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Introduction About one-third of critically ill patients with acute kidney injury (AKI) develop persistently decreased kidney function, known as acute kidney disease (AKD), which may progress to chronic kidney disease (CKD). Although sepsis is the most common cause of AKI, little is known about sepsis-associated AKD. Methods Using data from a large randomized trial including 1341 patients with septic shock, we studied patients with stage 2 or 3 AKI on day 1 of hospitalization. We defined AKD as a persistently reduced glomerular filtration rate for >7 days. In addition to clinical data, we measured several urinary biomarkers (tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2∗IGFBP7], neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1], liver-type fatty acid binding protein, and type 4 collagen) at 0, 6, and 24 hours, to predict AKD. Results Of 598 patients, 119 (19.9%) died within 7 days, 318 (53.2%) had early reversal of AKI within the first 7 days, whereas 161 (26.9%) developed AKD. In patients with early reversal, 45 (14.2%) had relapsed AKI after early reversal, and only about one-third of these recovered. Among patients developing AKD, only 15 (9.3%) recovered renal function prior to discharge. Male sex, African American race, and underlying CKD were more predominant in patients developing AKD. None of the biomarkers tested performed well for prediction of AKD, although NGAL modestly increased the performance of a clinical model. Conclusions AKD is common in patients with septic shock, especially among African American males and those with underlying CKD. Existing AKI biomarkers have limited utility for predicting AKD but might be useful together with clinical variables. Novel predictive biomarkers for renal recovery are needed., Graphical abstract

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Operating room waste is categorized as noncontaminated solid waste (SW) and regulated medical waste (RMW). RMW is treated by autoclaving at an increased economic and environmental cost. We evaluated these costs with a focus on the disposable carbon dioxide (CO2) absorbers. At our institution, exhausted CO2 absorbers were discarded as RMW. We collaborated with product representatives, anesthesia and perioperative staff, and waste management personnel to identify opportunities and barriers for recycling and waste reduction. Ultimately, we agreed to discard CO2 absorbers as SW instead of RMW, a strategy that is practical, less expensive, and more environmentally appropriate.

Background We sought to determine the effects of alternative resuscitation strategies on microcirculatory perfusion and examine any association between microcirculatory perfusion and mortality in sepsis. Methods This was a prospective, formally designed substudy of participants in the Protocolized Care in Early Septic Shock (ProCESS) trial. We recruited from six sites with the equipment and training to perform these study procedures. All subjects were adults with septic shock, and each was assigned to alternative resuscitation strategies. The two main analyses assessed (1) the impact of resuscitation strategies on microcirculatory perfusion parameters and (2) the association of microcirculatory perfusion with 60-day in-hospital mortality. We measured sublingual microcirculatory perfusion using sidestream dark field in vivo video microscopy at the completion of the 6-h ProCESS resuscitation protocol and then again at 24 and 72 h. Results We enrolled 207 subjects (demographics were similar to the overall ProCESS cohort) and observed 40 (19.3%) deaths. There were no differences in average perfusion characteristics between treatment arms. Analyzing the relationship between microcirculatory perfusion and mortality, we found an association between vascular density parameters and mortality. Total vascular density (beta = 0.006, p

Objective To test the hypothesis that obstructive sleep apnea (OSA) is a risk factor for development of postoperative atrial fibrillation (POAF) after cardiac surgery. Design Retrospective analysis. Setting Single-center university hospital. Participants Five hundred forty-five patients in sinus rhythm preoperatively undergoing coronary artery bypass grafting (CABG), aortic valve replacement, mitral valve replacement/repair, or combined valve/CABG surgery from January 2008 to April 2011. Interventions Retrospective review of medical records. Measurements and Main Results Postoperative atrial fibrillation was defined as atrial fibrillation requiring therapeutic intervention. Of 545 cardiac surgical patients, 226 (41%) patients developed POAF. The risk was higher in 72 OSA patients than 473 patients without OSA (67% v 38%, adjusted hazard ratio 1.83 [95% CI: 1.30-2.58], p

Objective To evaluate the efficacy of tezosentan in reducing the incidence of right ventricular (RV) failure and associated mortality in patients with pre-existing pulmonary hypertension. The primary endpoint was the proportion of patients with RV failure during weaning from cardiopulmonary bypass (CPB), assessed 30 minutes after the end of CPB. Design Multicenter, double-blind, randomized, placebo-controlled trial. Setting Thirty-one cardiac surgical centers in 14 countries. Participants Two hundred seventy-four patients with pulmonary hypertension aged≥18 years scheduled to undergo cardiac surgery. Intervention Intravenous tezosentan (5 mg/h) during surgery and up to 24 hours afterwards (1 mg/h), or matched placebo. Measurements and Main Results One-hundred thirty-three patients received tezosentan and 141 placebo. RV failure occurred in 30 patients (10.9%), 37% of whom died. There was no difference in the incidence of RV failure between the two treatment groups (relative risk reduction: 0.07 [95% CI−0.83, 0.53; P = 0.8278]). Conclusion A reduction in RV failure with tezosentan was not observed in this study.(Current Controlled Trials, identifier NCT00458276).

