Screening for predictors of adverse outcome in onco-geriatric surgical patients: A multicenter prospective cohort study.

AIMS: The aim of this study was to investigate the predictive ability of screening tools regarding the occurrence of major postoperative complications in onco-geriatric surgical patients and to propose a scoring system. METHODS: 328 patients ≥ 70 years undergoing surgery for solid tumors were prospectively recruited. Preoperatively, twelve screening tools were administered. Primary endpoint was the incidence of major complications within 30 days. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. A scoring system was derived from multivariate logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was applied to evaluate model performance. RESULTS: At a median age of 76 years, 61 patients (18.6%) experienced major complications. In multivariate analysis, Timed Up and Go (TUG), ASA-classification and Nutritional Risk Screening (NRS) were predictors of major complications (TUG>20 OR 3.1, 95% CI 1.1-8.6; ASA ≥ 3 OR 2.8, 95% CI 1.2-6.3; NRS impaired OR 3.3, 95% CI 1.6-6.8). The scoring system, including TUG, ASA, NRS, gender and type of surgery, showed good accuracy (AUC: 0.81, 95% CI 0.75-0.86). The negative predictive value with a cut-off point >8 was 93.8% and the positive predictive value was 40.3%. CONCLUSIONS: A substantial number of patients experience major postoperative complications. TUG, ASA and NRS are screening tools predictive of the occurrence of major postoperative complications and, together with gender and type of surgery, compose a good scoring system.

Upper thoracic epidural anaesthesia: effects of age on neural blockade and cardiovascular parameters.

BACKGROUND: Segmental dose reduction with increasing age after thoracic epidural anaesthesia (TEA) has been documented. We hypothesised that after a fixed loading dose of ropivacaine at the T3-T4 level, increasing age would result in more extended analgesic spread. In addition, other aspects of neural blockade and haemodynamic changes were studied. METHODS: Thirty-five lung surgery patients were included in three age groups. Thirty-one patients received an epidural catheter at the T3-T4 interspace followed by an injection of 8-ml ropivacaine 0.75%. Analgesia was assessed with pinprick and temperature discrimination. Motor block was tested using the Bromage and epidural scoring scale for arm movements score. An arterial line was inserted for invasive measurement of blood pressure, cardiac index (CI) and stroke volume (SV). RESULTS: There was no influence of age on quality of TEA except for the caudal border of analgesia being somewhat lower in the middle and older age group compared with the young age group. Heart rate (6.0 ± 5.9, P < 0.001), mean arterial pressure (16.1 ± 15.6, P < 0.001), CI (0.55 ± 0.49, P < 0.001) and SV (9.6 ± 14.6, P = 0.001) decreased after TEA for the total group. Maximal reduction in heart rate after TEA was more extensive in the young age group compared with the other age groups. There was no effect of age on other cardiovascular parameters. CONCLUSION: We were unable to demonstrate an effect of age on the maximal number of spinal segments blocked after TEA; however, the caudad spread of analgesia increased with advancing age. In addition, reduction of heart rate was greater in the youngest group.

Effect of age on the clinical profile and systemic absorption and disposition of levobupivacaine after epidural administration.

BACKGROUND: Pharmacokinetic and/or pharmacodynamic changes, which may occur with increasing age, could alter the clinical profile of the new local anaesthetic levobupivacaine. We investigated the effect of age on the absorption and disposition kinetics and the neural block characteristics after epidural administration of levobupivacaine 0.75%. METHODS: Thirty-one patients were enrolled in one of three age groups (Group 1, 18-44 yr; Group 2, 45-70 yr; Group 3, >70 yr). Twenty-five minutes after epidural administration of levobupivacaine (127.5 mg), they received approximately 25 mg deuterium-labelled levobupivacaine (D(3)-levobupivacaine) intravenously. Arterial blood samples were collected until 24 h after the epidural administration. Plasma concentrations were determined using liquid chromatography mass spectrometry. Plasma concentration-time data were analyzed by compartmental and non-compartmental analysis. Assessments of analgesia and motor block were made at set intervals until complete regression of the block. RESULTS: The upper levels of analgesia in the two oldest groups of patients were 3 dermatomes (95% confidence interval (95% CI): 0.5-5.0 dermatomes) higher than in the youngest group. The fraction absorbed (F(1)) was 0.07 (95% CI: 0.02-013) smaller and the absorption half-life (t(1/2,a1)), characterizing the initial fast absorption phase, 3.6 min (95% CI: 0.8-6.4) shorter in the oldest group compared with the youngest group. CONCLUSIONS: Age influences the pharmacokinetics, in particular the early absorption kinetics, and the neural block characteristics after epidural administration of levobupivacaine. Changes in the upper level of analgesia are best explained by anatomical considerations and possibly pharmacodynamic changes in the elderly.

