Anesthesia for Hip Replacement

Abstract

The improvement of surgical and anesthesia techniques has markedly extended the range of patients undergoing hip replacement both in terms of age and comorbidity. Hence, the risk of perioperative complications has increased ranging from hemorrhages, postoperative delirium, incomplete pain control, hypotension, and others. In this regard, a personalized approach from the preoperative evaluation to the choice of the type of anesthesia and the pain control strategy is preferred in order to minimize the risk of complications and accelerate patient’s recovering time. In this chapter, we aim to describe different options and propose different possible approaches for the possible scenarios in the light of the existing evidence in the field.

1. Introduction

Total hip replacement is one of the most widespread and invasive orthopedic procedures worldwide [1]. In 2007, in the United States, 300,000 surgeries were performed. In the same year, from 50 up to 250 replacements for 100,000 people were carried out in Europe [2]. Total hip replacement has been performed since the 1970s, and upon an appropriate selection of patients, it significantly improves the quality of life by relieving the pain and functional disability experienced by patients with moderate-to-severe arthritis of the hip [2]. Moreover, it is a highly cost-effective procedure [3]. The main indication for surgical treatment remains osteoarthritis, which is particularly disabling among the elderly and obese patients who represent the most prevalent candidates. The other most common indications are:

• primary hip’s arthrosis

• rheumatoid arthritis or seronegative autoimmune forms

• femoral epiphysis aseptic osteonecrosis

• post-traumatic arthrosis (results of fractures-dislocations of the femur and/or pelvis)

• secondary arthrosis (associated either with congenital hip dysplasia or with epiphysiolysis or septic arthritis)

• femoral neck’s subcapital fractures

Notably, apart from fractures, surgery is, however, recommended only in the event that one of the mentioned pathologies is present in association with severe pain or stiffness that limits daily activities, such as walking, getting up or sitting down, and dressing. Hip prostheses have been performed successfully at all ages, from the young adolescent with juvenile arthritis to the elderly patient with degenerative osteoarthritis [4]. Most of the patients undergoing total hip replacement are between the ages of 50 and 80. However, there is no absolute age or weight limitation for the prosthetic surgery of the hip. The duration of the implants should also be considered; although it has been estimated that roughly 58% of hip replacements will last 25 years [5], their lifespan may markedly vary depending on several factors, being obesity the major cause of a minor longevity of the prosthesis. The indication for surgery is given on the basis of the pain reported by the patient as well as in relation to the degree of disability.

2. Preoperative evaluation

2.1 General considerations

According to the guidelines provided by the European Society of Anesthesia and Intensive Care (ESAIC) for noncardiac surgery, patient’s eligibility for surgery should not be based exclusively on strict criteria related to surgery indication, patient’s age, weight, and comorbidity, but it is the result of patient’s multidimensional assessment with the aim to evaluate the patient’s capacity to face and recover from surgery and anesthesia. Such assessment includes the evaluation of the presence and the degree of severity of cardiovascular and respiratory diseases, smoking habit, obstructive sleep apnea syndrome (OSAS), kidney diseases, diabetes, obesity, liver diseases, and alcohol abuse [6]. The assessment of the American Society of Anesthesiologists (ASA) physical status classification system and patient’s functional capacity, expressed in terms of metabolic equivalents of task (METS) used to assess energy cost for physical activities or exercise capacity, are two pivotal tools in the evaluation of all patients but may not be sufficient [7, 8]. Interestingly, although the absolute risk for 90-day mortality following total hip replacement is small, a significant increased relative risk has been reported for patients with osteoarthritis younger than 60 and without comorbidity when compared with subject with the same characteristics not undergoing hip surgery [9]. Such increased risk disappears in the long term. On the contrary, there is no increased risk for mortality both in the short and long terms for patients older than 60 and with mild-to-severe comorbidity burden [9]. Such findings indicate that although total hip replacement is a low-risk procedure, it still imposes a risk that becomes most evident in patients with a low baseline mortality risk. The increased relative risk among patients who are young or with a good preoperative prognostic profile may reflect patient-related factors, such as obesity, which may be associated with both the development of osteoarthritis at a young age and an increased procedure-related risk of adverse outcome, including death, as well as system-related factors that might include a lower level of awareness by health professionals toward the prevention, detection, and treatment of thromboembolic complications in patients considered to have a low risk. In addition, relevant comorbidities associated with an increased risk of postoperative mortality, such as liver disease [10], may be undiagnosed in young patients and lead to an inaccurate estimate of the patient’s general conditions. Another possible explanation may be the fact that any surgical procedure carries a risk, which, added to a small baseline risk in these patients, results in a high relative mortality.

In conclusion, a systematic preoperative multidimensional assessment of patients undergoing hip replacement should be routinely adopted to detect unrecognized disease and risk factors that may increase the risk associated with the surgical procedures and/or anesthesia techniques above baseline and to propose strategies to reduce this risk.

2.2 Cardiovascular disease

According to the guidelines of the American College of Cardiology (ACA)/American Heart Association (AHA) Task Force, surgical interventions can be classified into three categories according to the risk associated with the procedure itself [11]:

• High risk: major surgery in urgency, especially in the elderly, aortic and peripheral arterial vascular surgery, prolonged surgical procedures, and/or associated with significant volume changes.

• Intermediate risk: carotid thromboendarterectomy, thoracic and abdominal surgery, head and neck surgery, orthopedic procedures, and prostate surgery.

• Low risk: endoscopic procedures, surface surgical procedures, cataract surgery, and breast surgery.

Similarly, patients can be stratified in three categories based on the presence of risk factors for perioperative complications:

• Major risk factors: unstable coronary syndromes, acute myocardial infarction (<30 days) with clinical or instrumental evidence of residual ischemia, unstable or disabling angina, heart failure with acute pulmonary edema, severe valvopathy and arrhythmias, atrioventricular block (Mobitz 2 > 2: 1; complete atrioventricular block), and supraventricular arrhythmias with uncontrolled ventricular response.

• Intermediate risk factors: stable or controlled angina, previous myocardial infarction, compensated heart failure or previous heart failure, and diabetes mellitus.

