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.

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.

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.

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.

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.

Race differences in reproducibilities: The HERITAGE family study.

The HERITAGE (HEalth, RIsk factors, exercise Training And GEnetics) Family Study is a multicenter clinical trial conducted by five institutions in the United States and Canada. The overall objective of the study is to investigate the role of the genotype in cardiovascular, metabolic, and hormonal responses to aerobic exercise training and the contribution of regular exercise to changes in cardiovascular disease and diabetes risk factors in white and black families. Since the accuracy of the assessment of the response to training depends on how repeatable or reproducible the measurements are, it is important to assess potential racial differences in reproducibilities, which may have implications for pooling data across races. The sample studied consisted of 96 blacks and 304 whites. The black sample had 46 males with mean age 33.6 ± 14.2 years and 40 females with mean age 33.9 ± 12.7 years. The white sample had 152 males with mean age 35.5 ± 14.9 years, and 152 females with mean age 34.9 ± 14.3 years. Reproducibilities, as measured by intraclass correlations among repeated measures, were comparable between whites and blacks for variables in the anthropometry, i.e, lipid, exercise test, and blood pressure domains. Reproducibilities in both races exceeded 0.85 for most of the variables. When the within-race reproducibilities are very high, statistical significance of any observed racial difference in the reproducibilities may not be very meaningful. There was a significant racial difference in the reproducibility for Apoprotein A1 (0.73 in blacks, 0.89 in whites, P < 0.01). However, this is not a cause for concern, since only one among 37 comparisons was significant. Am. J. Hum. Biol. 9:415-424, 1997. © 1997 Wiley-Liss, Inc.