affected by age [33]. Benzodiazepine premedication can cause hypoxemia due to respiratory depression; however, 1 mg of sublingual lorazepam can be safely used in elderly patients [34].
In addition, it is prudent to exercise caution when benzodiazepines are administered for sedation prior to spinal anesthesia with a local anesthetic and fentanyl because of the potential for oxygen desaturation [35].
Opioids
Use of low-dose opioids in combination with other agents can provide good sedation in the elderly patient undergoing a regional anesthesia procedure. Opioids have a synergistic effect with other sedatives; hence, the doses used for all agents used must be reduced [36, 37]. Appropriate patient monitoring must be employed when combinations of opioid and other sedative agents are utilized because of the danger of enhanced respiratory depression as a result of the synergy between the agents used. Nevertheless, remifentanil 0.5 μg/kg combined with propofol 0.5 mg/kg, as well as midazolam 0.015 mg/kg combined with alfentanil 5 μg/kg, has been used successfully in the elderly, specifically for sedation for cataract surgery utilizing retrobulbar block [38, 39]. In addition, single-dose fentanyl (0.7 μg/kg) has been used successfully in elderly patients undergoing cataract surgery, with minimal impact on cardiorespiratory function [40].
Remifentanil
Remifentanil is an ultra-short-acting opioid. Because of its favorable pharmacokinetic profile, it has become a popular sedative agent for regional anesthesia. The effects of age on the pharmacokinetics and pharmacodynamics of remifentanil have been documented [41]. It has been recommended that half of the bolus dose should be administered in the elderly patient (as compared to their younger counterpart), and the infusion rates to maintain an adequate sedative effect in the elderly should be approximately one-third the rate of that used in a younger patient [36]. Initial suggestions for a remifentanil infusion rate in elderly patients have been 3 μg/kg/h for the elderly patient, but even further reductions to 1.5–2 μg/kg/h have been proposed to minimize cardiovascular and respiratory complications in the elderly population [42, 43]. In regional anesthesia for carotid endarterectomy, a continuous intravenous remifentanil infusion at a rate of 0.04 μg/kg/min has also been used effectively [44].
Other Sedatives
Dexmedetomidine
Dexmedetomidine is a highly selective α2-adrenoreceptor agonist which is approved for the purpose of sedation and analgesia in the intensive care unit in the United States and other countries [45]. It is administered as a continuous infusion (recommended dose of 0.2–0.7 μg/kg/h for up to 24 h). One major benefit of using dexmedetomidine as a sedative is that it does not induce respiratory depression; however, adverse effects include hypotension and dose-dependent bradycardia [45]. A recent case report documented successful use of dexmedetomidine (6 μg/kg/h load for 10 min followed by 0.7 μg/kg/h infusion) as a sedative in a 98-year-old patient undergoing hip fracture surgery with a spinal anesthetic [46]. Another study has also demonstrated success with the use of dexmedetomidine sedation in the elderly population [47].
Ketamine
Ketamine is phencyclidine derivative and is a nonbarbiturate intravenous anesthetic agent used principally for the induction and maintenance of anesthesia. Ketamine has potent analgesic properties at subanesthetic doses and does not negatively affect ventilation, airway patency, or cardiovascular stability [48, 49]. There is not a great deal of information regarding the pharmacokinetic and pharmacodynamic profiles of ketamine in the elderly, but studies implicate a decrease in clearance and prolonged duration of action in this patient population [50]. Frey et al. demonstrated that a mean dose of 13.2 mg of ketamine to supplement a mean dose of 44 mg of propofol provided a quicker onset with enhanced quality of sedation for retrobulbar anesthesia in patients aged >65 years old [51]. Likewise, combination sedation with midazolam (0.025 mg/kg intravenously infused over 5 min) followed by ketamine (0.2 mg/kg, up to 15 mg maximum) has been used to enhance quality of sedation for peribulbar anesthesia [52].