The systemic absorption and disposition of levobupivacaine 0.5% after epidural administration in surgical patients: a stable-isotope study.

BACKGROUND AND OBJECTIVE: Absorption and disposition kinetics can be studied with a stable-isotope method. The aim of this study was to validate a stable-isotope method for levobupivacaine and to derive the relevant pharmacokinetics after epidural administration. METHODS: Eight volunteers (18-32 yr) received approximately 23 mg of both levobupivacaine and deuterium-labelled levobupivacaine simultaneously by intravenous infusion. Venous blood samples were taken for 8 h. Fifteen patients (23-85 yr) received 19 mL levobupivacaine 0.5% (including a 3 mL test dose) epidurally and, 25 min later, approximately 25 mg deuterium-labelled levobupivacaine (D3-levobupivacaine) intravenously. Arterial blood samples were collected for 24 h. Plasma concentrations were determined using liquid chromatography-mass spectrometry. Plasma concentration-time data were analysed by compartmental and non-compartmental analysis. RESULTS: Based on the ratio of the normalized areas under the curve of unlabelled and deuterium-labelled levobupivacaine in volunteers, as determined by both compartmental (mean ratio: 1.02, 90% CI: 1.00-1.04) and non-compartmental analysis (mean ratio: 1.02, 90% CI: 1.00-1.03) the two formulations were considered equivalent. In surgical patients the elimination half-life (mean +/- SD: 196 +/- 65 min), total body clearanc (349 +/- 114 mL min(-1)) and volume of distribution at steady state (56 +/- 14 L), derived by compartmental analysis, were similar to those obtained by non-compartmental analysis. The absorption was bi-phasic. The fractio absorbed and half-life of the fast absorption process were 0.22 +/- 0.06 and 5.2 +/- 2.7 min, respectively. Th values for the slow absorption process were 0.84 +/- 0.14 and 386 +/- 91 min, respectively. CONCLUSIONS: D3-levobupivacaine is pharmacokinetically equivalent to unlabelled levobupivacaine and can be used to study the absorption and disposition kinetics after perineural administration of levobupivacaine in a single experiment.

Spinal anaesthesia with 0.5% hyperbaric bupivacaine in elderly patients: effects of duration spent in the sitting position.

Sixty patients, aged 65-84 yr, undergoing minor urological surgery under spinal anaesthesia remained sitting for 2 (group 1, n = 15), 5 (group 2, n = 15), 10 (group 3, n = 15), or 20 (group 4, n = 15) min after completion of the subarachnoid administration of 3 ml of a 0.5% hyperbaric bupivacaine solution. They were then placed in the supine position. Analgesia levels were assessed bilaterally using pinprick. Motor block was scored using a 12-point scale. Systolic and diastolic arterial pressures and heart rate were also recorded. Twenty minutes after the injection the upper analgesia levels were lower (P<0.05) in group 4 (median T9.0) than in the groups 1-3 (medians T6.6-T8.5). The highest obtained levels (medians T5.7-T8.0) did not differ between the groups, but occurred later (P<0.05) in group 4 (median 35 min) than in groups 1-3 (medians 19-24 min). There were no significant differences in the maximum degree of motor block or haemodynamic changes between the four study groups.

Cardiovascular and pulmonary effects of epidural anaesthesia.

