Renin-angiotensin-system gene polymorphisms and depression.

Given the abundance of the renin-angiotensin system (RAS) components in the brain, their importance in behavior and cognition, and the data that implicates them in the etiology and treatment of depression, it is possible that those RAS gene polymorphisms associated with increased RAS activity may also be associated with depression. The frequencies of common polymorphisms of genes encoding for components of the RAS, namely angiotensinogen (M235T), angiotensin converting enzyme (ACE) (insertion, I; deletion, D), angiotensin receptor type I (A1166C), and angiotensin receptor type II (C3123A) were determined in DNA extracted from buccal cells from a Lebanese population of 132 depressed patients and their first-degree relative case-controls. The angiotensin receptor type 1 (A1166C) CC genotype was significantly associated with depression (p=0.036). None of the other common RAS-associated polymorphisms were significantly associated. The results support the hypothesis that increased RAS activity may increase relative risk of depression in that the angiotensin receptor type 1 (A1166C) CC genotype is associated with increased responsiveness to angiotensin II.

Inappropriate medication use in elderly lebanese outpatients: prevalence and risk factors.

BACKGROUND: Inappropriate use of medications has become an international cause for concern in geriatric patients, who are at high risk of drug-related morbidity. This study is the first attempt to determine the prevalence of inappropriate drug use in elderly Lebanese outpatients, using community pharmacy data, and to identify factors that predict potentially inappropriate drug intake in this population. METHODS: Records of elderly patients aged > or =65 years were selected from different community pharmacies. Each patient profile was reviewed and to confirm patient record information, in-person interviews were conducted with elderly patients between November 2004 and May 2005 by qualified pharmacists. Based on a literature review describing guidelines for the inappropriate use of medications in the elderly, courses of therapy were assessed and classified as either appropriate or inappropriate. Courses of therapy that were judged inappropriate were further classified according to the specific area of inappropriate use (i.e. Beers' criteria, duplicate therapy, indication, dose, dose frequency including missing doses, duration and discontinuation of therapy, adverse effects, drug-drug and/or drug-disease interactions, and poor memory). Statistical analyses were performed to estimate the prevalence of inappropriate medication use and to identify potentially predictive factors of such use arising from patients' sociodemographic characteristics, health factors and drug regimen intake. RESULTS: A total of 350 elderly patient profiles were reviewed, from which 277 evaluable records were obtained. More than half (59.6%) of the patients taking drugs at the time of the study were taking at least one inappropriate medication. Inappropriate medication use was most frequently identified in terms of Beers' criteria (22.4%), missing doses (18.8%) or incorrect frequency of administration of drugs (13.0%). Factors predicting potentially inappropriate drug intake included female sex (65.7% vs 53.3% for males, p = 0.03) and alcohol intake (p = 0.007). There were also significant associations between the likelihood of use of an inappropriate drug and (i) increased number of medical illnesses (p < 0.00002); and (ii) consumption of an over-the-counter drug (OTC) and/or prescription drug (p = 0.048 and p = 0.0035, respectively). The likelihood of use of an inappropriate drug was higher again when patients concurrently used both OTC and prescription drugs (p < 0.0002). CONCLUSION: The present study is the first to describe and assess inappropriate medication use by elderly outpatients in the Lebanese community setting. With increasing availability of newer and more appropriate medications, use of potentially inappropriate drugs may decrease. Pharmacists have a major role to play in counselling patients about the importance of appropriate drug use.

Preoperative anti-PF4/heparin antibody level predicts adverse outcome after cardiac surgery.