Propofol
Propofol is an alkyl phenol intravenous anesthetic agent with a rapid onset and short duration of action due to its rapid redistribution. As such, intermittent propofol bolus injections as well as low-dose propofol infusions are frequently used for sedation for surgical procedures using regional anesthesia. In regards to pharmacokinetics in the elderly, although the volume of distribution remains relatively unchanged and its rate of clearance is decreased, plasma propofol concentrations increase and decrease more rapidly than in younger patients [53–55]. Pharmacodynamics is also altered in the aging process, including an increased sensitivity to propofol’s anesthetic effects. It has been shown that in 75-year-old patients when compared to 25-year-old patients, the EC50 for loss of consciousness was reduced by 50 % [54]. Additionally, the neurologic depressant effects of propofol as assessed by electroencephalography are increased with age, despite a lack of age-related changes in blood-effect site equilibrium half-life [54]. Propofol can also adversely affect hemodynamic function in the aging population [56]. The concentration of propofol that cause a 50 % decrease in blood pressure is lower in elderly patients (aged 70–85 years) compared to younger patients (aged 20–39 years) [57]. This is due, in part, to the decrease of physiologic reserve that occurs with the aging process [56]. Therefore, administered doses of propofol must be reduced to achieve hemodynamic stability in the aging population. For instance, it was suggested that doses should be reduced by 20–30 % in patients greater than 55 years of age, translating into 0.3–0.6 mg/kg intravenous injection for initial sedation followed by 0.9–2.7 mg/kg/h for maintaining sedation [58]. However, continuous infusion rates of up to 4 mg/kg/h have been successfully used in elderly males undergoing urologic surgical procedures [59]. Propofol therefore is a suitable agent for sedating elderly patients; however, caution must be advised for elderly patients with neurodegenerative disease such as Parkinson’s disease, since it can induce spontaneous involuntary movements [59, 60].
Regardless of which sedation is chosen for the respective procedure, it is vital to ensure supplemental oxygen is delivered and vigilant monitoring of the patient ensues, and administration of the chosen agents(s) involves careful titration in order to reduce the occurrence of untoward side effects while ensuring patient comfort for the procedure.
Local Anesthetics
General Considerations
Aging is associated with a multitude of changes in tissues and organ systems, involving changes in both structure and function. These changes affect the pharmacokinetic profiles of local anesthetics that are used for regional anesthesia. As a result, increased plasma levels of local anesthetics can result, leading to a greater danger of toxicity of the cardiovascular or central nervous systems.
Systemic Absorption
It has been shown that epidural or intrathecal administration of local anesthetics results in a biphasic absorption consisting of a rapid initial phase followed by a slower phase [59, 61–68]. When administered epidurally, the initial rapid phase of absorption is due to the high concentration gradient in combination with the vascularity of this potential space. The slow absorption phase, on the other hand, is due to partitioning of the local anesthetic into epidural fat. When administered intrathecally, the initial rapid phase of absorption is actually slower than that seen when administered after epidural administration because of decreased perfusion of the subarachnoid space in combination with a lower concentration gradient. Aging does not affect absorption of bupivacaine following epidural injection [67]. Conversely, systemic absorption of bupivacaine following intrathecal injection increases with age due to a faster late absorption rate; despite this, the duration of action is not reduced in older patients [66]. Therefore, increased sensitivity of neuraxial anesthesia in the elderly population is not likely related to impairment of vascular absorption. In fact, the increased sensitivity more likely stems from a decrease in neuronal population in the central nervous system coupled with a decreased neuronal conduction velocity that occurs with the aging process [68].
It is often believed that cardiac output decreases as patients age. However, there is no clear consensus regarding this physiologic attribute. Although studies suggest that there is a strong negative correlation between increasing age and cardiac output, others exist that show no correlation when investigating only healthy patients of advanced age [69–71]. Even so, nearly all anesthetic agents decrease cardiac output to varying degrees, which may be affected by aging. This can result in decreased peak concentrations in concert with delaying the time to achieve peak concentration. Also, if there is decreased tissue perfusion, there will be a delay in transporting drugs to their tissue effect sites.
Distribution
Aging is associated with an increase in total body fat while there is a decrease in both total body water and lean body mass. These changes can result in a greater volume of distribution of local anesthetics [72]. Accordingly, patients of advanced aged may exhibit varying peak drug concentrations following rapid bolus injections or infusions; therefore, drug toxicity can be unpredictable in the elderly [73].
The most important plasma protein involved with local anesthetic binding is alpha 1-acid glycoprotein (α-1AG), with the free fraction of local anesthetics such as lidocaine and bupivacaine being inversely proportional to the plasma concentration of α-1AG [74–78]. In the absence of disease, the aging process minimally affects α-1AG concentration in the blood [79, 80]. However, many older patients have existing comorbidities or conditions that can decrease the free fractions of lidocaine and bupivacaine due to elevated levels of α-1AG [81]. For instance, α-1AG concentrations increase in response to different types of stress, including inflammation, infection, the presence of cancer, and surgery itself [81].