• Minor risk factors: advanced age, abnormal electrocardiogram (ECG) (left bundle branch block, left ventricular hypertrophy, repolarization’s abnormalities, nonsinus rhythm), reduced functional capacity, previous cerebral infarction, and arterial hypertension not controlled by medical therapy or not treated.

The recommendations provided by the AHA/ACC and the ESAIC can be schematically summarized for patients undergoing elective hip replacement as follows: patients with major risk factors require immediate cardiological evaluation, which, in most cases, will lead to myocardial revascularization, valve surgery, or modification of current medical therapy. In this case, the surgery can only be postponed unless it is considered an emergency and, therefore, undelayable. Patients with intermediate risk factors can undergo elective surgery without additional investigations if their functional reserve is at least moderate, and the proposed intervention is at (low or) intermediate risk such as hip replacement. The use of the risk calculator of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) is a recommended tool for cardiac perioperative risk stratification. In addition, the assessment of high-sensitivity cardiac troponins in high-risk patients 48 hours before and 72 hours after major surgery is recommended to detect preexisting or postoperative cardiac failure [12]. Therapy with beta blockers should be continued throughout the perioperative period, mostly in patients who have known ischemic heart disease or myocardial ischemia. In patients treated with acetylsalicylic acid, the discontinuation of the therapy should be considered in the perioperative period and should be balanced among the risk of bleeding and the risk of thrombotic complications. For patients undergoing hip replacement, the execution of a baseline electrocardiogram (ECG) in the preoperative period should be mandatory. In the case of patients belonging to the minor-risk class of cardiovascular risk (i.e., elderly patients and patients with a traumatic femur or pelvis fracture) with indication for hip replacement, prolonged monitoring outside the operating room (recovery room/ICU) is strongly recommended, as a good clinical practice to reduce the overall postoperative risk.

2.3 Respiratory disorders

Since chest radiograph rarely alters the perioperative management, it should not be included among the routine investigations. Similarly, spirometry is not recommended as a preoperative routine examination in all patients affected by respiratory problems. On the contrary, patients with obstructive sleep apnea syndrome (OSAS) should be evaluated carefully for potentially difficult airway in the need of ventilatory support or endotracheal intubation. History of previous surgical procedures and referred difficult airway should be investigated especially in patients with diagnosed or suspected OSAS. The use of specific questionnaires to screen for patients with OSAS is recommended when polysomnography (gold standard) is not available. In particularly, among others, the STOP-BANG questionnaire is the most sensitive, specific, and best validated score [13]. Perioperative continuous positive airway pressure (CPAP) must be continued in patients with OSAS to reduce hypoxic events. Moreover, patients with suspected or diagnosed OSAS receiving sedative or general anesthesia during or before surgery should be monitored in the immediate postoperative phase. Of note, stop smoking at least 4 weeks prior to surgery reduces postoperative complications [14].

2.4 Management of antiplatelets/anticoagulant drugs

The perioperative management of anticoagulant therapy is cumbersome due to the complexity of the issue, as well as the simultaneous need to balance the risk of bleeding and the risk of thromboembolic events. On the one hand, surgery should be performed when coagulation is almost normalized to limit the risk of bleeding complications from excessive anticoagulation both during surgery and in the postoperative period. On the other hand, it is necessary to limit as much as possible the interval between the suspension and the restoration of the anticoagulant therapy in order to avoid thromboembolic complications.

A rational approach to the management of anticoagulant therapy should be multidisciplinary and involves the other specialists aiming to carefully evaluate the rationale of the ongoing therapy, the risk of bleeding related to the specific surgical procedure, and the risk of the patient to develop thromboembolic or hemorrhagic events during the complete or suboptimal anticoagulation therapy in the perioperative phase. Taken all together, the final decision should also consider all the therapeutic tools available that are able to modify the coagulation cascade in relation to the specific clinical context [15, 16, 17, 18]. Many patients undergoing total hip replacement are on antiplatelet therapy, generally, with low-dose acetylsalicylic acid, ticlopidine, or clopidogrel, more rarely with dipyridamole, indobuphene, or picotamide monohydrate. As for beta blockers, acetylsalicylic acid should be continued in the perioperative period, and its use is associated with a lower incidence of myocardial ischemia in the absence of a substantial increase in surgical bleeding [15]. In general, for medium- and high-risk procedures, clopidogrel should be routinely stopped 7 days before surgery with an exception for patients at high risk of thromboembolic events in whom an interval of 5 days before surgery is recommended and, if available, a platelet function test should be performed to evaluate an adequate platelet function. However, the ACC/AHA Task Force suggests that hip replacement surgery can be safely performed without stopping clopidogrel perioperatively [19]. Ticlopidine is the antiaggregant of choice in patients that are intolerant and/or allergic to acetylsalicylic acid. The antiplatelet effect persists for over 8 days after stopping the drug. The management of ticlopidine therapy in the perioperative period is not codified. For elective hip surgery, it is recommended to discontinue ticlopidine therapy, whereas for emergency procedures, in the case of significant bleeding risk, it would be preferable to perform a platelet transfusion of platelet concentrates [20, 21]. In view of the limited number of relevant publications, it is difficult to release recommendation regarding the perioperative management of antiplatelet therapy with dipyridamole, indobufen, and picotamide. Although some cases of epidural hematoma after locoregional anesthesia have been described in patients receiving acetylsalicylic acid or nonsteroidal anti-inflammatory drugs, the incidence of this complication does not appear to be significantly increased in patients treated with antiplatelet drugs [22, 23]. According to the existing knowledge, locoregional anesthesia is considered suitable for patients on antiplatelet therapy [15, 24]. Similar conclusions may not be drawn for ticlopidine because there is not yet sufficient evidence in the literature. Regarding patients treated with low-molecular-weight heparin (LMWH), heparin should be suspended based on the dosage administered depending on its use as prophylaxis or therapeutic of thromboembolic events. For hip replacement surgery, a 12-hour interval before surgery is recommended when LMWH is used at prophylactic dose. Noteworthy, when a therapeutic dose of enoxaparin (1 mg/kg) is used, a 24-hour interval is recommended. The LMWH can be generally resumed at least 12 hours after hip replacement surgery. The new oral anticoagulants (NAO or DOAC) are a recent class of drugs that act by selectively inhibiting a single coagulation factor, either II or X (Table 1), unlike the antivitamin K antagonists (AVK) Warfarin and Acenocoumarol, which act on several factors at the same time (VII, II, IX, and X). DOACs have been introduced into clinical practice for the prevention of stroke and systemic thromboembolism in patients with atrial fibrillation and for the prevention and treatment of venous thromboembolism. Currently, the DOACs approved by the European Medicines Agency (EMA) on the market are the following:

	Dabigatran	Rivaroxaban	Apixaban	Endoxaban
Mechanism of action	Direct,reversible inhibitor of free anc clot-bound thrombin	Direct, reversible inhibitors of free and prothrombinase bound factor Xa
Bioavailability	3–7%	80–100%	50%	62%
Protein binding	35%	92–95%	87%	55%
Primary clearance	80% renal	67%renal	56%fecal	50%renal
Tmax	1.5–3 hours	2–3 hours	3–4 hours	1–2 hours
Half-life*	12–14 hours	5–13 hours	12 hours	10–14 hours

Table 1.

Mechanisms of action and characteristics of new oral anticoagulants.

Abbreviation: Tmax, time to peak drug concentration after dose.

*Half-life varies with renal function, with increasing half-life, with increased renal impairment.

• Dabigatran etexilate: anti-IIa.

• Rivaroxaban: antiXa.

• Apixaban: antiXa.

• Edoxaban: antiXa.

Table 1summarizes the mechanisms of action of DOACs. Table 2 reports the withdrawal times in relation to surgery and renal function.

Creatinine clearance	Dabigatran		Apixaban-Rivaroxaban-Endoxaban
	Low risk surgery	High risk surgery	Low risk surgery	High risk surgery
> = 80 mL/min	> = 24 hours	> = 48 hours	> = 24 hours	> = 48 hours
50-80 mL/min	> = 36 hours	> = 72 hours	> = 24 hours	> = 48 hours
30-50 mL/min	> = 48 hours	> = 96 hours	> = 24 hours	> = 48 hours
15-30 mL/min	Not indicated	Not indicated	> = 36 hours	> = 48 hours

Table 2.

Summary of withdrawal time of new oral anticoagulant stratified by renal clearance and type low versus high risk surgery.

2.5 Patient blood management and preoperative blood conservation strategies

Anemia is frequent among patients undergoing hip replacement, and its prevalence has been estimated to be up to 25% in patients undergoing hip surgery and markedly increased in the postoperative [25, 26]. The main causes of preoperative anemia are summarized in Table 3. Preoperative anemic patients are more likely to receive allogeneic blood transfusions than nonanemic patients. It has been suggested that preoperative anemia and increased blood transfusion rates were independently associated with an increased risk of perioperative adverse outcomes, such as increased postoperative infections, increased hospital length of stay, and increased mortality [27]. Large variability in clinical practice in patient blood management in major orthopedic surgery has been described despite orthopedic surgery is one of the field with the greatest tradition in these programs [26]. Moreover, among patients with anemia, the currently available evidence does not support the use of liberal red blood cell transfusion thresholds based on a 10 g/dL hemoglobin trigger in preference to more restrictive transfusion thresholds based on lower hemoglobin levels or symptoms of anemia in patients undergoing hip fracture surgery [28]. However, criticism on the randomized clinical studies on blood transfusion threshold has been raised regarding the study design and the fact that the decision to transfuse should not be based only on hemoglobin concentrations [29]. Moreover, recent studies using sublingual microcirculation monitoring have shown that in critically ill patients with microcirculatory impairment, blood transfusion is able to improve the microcirculation regardless of hemoglobin levels [30, 31]. On the contrary, among patients with normal microcirculation, there are no changes regardless of hemoglobin concentration [30, 31]. Finally, the treatment of preoperative anemia with iron, with or without erythropoietin, and perioperative cell salvage has been reported to decrease the need for blood transfusion [27].

Insufficient iron intake	Malnutrition, vegetarian diet, vegan diet
Reduced absorption	Gastrectomy,
	Duodenal bypass, bariatric surgery
	H.p. infection, celiac disease
	Atrophic gastritis,
	Inflammatory bowel disease
Chronic blood loss	Gastrointestinal benign and malignant lesions,
	Drugs (salicylates,nonsteroidal anti-inflammatory drugs, corticosteroids)
	Chronic inflammatory bowel diseases
	Polymenorrhea, bladder polyposis
	Congenital hemorrhagic telangiectasia
	Periodic blood donation
Other conditions	Chronic renal failure, heart failure

Table 3.

Main cause of anemia in patients undergoing hip surgery.

A patient blood management protocol should be adopted in each center and updated regularly. Where feasible, patients programmed for elective surgery should receive a blood count no more than 30 days before surgery, and anemic patients should be referred to the specialist to investigate and treat anemia. The reports of the blood chemistry tests and martial balance are the most common tests for the evaluation of preoperative anemia. The dosage of ferritin, transferrin saturation, and sideremia allow, together with the complete blood count, to make a differential diagnosis of anemia and to personalize the preoperative therapy. Figure 1 shows a proposed protocol for patient blood management in the preoperative phase.

Figure 1.

One of the possible protocols to adopt in the preoperative evaluation of patients undergoing hip surgery inside a patient blood management program.

For the treatment of anemia, there are both intravenous (IV) and oral preparations. Iron sulfate, iron gluconate, and ferric carboxymaltose are the most common in use. Ferric carboxymaltose is usually preferred since it penetrates the bone marrow faster than the other preparation and more rapidly raises the level of serum hemoglobin. This preparation is for intravenous administration only (Table 4).

Hb g/dl	Patients with body weight between 35 Kg and < 70 Kg	Patients with body weight > 70Kg
<10	1500 mg	2000 mg
>/= 10	1000 mg	1500 mg

Table 4.

The cumulative dose of ferric carboxymaltose to be administered on the basis of body weight and hemoglobin levels.