OBJECTIVE: Preexisting serum antibodies to heparin/platelet factor 4 complexes may predispose adult cardiac surgical patients to increased perioperative morbidity and mortality. We sought to determine the association between preoperative serum antibodies directed against platelet factor 4/heparin complexes and major complications (in-hospital death or length of stay >10 days) in adult cardiac surgical patients. METHODS: In a prospective observational study of 466 patients undergoing elective coronary artery bypass grafting, valvular heart surgery, or both, preoperative serum was assayed for anti-platelet factor 4/heparin antibody by using a commercially available enzyme-linked immunosorbent assay (Asserachrom HPIA). Known preoperative risk factors were assessed, and patients were assigned a risk score by using the validated method of Parsonnet and colleagues. RESULTS: Major complications (death or postoperative hospitalization >10 days) occurred in 108 patients (23%). Overall, 59 (13%) patients had a positive preoperative anti-platelet factor 4/heparin antibody screen (upper limit of normal is 0.5 optical density units). A positive assay result independently predicted an increased risk of major complications (P = .0284; odds ratio, 1.98; 95% confidence interval, 1.06-3.62) over and above the effect of the Parsonnet risk score (P < .001; odds ratio, 1.07; 95% confidence interval, 1.05-1.10). The level of preoperative anti-platelet factor 4/heparin antibody was also significantly associated with major complications (P = .036; odds ratio, 1.31; 95% confidence interval, 1.02-1.68) independently of the Parsonnet risk score. No association (P > .75) existed between the Parsonnet risk score and preoperative anti-platelet factor 4/heparin antibody level. CONCLUSIONS: Serum antibodies directed against platelet factor 4/heparin complexes are prevalent in the adult patient population undergoing cardiac surgery. The presence of these antibodies before surgery is an independent predictor for death or prolonged hospitalization after adult cardiac surgery.

A method to attenuate pneumoperitoneum-induced reductions in splanchnic blood flow.

OBJECTIVE: To determine if increasing nitric oxide bioactivity by inclusion of ethyl nitrite (ENO) in the insufflation admixture would attenuate pneumoperitoneum-induced decreases in splanchnic perfusion. SUMMARY BACKGROUND DATA: Organ blood flow is reduced during pneumoperitoneum and can contribute to laparoscopy-associated morbidity and mortality. Previous attempts to control such decreases in flow have been ineffective. METHODS: Laser-Doppler flow probes were placed on the liver and right kidney of anesthetized pigs. After a baseline recording period, animals were insufflated to a final intraperitoneal pressure of 15 mm Hg. Group one received CO2 (standard practice), whereas group 2 received CO2 plus 100 ppm ENO. Insufflation was maintained for 60 minutes and then the abdomen was manually deflated; monitoring was continued for another 60 minutes. RESULTS: CO2 insufflation (n = 5) cut liver blood flow in half; liver flow remained at this level throughout the postinsufflation period. Inclusion of 100 ppm ENO (n = 6) attenuated both the acute and prolonged blood flow decreases. Statistical modeling of the data showed that, on average, liver blood flow was 14.3 U/min higher in the ENO pigs compared with the CO2 group (P = 0.0454). In contrast, neither treatment significantly altered kidney blood flow (P = 0.6215). CONCLUSION: The data indicate that ENO can effectively attenuate pneumoperitoneum-induced blood flow decreases within the peritoneal cavity. The result suggests a novel therapeutic method of regulating hemodynamic changes during laparoscopic procedures.

Predictors of inotrope use during separation from cardiopulmonary bypass.

OBJECTIVE: To identify the demographic, clinical, and echocardiographic features that predict the use of inotropic support at separation from cardiopulmonary bypass (CPB). DESIGN: Retrospective study of consecutive patients undergoing coronary artery bypass graft (CABG) surgery. SETTING: Referral center for cardiothoracic surgery at a university hospital. PARTICIPANTS: One thousand nine patients undergoing either CABG or combined CABG and valve surgery with CPB in whom an intraoperative transesophageal echocardiography (TEE) examination was performed. INTERVENTIONS: Inotropic support was defined as the use of dopamine >/=5 microg/kg/min; any dose of epinephrine, norepinephrine, dobutamine, and milrinone; or the insertion of an IABP during separation from CPB. Support was implemented by the anesthesia care team as clinically indicated. Comprehensive TEE examinations were conducted before CPB in all patients according to published guidelines and subsequently reviewed by a single, independent operator. MEASUREMENTS AND MAIN RESULTS: Inotropic support was used in a total of 394 patients (39%) at separation from CPB. The study identified 6 significant, independent predictors of inotrope use: (1) Wall Motion Score Index, (2) combined CABG and mitral valve repair or replacement surgery, (3) left ventricular ejection fraction <35%, (4) reoperation, (5) moderate-to-severe mitral regurgitation, and (6) aortic cross-clamp time. CONCLUSIONS: Incorporating data from a comprehensive intraoperative TEE examination, the authors identified 6 reproducible factors that independently predict the use of inotropic support at separation from CPB.