Epidural anaesthesia has been used since the early 1900s. Consequently the general characteristics of these procedures have been well defined. More studies have provided a better understanding of the cardiopulmonary changes produced by epidural anaesthesia. The cardiovascular effects observed with epidural anaesthesia are complex and variable, depending on a multitude of factors. The extent of sympathetic denervation, balance of sympathetic and parasympathetic activity, the pharmacological effect of systemically absorbed local anaesthetic agents, inclusion of adrenaline in the anaesthetic solution, the distribution of blood in relation to cardiac filling and cardiovascular function of the patient must be taken into account when considering the circulatory effects of epidural anaesthesia. Individual cardiovascular response to different levels of sympathetic blockade varies widely, depending on the degree of sympathetic tone before the block. Epidural anaesthesia that is restricted to the level of the low thoracic and lumbar region (T5-L4) results in a "peripheral" sympathetic blockade with vascular dilatation in the pelvis and lower limbs. High thoracic epidural anaesthesia, from the first to fifth thoracic, blocks the cardiac afferent and efferent sympathetic fibres with loss of chronotropic and inotropic drive to the myocardium. Thoracic epidural anaesthesia appears to at least partly reverse the diaphragmatic dysfunction that is a major determinant of the decrease in lung volumes observed after upper abdominal surgery. This article summarizes cardiovascular and pulmonary responses to epidural anaesthesia. Details of clinical management are not included in the review.

The epidural "top-up" in combined spinal-epidural anesthesia: the effect of volume versus dose.

UNLABELLED: The reinforcement of anesthesia by an epidural "top-up" in combined spinal-epidural anesthesia may be explained by a dual mechanism: a volume effect compressing the dural sac and a local anesthetic effect. The purpose of our study was to investigate the relative importance of each of these factors. Fifty patients scheduled for lower limb orthopedic surgery under combined spinal-epidural anesthesia were randomly allocated to one of five groups comprising 10 patients each. Using a needle-through-needle technique, all patients received a subarachnoid injection of 10 mg of plain bupivacaine and an epidural catheter. After the maximal level of sensory blockade as a result of the subarachnoid injection had been established, an epidural top-up was given according to the randomization code. Patients in Group 1 received 10 mL of bupivacaine 0.25%; patients in Group 2 received 10 mL of saline; patients in Group 3 received 5 mL of bupivacaine 0.5%; patients in Group 4 received 5 mL of saline; and patients in Group 5 received no epidural top-up. The maximal level of sensory blockade was then assessed for an additional 30 min. In Groups 1-4, the maximal level of sensory blockade increased significantly, whereas there was no significant increase in Group 5. There was no significant difference in the increase in the maximal level of sensory blockade among Groups 1-4. We conclude that, under the conditions of our study, there is no difference between 5 and 10 mL with regard to the volume effect of an epidural top-up in combined spinal-epidural anesthesia and that to produce an additional local anesthetic effect with bupivacaine, the dose must be larger than 25 mg. IMPLICATIONS: In combined spinal-epidural anesthesia, an epidural "top-up" may increase the maximal level of sensory blockade by means of a volume effect and a local anesthetic effect. In this study, volumes of 5 and 10 mL produced a similar increase, and 25 mg of bupivacaine was insufficient to produce an additional local anesthetic effect.

Management of anaesthesia in elderly patients.

Increasing numbers of very elderly patients require surgery. Elderly patients are at increased risk of perioperative morbidity and mortality because of the high incidence of co-existing age-related diseases. With greater experience, outcomes from major operations in octogenarians have improved. The increased risks of surgery in the elderly must, however, be individually weighed against the benefits to be gained from symptom relief and improved quality of life.

Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep.

UNLABELLED: Commercially available bupivacaine is an equimolar mixture of R(+)- and S(-)-bupivacaine. S(-)-bupivacaine (i.e., levobupivacaine) is currently undergoing preclinical evaluation. Cross-over studies with i.v. levobupivacaine and bupivacaine were conducted in two groups of seven conscious sheep. Doses were chosen to avoid convulsions (smaller dose 6.25-37.5 mg/min) or to be potentially toxic (larger dose 75-200 mg/3 min). In subconvulsive doses, both drugs produced similar time- and dose-dependent depression of left ventricular systolic contractility (dP/dt(max)). Convulsions occurred consistently with > or = 75 mg of bupivacaine and > or = 100 mg of levobupivacaine, producing an abrupt reversal of dP/dt(max) depression. Subconvulsive doses produced minor cardiovascular effects on heart rate and blood pressure, whereas both were increased by convulsions. Cardiac output and myocardial blood flow were decreased with larger doses of both drugs. Doses > 75 mg of bupivacaine or > 100 mg of levobupivacaine induced QRS widening and ventricular arrhythmias, but significantly fewer and less deleterious arrhythmias were induced by levobupivacaine. Three animals died after 150, 150, and 200 mg of bupivacaine from the sudden onset of ventricular fibrillation. These doses of levobupivacaine produced nonfatal arrhythmias that automatically returned to sinus rhythm. We conclude that levobupivacaine could offer a greater margin of clinical safety than bupivacaine. IMPLICATIONS: Levobupivacaine comprises 50% of commercially available bupivacaine and is being considered for use in its own right. Local anesthetics can cause toxicity to the cardiovascular and central nervous systems. As a part of a preclinical evaluation of levobupivacaine, this study compared the toxic effects of levobupivacaine and bupivacaine in sheep.