Clearance
Given that there is a decrease in hepatic enzymatic activity, hepatic blood flow, and hepatic mass as people age, it makes intuitive sense that the clearance of local anesthetics will be decreased in this patient population, particularly since hepatic microsomal metabolism is the primary means of clearance for amide local anesthetics such as lidocaine and bupivacaine. Plasma clearance of lidocaine and bupivacaine is indeed decreased primarily in elderly males, although a high degree of interindividual variation exists [81–83]. Specifically, it has been demonstrated that clearance of lidocaine was reduced by approximately 35 % in males >65 years of age, but there was a lack of age effect in females [83]. This observation may be due to hormonal differences and their influences on local anesthetic protein binding [84, 85]. Regardless, it would be prudent to accept that the rate of clearance of local anesthetics is reduced with aging, so the anesthesiologist should exercise caution when repeat doses or continuous infusions of local anesthetics are administered to the elderly population.
Clinical Implications
Based on the information presented, the aging population will exhibit an enhanced sensitivity to the effects of local anesthetic agents. A greater than expected sensory level of blockade (when compared to the younger population) occurs following spinal as well as epidural anesthesia. Pharmacokinetic changes cannot fully justify the age-related changes to neuraxial anesthesia; as such, it is likely that the changes are more likely due to changes in pharmacodynamic alterations [73, 86]. These pharmacodynamic alterations may be due to a decrease in neuronal number in the central nervous system, deterioration of myelin, decreased conduction velocity in neurons, as well as altered anatomy of the spinal and intervertebral foramina that occurs with the aging process [73, 86]. It was initially demonstrated that the local anesthetic dose required to achieve segmental dermatomal blockade with epidural anesthesia progressively declined with age [87]. However, a subsequent study revealed that age minimally affects the number of dermatomes anesthetized with epidural anesthesia (using 1.5 % lidocaine with 1:200,000 epinephrine) [88]. Although not linear, the number of spinal segments that get blocked is linked to the total dose of epidural anesthetic administered. This may be due, in part, to initial filling of the epidural space when local anesthetic is injected in the epidural space, where the pressure is low; when additional volume is introduced, the resulting pressure increase causes local anesthetic to escape through the intervertebral foramina. This leakage through the intervertebral foramina may be part of the reason for prolonged anesthesia with potentially greater intensity. Therefore, a doubling of the anesthetic dose administered through the epidural space does not equate to doubling the number of spinal segments/dermatomes anesthetized. Notwithstanding, it is recognized that epidural dosing (i.e., volume) should be reduced in patients over 40 years of age [89].
On the contrary, the primary determinant of level achieved with spinal anesthesia is the baricity of the solution [73]. In the elderly, hyperbaric solutions have quicker onset and greater degree of spread (3–4 spinal segments) compared to younger patients; this effect is minimized with the use of isobaric solutions [73]. The hypotensive effects of neuraxial anesthesia exhibit a higher incidence in the elderly when compared to young patients because of decreased physiologic reserve, underpinned by altered cardiac capacity, structural and functional changes in the vascular system, and changes in the autonomic nervous system [56]. Given the increase in neuronal sensitivity mentioned earlier coupled with the increased potential spread of neuraxial local anesthesia in the elderly, the prevalence of hypotension is increased [73]. In addition, spinal anesthesia in elderly patients also results in a decrease of cerebral blood flow in elderly patients [90], whose organs are accustomed to increased perfusion pressures which potentially leads to danger [56]. Moreover, it has been documented that spinal anesthesia may cause increased episodes of cerebral desaturation, further exacerbating the effects of decreased cerebral blood flow [91]. Thus, the overall dose of local anesthetics and judicious use of sedative medications, which can further impact hemodynamic status of the aging population, should be decreased in the elderly in order to reduce the possibility of untoward effects.
