Measurement of endogenous nitric oxide production.

The measurement of exhaled pulmonary nitric oxide concentrations requires that contamination from the upper respiratory tract and inhaled gases be eliminated. This can be achieved with no risk in the clinical setting of intubated patients of all ages in the operating room or intensive care unit. Further modifications of the anesthetic/ventilatory circuit allow for accurate determination of tidal volume and minute ventilation.

The "Balanced Scorecard": development and implementation in an academic clinical department.

If quality medical education is to survive in the increasingly competitive marketplace, medical schools need to adopt new tools that measure the value of all initiatives, both financial and non-financial, so that they can make informed decisions about their missions and future direction. The authors describe a tool of this kind called the Balanced Scorecard (originally created for traditional businesses), outline the version of it that they developed for the Department of Anesthesiology at Yale University School of Medicine, and discuss the first year of implementation (which began in 1997). The Balanced Scorecard is a set of measures designed to examine an organization's performance from the following four perspectives and to answer the key question suggested by each perspective: (1) The learning and growth perspective: Can we continue to improve and create value? (2) The internal business perspective: What must we excel at? (3) The customer perspective: How do our customers see us? (4) The financial perspective: How do we look to our shareholders? The first year of implementation of this approach at the Department of Anesthesiology involved creating measures of the four perspectives, determining whether data could be found for each measure and whether the data were in usable forms, and educating and involving the faculty in the process. The authors discuss the pros and cons of the Balanced Scorecard approach that they observed during the first year, and conclude with a list of seven lessons learned (e.g., start with measures that already exist). Overall, they are convinced that the Balanced Scorecard can be of great value to a department, even if the full implementation takes several years to complete.

Establishment of a pediatric surgery center: increasing anesthetic efficiency.

STUDY OBJECTIVE: To examine whether the establishment of dedicated pediatric operating rooms (ORs) staffed exclusively by pediatric anesthesiologists has had a significant impact on anesthetic efficiency during surgery. STUDY DESIGN: Before and after design. SETTING: General and pediatric operating rooms at Yale-New Haven Hospital. MEASUREMENTS AND MAIN RESULTS: Using Operating Room Information System data (1991 to 1997), we examined whether the anesthesia-controlled time, the time it takes for induction and emergence of anesthesia of a selected surgical procedure (tonsillectomy and adenoidectomy), was affected by the change of practice from general to pediatric ORs. The average length of anesthesia induction decreased by 30% (p = 0.0007). Similarly, the average length of emergence from anesthesia decreased by 42% (p = 0.01) and anesthesia-controlled time decreased by 31% (p = 0.0008). Of particular importance is the decrease by 75% in the anesthesia-controlled time range (maximum-minimum). CONCLUSIONS: The establishment of dedicated pediatric ORs resulted in significantly shorter anesthesia induction and emergence times. Furthermore, the decreased variability of anesthesia-controlled time may allow for better scheduling of surgical cases and for better surgeon and patient satisfaction.

Single-dose ondansetron prevents postoperative vomiting in pediatric outpatients.

UNLABELLED: This randomized, double-blind, parallel-group, multicenter study evaluated the safety and efficacy of ondansetron (0.1 mg/kg to 4 mg intravenously) compared with placebo in the prevention of postoperative vomiting in 429 ASA status I-III children 1-12 yr old undergoing outpatient surgery under nitrous oxide- and halothane-based general anesthesia. The results show that during both the 2-h and the 24-h evaluation periods after discontinuation of nitrous oxide, a significantly greater percentage of ondansetron-treated patients (2 h 89%, 24 h 68%) compared with placebo-treated patients (2 h 71%, 24 h 40%) experienced complete response (i.e., no emetic episodes, not rescued, and not withdrawn; P < 0.001 at both time points). Ondansetron-treated patients reached criteria for home readiness one-half hour sooner than placebo-treated patients (P < 0.05). The age of the child, use of intraoperative opioids, type of surgery, and requirement to tolerate fluids before discharge may also have affected the incidence of postoperative emesis during the 0- to 24-h observation period. Use of postoperative opioids did not have any effect on complete response rates in this patient population. We conclude that the prophylactic use of ondansetron reduces postoperative emesis in pediatric patients, regardless of the operant influential factors. IMPLICATIONS: Postoperative nausea and vomiting often occur after surgery and general anesthesia in children and are the major reason for unexpected hospital admission after ambulatory surgery. Our study demonstrates that the prophylactic use of a small dose of ondansetron reduces postoperative vomiting in pediatric patients.

Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group.

BACKGROUND: Persistent pulmonary hypertension of the newborn causes systemic arterial hypoxemia because of increased pulmonary vascular resistance and right-to-left shunting of deoxygenated blood. Inhaled nitric oxide decreases pulmonary vascular resistance in newborns. We studied whether inhaled nitric oxide decreases severe hypoxemia in infants with persistent pulmonary hypertension. METHODS: In a prospective, multicenter study, 58 full-term infants with severe hypoxemia and persistent pulmonary hypertension were randomly assigned to breathe either a control gas (nitrogen) or nitric oxide (80 parts per million), mixed with oxygen from a ventilator. If oxygenation increased after 20 minutes and systemic blood pressure did not decrease, the treatment was considered successful and was continued at lower concentrations. Otherwise, it was discontinued and alternative therapies, including extracorporeal membrane oxygenation, were used. RESULTS: Inhaled nitric oxide successfully doubled systemic oxygenation in 16 of 30 infants (53 percent), whereas conventional therapy without inhaled nitric oxide increased oxygenation in only 2 of 28 infants (7 percent). Long-term therapy with inhaled nitric oxide sustained systemic oxygenation in 75 percent of the infants who had initial improvement. Extracorporeal membrane oxygenation was required in 71 percent of the control group and 40 percent of the nitric oxide group (P=0.02). The number of deaths was similar in the two groups. Inhaled nitric oxide did not cause systemic hypotension or increase methemoglobin levels. CONCLUSIONS: Inhaled nitric oxide improves systemic oxygenation in infants with persistent pulmonary hypertension and may reduce the need for more invasive treatments.

Premedication in the United States: a status report.

We undertook a mailing survey study to assess the current practice of sedative premedication in anesthesia. A total of 5396 questionnaires were mailed to randomly selected physician members of the American Society of Anesthesiologists. Forty-six percent (n = 2421) of those sampled returned the questionnaire after two mailings. The reported rate of sedative premedication in the United States varied widely among age groups and geographical locations. Premedicant sedative drugs were least often used with children younger than age 3 years and most often used with adults less than 65 years of age (25% vs 75%, P = 0.001). Midazolam was the most frequently used premedicant both in adults and children (> 75%). When analyzed based on geographical locations, use of sedative premedicants among adults was least frequent in the Northeast region and most frequent in the Southeast region (50% vs 90%, P = 0.001). When the frequency of premedication was examined against health maintenance organization (HMO) penetration (i.e., HMO enrollment by total population) in the various geographical regions, correlation coefficients (r) ranged from -0.96 to -0.54. Multivariable analysis revealed that HMO penetration is an independent predictor for the use of premedication in adults and children. The marked variation among geographical areas in premedicant usage patterns underscores the lack of consensus among anesthesiologists about the need for premedication. The data suggest that HMO participation may affect delivery of this component of anesthetic care.

Pulmonary protective and vasodilator effects of a standardized Panax ginseng preparation following artificial gastric digestion.

We have previously demonstrated that purified ginsenosides produce pulmonary vasodilation and prevent effects of free radical injury on the lung. We examined the effect of artificially digested standardized ginseng preparation G115 in perfused rabbit lungs. G115 was incubated in artificial gastric juice (0.03 M NaCl + 0.08 M HCl) 37 degrees C for 1 h, and artificial intestinal juice (0.05 M KH2PO4 + 0.02 M NaOH) 37 degrees C for 5 h, neutralized with NaOH and lyophilized. Pulmonary vasoconstriction was induced with U46619, and cumulative additions of G115 in undigested, gastric digested and gastric and intestinal digested forms were made to the perfusate. In separate experiments, oxygen free radical injury by electrolysis was produced in the presence of G115 in the perfusate and ACh-induced vasodilation assessed before and after injury. Undigested, gastric digested and combined gastric and intestinal digested G115 significantly dilated lungs (44%, undigested; 26%, gastric digested; 45%, gastric and intestinal digested). In addition, both undigested (-27 +/- 5% vs. -24 +/- 5%) as well as gastric and intestinal digested G115 (-23 +/- 3% vs. -16 +/- 2%) preserved ACh-induced vasodilation following injury. Artificially digested G115 is a pulmonary vasodilator which protects against free radical injury, suggesting that oral G115 has the same effects.