Metoprolol and coronary artery bypass grafting surgery: does intraoperative metoprolol attenuate acute beta-adrenergic receptor desensitization during cardiac surgery?

UNLABELLED: Cardiac surgery results in significant impairment of beta-adrenergic receptor (beta AR) function and is a cause of depressed myocardial function after surgery. We previously demonstrated that acute administration of beta AR blocker during cardiopulmonary bypass (CPB) in an animal model of coronary artery bypass grafting (CABG) surgery attenuates beta AR desensitization, whereas chronic oral beta-blockade therapy in patients undergoing CABG surgery does not prevent it. Therefore we hypothesized that acute administration of metoprolol during CABG surgery would prevent acute myocardial beta AR desensitization. A placebo-controlled initial phase (n = 72) was performed whereby patients were randomized to either metoprolol 10 mg or placebo immediately before CPB. Then a second dose-finding study was performed where patients received 20 mg (n = 20) or 30 mg (n = 20) of metoprolol. Hemodynamic monitoring, atrial membrane adenylyl cyclase activity, atrial beta AR density, and postoperative outcomes were measured. All groups showed similar decreases in isoproterenol-stimulated adenylyl cyclase activity (13%-24%). Cardiac output remained similar in all 4 groups throughout the intraoperative and postoperative period. In addition, patients receiving metoprolol 20 or 30 mg had less supraventricular arrhythmias 24 h postoperatively compared with patients receiving metoprolol 10 mg or placebo. Therefore, unlike our previous animal model of CABG surgery, metoprolol did not attenuate myocardial beta AR desensitization. IMPLICATIONS: We investigated whether IV metoprolol given during cardiac surgery attenuates myocardial beta-adrenergic receptor (beta AR) desensitization. Although metoprolol did not reduce beta AR desensitization, the incidence of supraventricular arrhythmias was reduced by 75% in patients receiving 20 mg or 30 mg metoprolol.

The efficacy of the 5-HT3 receptor antagonists combined with droperidol for PONV prophylaxis is similar to their combination with dexamethasone. A meta-analysis of randomized controlled trials.

PURPOSE: The aim of this quantitative systematic review is to compare the efficacy and side effects of combining one of the 5-HT(3) receptor antagonists (5-HT) with droperidol or dexamethasone for postoperative nausea and vomiting (PONV) prophylaxis. METHODS: We performed a systematic search (Medline, Embase, and the Cochrane Library) for randomized controlled trials that compared the antiemetic efficacy of combining one of the 5-HT with droperidol or dexamethasone vs 5-HT alone. Relevant endpoints were prevention of early (0 to 6 hr), and overall (0 to 24 hr) PONV, and side effects. The articles that could meet the inclusion criteria were scored for inclusion and methodological validity using the three-item, five-point, Oxford-scale. Relative risk and numbers needed-to-treat with 95% confidence intervals were calculated for each combination vs 5-HT alone. The two combinations were then indirectly compared. A random effects model was used. RESULTS: We considered 41 trials for analysis but subsequently excluded eight. Thirty-three trials with data from 3,447 patients were analyzed. Except for early nausea with the 5-HT plus droperidol, both combinations were significantly more effective than 5-HT in preventing early and overall PONV. There was no difference in antiemetic efficacy between the two combinations. The incidence of commonly reported side effects was also similar in the two combination groups. CONCLUSION: We conclude that there is no statistically significant difference in antiemetic efficacy or side effects profile when one of the 5-HT is combined with either droperidol or dexamethasone and that both combination regimens are significantly more effective than 5-HT alone.

Cigarette smoking and decompression illness severity: a retrospective study in recreational divers.

