Anesthesia for geriatric patients.

The number of elderly surgical patients will be increasing in Italy. Slowly, anesthesiologists are developing the expertise to care for these patients. The information available to apply to these cases is now the topic of a number of anesthesia textbooks dedicated to the elderly. In this article, we review some of the more recent findings and provide some tips to help guide the care of elderly patients. It is hoped that practitioners will use this information to improve the care of these patients and conduct additional research to further improve care in the future.

Postoperative delirium and cognitive dysfunction.

Postoperative delirium and cognitive dysfunction (POCD) are topics of special importance in the geriatric surgical population. They are separate entities, whose relationship has yet to be fully elucidated. Although not limited to geriatric patients, the incidence and impact of both are more profound in geriatric patients. Delirium has been shown to be associated with longer and more costly hospital course and higher likelihood of death within 6 months or postoperative institutionalization. POCD has been associated with increased mortality, risk of leaving the labour market prematurely, and dependency on social transfer payments. Here, we review their definitions and aetiology, and discuss treatment and prevention in elderly patients undergoing major non-cardiac surgery. Good basic care demands identification of at-risk patients, awareness of common perioperative aggravating factors, simple prevention interventions, recognition of the disease states, and basic treatments for patients with severe hyperactive manifestations.

Delirium is associated with early postoperative cognitive dysfunction.

The purpose of this analysis was to determine if postoperative delirium was associated with early postoperative cognitive dysfunction (at 7 days) and long-term postoperative cognitive dysfunction (at 3 months). The International Study of Postoperative Cognitive Dysfunction recruited 1218 subjects >or= 60 years old undergoing elective, non-cardiac surgery. Postoperatively, subjects were evaluated for delirium using the criteria of the Diagnostic and Statistical Manual. Subjects underwent neuropsychological testing pre-operatively and postoperatively at 7 days (n = 1018) and 3 months (n = 946). Postoperative cognitive dysfunction was defined as a composite Z-score > 2 across tests or at least two individual test Z-scores > 2. Subjects with delirium were significantly less likely to participate in postoperative testing. Delirium was associated with an increased incidence of early postoperative cognitive dysfunction (adjusted risk ratio 1.6, 95% CI 1.1-2.1), but not long-term postoperative cognitive dysfunction (adjusted risk ratio 1.3, 95% CI 0.6-2.4). Delirium was associated with early postoperative cognitive dysfunction, but the relationship of delirium to long-term postoperative cognitive dysfunction remains unclear.

Is peri-operative cortisol secretion related to post-operative cognitive dysfunction?

BACKGROUND: The pattern of cortisol secretion is influenced by surgery. As cortisol can adversely affect neuronal function, this may be an important factor in the development of post-operative cognitive dysfunction (POCD). We hypothesized that the incidence of POCD would be related to changes in cortisol level. METHODS: We studied 187 patients aged over 60 years undergoing major non-cardiac surgery with general or regional anaesthesia. Saliva cortisol levels were measured pre-operatively and at 1 day, 7 days and 3 months post-operatively in the morning (08.00 h) and in the afternoon (16.00 h) using salivettes. Cognitive function was assessed pre-operatively, on day 7 and at 3 months using four neuropsychological tests. POCD was defined as a combined Z score of greater than 1.96. RESULTS: After surgery, salivary cortisol concentrations increased significantly. POCD was detected in 18.8% of subjects at 1 week and in 15.2% after 3 months. The pre-operative ratios between the morning and afternoon cortisol concentrations (am/pm ratios) were 2.8 and 2.7 in patients with POCD at 1 week vs. those without POCD at 1 week, respectively. The am/pm ratios decreased significantly post-operatively to 1.9 and 1.6 at 1 week, respectively (P = 0.02 for both). In an analysis considering all am/pm ratios, it was found that the persistent flattening in am/pm ratio was significantly related to POCD at 1 week. CONCLUSION: The pattern of diurnal variation in cortisol level was significantly related to POCD. Thus, circadian rhythm disturbance or metabolic endocrine stress could be an important mechanism in the development of cognitive dysfunction after major surgery.

Blood lymphocyte chimerism associated with IVF and monochorionic dizygous twinning: case report.