Parental presence during induction of anesthesia. A randomized controlled trial.

BACKGROUND: To determine whether parental presence during induction of anesthesia is an effective preoperative behavioral intervention, a randomized controlled trial with children undergoing outpatient surgery was conducted. METHODS: Eighty-four children were randomly assigned to a parent-present or parent-absent group. Using multiple behavioral and physiologic measures of anxiety, the effect of the intervention on the children and their parents was assessed. Predictors for the response to the intervention were examined using multivariate linear regression analysis. RESULTS: When the intervention group (parent-present) was compared to the control group (parent-absent), overall there were no significant differences in any of the behavioral or physiologic measures of anxiety tested during induction of anesthesia. Using the child's serum cortisol concentration as the outcome, parental presence, the child's age and baseline temperament, and trait anxiety of the parent, were identified as predictors of the child's anxiety during induction. Analysis of variance demonstrated that three groups showed diminished cortisol concentrations with parental presence: children older than 4 yr (P = 0.001), children whose parent had a low trait anxiety (P = 0.02), and children who had a low baseline level of activity as assessed by temperament (P = 0.05). CONCLUSIONS: Children who were older than 4 yr or those with a parent with a low trait anxiety or who had a low baseline level of activity/temperament benefited from parental presence during induction.

Parental presence during induction of anaesthesia: practice differences between the United States and Great Britain.

A questionnaire was sent to 1353 paediatric anaesthetists in Great Britain and the United States. Nineteen questions were asked about attitudes toward parental presence during induction of anaesthesia and the prevalence of such practice. Overall, respondents from Great Britain support parental presence more than the United States respondents. For example, 82% of the Great Britain respondents, vs 64% of the United States respondents thought that parental presence during induction decreases the anxiety (P = 0.001) and increases the cooperation of the child (P = 0.001). Most United States respondents (58%) allow parental presence in less than 5% of their cases, but most Great Britain respondents (84%) allow parental presence in more than 75% of their cases. We conclude that in contrast to the respondents from Great Britain, the majority of the United States sample does not feel that parental presence is useful and so does not routinely use this technique in their practice.

Management of chronic pain in children.

Much has been written about the recognition and treatment of acute pain, but the syndrome of chronic pain in the pediatric population has received little attention. A pediatrician faced with a child suffering from recurrent or chronic pain first should exclude an underlying organic illness. However, the clinician also should understand that recurrent painful episodes may lack an organic cause; they may be triggered by a variety of external and internal factors, particularly perceived stress. The consequences of the child's pain and its relief must be evaluated and viewed in the context of rewards, secondary gain, and parental anxiety. Chronic pain may influence self-esteem, socialization, and academic achievement, and these issues must be addressed.

Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung.

To determine the site of inhaled nitric oxide (NO)-induced pulmonary vasodilation, a double vascular occlusion technique was used with rabbit lungs ventilated and perfused at 20 ml/min with Krebs solution containing 3% dextran and 30 microM indomethacin. Inhaled NO (120 ppm for 3 min) reduced pulmonary vasoconstriction produced by U-46619 infusion (0.5-1.2 nmol/min), significantly decreasing total resistance (RT) [1,080 +/- 51 (SE) vs. 1,545 +/- 109 mmHg.l-1.min; P < 0.01]. Acetylcholine infusion (ACh; 2-5 nmol/min) and nitroglycerin (NTG; 0.35 mumol) likewise decreased RT. Arterial resistance (Ra) was also significantly less with inhaled NO, ACh, and NTG compared with U-46619 alone. Venous resistance (Rv), however, was unchanged. When the direction of perfusion was reversed in the lung, inhaled NO, ACh, and NTG significantly decreased RT compared with U-46619 alone, and Rv was also reduced by all three agents. After electrolysis-induced acute lung injury, inhaled NO significantly reduced both RT and Ra compared with U-46619 alone, whereas Rv was unaffected. Our results demonstrate that inhaled NO gas affects primarily the arterial (precapillary) component of the pulmonary circulation but, under conditions of extreme venous constriction, may dilate the postcapillary component as well.