BACKGROUND: Severe decompression illness (DCI) could be more likely in cigarette smokers because of airway obstruction or vascular disease. The present study evaluated the severity of DCI as a function of cigarette smoking in recreational divers. METHODS: We examined all DCI reports recorded in the Divers Alert Network (DAN) database from 1989 through 1997. Smoking history was quantified as heavy (>15 pack-years), light (0 to 15 pack-years), and never smoked. DCI symptoms were classified as severe (alteration in consciousness, balance or bladder/bowel control, motor weakness, visual symptoms, convulsions), moderate (other neurological symptoms), or mild (pain, skin, or nonspecific symptoms). The proportional odds model and generalized logits were used for the adjusted analysis when accounting for other covariates. RESULTS: There were 4,350 patients included in the analysis. After adjustment for confounding variables, heavy smokers were more likely to have severe vs. mild symptoms than nonsmokers (OR = 1.88) (95% CI 1.36, 2.60) or light smokers (OR = 1.56) (95% CI 1.09, 2.23). Heavy smokers and light smokers were more likely to have severe vs. moderate symptoms than nonsmokers (OR = 1.36) (95% CI 1.06, 1.74) and (1.22) (1.02, 1.46), respectively. Although these data do not reveal whether smoking predisposes to DCI, the results are consistent with a tendency, when DCI occurs, for cigarette smoking to trigger more severe symptoms. CONCLUSIONS: The data suggest that when DCI occurs in recreational divers, smoking is a risk factor for increased severity of symptoms.

Age increases expression and receptor-mediated activation of G alpha i in human atria.

Recently, we demonstrated that beta2AR and several other Galphas-coupled receptors in human atria also couple to Galphai, a G protein that inhibits adenylyl cyclase (AC). The present study was undertaken to determine whether age increases expression of Galphai in human atrium, and more specifically whether it results in an increase in receptor-mediated activation of Galphai. Right atrial appendages were obtained from 14 mature adult (40-55 years) and 14 elderly (71-79 years) patients undergoing cardiac surgery. Immunoblotting of atrial membranes indicates that elderly atria have 82 +/- 18% more Galphai2 than atria from mature adults (P < 0.002); this increase in Galphai with age is confirmed by pertussis toxin-catalyzed ADP-ribosylation as well as by photoaffinity labeling with [32P]azidoanilido-GTP. We also find that receptor-mediated activation of Galphai is greater in elderly atria and that both basal and receptor-mediated AC activities decrease in elderly atria. These decreases in AC activity can be reversed by disabling Galphai with pertussis toxin, indicating that the age-dependent increases in Galphai expression and activation have functional consequences. Because beta2ARs in human atria mediate contractility through cAMP-mediated phosphorylation of phospholamban, we conclude that an age-induced increase in Galphai may have a role in depressing cardiac function in aged human atria.

The relationship between ionized and total serum magnesium concentrations during abdominal surgery.

STUDY OBJECTIVE: To determine the necessity for ionized magnesium (iMg) assay by evaluating the effect of abdominal surgery without massive transfusion on total magnesium (Mg) and iMg concentrations. DESIGN: Prospective, observational study. SETTING: Operating rooms at a university teaching hospital. PATIENTS: 31 patients without electrolyte abnormalities who were scheduled for abdominal surgery. INTERVENTIONS: None. MEASUREMENTS: Serum electrolytes, iMg, ionized calcium, proteins before and after surgery, and urine Mg were recorded. MAIN RESULTS: Total Mg and iMg decreased: Mg 23%, iMg 15%; p < 0.0001. Total and iMg were highly correlated (r = 0.728, p < 0.0001). Urine Mg output remained within normal limits (mean 0.24 mmol/hr). CONCLUSIONS: During abdominal surgery without massive transfusion, both total and ionized hypomagnesemia occur. Changes in iMg and total serum Mg concentrations are closely correlated. Total serum Mg assay, while overestimating the prevalence of ionized hypomagnesemia, is sufficient to screen for hypomagnesemia.

How much are patients willing to pay to avoid intraoperative awareness?