We report on dizygotic (DZ) twins, conceived by IVF and ICSI with assisted hatching, who each had a mixture of 46,XX and 46,XY cells in blood lymphocytes. The female twin had mild genitalia abnormalities but further study revealed anatomically normal reproductive anatomy. Chromosome and fluorescence in situ hybridization studies of buccal, skin and ovarian tissue were normal, as were buccal tissue DNA studies. Fetal ultrasound and fetal membrane pathology were consistent with a monochorionic, diamniotic placenta (MCDAP). These twins thus have blood chimerism but are not chimeric in the other tissues studied. The mechanism for the chimerism could be due to either placental vascular anastamoses (after the development of the haematoblast stem cells) or due to an admixture of trophoblast cells during early blastocyst development. Such trophoblast cell admixtures would be restricted to the extraembryonic tissues so that general physical development in the fetus is normal and without somatic cell chimerism. This case in combination with others previously reported suggests that in IVF conceptions, the prevalence of blood chimerism associated with twinning, and the occurrence of DZ twinning associated with MCDAP, may be higher than previously thought.

Cognitive dysfunction after minor surgery in the elderly.

BACKGROUND: Major surgery is frequently associated with postoperative cognitive dysfunction (POCD) in elderly patients. Type of surgery and hospitalization may be important prognostic factors. The aims of the study were to find the incidence and risk factors for POCD in elderly patients undergoing minor surgery. METHODS: We enrolled 372 patients aged greater than 60 years scheduled for minor surgery under general anesthesia. According to local practice, patients were allocated to either in- (199) or out-patient (173) care. Cognitive function was assessed using neuropsychological testing preoperatively and 7 days and 3 months postoperatively. Postoperative cognitive dysfunction was defined using Z-score analysis. RESULTS: At 7 days, the incidence (confidence interval) of POCD in patients undergoing minor surgery was 6.8% (4.3-10.1). At 3 months the incidence of POCD was 6.6% (4.1-10.0). Logistic regression analysis identified the following significant risk factors: age greater than 70 years (odds ratio [OR]: 3.8 [1.7-8.7], P = 0.01) and in- vs. out-patient surgery (OR: 2.8 [1.2-6.3], P = 0.04). CONCLUSIONS: Our finding of less cognitive dysfunction in the first postoperative week in elderly patients undergoing minor surgery on an out-patient basis supports a strategy of avoiding hospitalization of older patients when possible.

Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after cardiac and major non-cardiac surgery with general anaesthesia in the elderly. We hypothesized that the incidence of POCD would be less with regional anaesthesia rather than general. METHODS: We included patients aged over 60 years undergoing major non-cardiac surgery. After giving written informed consent, patients were randomly allocated to general or regional anaesthesia. Cognitive function was assessed using four neuropsychological tests undertaken preoperatively and at 7 days and 3 months postoperatively. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in two or more test parameters. RESULTS: At 7 days, POCD was found in 37/188 patients (19.7%, [14.3-26.1%]) after general anaesthesia and in 22/176 (12.5%, [8.0-18.3%]) after regional anaesthesia, P = 0.06. After 3 months, POCD was present in 25/175 patients (14.3%, [9.5-20.4%]) after general anaesthesia vs. 23/165 (13.9%, [9.0-20.2%]) after regional anaesthesia, P = 0.93. The incidence of POCD after 1 week was significantly greater after general anaesthesia when we excluded patients who did not receive the allocated anaesthetic: 33/156 (21.2%[15.0-28.4%]) vs. 20/158 (12.7%[7.9-18.9%]) (P = 0.04). Mortality was significantly greater after general anaesthesia (4/217 vs. 0/211 (P < 0.05)). CONCLUSION: No significant difference was found in the incidence of cognitive dysfunction 3 months after either general or regional anaesthesia in elderly patients. Thus, there seems to be no causative relationship between general anaesthesia and long-term POCD. Regional anaesthesia may decrease mortality and the incidence of POCD early after surgery.

Clinical testing results and high patient satisfaction with a new needle-free device for growth hormone in young children.

Fifty children ages 4-10 yr with type 1 diabetes mellitus volunteered to participate in a study to evaluate and compare a new needle-free device developed for growth hormone delivery. Children answered descriptive questions related to nervousness and worry, hurt or pain, redness or bleeding, and stinging and wetness. Choices for answers for each of these five questions were none, a little, or a lot. None or a little was also combined to give a minimal category. Children also answered four questions that compared the needle-free device to their morning insulin needle injection in reference to ease of use, pain, nervousness, and overall preference. Half the children had single comfort rings inserted to increase the injection pressure. Results indicated no difference in question responses with or without pressure rings. Pain (92%), erythema (96%), worry (90%), stinging (86%) and wetness (96%) were minimal and significant (0.001 > p < 0.03) following all questions. Results of the comparative questionnaire indicated that the device was easier (p < 0.03) to use than needles and significantly preferred (p < 0.001) in 74% of children under age 10.

