With the increase in life expectancy observed in recent decades, the number of people aged over 65 yr has reached 19% of the population in Europe , and this represents an increased workload for anaesthesiologists . Spinal anaesthesia is widely used for elderly orthopaedic patients. Restricting the block by using small doses of hyperbaric anaesthetic solutions, directional spinal needles and the lateral decubitus position has been suggested to minimize the incidence of cardiovascular adverse effects induced by sympathetic blockade [3,4].
Postoperative cognitive dysfunction is frequent in the aged population , and spinal block has been reported to be associated with a better maintenance of mental function in the early postoperative period . However, volatile anaesthetic agents with low blood-gas partition coefficients, such as sevoflurane, have been shown to shorten emergence times in elderly patients  and rapidly to restore cognitive function  compared with older inhalation anaesthetics. Sevoflurane also provides a good cardiovascular stability in this patient population . Its pleasant smell and lack of irritant effects on the airways makes it an attractive option for volatile induction and maintenance of anaesthesia .
Little information is available in the literature on the clinical use of volatile induction and maintenance of anaesthesia with sevoflurane in elderly patients compared with spinal anaesthesia. We therefore conducted a prospective, randomized study to compare unilateral spinal block with small dose hyperbaric bupivacaine with sevoflurane in elderly patients undergoing hemiarthroplasty of the hip for repair of fractured femur.
Approval was obtained from our Institutional Ethics Committee and written informed consent from 30 patients who were enrolled into the study. The patients were ASA II-III, due to undergo hemiarthroplasty of the hip for repair of fractured femur. Patients with contraindications to spinal anaesthesia or laryngeal mask placement, and those with severe and uncompensated cardiovascular or pulmonary disease or psychiatric pathology were excluded.
All patients received a standardized protocol for preoperative fluid resuscitation, including blood transfusion if required to maintain haemoglobin concentration ≥9 g dL−1. The day before surgery, all patients had a standard preoperative evaluation, including chest radiography, electrocardiography and routine laboratory tests. Preoperative analgesics consisted of intravenous (i.v.) ketorolac (30 mg every 8 h). During the preoperative visit, the cognitive function of the patients was assessed using the Mini Mental State Examination (MMSE) test. This cognitive screening test quantitatively assesses the cognitive aspects of mental function by asking patients 11 different questions that evaluate orientation to time and place, registration, attention, calculation, short-term recall, language, and constructional ability, and combines a high validity and reliability with brevity and ease of application . The maximum MMSE score is 30; scores ≤23 indicate cognitive impairment. A decline in postoperative cognitive function was defined as a decrease from baseline of ≥2 points .
When the patients arrived in the operating theatre, an i.v. cannula was inserted and Ringer's acetate solution given. Fentanyl 1 μg kg−1 was given before induction of either general or spinal anaesthesia. Standard monitoring was used throughout the procedure.
Using a sealed envelope technique, patients were randomly allocated to receive a sevoflurane induction and maintenance anaesthesia (Group SEVO, n = 15) or a unilateral spinal block (Group Spinal, n = 15). Dural puncture was performed with a 25-G Whitacre spinal needle (Becton-Dickinson, Franklin Lake, NJ, USA) at the L3-L4 interspace with the patient lying in the lateral position and the side to be operated upon dependent. Hyperbaric bupivacaine 0.5% 7.5 mg was injected over 60 s. The lateral decubitus position was maintained for 15 min; then the patient was turned into the supine position and surgery started.
For induction of general anaesthesia, the sevoflurane concentration was increased by 1% increments every three breaths until a 5% inspiratory concentration was achieved. When loss of the eyelash reflex and adequate jaw relaxation was obtained, a laryngeal mask airway was inserted. The fresh gas flow was then decreased to 3 L min−1 and anaesthesia maintained with nitrous oxide 60% in oxygen and an end-tidal concentration of sevoflurane between 0.8 and 2% based on cardiovascular responses. No muscle relaxants or other analgesic drugs were given. The lungs of all patients were mechanically ventilated to maintain an end-tidal PCO2 between 4.5 and 5.3 kPa .
The attending anaesthesiologist's aim was to maintain heart rates and blood pressures to within ±20% of baseline. Crystalloid solution (3 mL) was given per each 1 mL blood lost. Blood transfusion was given to maintain the haemoglobin concentration ≥9 g dL−1. Blood absorbed by the surgical swabs was washed with physiological saline (0.9%) and aspirated into the suction apparatus. The total amount of blood lost was estimated by subtracting the amount of physiological saline used by the surgeon for irrigation and washing of the surgical swabs from the total volume of fluid aspirated in the suction apparatus.
The following criteria for haemodynamic side-effects were considered: hypotension was taken to be a reduction in systolic arterial pressure >20% of baseline; hypertension an increase in systolic arterial pressure >20% from baseline; bradycardia a decrease in heart rate to <50 beats min−1. In the Group SEVO, the occurrence of haemodynamic side-effects led to a stepwise change in the inspired concentration of sevoflurane in order to restore values to baseline. If this proved ineffective, specific treatment was given. A two-step treatment was planed for hypotension: first a 250 mL bolus of crystalloid solution; second, i.v. boluses of phenylephrine 2 mg. Hypertension was treated with nitrate infusion 1-4 mg h−1. Bradycardia was treated with atropine 0.5 mg. The need for pharmacological treatment was recorded as a minor haemodynamic adverse effect.