From a pharmacokinetic standpoint , peak concentrations and protein binding of local anesthetics in plasma following a single injection are comparable in elderly and young patients [92–94]. However, following a single injection of local anesthetics in the epidural space, terminal half-lives are increased for bupivacaine and lidocaine, leading to a decrease in total plasma clearance as age increases [68]. This reduction in clearance plays an important role particularly during continuous infusions of local anesthetics, since increased plasma concentrations imply a need to reduce infusion rates and doses for top-ups in the elderly. Indeed, in elderly patients it has been previously shown that the concentration of free lidocaine was increased during continuous epidural anesthesia [95], necessitating the reduction and appropriate adjustment of epidural dosing in this age group. One would think that a reduction of epidural dose would affect the quality of anesthesia; however, this may not be the case since the increased neuronal sensitivity may compensate for the decreased dose [68]. The introduction of levobupivacaine (the isolated S(−)-enantiomer of a racemic mixture of bupivacaine) and ropivacaine into clinical practice has allowed for additional alternatives for regional (neuraxial) anesthesia. Notwithstanding the fact that levobupivacaine has a lower volume of distribution, marginally increased amount of protein binding, higher rate of clearance, and hence shorter half-life compared to the R(+)-enantiomer [96], it has similar potency and clinical attributes for neuraxial and peripheral nerve block techniques, but accomplishes this with a decreased risk of central nervous system toxicity and cardiovascular toxicity when compared to racemic bupivacaine [97, 98]. Similarly, ropivacaine also exhibits a high level of potency and lipid solubility, but decreases the risk of central nervous system toxicity and cardiovascular toxicity compared to bupivacaine. Basic science work has demonstrated that the doses of ropivacaine and levobupivacaine to cause seizures are higher than those required of bupivacaine [99]. In regards to cardiovascular toxicity, ropivacaine may demonstrate superiority since the doses of ropivacaine to cause arrhythmias and asystole in rats are larger than those required of both levobupivacaine and bupivacaine [99]. Hence, ropivacaine and levobupivacaine may be used for advantage in the elderly population. Again, it is important to remember that individual variability exists (particularly as patients get older, given the increased incidence of existing comorbid disease states), and thus it is necessary to carefully assess each patient prior to administering any anesthetic .
Peripheral Nerve Block
Peripheral nerve blocks can be used in the elderly to help reduce stresses of surgery and minimize the risks or POCD . As such, there are multiple options for peripheral nerve blocks that are appropriate for the elderly [100].
Anatomic and Physiologic Considerations
Landmarks requiring bony prominences are usually easily identified in elderly patients because of decreased lean mass and total body fat. However, arthritic changes can affect optimal positioning of the patient for regional anesthesia procedures, but this issue can often be overcome with proper padding and support of the head, pressure points, and extremities.
The primary concern regarding peripheral nerve blocks in the aging population is the effect of local anesthetics on neural structures. The changes to neural and perineural tissues associated with aging can affect the efficacy of the peripheral nerve block. For example, the number and diameter of myelinated fibers in both the ventral and dorsal roots decreases as age increases [101, 102]. Moreover, there are increased acceptor sites accessible to local anesthetics because of decreased distances between Schwann cells in myelinated nerves as a person gets older [101, 103, 104]. Furthermore, there is a decline of mucopolysaccharide composition in connective tissue sheaths that allows for increased local anesthetic infiltration of the nerves [101].
Neuronal sensitivity is also increased with age since there is a decrease in neuronal numbers as well as a slowing of peripheral nerve conduction velocity [103, 104]. Due to a decline in drug clearance, cumulative toxicity is a risk in elderly patients; thus, large doses as well as repeated doses should be administered with extreme caution if not avoided altogether. In addition, using ultrasound imaging, a reported reduction in minimum effective local anesthetic volume for supraclavicular brachial plexus block was observed in part due to smaller cross-sectional surface area of the brachial plexus in elderly patients [105].
As with any regional anesthesia technique, the local anesthetic agent of choice for a given peripheral nerve block is dependent on the length of time anticipated for surgery.
Clinical Observations
In a study by Paqueron et al., ropivacaine (20 mL of 0.75 %) utilized for brachial plexus block provided good analgesia in all patients (age range 27–81), but this dose had a faster onset and lasted longer in patients who were 70 years of age and older, demonstrating a relationship between age and drug sensitivity in peripheral nerve blocks [106]. Regional anesthesia for carotid endarterectomy may potentially avoid complications related to shunt use intraoperatively [107]. The effectiveness of comparable volumes (0.2 mL/kg of 0.75 % ropivacaine, 1 % ropivacaine, and 2 % mepivacaine) for cervical plexus anesthesia in the elderly undergoing carotid endarterectomy was studied [108]: all three local anesthetics are suitable choices, but both concentrations of ropivacaine provided longer postoperative pain relief than mepivacaine. In elderly patients administered femoral 3-in-1 nerve blocks, a 20 mL of bolus of 0.5 % of levobupivacaine or bupivacaine has been used successfully; in addition, 20 mL of 0.2 % bupivacaine followed by an additional 10 mL of 0.2 % bupivacaine has been used with success [98, 109].