The erythropoiesis stimulating agents (erythropoietin) represents another therapeutic strategy in the patient blood management. The most important indication for the use of erythropoietin perioperatively is the optimization of autologous donation, when indicated or to reduce exposure to allogeneic blood transfusions in adult patients undergoing major elective orthopedic surgery who are at high risk of massive transfusion or for whom a predeposit autologous donation is not available and a blood loss of more than 1000 mL is expected. There are two possible schemes for the use of erythropoietin:

• DIAGRAM 1: Erythropietin 600 U/kg (40.000 U) weekly on days: −21, −14, −7, and on the day of surgery

• DIAGRAM 2: Erythropoietin 300 U/kg (20.000 U) daily from day −10 to day +4 of the surgery.

2.6 The geriatric patient

With the aging of the population and the improvement of surgical and anesthesia techniques, the prevalence of elderly patients undergoing hip replacement is growing. In this scenario, the assessment of the functional status become essential, preferably through comprehensive geriatric measures to identify patients at risk and/or to predict postoperative complications. It is strongly recommended to assess the level of independence using validated tools such as basal and instrumental activities of daily living. Comorbidities and multiple morbidities become more frequent with aging and are related to increased postoperative morbidity and mortality. It is very useful to assess multiple morbidities using age-adjusted scores, such as the Charlson comorbidity index [32, 33]. Elderly patients also take various combinations of drugs (mainly anticholinergics or sedative-hypnotics) increasing the risk of pharmacological interactions with other drugs administered during the hospital admission such as sedative, analgesic, etc. Moreover, these multiple associations often induce unwanted symptoms such as fatigue, anxiety, and delirium, increasing perioperative mortality [34]. It is recommended to consider appropriate perioperative drug adjustments by systematically performing the BEERS Criteria for the evaluation of multiple preoperative therapy [35]. Cognitive impairment and depression are common and often underestimated. They can affect patients’ ability to understand, thus hindering the full comprehension of the informed consent. The multidimensional geriatric evaluation and teamwork with orthopedics and geriatrics is fundamental. Sensory impairment weakens communication and is associated with postoperative delirium (POD). The assessment of sensory disability should be performed, and the time spent in the perioperative setting without sensory aids should be minimized. Furthermore, malnutrition is relatively common in the elderly, and its impact is often an underestimated factor leading to complications [36]. Malnutrition may also coexist with obesity, further increasing the negative impact on prognosis. Moreover, obesity is associated with an increased risk of kidney damage [37]. The assessment of the nutritional status is very important in order to reduce the duration of hospitalization and shortening the recovery time and must be performed in patients at risk before invasive maneuvers are performed. Finally, as fragility is a known state of extreme vulnerability, frailty assessment in a structured and multimodal way such as the Fried Score or the Edmonton Frailty Scale, avoiding single surrogate measurements, is also strongly recommended.

2.7 The obese patient

Obesity is associated with metabolic alteration and promote organ failures that should be investigated during the preoperative evaluation. In the preanesthesia evaluation of the obese patients, the evaluation of the airways is among the most important aspects. In addition to the classic Mallampati scale, the evaluation should also include the STOP-BANG questionnaire [13]. Oximetry and/or polysomnography are second-level exams in the overall assessment of OSAS. A neck circumference of at least 43 cm and a high Mallampati score are predictors of both difficult intubation and ventilation. The use of perioperative CPAP is strongly recommended to reduce respiratory complications after surgery.

3. Intraoperative management and anesthesia techniques

3.1 General considerations

There are several validated and safe anesthesia strategies for total hip replacement. In particular, hip replacement represents a challenge for the anesthesiologist who would practice a “tailored” technique, always evaluating the ratio between risk and benefits.