In Group SEVO, sevoflurane was discontinued after the last skin suture and the lungs were manually ventilated with 100% oxygen using a fresh gas flow of 6 L min−1 until spontaneous ventilation resumed. When the patient was judged to be awake (making purposeful movements), breathing regularly and swallowing, the laryngeal mask was removed and the patient transferred to the postanaesthesia care unit (PACU). Patients in Group Spinal were directly transferred to the PACU at the end of surgery. Criteria for PACU discharge included the presence of an Aldrete score ≥9, stable vital signs, adequate airway control, alertness and responsiveness with pain and nausea controlled . The time from PACU admission to fulfilment of discharge criteria was recorded.
Twenty minutes before the end of surgery, post-operative analgesia was started with an i.v. loading dose of tramadol 100 mg, ketorolac 30 mg, ranitidine 50 mg and metoclopramide 10 mg. This was followed by a continuous i.v. infusion of a combination of tramadol (12 mg h−1) and ketorolac (3 mg h−1) . This pain treatment was continued for the first 48 h after surgery and then substituted with oral medications. The degree of pain was assessed using a five-point verbal rating scale (1 = no pain; 2 = mild pain; 3 = moderate pain; 4 = severe pain; 5 = unbearable pain) and recorded at PACU discharge and then 1, 3, 6 and 12 h after PACU discharge .
The day after surgery and on the seventh postoperative day, the MMSE test was repeated. Occurrence of any adverse event, including nausea, vomiting or other undesirable side-effects, was also recorded. Patients were discharged from hospital according to clinical criteria routinely used by the orthopaedic and rehabilitation staff, who were blinded to the anaesthesia technique used during surgery. Delay until discharge was recorded.
Statistical analysis was performed using Systat 7.0® (SPSS, Inc, Chicago, IL, USA). The Kologmorov-Smirnov test was used to evaluate the distribution of data. The U-test was used to compare continuous variables. Categorical data were analysed using the contingency table analysis and Fisher's exact test. Unless otherwise indicated, results are medians (range) or numbers (percentage). P ≤ 0.05 was considered as statistically significant.
There was no difference in age, height, weight, ASA physical status, gender distribution and duration of surgical procedure between the two groups (Table 1).
Systolic and diastolic arterial pressure decreased from baseline in both groups, but no differences were observed between the two groups (Fig. 1). Hypotension requiring crystalloid infusion was observed in seven patients of Group Spinal (46%) and in 12 of Group SEVO (80%) (P = 0.05). Phenylephrine was required in three patients of Group Spinal (21%) and in four of Group SEVO (26%) (n.s.). Heart rate significantly decreased in both groups from baseline. From 15 to 60 min after induction of anaesthesia, heart rates were lower in Group SEVO than in Group Spinal (P = 0.01) (Fig. 1). Three patients in Group SEVO (22%) and none in Group Spinal showed bradycardia requiring atropine (n.s.). Hypertension or other cardiovascular side-effects were not reported in either group. Intraoperative blood losses were greater in patients of Group SEVO (median 300 mL, range 100-500 mL) than in Group Spinal (250 mL, 100-250 mL) (P = 0.015).
The median time for fulfilment of PACU discharge criteria was shorter in Group Spinal (15 min; 25th-75th percentiles: 5-20 min) than in Group SEVO (55 min; 25th-75th percentiles: 26-72 min). Log-rank curves representing the Kaplan-Meier estimation of readiness to PACU discharge were significantly different (P = 0.0005) (Fig. 2). Five patients in Group SEVO required >1 h to fulfil PACU discharge criteria. In two of them (13%), the reason was the extra time required to complete the blood transfusion and check for adequate haemoglobin concentration after surgery (P = 0.48). In the other three (20%), the reason was agitation and mental confusion (P = 0.22). Figure 3 shows postoperative pain in the two groups. At PACU discharge and 1 h after surgery, the quality of pain control was better in patients of Group Spinal than in those receiving general anaesthesia; however, no differences in pain relief were observed between the two groups 3 h after surgery.
In both groups, the MMSE score decreased from baseline at the 24 h evaluation point, but recovered to normal values 7 days after surgery without differences between the two groups (Table 2). Mental confusion (a decrease in MMSE score ≥ 2 points from baseline) was observed in eight patients of Group Spinal (53%) and in nine of Group SEVO (60%) on the first day after surgery (n.s.). Seven days after surgery, confusion was still present in one patient of Group Spinal (6%) and in three patients of Group SEVO (20%) (n.s.). The median (range) duration of hospital stay was 12 (8-16) days in Group Spinal and 14 (10-20) days in Group SEVO (n.s.).