Adjuvant Epinephrine
Epinephrine , through its vasoconstrictor ability, can be combined with local anesthetics to prolong the duration of anesthetic action as well as improve hemostatic conditions. For example, the addition of 1:400,000 epinephrine to 0.375 % bupivacaine (at a dose of 2 mg/kg) for femoral nerve block provided successful and long-lasting analgesia for hip and knee surgery [110]. However, one must exercise caution since there is a potential for ischemic neurotoxicity with the use of epinephrine [111].
Central Neuraxial Block (Spinal and Epidural Analgesia)
General Pharmacokinetic Considerations
It is important to appreciate the normal physiologic changes as patients age, since these changes will affect the actions of drugs at point of uptake, site of action, and with clearance. Very little metabolism of local anesthetics takes place in the epidural and subarachnoid spaces, so essentially the entire administered dose is absorbed into the circulation. Therefore, the rise in plasma concentrations of local anesthetics is important for the possibility of systemic toxicity. As mentioned earlier, the early absorption of local anesthetics administered via the intrathecal route is far slower than for those administered through the epidural route because of poor perfusion of the former relative to the latter. Although the absorption of bupivacaine, along with the total duration of epidural anesthesia, is minimally altered with aging, the absorption of hyperbaric bupivacaine when administered via the intrathecal route is shorter in older patients compared to the young because of a rapid second phase of absorption in older patients [61–68]. One may thus expect a diminished duration of action of spinal anesthetics in the elderly; however, this has not been definitively established.
Although there is an increase in plasma half-life of lidocaine in the aging population, peak plasma concentration is minimally affected by advancing age after a single dose epidural injection [81, 83, 93, 112, 113], suggesting that the dose of lidocaine administered through a single epidural injection need not be reduced. However, given the prolonged terminal half-life of lidocaine in the elderly, in combination with decreased systemic clearance, the accumulation of systemic lidocaine can happen with multiple single injections or continuous infusions through the epidural space [81, 95]. In regards to bupivacaine, both peak plasma concentration and time to achieve peak concentration following epidural injection are minimally affected by age [67]. On the other hand, increasing age may affect early absorption kinetics [114]. There is a prolonged terminal half-life of bupivacaine in elderly patients, and total plasma clearance is also decreased [67]. Intrathecal administration reveals a slow initial phase of absorption of bupivacaine into the systemic circulation, resulting in low peak levels in conjunction with a protracted time to achieve peak concentrations [62]. A multitude of factors may affect the systemic clearance of bupivacaine. These include a decrease in hepatic enzymatic activity, hepatic blood flow, and hepatic mass as people age. However, since bupivacaine has a low hepatic extraction ratio and minimal age-related changes for protein binding [94], the decrease in total plasma most likely stems from an alteration in the hepatic enzyme metabolic activity [68].
Epidural Anesthesia
Anatomic and Physiologic Considerations
Epidural analgesia has been demonstrated to improve recovery and the rehabilitation process following major surgery when compared to other techniques for analgesia [115, 116]. The technical aspects of epidural anesthesia are often more difficult than spinal anesthesia and can cause additional duress since there is enhanced risk of nerve injury given the relatively larger size of epidural needle as well as attempting placement at higher intervertebral levels. Notwithstanding, a satisfactorily placed epidural catheter offers excellent perioperative analgesia [117–120].
An aging patient can affect the ability of the anesthesiologist to perform adequate epidural anesthesia. For example, patient positioning for regional anesthesia becomes progressively more challenging with increasing age. Although many would argue that landmarks requiring bony structures for neuraxial anesthesia are more prominent in the aging population, calcification of spinal ligaments and the existence of osteophytes can be problematic for the ease of needle entry into the epidural and intrathecal spaces. To assist in overcoming this issue, a paramedian or lateral approach has been advocated for epidural and spinal anesthesia in the aging population [89].
In addition, the structures outlining the intervertebral foramina develop an increased density and firmness with advancing age; this reduces the overall volume of the epidural space, which in turn results in a higher spread of local anesthetic in the cephalad direction following injection in the epidural space [101, 121, 122]. This consequence is worsened by certain comorbidities, such as atherosclerosis and diabetes, which can cause premature and accelerated aging [123]. Additionally, a rapid onset of epidural blockade with local anesthetics can be seen with advanced age, which may be due in part to increased dura permeability as well as enlarged arachnoid villi [101, 124]. Although it has been suggested that age minimally affects the level of anesthesia with epidural blockade, it is still recommended to reduce overall dose of local anesthetics in the elderly, since this population is at increased risk of developing unwanted side effects such as hypotension [125]. Moreover, large volume injections of local anesthetics in the epidural space in elderly patients have been connected to cauda equina syndrome in the setting of spinal stenosis. As well, extended duration of epidural anesthesia in elderly patients has been linked to neurologic derangement from cauda equina syndrome [126, 127].