Disordered eating, body mass, and glycemic control in adolescents with type 1 diabetes.

OBJECTIVE: To examine the relationship between disordered eating attitudes and behaviors, BMI, and glycemic control in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a cross-sectional design, 152 adolescents (ages 11-19 years) completed three scales from the Eating Disorders Inventory (EDI): Body Dissatisfaction, Drive for Thinness, and Bulimia. All subjects had diabetes for > 1 year. Glycemic control was assessed by glycosylated hemoglobin (HbA1c). Height and weight were measured to assess BMI. RESULTS: Adolescents with type 1 diabetes did not report more disordered eating attitudes and behaviors than the normative comparison sample. Male subjects with type 1 diabetes reported fewer symptoms of bulimia and female subjects with type 1 diabetes reported greater body satisfaction than the normative group. A higher BMI was a significant predictor of greater body dissatisfaction, more so for female than male subjects. Symptoms of bulimia were associated with older adolescence and female sex. Those with more symptoms of bulimia were also more likely to have a higher BMI. Sex (female) and body dissatisfaction (more dissatisfied) predicted a stronger desire to be thin. Longer duration of disease, more symptoms of bulimia, and obesity all predicted poorer glycemic control. CONCLUSIONS: Female patients aged 13-14 years seem to be at greatest risk for developing disordered eating patterns. Using the clinical cutoff score (> or = 5) of the EDI Bulimia subscale as a screener in diabetes clinics may help identify adolescents whose disordered eating patterns are likely to compromise their glycemic control.

Changes in frequency and severity of limited joint mobility in children with type 1 diabetes mellitus between 1976-78 and 1998.

OBJECTIVE: Limited joint mobility (LJM), the earliest clinically apparent long-term complication of type 1 diabetes mellitus, is a risk indicator for microvascular complications, and its appearance is primarily affected by long-term metabolic control. We hypothesized that the prevalence of LJM had decreased during the past 20 years. STUDY DESIGN: We examined 312 subjects with type 1 diabetes mellitus, aged 7 to 18 years, using the same examination method and criteria as in studies of 515 subjects in this age group carried out between 1976 and 1978 for whom primary data were available, including age, duration of diabetes, and LJM stage. Statistical analyses included exact chi(2) tests, independent sample t tests, and unconditional logistic regression. RESULTS: There was a >4-fold reduction in frequency of LJM between 1976-78 and 1998 (31% vs 7%, P <.001), with a decrease in the proportion having moderate or severe LJM (35% vs 9%, P =.025). CONCLUSIONS: These findings confirm the hypothesis that the prevalence of LJM has decreased, most likely the result of improved blood glucose control during the past 2 decades.

Type 2 diabetes in children.

The emerging epidemic of type 2 diabetes (T2DM) in young people reflects increasing rates of obesity and parallels the increasing frequency of T2DM in adults. As in adults, T2DM in children is part of the insulin resistance syndrome that includes hyperandrogenism seen as premature adrenarche and polycystic ovary syndrome, hypertension, dyslipidemia, and other atherosclerosis risk factors. Recent studies in children document risk factors for T2DM, and associated cardiovascular risk factors, including obesity, family history, diabetic gestation, and underweight or overweight for gestational age. Genetically determined insulin resistance or limited beta-cell reserve has been demonstrated in high-risk individuals, including first-degree relatives of girls with premature adrenarche. This genetic background, considered advantageous in a feast-and-famine existence (the thrifty genotype), is rendered detrimental with abundant food and physical inactivity, a lifestyle demonstrated to be typical of families of children with T2DM. The increasing incidence of T2DM in children and adolescents threatens to become a major public health problem. Risk factors for cardiovascular disease, hypertension, hyperlipidemia, and microalbuminuria are present at diagnosis of T2DM in Native American adolescents, indicating that insulin resistance has been present for some time before the diagnosis of diabetes was made. Case finding is likely to be beneficial in high-risk youths. Treatment is the same as that of adults. The only data on use of oral hypoglycemic agents in children have been with metformin. Community and governmental efforts to educate all children and their parents about the need for physical activity and dietary modification are essential to control this epidemic.

Molecular and genetic bases for maturity onset diabetes of youth.