Surgical and anaesthesia techniques have markedly improved during the last few years, but major surgery in elderly patients can be still associated with a high mortality and morbidity in the perioperative period . Regional anaesthesia is usually preferred in elderly orthopaedic patients to minimize the interference with cognitive function that may be produced by general anaesthesia. However, quite often spinal block cannot be used because of inadequate patient co-operation or because of anticoagulation. For this reason, the use of volatile agents with a low blood-gas partition coefficient, e.g. sevoflurane, can be appealing in this geriatric population because of rapid elimination and minimal metabolization. We did not find any studies in the literature that compared induction and maintenance with sevoflurane with unilateral spinal anaesthesia for hip surgery. This randomized study suggested that sevoflurane and laryngeal mask placement without muscle relaxation could be used effectively in elderly patients undergoing hemiarthroplasty of the hip. This technique may be a good alternative to spinal anaesthesia, with rapid emergence from anaesthesia and minor effects on cognitive function in the postoperative period.
In previous investigations, long induction times with sevoflurane have been reported when low inspired concentrations are used with a stepwise incremental technique [10,17]. The evaluation of induction times was not the aim of this study; however, patients in Group SEVO were induced easily without delay or associated problems despite the use of a step-up technique with a maximum inspired sevoflurane concentration of only 5%. On the other hand, it must be considered that the use of a smooth and progressive induction technique might help to reduce the risk of sudden cardiovascular depression induced by the volatile agent. This can be useful when inducing general anaesthesia in very old patients who often suffer from several concomitant diseases.
Although no differences in arterial pressure were observed between the two groups, clinically relevant hypotension requiring volume expansion was nearly 40% more frequent in Group SEVO than in patients receiving unilateral spinal anaesthesia. This difference could be related to a more extensive effect produced by the volatile agent on the sympathetic system compared with that produced by a restricted spinal block [4,18]. The complex and integrated autonomic reflex responses maintaining cardiovascular homeostasis progressively decrease with age, resulting in an underdamped and less tightly self-regulated autonomic nervous system with increasing age . Inhalation agents are known to cause a more marked cardiovascular depression in elderly than in young patients  with negative effects on baroreflexes . On the contrary, restricting the block at the operated side has been demonstrated to reduce the incidence rate of clinically relevant hypotension during spinal anaesthesia by nearly 75% . Nonetheless, reducing the depth of anaesthesia and giving a rapid volume expansion with crystalloid solution allowed a prompt and effective restoration of arterial blood pressure in most patients, and no differences in the use of phenylephrine were observed between the two groups.
Interestingly, the use of spinal anaesthesia was also associated with less intraoperative bleeding than with general anaesthesia. Similar results have been reported by others . In a meta-analysis, the odds for blood transfusion were reduced by nearly 50% when using a central block compared with general anaesthesia . In the same study, it was also demonstrated that patients treated with a central neuraxial blockade had lower mortality and perioperative morbidity, with a significant reduction in the incidence of thromboembolic complications . However, a large multicentre randomized study recently failed to show any difference in perioperative morbidity and 30 day mortality in high-risk patients receiving a central neuraxial blockade or parenteral opioids for postoperative analgesia .
The time for PACU discharge was shorter in patients receiving unilateral spinal anaesthesia than in Group SEVO. Previous studies reported that sevoflurane shortened emergence and discharge from the PACU compared with isoflurane in both adults  and obese patients . However, in a population of elderly patients, spinal block may provide a more rapid recovery of the Aldrete's score, explaining the earlier fulfilment of PACU discharge criteria.
Immediately after PACU discharge, pain relief was better controlled in patients receiving spinal block. However, 3 h after PACU discharge, the quality of pain control was similar in the two groups. This difference was probably related to the delay in the resolution of the spinal block, which provided complete pain relief for the first hours after PACU discharge.
No differences in cognitive function were found between the two groups. The MMSE score significantly decreased 24 h after surgery in both groups, and 50-60% of the patients were confused (defined as a reduction of the MMSE score ≥ 2 points from baseline). However, 7 days after surgery, the MMSE score completely recovered to preoperative values in both groups. Chung and colleagues demonstrated that general anaesthesia with isoflurane produced more marked effects on cognitive function than spinal block, while the MMSE score returned to preoperative values 5 days after surgery . More recently, others have evaluated the effects of sevoflurane anaesthesia on cognitive function in elderly patients, reporting its complete recovery 6 h after surgery . However, in agreement with our findings, a multicentre observational study on a large population reported a very high incidence of cognitive dysfunction in elderly patients after surgery . The odds for this cognitive decline increased with age, but the study failed to demonstrate any significant association between the decline in cognitive function and the anaesthesia technique used to perform surgery .
In conclusion, this prospective, randomized study demonstrated that induction and maintenance of anaesthesia with sevoflurane and laryngeal mask placement can be used effectively for hemiarthroplasty of the hip in elderly patients. This technique provides rapid emergence from anaesthesia without more marked depression of postoperative cognitive function than that produced by unilateral spinal anaesthesia. This may represent an attractive option when patient refusal, lack of adequate co-operation or concomitant anticoagulant therapy contraindicate the use of spinal anaesthesia.
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