Spinal anaesthesia with 0.5% hyperbaric bupivacaine in elderly patients: effect of site of injection on spread of analgesia.

In this randomized, observer-blind study, we have examined, in elderly patients, the effect of site of injection on analgesia levels after spinal injection of 0.5% hyperbaric bupivacaine solution. Thirty male patients, aged 68-87 yr, undergoing minor urological surgery during spinal anaesthesia received 3 ml of a 0.5% hyperbaric bupivacaine solution at either the L3-4 (n = 15) or L4-5 (n = 15) interspace. The solution was injected with the patient in the sitting position. The patient remained sitting for 2 min and was then placed in the supine horizontal position. Analgesia levels were assessed bilaterally using pin-prick. The highest analgesia levels did not differ between groups (medians were approximately T7). There were no significant differences in the time to maximum cephalad spread of analgesia, maximum degree of motor block or haemodynamic changes. We conclude that injection at the L4-5 interspace has no advantage compared with injection at the L3-4 interspace.

Spinal anesthesia with ropivacaine: a double-blind study on the efficacy and safety of 0.5% and 0.75% solutions in patients undergoing minor lower limb surgery.

The purpose of this study was to determine the clinical efficacy and safety of ropivacaine as a local anesthetic for spinal anesthesia. Forty patients between the ages of 18 and 75 yr, scheduled for minor lower limb surgery, were studied. They were randomly allocated to receive either 3 mL glucose-free 0.5% (15 mg) or 0.75% (22.5 mg) ropivacaine in a double-blind fashion. The subarachnoid puncture was performed with a 26-gauge Quincke-point needle at the L3-4 interspace with the patients in the sitting position. The onset of analgesia to pinprick was similar with both concentrations. The median (range) upper level of analgesia obtained with the 0.5% solution was T11 (L4-T5) and was T10-11 (L4-T4) with the 0.75% solution. The duration of analgesia at T12 (P < 0.01) and the total duration of analgesia (P < 0.002) were longer in the 0.75% group. In addition, the area under the number of blocked segments versus time curve was larger with the 0.75% ropivacaine solution (P < 0.001). The incidence of complete motor block of the lower limbs was higher (P < 0.02) and the total duration of motor block longer (P < 0.002) in the 0.75% group. No unexpected adverse events were registered. We conclude that subarachnoid injection of glucose-free ropivacaine solutions results in a variable spread of analgesia, mostly accompanied by a good quality of motor block, in particular with the 0.75% solution.

The effect of age on the systemic absorption, disposition and pharmacodynamics of bupivacaine after epidural administration.

The influence of age on the systemic absorption and disposition of bupivacaine following epidural administration in 20 male patients (22 to 81 years) was examined using a stable isotope method to determine whether pharmacokinetics play a role in age-related pharmacodynamic changes seen with the drug. After epidural bupivacaine administration a deuterium-labelled analogue was administered intravenously. Bi- and triexponential functions were fitted to plasma concentration-time data of deuterium-labelled bupivacaine. The systemic absorption was described by 2 parallel first-order absorption processes. The upper level of analgesia and the duration of analgesia at dermatome T-12 increased with age (r = 0.68, p less than 0.001; r = 0.56, p less than 0.01, respectively). The time to maximal caudad spread of analgesia and the time to onset of motor block decreased with age (r = -0.76, p less than 0.0001; r = -0.72, p less than 0.001, respectively). Age did not influence systemic absorption or disposition of bupivacaine. We conclude that the changes in the clinical profile of bupivacaine with age are not due to altered pharmacokinetics, but may be related to changes in the pharmacodynamics of the drug.