Maturity onset diabetes of youth (MODY) occurs in children, adolescents and young adults as a non-insulin-requiring form of diabetes mellitus that is inherited as an autosomal dominant trait. Maturity onset diabetes of youth in whites presents subtly similar to type 2 diabetes in adults. In contrast, a MODY variant that occurs in young blacks, termed atypical diabetes mellitus, presents as an acute-onset form of diabetes. Months to years after diagnosis, atypical diabetes mellitus reverts to a noninsulin requiring course similar to MODY in whites. Five molecular causes for MODY have been identified: mutations in four transcription factors and mutations in one enzyme (glucokinase). Transcription factors regulate gene expression within cells. Mutations in hepatocyte nuclear factor-4alpha, hepatocyte nuclear factor-1alpha, insulin promoter factor-1 and hepatocyte nuclear factor-1beta, respectively, cause MODY1, MODY3, MODY4, and MODY5. Glucokinase is the glucosensor of the beta cell. MODY2 is caused by glucokinase mutations. Although testing for MODY mutations is only available in research laboratories, a careful history and review of the patient's clinical course can often allow the clinician to diagnose MODY. The diagnosis of MODY has implications for the clinical management of the patient's diabetes.

New developments in type 1 (insulin-dependent) diabetes.

The Diabetes Control and Complications Trial has conclusively demonstrated that improved metabolic control leads to reduction in the rate of microvascular complications of diabetes. In order to allow patients to achieve improved metabolic control, much research has focused on improved methods of glucose monitoring and more physiologic ways of insulin delivery. The 2 most promising methods of minimally invasive blood glucose monitoring are the Glucowatch, using the technique of reverse iontophoresis to measure interstitial fluid glucose levels every twenty minutes and an implantable sensor, in which a catheter resembling that used for insulin delivery through a pump is impregnated with glucose oxidase at the tip. This device monitors blood sugars every few minutes, but like a holter monitor, must be downloaded in the physician's office. Still under development are (1) implantable subcutaneous sensors with a high and low blood glucose alarm and (2) sensors in which the patient will be able to download the data using a home PC. Advances in insulin delivery have included the availability of new insulin analogs which more closely simulate endogenous insulin release, with rapid acting analogs simulating the increase in insulin production that normally occurs after meals. Phase III clinical trials are in progress of a long-acting basal insulin without peak actions to simulate the low dose continuous production of the insulin which normally inhibits hepatic glucose production. In addition, use of the insulin pump has increased markedly since publication of the DCCT with the greatest increase being among adolescents. In addition to advances in treatment of diabetes, research has continued on curing the disease using islet cell transplantation and preventing the disease with agents such as insulin (DPT-1 Trial) and nicotinamide (ENDIT). This article provides an overview of recent advances in diabetes management and prevention.

Response to hypo- and hyperglycemia in adolescents with type I diabetes.

OBJECTIVE: To assess the appropriateness of adolescents' responses to hypo- and hyperglycemia and to examine the relationship of patient age, gender, diabetes duration, diabetes knowledge, parental supervision, and glycemic control to response appropriateness. METHODS: We assessed 125 adolescents' responses to daily episodes of hypo- and hyperglycemia by 24-hour recall interviews; responses were coded for type and appropriateness. RESULTS: Adolescents responded inappropriately to 38% of hypoglycemic and 29% of hyperglycemic episodes. Parental supervision of blood glucose testing did not increase the likelihood of an appropriate response; in the case of hyperglycemic episodes, it appeared to be counterproductive. Adolescents who responded inappropriately to hyperglycemia were also older but not different from those who responded appropriately by gender, disease duration, diabetes knowledge, or glycemic control. CONCLUSIONS: Health providers and family members may underestimate adolescents' difficulty managing hypo- and hyperglycemia appropriately. The presence of parental supervision does not ensure an appropriate response; parents may be particularly misinformed about the management of hyperglycemia.

Treatment of type 2 diabetes mellitus in children and adolescents.

The treatment of type 2 diabetes mellitus (DM) is directed at decreasing insulin resistance and increasing insulin secretion. alpha-Glucosidase inhibitors slow carbohydrate absorption, resulting in reduced postprandial hyperglycemia; thiazolidinediones increase insulin sensitivity, especially in muscle and adipocytes; metformin decreases hepatic gluconeogenesis; sulfonylureas result in prolonged increases in insulin secretion; and meglitinide causes rapid, short-lived increases in insulin secretion. A survey of 130 pediatric endocrinology practices in the USA and Canada indicated that 48% of children with type 2 DM were treated with insulin and 44% with one or more oral hypoglycemic agents (OHA). Of those treated with OHA, 71% received metformin, 46% sulfonylureas, 9% thiazolidinediones and 4% meglitinide. Similarly, in the three university-based diabetes centers in Florida, 50% of the children with type 2 DM were treated with OHA. Treatment is based on symptoms at presentation. Patients identified on routine testing are often treated with exercise and diet alone. Those who are mildly symptomatic at onset are often started on OHA. Patients with substantial ketosis, ketoacidosis or markedly elevated blood glucose levels are initially treated with insulin, followed by a tapering of the dose and the addition of an OHA after blood glucose control is established and symptoms subside. There are no studies of the efficacy or compliance with treatment for type 2 DM in adolescents. Treatment is currently based on the clinical experience with adults. Controlled clinical trials in children are essential.