STUDY OBJECTIVE: To determine how much patients are willing to pay to avoid intraoperative awareness? DESIGN: Observational study SETTING: University-affiliated metropolitan hospital. PATIENTS: 60 patients who completed a questionnaire (39 F, 21 M). The mean age was 43 years and the median household income range of 45,000-60,000 US dollars. INTERVENTIONS: Patients completed an interactive computer-generated questionnaire on the value of preventing intraoperative awareness and their willingness to pay for a "depth of anesthesia" monitor. Their willingness to pay for the prevention of postoperative pain, nausea and vomiting, postoperative grogginess, and sleepiness was also determined as a means of comparison. MEASUREMENTS AND MAIN RESULTS: Patients were willing to pay (WTP) 34 US dollars, 10 US dollars to 42 US dollars (median, interquartile range) for a monitor that would assist an anesthesia care provider assess the depth of anesthesia in an effort to avoid awareness. This increased to 43 US dollars, 20 US dollars to 77 US dollars (p < 0.0,001) (median, interquartile range), if the insurance company was making the payment and the WTP value only decreased minimally to 33 US dollars if the incidence of awareness was reduced 10-fold. CONCLUSION: The incidence of intraoperative awareness and WTP value for monitoring awareness have a nonlinear relationship (a risk averse utility function), which suggests that patients assign an intrinsic base value for a rare or very rare possibility of an event. Other healthcare economic analyses (such as cost effectiveness) do not take this factor into account and assume a linear value relationship (i.e., if something occurs ten times less frequently, it has ten times less value). IMPLICATION: The median value for patients' WTP for a monitor that might prevent awareness under anesthesia was 34 US dollars given an incidence of 5/1,000 cases. The incidence of awareness and WTP value have a nonlinear relationship suggesting that patients assign an intrinsic base value for the possibility of awareness.

Intraoperative colloid administration reduces postoperative nausea and vomiting and improves postoperative outcomes compared with crystalloid administration.

The debate over colloid versus crystalloid as the best solution for intraoperative fluid resuscitation is not resolved. Published studies have shown that mortality is not related to the specific fluid used for resuscitation. In addition, the quality of postoperative recovery between colloid and crystalloid has not been well investigated. In a prospective, blinded fashion, we investigated the effects of colloid and crystalloid resuscitation on nausea and vomiting and on the postoperative patient recovery profile. Patients undergoing major elective noncardiac surgery were randomized to receive 6% hetastarch in saline (HS-NS), 6% hetastarch in balanced salt (HS-BS), or lactated Ringer's solution (LR) on the basis of a fluid administration algorithm. The anesthetic was standardized. Hemodynamic targets included maintenance of arterial blood pressure, heart rate, and urine output within a predefined range. A postoperative morbidity survey was performed at baseline and daily after surgery. Ninety patients participated in the study, with 30 patients in each group. The amounts of study fluid (mean +/- SD) administered were 1301 +/- 1079 mL, 1448 +/- 759 mL, and 5946 +/- 1909 mL for the HS-NS, HS-BS, and LR groups, respectively (P < 0.05, HS-NS and HS-BS versus LR). Both the HS-NS and HS-BS (colloid) groups had a significantly less frequent incidence of nausea and vomiting, use of rescue antiemetics, severe pain, periorbital edema, and double vision. We concluded that intraoperative fluid resuscitation with colloid, when compared with crystalloid administration, is associated with an improvement in the quality of postoperative recovery.

Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood mononuclear cells.

BACKGROUND: Cardiopulmonary bypass (CPB) has been implicated in the development of organ injury associated with cardiac surgery. At the molecular level, CPB is accompanied by a pronounced proinflammatory response including an increase in plasma interleukin (IL)-6. The IL-6 has been shown to be increased in rheumatoid arthritis, a chronic inflammatory disease, where it has been implicated in decreasing G protein-coupled receptor kinases (GRKs) in peripheral blood mononuclear cells. Since IL-6 is substantially increased after CPB, the study tested whether the increase of IL-6 during CPB leads to a decrease of GRKs in mononuclear cells. This is important because GRKs regulate the function of G protein-coupled receptors involved in inflammation. METHODS: Fifteen patients had blood withdrawn before CPB, 2 h after CPB, and on postoperative day one (POD1). Plasma IL-6 concentrations were determined by enzyme-linked immunosorbent assay. The GRK protein expression and activity were determined by Western blot and phosphorylation of rhodopsin using [gamma-(32)P] adenosine triphosphate, respectively. RESULTS: Plasma IL-6 increased over 20-fold after CPB and remained increased on POD1. Cytosolic GRK activity in mononuclear cells decreased by 39 +/- 29%; cytosolic GRK2 and membrane-bound GRK6 decreased by 90 +/- 15 and 65 +/- 43%, respectively. The GRK activity and expression of GRK2/GRK6 on POD1 returned to basal levels in many but not all patients. CONCLUSIONS: The CPB causes a profound decrease in mononuclear cell GRKs, and the recovery of these kinases on POD1 is quite variable. The significance of the variable recovery of GRKs after CPB and their potential role as a marker of clinical outcome deserves further investigation.