Clinical Observations
Local anesthetic choice for epidural anesthesia and analgesia usually depends on the duration and type of surgery. Short-acting agents, such as procaine and chloroprocaine are suitable for procedures of short duration (i.e., 30–90 min); lidocaine, prilocaine, and mepivacaine are appropriate for procedures of intermediate duration (i.e., 60–90 min); for more prolonged procedures (i.e., 180–360 min), tetracaine, bupivacaine, and ropivacaine are indicated [100]. A study investigating the onset and duration, as well as quality of postoperative analgesia, of epidural anesthesia administration has been completed in elderly patients undergoing total hip arthroplasty [97]. The authors compared 0.125 % levobupivacaine, 0.125 % racemic bupivacaine, and 0.2 % ropivacaine, and found that all three solutions provided sufficient analgesia necessitating similar volumes (5 mL/h baseline infusion rate) with the incidence of hypotension not differing between the groups. Another study investigated the extent of motor blockade with ropivacaine and the effects of age: with the same amount of local anesthetic administered, the extent of motor blockade increases as age increases [128]. Along those lines, an epidural saline washout technique has been described in elderly patients following transurethral surgery: epidural washout with 30 mL of saline facilitates the regression of both motor and sensory blockade without affecting postoperative analgesic benefit [129]. The pharmacologic properties of prilocaine and lidocaine are similar, and it has been suggested that 1 % prilocaine at a dose of 150 mg is a safe and reliable choice for epidural anesthesia for transurethral resection of the prostate in males over 60 years of age [130]. In addition to improving pain profiles, the use of epidural anesthesia in cardiac surgery has also been suggested to confer benefit, including improving cardiac performance, decreasing release of markers for cardiac damage, and shorter length of stay in the intensive care unit postoperatively [131, 132].
Adjuvant Epinephrine
Local anesthetic duration of action can be enhanced with the addition of 1:400,000 to 1:200,000 epinephrine, as has been documented with lidocaine and 2-chrloroprocaine [133]. Epinephrine also provides some additional analgesia to the local anesthetic mixture by activating central α2-adrenoreceptors. Epinephrine can, however, augment the drop in blood pressure and rise in cardiac output that can be seen with lidocaine use for epidural anesthesia [134]. Fortunately, increasing age does not appear to exacerbate this consequence. Indeed, it has been suggested that the reduction in systolic blood pressure observed with the addition of epidural epinephrine is less prominent with advancing age, and there is also an increase in the dose necessary to cause a rise in heart rate [135, 136]. This may pose an issue when a test dose utilizing epinephrine is used to assess epidural catheter placement: the anesthesiologist should be aware that a small deviation in heart rate may indicate that the tip of the epidural catheter may still in fact have an intravascular placement, particularly since there is already an upregulation of the autonomic nervous system in the elderly (i.e., an overt increase in heart rate may not be readily observed) [56].
Adjuvant Opioids
Low-dose preservative-free opioids can be added to local anesthetic solutions used for epidural analgesia. Due to enhanced central nervous system depressant effects of opioids in the elderly, caution must be exercised with the use of opioids in epidural anesthesia, with a reduction in the total dose of opioid used [137, 138]. It has been suggested that up to a 50 % reduction in epidural bolus injection and continuous infusion rates would be sensible when epidural opioids are delivered to the elderly [73]. In total hip arthroplasty, ropivacaine 0.1 % combined with 0.5–1 μg/mL sufentanil has provided very good analgesia in the elderly [139–141]. Bupivacaine 0.125 % administered as a constant epidural infusion (4 mL/h) in combination with either 0.05 or 0.005 mg/ml has also been used successfully for postoperative analgesia following total hip arthroplasty [142]. Although not in the opioid class, epidural ketamine (40 mg bolus injection followed by 2 mg/mL) in combination with bupivacaine 0.125 % has been used successfully in the elderly population [143]. However, when compared to epidural morphine, the use of epidural ketamine resulted in less sedation and postoperative nausea and vomiting, pain scores were higher suggesting a possible need for increased amounts of ketamine to achieve a similar analgesic effect to epidural opioids [143].