A first-pass cost analysis of propofol versus barbiturates for children undergoing magnetic resonance imaging.

Intravenous (IV) propofol was compared with IV thiopental/pentobarbital as a sedative for children undergoing magnetic resonance imaging (MRI) of the brain or spine. Fifty-eight outpatients (aged 11 mo to 6 1/2 yr, ASA grade I and II) were enrolled in the study and randomized to two groups. After IV cannulation, Group I received IV propofol (1-2 mg/kg), followed immediately by a propofol infusion (75-100 micrograms.kg-1.min-1). Group II received IV thiopental (1-3 mg/kg) followed by a pentobarbital bolus (2-3 mg/kg). Supplemental thiopental doses (1-2 mg/kg) were administrated to maintain adequate sedation. Discharge time and postanesthesia recovery scores were determined by an independent blinded observer. Time of recovery to full consciousness in Group I was significantly less than in Group II (19 +/- 7 min vs 35 +/- 20; P < 0.005). Time to discharge was also significantly less in Group I (24 +/- 6 min vs 40 +/- 11; P < 0.05). A preliminary cost analysis was applied to the clinical data obtained and to a theoretical model of a pediatric MRI center. Cost analysis of anesthesia services revealed added drug costs ($1600.76 per year for the propofol group) but significant savings of postanesthesia care unit (PACU) nursing time ($5086.67 per year). Outcomes such as patient morbidity and technical quality of the MRI scans did not differ significantly between the two groups. In conclusion, analysis of the clinical data suggests that propofol may be more suitable than barbiturates for children undergoing outpatient procedures despite its higher price.

Nicotine regulates collagen gene expression, collagenase activity, and DNA synthesis in cultured cardiac fibroblasts.

Cardiac fibroblasts that reside in the interstitium are the cellular origin of collagen and other proteins of the extracellular matrix in the heart. We have previously shown that in vitro gene expression, proliferation and even phenotypic features of cardiac fibroblasts are subject to regulation by biological factors such as hormones, growth factors and neurotransmitters. The influence of nicotine, the active ingredient of tobacco, on risk factors for cardiac diseases is well known. In vivo adverse effects of nicotine are as the result of its direct and indirect effects. The cellular and molecular mechanisms of direct effects of nicotine in the heart are widely unknown. The objective of this study was to investigate if nicotine has direct influence on cardiac fibroblasts. To this end, we studied the effects of nicotine on cultured cardiac fibroblasts. Northern hybridization analysis of RNA extracted from cardiac fibroblasts, enzymography of conditioned medium of cardiac fibroblasts and [3H]-thymidine incorporation into DNA of cardiac fibroblasts were used to examine the effects of nicotine on collagen gene expression, collagenase activity and DNA synthesis respectively. Treatment of cardiac fibroblasts with nicotine (10 micrograms/ml) led to a 31% (P < 0.05) decrease in the abundance of mRNA for pro alpha 1(I) but not pro alpha 2(I) collagen compared with control untreated cells. Nicotine treatment of cardiac fibroblasts also led to decreased collagenase activity (62%, P < 0.001) in the conditioned medium of those cells in culture. Studies with [3H]-thymidine incorporation into DNA of cardiac fibroblasts showed a nicotine-induced decrease (39%, P < 0.001) in DNA synthesis in those cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective pulmonary vasodilation by inhaled nitric oxide is due to hemoglobin inactivation.