Synchronous rhythmical vasomotion in the human cutaneous microvasculature during nonpulsatile cardiopulmonary bypass.

BACKGROUND: The origin, control mechanisms, and functional significance of oscillations in microvascular flow are incompletely understood. Although the traditional belief has been that only low-frequency oscillations (0.04-0.10 Hz) can originate at the microvascular level, recent evidence in healthy volunteers has suggested that high-frequency oscillations (> 0.10 Hz) also may have a microvascular origin (as opposed to being mechanically transmitted respiratory-induced variations in stroke volume). The current study determined if such oscillations would emerge in the absence of cardiac and respiratory activity during nonpulsatile cardiopulmonary bypass (NP-CPB). METHODS: Forehead and finger laser Doppler flow, arterial pressure, and core temperature were simultaneously recorded in eight patients during NP-CPB. Analyses included time- domain indices, frequency-domain indices (auto power spectral density), and a measure of regularity (approximate entropy) for standardized time segments. RESULTS: Nonpulsatile cardiopulmonary bypass was associated with the emergence of rhythmical oscillations in laser Doppler flow, with characteristic frequencies for the forehead (0.13 +/- 0.03 Hz) and finger (0.07 +/- 0.02 Hz). Forehead vasomotion became progressively synchronized, with a gain in high-frequency spectral power from 17.5 (minute 1) to 89.1 (minute 40) normalized units, and a decrease in approximate entropy from 1.2 (before NP-CPB) to less than 0.5 (minute 40). CONCLUSIONS: The emergence of forehead microvascular oscillations at greater than 0.10 Hz (characteristic of parasympathetic frequency response), in the absence of cardiac and respiratory variability, demonstrates their peripheral origin and provides insights into parasympathetic vasoregulatory mechanisms. The progressive synchronization of forehead vasomotion during NP-CPB, suggestive of increased coupling among microvascular biologic oscillators, may represent a microcirculatory homeostatic response to systemic depulsation, with potential implications for end-organ perfusion.

A new teaching model for resident training in regional anesthesia.

UNLABELLED: The adequacy of resident education in regional anesthesia is of national concern. A teaching model to improve resident training in regional anesthesia was instituted in the Anesthesiology Residency in 1996 at Duke University Health System. The key feature of the model was the use of a CA-3 resident in the preoperative area to perform regional anesthesia techniques. We assessed the success of the new model by comparing the data supplied by the Anesthesiology Residency to the Residency Review Committee for Anesthesiology for the training period July 1992-June 1995 (pre-model) and the training period July 1998-June 2001 (post-model). During the 3-yr training period, the pre-model CA-3 residents (n = 12) performed a cumulative total of 80 (58-105) peripheral nerve blocks (PNBs), 66 (59-74) spinal anesthetics, and 133 (127-142) epidural anesthetics. The CA-3 post-model residents (n = 10) performed 350 (237-408) PNBs, 107 (92-123) spinal anesthetics, and 233 (221-241) epidural anesthetics (P < 0.0001). All results are reported as median (interquartile range). We conclude that our new teaching model using our CA-3 residents as block residents in the preoperative area has increased their clinical exposure to PNBs. IMPLICATIONS: Inadequate exposure to peripheral nerve blocks has been a national problem. A teaching model instituted at Duke University Health System has resulted in a fourfold increase in exposure to peripheral nerve blocks compared with the national averages.

Lithium dilution cardiac output measurement: a clinical assessment of central venous and peripheral venous indicator injection.