Spinal Anesthesia
Anatomy and Physiological Considerations
Spinal anesthesia can be used for surgeries of the lower body, including gynecologic, vascular, orthopedic, and urologic procedures. Despite its technical straightforwardness and general effectiveness, risks and complications are still possibilities when this technique is used in the aging population.
As mentioned earlier, positioning of patients as well as spinal needle target localization can pose some difficulties in elderly patients. Changes to neural tissues, including anatomic changes to the spinal column, will affect the pharmacokinetic properties (absorption, distribution) and resultant duration of action of local anesthetics. Total cerebral spinal fluid volume is decreased, whereas cerebrospinal fluid specific gravity is increased [68]. With bupivacaine (both hyperbaric and isobaric), there may be a quicker onset and a greater degree of spread than in younger patients [89]. However, inconsistencies have been identified between studies correlating age with spread of anesthesia following subarachnoid injection of local anesthetic because of differences in the types of local anesthetic as well as the varying doses used and the baricity of the solution used [68]. Studies investigating the characteristics of blockade with hyperbaric tetracaine are inconsistent [144–146], while others suggest that subarachnoid administration of hyperbaric bupivacaine and mepivacaine has widespread distribution throughout the spinal levels in comparison to glucose-free bupivacaine [147–150]. These discrepancies can be attributed, in part, to the alteration of cerebrospinal fluid volume and baricity in combination with the altered anatomical configuration of the spine with advancing age. High spinal anesthesia can be problematic in the elderly, since large decreases in blood pressure of up to 30–40 mmHg and bradycardia can occur with this anesthetic technique [89]. Hence, the need for vigilant monitoring of this patient population is essential. Nevertheless, blockade of up to the T10–12 dermatomes for operations on the lower abdominal or inguinal areas of patients of advanced age can be achieved with the use of hyperbaric as well as glucose-free bupivacaine.
Clinical Observations
Although spinal anesthesia results in hypotension, it may provide better hemodynamic stability compared to general anesthesia in American Society of Anesthesiologists Class III elderly patients [151]. Previous meta-analysis also suggests that spinal anesthesia has consistent evidence of benefit for elderly patients with hip fractures [152]. Despite this established benefit, the optimal effective and safe dose of glucose-free bupivacaine remains controversial [147, 149, 153]. Spinal anesthesia results in a biphasic response to changes in cardiac output, with an initial increase in cardiac output followed by a reduction below baseline [154]. Doses less than 10 mg have been suggested to be used in older patients to reduce the occurrence of hypotension [155] although moderate amounts of hypotension (37.5 and 25 % reduction in blood pressure) still occurred when 5 mg [156] and 7.5 mg [157] of bupivacaine were used. To combat hypotension, prophylactic intramuscular administration of glycopyrrolate has been shown to be beneficial in the elderly [158]. Ropivacaine administered at a 5 mg dose in the subarachnoid space has shown effectiveness for total hip replacement in both young and elderly patients [159]. Ropivacaine administered at other dosages and baricities has proved satisfactory in older patients undergoing total hip arthroplasty (isobaric ropivacaine 7.5 and 10 mg/mL) [160], transurethral resection of the bladder or prostate (isobaric ropivacaine 0.3 %, 15 mg) [161], and lower abdominal or lower limb surgery [162, 163]. Hyperbaric tetracaine (administered at a dose of 8 mg), with its long duration of action, has also been used for spinal anesthesia for transurethral resection of the prostate [164]. Lidocaine provides a quick onset as well as a quick regression of spinal blockade when administered in the subarachnoid space [165]. However, there is concern over intrathecal lidocaine and its association with transient neurological symptoms, which has influenced many anesthesiologists to utilize alternative local anesthetic agents as their primary choice. Prospective randomized trials have revealed an incidence of transient neurological symptoms with intrathecal lidocaine to be somewhere between 5 and 40 % [166–171], although the etiology behind this phenomenon remains uncertain [172, 173].