3.2 Monitoring fluid and transfusion administration

All anesthesia techniques may undergo complications. Patient monitoring cannot prevent all adverse events, but there is clear evidence that its application reduces perioperative risks [38, 39]. Total hip replacement surgery can be performed either under general or locoregional anesthesia, and the monitoring must clearly follow standards. All patients should receive electrocardiographic tracing, pulse oximeter, and frequency monitoring. Blood pressure can be reached by noninvasive measurement every 3–5 minutes, otherwise by different interval according to the clinician’s opinion [40]. Additional monitoring such as invasive blood pressure, echocardiography, central venous pressure, cardiac output, or other derivative parameters can be adopted in high complexity patients [40, 41]. During general anesthesia and deep sedation, patient’s ventilation must be monitored continuously by capnometry in order to confirm a correct ventilation, wherein signs such as respiratory excursions, respiratory rate, and chest auscultation can integrate instrumental monitoring. Although often patients undergoing hip replacement surgery are in spontaneous breathing, capnometry can be used in these cases. Patient’s body temperature should also be monitored during anesthesia or sedation in order to minimize patient’s discomfort and risk of bleeding. Temperature monitoring and active control systems should be systematically used either in subjects particularly vulnerable to the risk of unintentional hypothermia, such as children and elderly, or during long-lasting procedures with extensive tissue exposure [41]. When neuromuscular blockers are administered, a peripheral stimulator must be available for the monitoring of neuromuscular transmission, and the resumption of normal activity must be measured by the train-of-four (TOF) monitoring. In the last 15 years, specific brain monitoring systems have been introduced into clinical practice. They are based on the analysis of electroencephalogram (EEG) processing or on evoked potentials. However, their use in the routine cannot be considered an integral part of standard monitoring although their use is strongly recommended during total intravenous anesthesia. However, the literature on the possibility of preventing intraoperative awareness using brain monitoring is quite controversial [42, 43]. The use of goal-directed fluid protocols in intermediate-risk patients undergoing hip replacement was studied in few clinical trials. A fluid protocol based on pulse pressure variation (PPV) assessed using continuous invasive arterial pressure measurement seems to be associated with a reduction in postoperative complications and red blood cell transfusion as compared to standard no-protocol treatment [44, 45]. The goal-directed fluid therapy can be guided, in addition to standard monitoring (invasive blood pressure), with devices using pulse contour analysis able to extrapolate the main hemodynamic parameters from the analysis of the pressure wave. Some studies show that by maximizing the stroke volume and the oxygen delivery index, there is a reduction of postoperative complication and a reduction of hospitalization [44, 45]. The rotational thromboelastometer is a point-of-care instrument that studies the viscoelastic properties of whole blood and graphically displays the properties of the clot and its kinetics, from formation to lysis. In particular, it determines the clotting time, the initial time of fibrin formation, the kinetics of fibrin formation and clot development, the strength and stability of the clot, the lysis time, and the platelet function. The thromboelastometer is indicated for the diagnosis, treatment, and monitoring of hemostasis during perioperative bleeding. Among the most frequent causes of bleeding, fibrinolysis is an important one and may be prevented by the infusion of tranexamic acid (TXA) before surgery. Tranexamic acid (TXA) is a synthetic substance, structurally attributable to the amino acid lysine. Tranexamic acid blocks the lysine binding site on the fibrinolytic enzyme plasmin, which is essential for binding plasmin to fibrin. In this way, the fibrinolysis is blocked. TXA reduces blood loss and transfusion administration regardless of the surgical technique. With intravenous preoperative routine use these benefits were seen with both the anterior surgical approach and bilateral hip replacement [46, 47]. The usual dosage of TXA consists of an initial dose of 10–15 mg/kg before surgery that may be followed by an infusion of 1 mg/kg/hour over 4–6 hours or by repeating the initial dose in the postoperative period according to the presence or high risk of bleeding. Recently, local TXA administration in total hip replacement has been investigated, but its use is still controversial. The local application of TXA has been suggested in the consideration of some potential advantages such as easy application, directly affecting the bleeding site, minimizing systemic drug absorption, and, thus, reducing the potential complications of intravenous TXA administration. Local administration should be performed at the end of the surgery, once the fascia is closed, with local injection of 2 g of TXA [48]. In support of this practice, it has been reported that the intravenous use of TXA in total hip replacement significantly reduced blood loss and blood transfusion rates [49]. A recent study shows that the addition of oral TXA for 24 hours postoperatively does not reduce blood loss beyond that achieved with a single 1-g IV perioperative dose alone [50]. An assessment of the risks and benefits in patients is usually recommended. Indeed, in patients with previous thromboembolic events, over 60 years of age, female sex, or undergoing oncological surgery, there is a hypercoagulability’s induction and may be not recommended to administer a dose following the initial bolus. As fibrinogen ensures clot formation, the preoperative dosage in patients undergoing elective hip surgery is strongly recommended. Its monitoring during intraoperative bleeding allows for an early supplementation. Fibrinogen’s concentrates are the most used molecules. The most recent published guidelines indicate the trigger levels of fibrinogenemia <1.5–2 g/L during massive bleeding. When the indication comes from the monitoring of coagulation carried out through thromboelastographic and metric methods, there is a saving in the use of fibrinogen concentrates. In any case, the use of fibrinogen’s concentrate has been shown to have a better cost-benefit ratio. The most common dosage used is 25–50 mg/kg. Intraoperative recovery (RIO) is a blood-saving technique used during intraoperative bleeding. This procedure allows one to reduce the risk of allogeneic transfusions [51]. The blood aspirated and anticoagulated goes into a reservoir, and from there, through filters for microaggregates, it passes into a cell separators bowl to be concentrated by centrifugation, washed with physiological solution and then reinfused. The RIO is indicated with a blood loss of at least 1000 mL or in any case when is expected a blood loss ≥20% of the global volemia, in patients with antibodies which may cause difficulties in transfusion from donor, and in patients who refuse donor blood transfusion. In the case of RIO, the reinfusion consists of red blood cells only. Therefore, in the case of recovery and reinfusion of large volumes, it is important to monitor the platelet count and coagulation [52].

3.3 The importance of normothermia

The relationship between the extent of transfusion support and body temperature is now well established [53, 54]. Hypothermia during surgical procedures is produced by the combination of several factors that participate in the loss of body heat: low temperature in the operating room, administration of unheated fluids, alteration of the mechanisms of thermoregulation induced by anesthesia, and perspiratio insensibilis mainly due to mechanical ventilation. A drop, even moderate, in body temperature is able to modify the physiological mechanisms of hemostasis by altering platelet function and inhibiting the temperature-dependent enzymatic reactions of coagulation [55]. It has been demonstrated that even mild hypothermia (reduction of <1°C in body temperature) can increase blood losses by up to 16%, with a relative increase in the possibility of receiving transfusion therapy (22%) [53, 56]. For these reasons, it is fundamental to ensure the monitoring of the temperature in the operating room and the use of measures aimed at the prevention of hypothermia such as administration of heated fluids, dressing, and active heating.

3.4 Neuraxial strategies

Ideally, all neuraxial techniques for total hip replacement are validated. Therefore, the choice of the specific technique remains at the clinician’s discretion. Different techniques can be chosen in relation to the patient, the type of surgical access (e.g., anterior versus posterolateral approaches), and the presumed duration of the surgery. Among the neuraxial procedures, the following are included:

• single-shot spinal anesthesia

• epidural anesthesia

• combined spino-epidural anesthesia

• continuous spinal anesthesia

The single-shot spinal anesthesia is the most used technique. It allows one to keep the patient awake during the surgery, to reduce intraoperative time, and to minimize the administration of intraoperative analgo-sedative drugs, thus allowing for a more rapid discharge from the operating room and reduction of stay [57, 58]. The puncture site is usually at the L3/L4 level, and the most used anesthetic drugs are levobupicavaine or hyperbaric versus isobaric bupivacaine [59]. It is a clinician’s choice whether to perform a selective spinal or a total spinal anesthesia for both lower limbs. In any case, the most used dosages vary from 10 to 15 mg for both molecules. With the addition of adjuvant drugs (i.e., clonidine and/or morphine), the duration of anesthesia can be prolonged [60, 61]. Thin needles (27/25 gauge) with Whitacre tip type are less painful on insertion and reduce the number of local complications, such as headache or spinal hematoma [62]. Epidural catheter placement alone is rarely used in this type of surgery. The motor and sensory block necessary for the surgery phase can be reached with high doses of anesthetics. The needle normally used is the Thuoy needle (16/18G) through which a catheter is left in the epidural space. The catheter in place allows the anesthesia to be extended according to the clinician’s decision. Managing total surgery time with epidural anesthesia alone may increase the risk of local anesthetic overload toxicity. Combined spino-epidural anesthesia allows for a rapid onset and, if the surgery is prolonged, to continue anesthesia and postoperative analgesia [63, 64]. For elderly patients with fracture surgery, both the general anesthesia and the combined spinal-epidural anesthesia are able to maintain a good anesthesia effect, but the combined spinal-epidural anesthesia is preferable as it may shorten the onset time and it has less impact on the patient’s hemodynamic parameters. In addition, combined spinal-epidural anesthesia is associated with lower incidence of complications [63, 64]. Continuous spinal anesthesia is rarely used in hip surgery. It represents a valid alternative to the combined technique as it guarantees an optimal anesthetic plan by reducing the dosage of local anesthetics. On the other hand, it is a procedure that requires an expert team who is familiar with the method [65]. The use of neuraxial anesthesia in routine hip surgery was associated with lower immediate postoperative pain scores, lower intraoperative, and immediate postoperative opioid requirements and may be associated with shorter anesthesia recovery time, without any major adverse events when compared with general anesthesia [66].