Age does not influence the serum protein binding of bupivacaine.

The serum protein binding of bupivacaine was studied in 74 subjects, 39 males and 35 females, aged 20-90 years, without evidence of acute or chronic inflammatory disease or malignancy. Subjects were drug free for at least 1 month. The free fractions of bupivacaine did not change with age in either males or females. This is in keeping with the lack of effect of age on AAG concentrations. Free fractions of bupivacaine were slightly higher in females as compared with males. The previously observed decline in clearance of bupivacaine with age probably reflects a concomitant decline in the metabolic activity of hepatic enzymes.

The effect of age on systemic absorption and systemic disposition of bupivacaine after subarachnoid administration.

In order to evaluate the role of the pharmacokinetics of the age-related changes in the clinical profile of spinal anesthesia with bupivacaine, we studied the influence of age on the systemic absorption and systemic disposition of bupivacaine after subarachnoid administration in 20 male patients (22-81 yr), ASA Physical Status 1 or 2, by a stable isotope method. After subarachnoid administration of 3 ml 0.5% bupivacaine in 8% glucose, a deuterium-labeled analog (13.4 mg) was administered intravenously. Blood samples were collected for 24 h. Plasma concentrations of unlabeled and deuterium-labeled bupivacaine were determined with a combination of gas chromatography and mass fragmentography. Biexponential functions were fitted to the plasma concentration-time data of the deuterium-labeled bupivacaine. The systemic absorption was evaluated by means of deconvolution. Mono- and biexponential functions were fitted to the data of fraction absorbed versus time. The maximal height of analgesia and the duration of analgesia at T12 increased with age (r = 0.715, P less than 0.001; r = 0.640, P less than 0.01, respectively). In 18 patients the systemic absorption of bupivacaine was best described by a biexponential equation. The half-life of the slow systemic absorption process (r = -0.478; P less than 0.05) and the mean absorption time (r = -0.551; P less than 0.02) decreased with age. The total plasma clearance decreased with age (r = -0.650, P less than 0.002), whereas the mean residence time and terminal half-life increased with age (r = 0.597, P less than 0.01; r = 0.503, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of age on serum concentrations of albumin and alpha 1-acid glycoprotein.

1. Human serum albumin (HSA) concentrations and alpha 1-acid glycoprotein (AAG) concentrations were measured in 68 subjects, 35 males and 33 females, aged 20-90 years without evidence of acute or chronic inflammatory disease or malignancy. Subjects were drug free for at least 1 month. HSA and AAG concentrations were measured using rate nephelometry. 2. Age had no effect on alpha 1-acid glycoprotein concentration, whereas plasma albumin levels decreased as a function of age in both sexes. We observed no differences between males and females in the plasma concentrations of HSA and AAG. 3. These data show that in healthy subjects the HSA concentration decreases with increasing age, whereas age, uncomplicated by disease does not influence AAG concentration.

Threshold serum concentrations of bupivacaine associated with early CNS toxicity and pharmacokinetics of bupivacaine in young versus old rhesus monkeys.

Effects of aging on the onset of early signs of central nervous system (CNS) toxicity, associated total and free arterial threshold serum concentration, and the disposition of bupivacaine were studied in eight younger (11-15 years) and eight older (16-28 years) rhesus monkeys. Bupivacaine was infused at a rate of 0.15 mg/kg minute until unceasing movements of the eye, oscillating from side to side and up and down (nonpositional nystagmus). This was regarded as an objective sign of early CNS toxicity. Most animals showed drowsiness and sedation by the end of the infusion. CNS toxicity occurred significantly faster (p less than 0.025) in the younger (13.7 +/- 2.5 minutes) than in the older (17.1 +/- 2.6 minutes) animal group. A significant correlation was found between the onset time of CNS toxicity and age. The coefficient of determination (R2) for this correlation was 0.48. Also, the dose associated with the onset of CNS toxicity was significantly smaller in the younger (2.06 +/- 0.38 mg/kg) than in the older (2.60 +/- 0.39 mg/kg) animals. However, the total and free arterial threshold serum concentration of bupivacaine was similar in both groups. Age did not influence the disposition of bupivacaine.