BACKGROUND: Inhaled nitric oxide gas selectively decreases pulmonary artery pressure without affecting systemic arterial pressure. To determine if the selective pulmonary vasodilating effect of inhaled nitric oxide gas is due to inactivation by hemoglobin, we studied the ability of whole blood to inhibit the vasodilator activity of effluent from isolated lungs exposed to inhaled nitric oxide. METHODS AND RESULTS: The effluent from ventilated, Krebs-perfused rabbit lungs was passed directly over 3- to 4-mm rabbit aortic rings. Inhaled nitric oxide (150 ppm for 3 minutes) reduced pulmonary perfusion pressure, elevated by a continuous infusion of U46619, by 35 +/- 7% (mean +/- SEM, n = 5). Lung effluent from this series of experiments caused 40 +/- 13% relaxation of phenylephrine-preconstricted aortic rings. When blood was added to the combined lung/ring perfusion cascade (final hemoglobin concentration, 1 g/dL), inhaled nitric oxide again significantly reduced pulmonary perfusion pressure, but the effluent now failed to relax the aortic rings (30 +/- 6% [control] versus 1.5 +/- 1% [blood]). Both reduction in pulmonary perfusion pressure and relaxation of the rings during nitric oxide exposure were unchanged from control values after discontinuing the blood infusion. CONCLUSIONS: The presence of hemoglobin, even in extremely small amounts, restricts the vasodilating effect of inhaled nitric oxide gas to the pulmonary circulation.

Cocaine abuse in the parturient and effects on the fetus and neonate.

The growing use of cocaine among pregnant women and women of childbearing age has become an issue of great concern to physicians. Cocaine abuse among parturients is associated with multi-target organ involvement, including the cardiovascular, respiratory, neurologic, and hematologic systems. Cocaine use during pregnancy is also an independent contributor to the risk of placental abruption, preterm labor, precipitate delivery, stillbirth, and others. Although a history of premature rupture of membranes, smoking, alcohol use, syphilis serology, and use of other illicit drugs suggests cocaine abuse, the single most important predictor is the absence of prenatal care. The intraoperative anesthetic management should take into consideration the different effects of cocaine on the mother, the fetus, and the neonate.

Pulmonary vasodilation by inhaled nitric oxide after endothelial injury.

Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally induced pulmonary vasoconstriction. To examine the effect of free radical injury and methylene blue exposure on inhaled NO-induced pulmonary vasodilation we studied ventilated rabbit lungs perfused with Krebs solution containing 3% dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by the thromboxane analogue U-46619 was significantly reduced [8 +/- 2 (SE) mmHg]. Acetylcholine similarly reduced Ppa (9 +/- 1 mmHg). After free radical injury and methylene blue exposure, inhaled NO again produced significant vasodilation (5 +/- 1 and 9 +/- 2 mmHg, respectively), but acetylcholine resulted in an increase in Ppa (-9 +/- 3 and -4 +/- 1 mmHg, respectively). These data demonstrate that pulmonary vasodilation produced by inhaled NO is unaffected by free radical injury or methylene blue in the intact lung despite concomitant reversal of acetylcholine-induced vasodilation.

Differential uptake of endothelin-1 by the coronary and pulmonary circulations.

Substantial removal of the vasoconstrictor peptide endothelin-1 (ET-1) by the pulmonary circulation has been reported to occur in perfused guinea pig and rat lungs. We examined the uptake of ET-1 by coronary and pulmonary circulations of the rabbit by measuring single-pass extraction of ET-1 in the isolated heart and lung. In separate experiments, each organ was perfused at 30 ml/min with Krebs-albumin (3%) solution. A bolus of 125I-ET-1 and [14C]dextran in 0.3 ml Krebs-albumin solution was injected, and extraction of endothelin (EET), relative to that of an intravascular reference indicator, [14C]dextran, was determined by multiple indicator-dilution technique. EET was 5 +/- 2% (SE) in the heart and 49 +/- 4% in the lung. Increasing flow rate in the lung preparation to approximate the mean transit time in the heart preparation did not significantly alter EET. Despite insignificant uptake of ET-1, the coronary circulation extracted an angiotensin-converting enzyme inhibitor (351A) and metabolized a synthetic angiotensin-converting enzyme substrate (benzoyl-phenyl-alanyl-proline), both properties of the normal pulmonary circulation. We therefore conclude that there is no significant ET-1 uptake in the coronary vascular bed.