3.5 Peripheral nerve and fascial blocks

Nerve blocks consists of the injection of a local anesthetic around a nerve causing pain relief by interrupting transmission of pain signals from the peripheral nerves to the cortex. Nerve blocks for orthopedic procedures have been shown to facilitate the execution of surgery, improve pain control and sleep after surgery, and decrease hospital stay [67, 68]. Nerve blocks may also reduce the need for other analgesic medications, thus limiting associated adverse effects. The hip area is innervated by branches of the lumbar plexus. The hip joint is supplied with femoral and obturator nerves, nerve to quadratus femoris, superior gluteal, and sciatic nerves. The dermatomal supply of the hip joint is typically from spinal nerve roots lumbar-4 to as low as sacral-2. The bony structures of the hip joint are supplied from spinal nerve roots lumbar-3 to sacral-1. It is difficult to achieve complete pain relief of the hip with peripheral nerve blocks [69], and some techniques, such as psoas compartment block, are suggested to be performed by experts [70]. There are many types and techniques for blocking the lumbar plexus nerves following hip replacement:

• Lumbar plexus, or psoas compartment block: a peripheral regional anesthetic technique to block the major nerves of the lumbar plexus (femoral, lateral femoral cutaneous and obturator nerves) in the psoas major muscle [71].

• Femoral nerve block is a safe and widely practiced techniques used for additional local anesthesia and provide postoperative analgesia after hip surgery [72]. Local anesthetic is infiltrated around the femoral nerve, which provides anesthesia to the anterior thigh (femoral nerve) and the medial lower leg (through the saphenous nerve). However, the cephalad spread of the local anesthetic may not be sufficient to block the obturator nerve (medial thigh) and the lateral cutaneous nerve of thigh [73].

• Fascia iliaca compartment block (FICB) is an anterior-thigh regional anesthetic block targeting the lumbar plexus [74]. This block was initially described by Dalens in 1989 for children where sensory blockade of the obturator nerve was believed to be observed. It was believed the local anesthetic spread underneath the iliac fascia proximally toward the lumbosacral plexus [74]. Then, it has been discovered that nearly half of patients do not have a skin component of the obturator nerve and that assessing adductor strength is the only effective way to measure obturator nerve function [75]. The effect of the FICB is similar to the femoral nerve block, but may provide a more reliable method of reaching the femoral lateral cutaneous nerve.

Compared to systemic analgesia alone, it is known that peripheral nerve blocks reduce postoperative pain, acute cognitive impairment, pruritus, and hospitalization [1]. Compared to neuraxial blocks, there is evidence that peripheral nerve blocks reduce pruritus [1]. Severe adverse events with peripheral nerve blocks are fortunately rare, and the use of ultrasound to guide locoregional anesthesia is highly recommended to reduce the risk of unwanted effects (intravenous puncture, local anesthetic systemic toxicity, and intraneural puncture). The ultrasound allows one to recognize the nerve structures in detail, to see in most cases the progression of the needle toward the target nerve structure, and to visualize the diffusion of the local anesthetic [75]. The combined use of the ultrasound system and the electrical nerve stimulator (ENS) increases the success rate in the localization of the nerve and minimizes the possibility of intraneural [76]. The techniques of regional anesthesia may also be useful for the postoperative pain control administering anesthetic drug continuously through a catheter left in the perineural space providing continuous perineural anesthesia/analgesia. A perineural catheter may be left either around the femoral nerve or around the lumbar plexus. The lumbar plexus (psoas compartment) is the first choice for the placement of the continuous perineural anesthesia for total hip replacement [77]. Ultrasound-guided psoas compartment block can be performed with different approaches (i.e., “Lumbar Ultrasound Trident” and “Shamrock technique”) [78] and has a lower hemodynamic impact compared to neuraxial techniques especially in elderly patients. Hence, a good anesthetic plan is guaranteed with the possibility to be extended and with a result comparable to other techniques [79]. Finally, an alternative procedure to those already mentioned is the use of the pericapsular nerve group block (PENG block) with local anesthetic infiltration. This technique is still poorly used, but its use is increasing, and it could be hypothesized as an effective and safety anesthesia technique for the total hip surgery [80].

3.6 General anesthesia and multimodal strategies

Sedative or anxiolytic drugs may be used to promote patient comfort and/or facilitate the successful completion of technical procedures such as spinal or locoregional anesthesia. Evidences supporting or the preoperative use of sedative or anxiolytic medication to reduce anxiety and accelerate the achievement of discharge criteria are sparse [81]. Short-acting sedative drugs may be used to facilitate successful completion of technical procedures, but routine administration of sedatives to reduce anxiety preoperatively is not recommended. Among patients undergoing elective primary total hip arthroplasty, general anesthesia has been associated with increased odds of adverse events, prolonged postoperative ventilator use, difficult intubation, stroke, cardiac arrest, other minor adverse events, and blood transfusion [82]. In addition, general anesthesia was associated with mild increases in operative time and postoperative room time [82]. General anesthesia has been previously shown to be associated with pulmonary adverse events following total hip arthroplasty [83].