OBJECTIVE: The lithium indicator dilution technique has been shown to measure cardiac output (CO) accurately by using central venous injection of lithium chloride (Li-CCO). This study aimed to compare the measurement of CO by using peripheral venous administration of lithium chloride (Li-PCO) with Li-CCO. DESIGN: Prospective, observational human study. SETTING: Surgical intensive care unit. PATIENTS: Thirty-one patients were studied after major surgery. All patients had arterial, central, and peripheral venous catheters. A total of 24 patients had pulmonary artery catheters. MEASUREMENTS: Serial measurements of Li-CCO and Li-PCO were made during hemodynamically stable conditions. CO was also measured using thermodilution (TDCO) when a pulmonary artery catheter was present. Data were analyzed by linear regression, the generalized estimating equation, and the comparison method described by Bland and Altman. MAIN RESULTS: There were 93 Li-CCOs, 93 Li-PCOs, and 216 TDCOs recorded. The ranges of COs were similar: Li-CCO, 2.36-11.52 L/min (mean, 5.22 L/min; n = 31); Li-PCO, 1.63-9.99 L/min (mean, 5.22 L/min; n = 31), and TDCO, 3.28-10.4 L/min (mean, 5.75 L/min; n = 24). There was good linear correlation between Li-CCO and Li-PCO (R2 =.845). The mean difference for Li-CCO-Li-PCO was very small and insignificant (p =.97), and the limits of agreement were acceptable (mean difference +/- sd, 0.0005 +/- 0.64 L/min). The mean difference for Li-CCO-Li-PCO was smaller if the peripheral injection site was proximal rather than distal to the wrist (p =.053). Li-PCO and Li-CCO values were lower than simultaneously obtained TDCO measurements (Li-PCO-TDCO, -0.538 +/- 0.95 L/min, p =.003; Li-CCO-TDCO, -0.526 +/- 0.67 L/min, p =.0001). CONCLUSIONS: Li-PCO gives a measurement that agrees well with Li-CCO. Accuracy of Li-PCO is probably improved if a proximal arm vein is used. Li-PCO provides accurate measurements of CO without the risks of pulmonary artery or central venous catheterization.

Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery.

BACKGROUND: Intraoperative hypovolemia is common and is a potential cause of organ dysfunction, increased postoperative morbidity, length of hospital stay, and death. The objective of this prospective, randomized study was to assess the effect of goal-directed intraoperative fluid administration on length of postoperative hospital stay. METHODS: One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were randomly assigned to a control group (n = 50) that received standard intraoperative care or to a protocol group (n = 50) that, in addition, received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume. Length of postoperative hospital stay and postoperative surgical morbidity were assessed. RESULTS: Groups were similar with respect to demographics, surgical procedures, and baseline hemodynamic variables. The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group. Patients in the protocol group had a shorter duration of hospital stay compared with the control group: 5 +/- 3 versus 7 +/- 3 days (mean +/- SD), with a median of 6 versus 7 days, respectively ( = 0.03). These patients also tolerated oral intake of solid food earlier than the control group: 3 +/- 0.5 versus 4.7 +/- 0.5 days (mean +/- SD), with a median of 3 versus 5 days, respectively ( = 0.01). CONCLUSIONS: Goal-directed intraoperative fluid administration results in earlier return to bowel function, lower incidence of postoperative nausea and vomiting, and decrease in length of postoperative hospital stay.

Esmolol improves left ventricular function via enhanced beta-adrenergic receptor signaling in a canine model of coronary revascularization.

BACKGROUND: Recent American Heart Association guidelines highlight the paucity of data on effectiveness and/or mechanisms underlying use of beta-adrenergic receptor (beta AR) antagonists after acute coronary syndromes in patients subsequently undergoing revascularization. It is important to assess whether beta AR antagonists might protect the heart and improve ventricular function in this scenario. The authors therefore used esmolol (an ultra-short-acting beta AR antagonist) to determine whether beta AR antagonist treatment improves left ventricular function in a canine model of acute reversible coronary ischemia followed by coronary reperfusion during cardiopulmonary bypass (CPB). The authors also tested whether the mechanism includes preserved beta AR signaling. METHODS: Dogs were randomized to either esmolol or saline infusions administered during CPB (n = 29). Pre-CPB and end-CPB transmyocardial left ventricular biopsies were obtained; plasma catecholamine concentrations, myocardial beta AR density, and adenylyl cyclase activity were measured. In addition, left ventricular systolic shortening and postsystolic shortening were determined immediately prior to each biopsy. RESULTS: While beta AR density remained unchanged in each group, isoproterenol-stimulated adenylyl cyclase activity decreased 26 +/- 6% in the control group but increased 38 +/- 10% in the esmolol group (pre-CPB to end-CPB, mean +/- SD, P = 0.0001). Left ventricular systolic shortening improved in both groups after release of coronary (LAD) ligature; however, the esmolol group increased to 72 +/- 23% of pre-CPB values compared to 48 +/- 12% for the control group (P = 0.0008). CONCLUSIONS: These data provide prospective evidence that esmolol administration results in improved myocardial function. Furthermore, the mechanism appears to involve enhanced myocardial beta AR signaling.