Poor metabolic control during menstruation and sexual abuse issues in an adolescent with diabetes.

A case study is presented that describes the deterioration of a patient's diabetes control during her menstrual cycle in terms of her psychological functioning and family context. Therapeutic interventions pertinent toward improving diabetes control, resolving issues of abuse, and increasing family communication are addressed. The outcome of this case study supports the contention that psychological factors can impact diabetes control significantly during menstruation in young women.

Beneficial effects from beta-adrenergic blockade in elderly patients undergoing noncardiac surgery.

BACKGROUND: Perioperative beta-blockade has been shown to improve long-term cardiac outcome in noncardiac surgical patients. A possible mechanism for the reduced risk of perioperative myocardial infarction is the attenuation of the excitotoxic effects of catecholamine surges by beta-blockade. It was hypothesized that beta-blocker-induced alteration of the stress response was responsible for the reported improvements in cardiovascular outcome. Several variables associated with the perioperative use of beta-blockade were also evaluated. METHODS: Sixty-three patients were randomly assigned to one of three groups: group I, no atenolol; group II, pre- and postoperative atenolol; group III, intraoperative atenolol. Hormonal markers of the stress response (neuropeptide Y, epinephrine, norepinephrine, cortisol, and adrenocorticotropic hormone) were evaluated preoperatively and for 72 h after surgery. RESULTS: Perioperative beta-blockade did not significantly alter the hormonal stress response. However, the beta-blocked patients showed improved hemodynamic stability during emergence and postoperatively. They also received less fentanyl intraoperatively (27.7%, P < 0.0001), experienced faster early recovery, had lower pain scores, and required less analgesia in the postanesthesia care unit. Cardiac troponin I release was detected in 8 of 19, 4 of 20, and 5 of 20 patients in groups I, II, and III, respectively (not significant). Three patients in group I had cardiac troponin I levels consistent with myocardial infarction. CONCLUSION: Beta-blockade does not reduce the neuroendocrine stress response, suggesting that this mechanism is not responsible for the previously reported improved cardiovascular outcome. However, it confers several advantages, including decreased analgesic requirements, faster recovery from anesthesia, and improved hemodynamic stability. The release of cardiac troponin I suggests the occurrence of perioperative myocardial damage in this elderly population, which appears to be independent of the neuroendocrine stress response.

The prevention of type I diabetes mellitus.

Now that prediction of type I diabetes mellitus has markedly improved, worldwide attempts to prevent the disease are under way (e.g., DPT-1, ENDIT, and TRIGR). Subjects are being recruited and families of children or parents with diabetes should be informed about the availability of such studies and given the option to participate. The creation of a network of study sites or cooperative groups will allow for the implementation of new protocols aimed at preventing the disease. The greatest barrier to the prevention of diabetes is the lack of proven effective interventional agents. The journey toward prevention of type I diabetes mellitus has only just begun.

Paradoxical locomotor behavior of dopamine D1 receptor transgenic mice.

The behavioral effects of augmenting dopamine D1 receptor expression in the brain were investigated in mice incorporating additional copies of the mouse D1 receptor gene. Two transgenic lines showed increases in brain D1 receptor binding sites, which were greatest in extrastriatal regions. The full D1 agonist SKF 81297, when administered systemically to control animals, stimulated a dose-dependent increase in locomotor activity. In contrast, in D1 receptor overexpressing transgenic mice, this drug caused a marked suppression of locomotion due to a decrease in the frequency of movement initiation. Amphetamine and cocaine induced comparable locomotor activation in both transgenic animals and their control littermates. In the transgenic animals, D1 agonist-induced rearing and climbing behaviors were suppressed. However, on rotarod testing, the agonist-treated transgenic and control mice performed comparably, indicating that sensorimotor coordination was unaffected. These studies demonstrate that altering the levels of D1 receptor expression reverses the effects of D1 agonism on locomotor initiation and rearing.