Compared with neuraxial anesthesia, general anesthesia has been reported to be associated with a higher percentage of intraoperative hypotensive events. This relationship may exist because high-volume surgical centers may be more likely to use spinal anesthesia and may have decreased operative time and room turnover time compared with other centers. In addition, patient extubation likely adds to the postoperative room time. However, despite the significance of these findings, there may be little clinical importance of these minor increases in operating room times [82]. The overall early postoperative mortality in adult patients undergoing hip arthroplasty is low in the absence of risk factors such as severe cardiac hearth failure, chronic obstructive pulmonary disease (COPD), ascites, acute renal failure, and ASA score of 4 or higher. Some studies suggest that there is no association between the type of anesthesia received (general versus regional) and early postoperative mortality rates in patients undergoing hip arthroplasty, regardless of type (total versus partial) [84]. Similarly, other studies show no significant difference between the perioperative blood loss and the occurrence of deep vein thrombosis. However, spinal anesthesia was more advantageous than general anesthesia in terms of the occurrence of nausea and length of stay [85]. In general, large multicenter study on hip and knee replacement are in favor of neuraxial techniques over general anesthesia, and this change in practice has been at the core of established Enhanced Recovery after Surgery (ERAS) guidelines [84, 86]. Large epidemiological studies support the decision toward the choice of central neuraxial anesthesia over general anesthesia showing regional anesthesia being independently associated with better outcomes [87]. However, the claimed superiority of regional anesthesia has been questioned by emerging research. In particular, one single-center randomized clinical trial (RCT) performed in established ERAS centers has questioned whether the reduced cardiopulmonary and thromboembolic complications associated with neuraxial techniques in comparison with general anesthesia are relevant when hip surgery is performed in an ERAS setting where the preoperative optimization and early mobilization of the patient are two important pillars [88]. Harsten et al. compared a modern general anesthesia with a traditional high dose of neuraxial anesthesia (bupivacaine 0.5% 3 mL) and found no clinically relevant differences in functional recovery, hospitalization, urinary complications, and mobilization [88]. General anesthesia may also reduce urinary bladder dysfunction and rare, but potentially severe, neurological complications [89]. Another strategy that may be adopted consists in a multimodal strategy that involved general anesthesia, often conducted with supraglottic airway device, with regional anesthesia most frequently associated with lumbar block. Compared to general anesthesia with endotracheal intubation and combined spinal-epidural anesthesia, general anesthesia with supraglottic airway devices and nerve block had better postoperative analgesic effect and less disturbances on intraoperative hemodynamics and postoperative cognition for elderly patients undergoing intertrochanteric fracture surgeries [90]. Besides the improvement of hemodynamic stability, other advantages of general anesthesia with supraglottic airway device and lumbar plexus and sciatic block (LPSB) included earlier extubation and more rapid weaning from ventilatory support, better control of postoperative pain including longer time to the first analgesic request, and a lower incidence of postoperative complications such as systemic inflammatory response syndrome, pneumonia, sore throat, and hoarseness. In addition, general laryngeal mask anesthesia with LPSB was reported to be associated with a longer postoperative analgesic effect than general anesthesia with endotracheal intubation alone [91]. Another possible option is combining general anesthesia with a supraglottic airway device with fascial block as quadratus lumborum block with or without transversalis fascia plane block) [92, 93]. Preoperative posterior quadratus lumborum block for primary total hip arthroplasty is associated with decreased opioid requirements up to 48 hours, decreased visual analog scale pain scores up to 12 hours, and shorter postanesthesia care unit length of stay [93]. Conversely, other studies did not report benefits in term of opioid postoperative consumption [79]. Therefore, future multicenter RCTs are warranted to further compare the safety issues and potential differences in postoperative morbidity between different anesthetic techniques.

4. Postoperative care

4.1 General considerations

Early mobilization is a key component of hip surgery. Prolonged bed rest causes a series of adverse physiological effects, including increased insulin resistance, myopathy, reduced pulmonary function, impaired tissue oxygenation, and increased risk of thromboembolism. Safe and effective analgesia is a prerequisite to encourage postoperative mobilization. There is substantial evidence that early mobilization facilitates recovery after hip replacement [94].

4.2 Postoperative pain control and acute pain service reality

Postoperative pain is usually a multifactorial acute-on-chronic pain caused by the surgical procedure and the preexisting disease. It is triggered by the response to the trauma of the tissues caused by the surgical act. The control of the postoperative pain is a cornerstone in the postoperative setting and the access to palliative care and pain therapy should be granted. Failure to control postoperative pain has repercussions on the entire system from the patient, by worsening his experience and memories of the already traumatic event, to the hospital structure, by prolonging length of stay, and to the healthcare system, by increasing costs [95]. The postoperative pain therapy should include a preventive approach starting from aiming to a surgical procedure as less invasive as possible such as in case of hip replacement, anterior surgical approach, or robotic surgery [96]. In addition, the so-called preemptive analgesia aims to reduce the initial acute response to pain preventing, or at least limiting, the neuronal modifications associated with windup that consist in a progressively increasing electrical response in the corresponding spinal cord (posterior horn) neurons by repeated stimulation of group C peripheral nerve fibers. Multimodal approach is another preventive technique, with the choice of drugs belonging to different analgesic classes and using techniques of locoregional anesthesia, optimizing analgesia, and minimizing side effects. Similarly, to the anesthesia approach, the pain management after hip replacement should be multimodal, and it must be monitored and managed by an acute pain service (APS). There are different possibilities for postoperative pain control in hip replacement: totally intravenous analgesic infusion, continuous and/or patient-controlled peridural analgesia, and continuous or patient-controlled perineural analgesia; since the first experience of treatment units for acute pain management [97], the benefits of a dedicated and multidisciplinary organization have been reported and accepted, also in terms of cost-effectiveness [98, 99]. Unfortunately, the correct management of postoperative pain is still a challenge in most realities, and APSs are not yet enough diffused. It is possible to differentiate two main APS models: the first is the US model, which consists of anesthesiologist-based comprehensive pain management teams; the second is a nurse-based supervised APS, more diffused in the European countries. A recent Italian study suggests that the creation of the APS model, managed by residents in anesthesia, may represent an alternative between the US model (expensive and difficult to apply in several healthcare systems) and a nurse-based model more frequent in European countries [95].