Comparison of the morphine-sparing effects of diclofenac sodium and ketorolac tromethamine after major orthopedic surgery.

STUDY OBJECTIVES: To compare the efficacy of diclofenac sodium with ketorolac tromethamine in reducing postoperative morphine use after major orthopedic surgery. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: Major teaching institution. PATIENTS: 102 ASA physical status II patients undergoing hip and knee replacement with general anesthesia. INTERVENTIONS: Before induction of anesthesia, patients were randomly allocated to receive intravenously either diclofenac sodium 75 mg (Group D), ketorolac tromethamine 60 mg (Group K), or placebo (Group P). Patient-controlled analgesia was supplied postoperatively using morphine. MEASUREMENTS: Visual analog scale (VAS), verbal pain score (VPS), sedation score, frequency of opioid side effects, and morphine consumption were recorded every 4 hours. MAIN RESULTS: There was a highly significant downward trend for VAS, VPS, and sedation scores over time, p = 0.001. The mean VAS and VPS scores were significantly lower in Groups D and K compared with Group P at time 0, p = 0.009 and 8 hours, p = 0.026. The mean (SD) 24-hour morphine requirements were 36.3 mg (16.9), 47.2 mg (34.9), and 51.6 mg (22.2) for Groups D, K, and P, respectively, p = 0.032. Fewer patients suffered from postoperative nausea and vomiting in the treatment groups (Groups D and K) compared with Group P (9, 8, and 19, respectively), p < 0.05. Fewer patients also suffered from pruritus in Groups D and K compared with Group P (3, 4, and 11, respectively), p < 0.01. CONCLUSIONS: Preoperative administration of intravenous diclofenac 75 mg or ketorolac 60 mg significantly reduces morphine requirements and associated side effects after major orthopedic surgery.

A randomized, double-blind comparison of ondansetron versus placebo for prevention of nausea and vomiting after infratentorial craniotomy.

Ondansetron was compared with placebo for nausea and vomiting prophylaxis after fentanyl/isoflurane/relaxant anesthesia and infratentorial craniotomy. Eight milligrams intravenous ondansetron or vehicle was administered at skin closure. Nausea, emesis, and antiemetic use were recorded at 0, 0.5, 1, 4, 8, 12, 24, and 48 hours. There were no significant intergroup differences for nausea incidence at any interval, but cumulatively the placebo group was 3.2 times more likely to develop nausea during the first 12 hours (P = .04). Nausea incidence was bimodal in both groups, peaking during the first 1 to 4 hours. A nadir occurred at 8 to 12 hours, but nausea increased during the next 36 hours. By 48 hours, approximately 40% of patients in both groups were still nauseated. Reduced vomiting frequency was seen with ondansetron at 4, 8, 12, and 24 hours (P < .05). Despite rescue antiemetics, emesis occurred in an irregular pattern with episodes still observed in 35% of placebo patients at 48 hours. For ondansetron, emesis was infrequent for the first 12 hours but then a persistent increase was observed (48 hours, 22%). The incidence of rescue antiemetic use was 65% for both groups. There was no effect of gender. Nausea and vomiting are frequent and protracted after infratentorial craniotomy. Administration of single-dose ondansetron (8 mg intravenously) at wound closure was partially effective in reducing acute nausea and vomiting but had little delayed benefit. Scheduled prophylactic administration of antiemetic therapy during the first 48 hours after infratentorial craniotomy should be evaluated for efficacy and safety.