Small, incremental amounts of local anesthetics can be introduced if there is an intrathecal catheter in place. Moreover, continuous spinal anesthesia with an intrathecal catheter allows for the titration of local anesthetics to achieve the appropriate levels of blockade while minimizing hemodynamic fluctuations, which can be very useful in the aging population [174–176]. This technique and its safety in practice has been called into question because of reports of harmful neurologic effects, such as cauda equina syndrome, as the use of microcatheters has been associated with this untoward outcome. In elderly patients, hyperbaric solutions did not appear to be a factor in the development of poor distribution of the local anesthetic—what appeared to be the primary factor was the caudal orientation of the catheter tip rather than its route of travel or position in regards to spinal level [177]. Therefore, the anesthesiologist should exercise caution if he or she plans to utilize continuous spinal anesthesia, since it would be difficult to predict and in fact control the manipulation of the catheter to ensure that the catheter tip is in an advantageous position (i.e., to avoid improper distribution of local anesthetic), even in the absence of microcatheter use or avoiding the use of hyperbaric local anesthetic solutions.
Adjuvant Epinephrine
Intrathecal adjuvants can provide additional analgesia and increase the duration and effectiveness of local anesthetic administration for spinal anesthesia. Although there is a lack of consistency regarding clinical benefit, epinephrine at typical doses ranging from 1:400,000 to 1:200,000 are often used [178–180]. Nonetheless, varying amounts of adjuvant intrathecal epinephrine have been demonstrated to be effective in prolonging the duration of isobaric bupivacaine (dose of 15 mg) anesthesia in elderly patients [181]. Alternatively, the α2-adrenergic receptor agonist clonidine can prolong the duration of spinal anesthesia while decreasing the dose of local anesthetic required to achieve anesthesia and being able to provide some analgesia itself (given its α2-adrenergic receptor agonism) [165, 182]. For instance, intrathecal clonidine (dose of 100 μg), when added to 40 mg of 2 % lidocaine, can provide adequate spinal anesthesia with minimal hemodynamic perturbations in patients aged 50–70 years for surgical procedures such as hysterectomies, open prostatectomies, or surgical correction of fractured hips [182].
Adjuvant Opioids
An alternative adjuvant for local anesthetic administered through the subarachnoid space is the use of an opioid. Opioids have a potent synergistic effect with local anesthetics, so the probability of achieving success with the spinal anesthetic is enhanced while reducing the risk of hypotension. Fentanyl, at a dose of 20–25 μg, when added to bupivacaine at low doses (i.e., 4 mg) can provide adequate anesthesia for older patients undergoing transurethral resection of the prostate as well as surgical repair of a hip fracture with fewer side effects when compared to bupivacaine if it alone was administered [157, 183]. Similar effects were achieved with the use of adjuvant sufentanil (5 μg) when administered intrathecally in combination with low-dose bupivacaine in the elderly undergoing repair of hip fractures [184]. Similarly, the addition of 10 μg of fentanyl to 4 mg of hyperbaric tetracaine provided adequate anesthesia with a decrease in side effects compared to a conventional tetracaine dose of 8 mg in elderly patients undergoing transurethral resection of the prostate [164]. In regards to longer acting opioids, an intrathecal dose of 0.1 mg of morphine has been safely used in elderly patients undergoing total hip arthroplasty, with excellent postoperative analgesia [185]. In addition, although not in the opioid family, intrathecal S(+) ketamine (0.1 mg/kg) has also been used successfully in transurethral resection of the prostate in elderly males [186].
Conclusion
Given the increasing life expectancy in today’s society, it is no wonder that geriatric medicine is gaining importance in all disciplines of clinical medicine including anesthesiology. The normal processes of aging affects multiple organ systems, not only anatomically but also physiologically. The caveat is that safe practice of regional anesthesia for the aging population requires modification of regional anesthesia techniques as well as generalized reduction in dosing of many of the anesthetic agents used to achieve a good effect. Additionally, elderly patients are at risk for negative perioperative outcomes, so adequate monitoring (as dictated by their overall health) and vigilance in the care of these patients are mandatory. The information presented in Tables 17.1 and 17.2 are based on available literature as well as the authors’ own experiences so the reader is cautioned when using these dosages in his or her own practice. The doses presented here are intended to be used as guidelines; therefore, the agents in question should be titrated by the anesthesiologist according to the patient’s individual needs and conditions. Nonetheless, excellent regional anesthesia can certainly be provided to the elderly patient in efforts to optimize patient safety, comfort, and satisfaction during the perioperative period.
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Gragasin, F.S., Tsui, B.C.H. (2017). Local and Regional Anesthesia in the Elderly. In: Finucane, B., Tsui, B. (eds) Complications of Regional Anesthesia. Springer, Cham. https://doi.org/10.1007/978-3-319-49386-2_17
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