4.3 Delirium prevention and reduction of length of stay

Postoperative delirium (POD) is one of the most severe complications after surgery, and it is a distressing syndrome both for old surgical patients and their families. It is a complex syndrome that affects 7–65% of patients after hip-fracture surgery [100, 101]. Its social consequences are likely to escalate with a growing old surgical population. The pathogenesis of POD is unclear and probably multifactorial. The most frequent causes are:

• perioperative hypoxemia

• postoperative restorations

• metabolic and electrolyte anomalies

• sleep disturbances

• drugs: opioids, anesthetics, anticholinergics, benzodiazepine, antiparkinsonian drugs

• general anesthesia

The most important predisposing risk factors are:

• elderly

• preexisting cognitive deficits

• multimorbidity

• associated pro-delirious polypharmacy

• insufficient analgesia

Pain is the most common complication after surgical procedures, and it is associated with increased risk of delirium [102]. Conversely, the use of opioids (particularly longer-acting opioids) has also been associated with increased risk of POD [103]. Postoperative mean oxygen saturation at night may also have a role in the development of POD [104]. The mean score of the Mini-Mental State Examination (MMSE) decreased significantly only in patients who received general anesthesia. This suggests that the use of a multimodal opioid-sparing analgesia regime may reduce risk of POD and, therefore, may be considered as a choice especially in patients at high risk for POD. However, there is no consistent evidence about the effects of general anesthesia and regional anesthesia on the incidence of POD following total hip replacement. Even in elderly patients, there was no significant difference in the incidence of cognitive dysfunction 3 months after the use of either general or regional anesthesia [105]. In an RCT among 950 patients aged 65 years and older undergoing hip fracture surgery, regional anesthesia without sedation did not significantly reduce the incidence of POD compared with general anesthesia [91]. The incidence of POD overall was 5.6%. Regardless of the techniques used, patients with POD have been independently associated with adverse clinical and economic outcomes such as death, decreased functional outcome, and cognitive decline, as well as higher cost of care and longer hospitalization. Therefore, it is important to characterize perioperative risk factors related to the incidence of POD and to optimize the quality of care in patients with total hip replacement arthroplasty. Despite the knowledge gaps in delirium pathogenesis, POD may still be preventable with targeted pharmacologic and nonpharmacologic strategies. The first-line preventative interventions for POD are the nonpharmacological interventions. Reorientation is a strategy to help patients get familiarized with the environment and the people. This is done through minimizing staff change and patient transfer, consistent introduction of staff members, access to natural light and time-keeping devices, reminders about the previous events, and future planning. A clinical trial has shown that reorientation alone can reduce the incidence of overt delirium by 40% [106]. Other nonpharmacological interventions include cognitive exercises, vision, sleep and hearing optimization, mobilization, hydration, and nutrition. These interventions are often instituted as a multicomponent care package. The Hospital Elder Life Program (HELP) is a multidisciplinary program designed to prevent cognitive and functional decline in older hospitalized patients, and the focus is on delirium [107]. Nonpharmacologic interventions, such as delirium education programs for medical staff, have led to reductions in delirium duration, hospitalization, and mortality. Antipsychotic drugs are dopamine antagonists and also have varying degrees of affinity to muscarinic, serotonergic, and adrenergic receptors [108]. They are divided into first-generation and second-generation agents, with the first generation (haloperidol) associated with higher risks of psychomotor complications and the second generation associated with higher risks of cardiovascular and metabolic complications. Several studies and meta-analyses have reported that prophylactic administration of second-generation antipsychotics, such as olanzapine and risperidone, may reduce the incidence of postoperative delirium [109]. Because of the risk of complications, the clinical value of antipsychotic prophylaxis is not clear. Pharmacologic ketamine has been found to reduce postoperative inflammation and improve perioperative pain outcomes [110]. In addition, results from a small trial also demonstrated decreased occurrence of delirium and decreased incidence of delayed neurocognitive recovery in cardiac surgery patients who received intraoperative ketamine compared with placebo [110]. Conversely, the PODCAST (Prevention of Delirium and Complications Associated with Surgical Treatments) trial shows that intraoperative ketamine does not prevent delirium. On the contrary, ketamine may increase the risk of adverse perioperative psychoactive experiences [111]. Dexmedetomidine has also been tested in large RCTs in relation to POD and its use is associated with reduction in the composite outcome of delirium, agitation, and confusion [112]. Other drugs have shown some promise as prophylactic agents in noncardiac surgery. These include acetaminophen, ramelteon, gabapentin, statins, clonidine, and melatonin [113].

5. Conclusions

Total hip replacement has been quoted as “the operation of the twentieth century” and one of the most successful and cost-effective procedures in orthopedics. It is usually associated with the high satisfaction of the patients and the improvement of the quality of life following surgery. Great advances in both surgical and anesthesia techniques have allowed us to extend indication for hip replacement to elderly patients with multiple comorbidities. In this regard, the role of the anesthesiologist is fundamental and should follow the patient along his/her entire journey from the preoperative assessment, in order to optimize patient’s conditions and plan the best anesthesia technique, to the postoperative recovering to provide an adequate pain control and minimize the risk of preventable complications such as postoperative delirium. A personalized approach has, therefore, become a routinely strategy for anesthesiologists in many specialized centers with all facilities and the necessary know-how. However, there are still several open controversies such as pro and cons related to general versus locoregional anesthesia and the prevention of postoperative complications. Artificial intelligence is among the most promising technology that may further innovate the field of hip replacement in the next years. In particular, machine learning and deep learning methods could markedly improve patient risk stratification and support anesthesiologists in the decision of the best approach to adopt with a specific patient. Such algorithms will need high-quality data to perform with high accuracy and a strong validation process to be trustable but, in return, will provide clinical decision support systems (CDSSs) able to aid physicians in weighing competing healthcare goals and numerous risks by facilitating multiple outcome optimization of outcomes that are too difficult to recognize and navigate on an individual and isolated basis.

This chapter is dedicated to the memory of Tobia Maria.

Conflict of interest

The authors declare no conflict of interest.