Background The Stanford Anesthesia Teaching Scholars Program was launched in 2007 to further pedagogic training of faculty and improve residency education. Objectives The goals of this article are to describe the program intervention and improvements made based on participant feedback, summarize the characteristics of the faculty enrolled and projects undertaken, and report on program outcomes tracked to date. Intervention The Teaching Scholars Program housed within the Department of Anesthesia supports faculty in these areas: (1) attending education-related meetings; (2) engaging in a monthly seminar on core topics paired with independent study reading; and (3) undertaking a project to improve resident education. Structured interviews with all graduates (n = 19; 47% women) were conducted using a pilot-tested questionnaire. Results A total of 15 of 19 Scholars (79%) were instructors/assistant professors. Sixteen Scholars (84%) attended an off-site education meeting. The Scholars pursued a variety of projects, including curriculum (53%), teaching (26%), administration (11%), assessment (5%), and advising/mentoring (5%). Projects were fully completed by 13 of 19 participants (68%), and 12 of 19 projects (63%) are currently integrated into the residency. Completed projects were published/presented at conferences by 4 of 13 participants (31%), and education grants were received by 3 of 19 participants (16%). Conclusions This is the first description of a faculty development (education) program in an anesthesiology department. The program has been well accepted by participants and resulted in increased educational products, some of which have become a permanent part of the residency curriculum. This educational innovation can be replicated in other departments of anesthesiology provided that funding is available for faculty time and meeting expenses.

Background The transition from internship to residency training may be a stressful time for interns, particularly if it involves a change among programs or institutions after completing a preliminary year. Objective We explored whether an e-learning curriculum would increase interns' preparedness for the transition to the first year of clinical anesthesiology training and reduce stress by improving confidence and perceived competence in performing professional responsibilities. Intervention We tested a 10-month e-learning program, Successful Transition to Anesthesia Residency Training (START), as a longitudinal intervention to increase interns' self-perceived preparedness to begin anesthesiology residency training in a prospective, observational study and assessed acceptance and sustainability. After a needs assessment, we administered the START modules to 22 interns, once a month, using an integrated learning management and lecture-capture system. We surveyed interns' self-assessed preparedness to begin anesthesiology residency before and after completing the START modules. Interns from the prior year's class, who did not participate in the online curriculum, served as controls. Results After participation in the START intervention, self-assessed preparedness to begin residency improved by 72% (P = .02). Interns also felt more connected to, and had improved positive feelings toward, their new residency program and institution. Conclusion Participation in our novel 10-month e-learning curriculum and virtual mentorship program improved interns' impression of their residency program and significantly increased interns' subjective assessment of their preparedness to begin anesthesiology residency. This e-learning concept could be more broadly applied and useful to other residency programs.

Background Despite the use of web-based information resources by both anesthesia departments and applicants, little research has been done to assess these resources and determine whether they are meeting applicant needs. Evidence is needed to guide anesthesia informatics research in developing high-quality anesthesia residency program Web sites (ARPWs). Methods We used an anonymous web-based program (SurveyMonkey, Portland, OR) to distribute a survey investigating the information needs and perceived usefulness of ARPWs to all 572 Stanford anesthesia residency program applicants. A quantitative scoring system was then created to assess the quality of ARPWs in meeting the information needs of these applicants. Two researchers independently analyzed all 131 ARPWs in the United States to determine whether the ARPWs met the needs of applicants based on the scoring system. Finally, a qualitative assessment of the overall user experience of ARPWs was developed to account for the subjective elements of the Web site's presentation. Results Ninety-eight percent of respondents reported having used ARPWs during the application process. Fifty-six percent reported first visiting the Stanford ARPW when deciding whether to apply to Stanford's anesthesia residency program. Multimedia and Web 2.0 technologies were "very" or "most" useful in "learning intangible aspects of a program, like how happy people are" (42% multimedia and Web 2.0 versus 14% text and photos). ARPWs, on average, contained only 46% of the content items identified as important by applicants. The average (SD) quality scores among all ARPWs was 2.06 (0.59) of 4.0 maximum points. The mean overall qualitative score for all 131 ARPWs was 4.97 (1.92) of 10 points. Only 2% of applicants indicated that the majority (75%-100%) of Web sites they visited provided a complete experience. Conclusion Anesthesia residency applicants rely heavily on ARPWs to research programs, prepare for interviews, and formulate a rank list. Anesthesia departments can improve their ARPWs by including information such as total hours worked and work hours by rotation (missing in 96% and 97% of ARPWs) and providing a valid web address on the Fellowship and Residency Electronic Interactive Database Access System (FREIDA) (missing in 28% of ARPWs).

There are substantial data supporting the concept that algorithms that effectively limit fluid volumes to patients undergoing elective surgery, particularly intraoperatively, significantly reduce perioperative morbidity. We hypothesized that intraoperative fluid limitation could be safely accomplished when guided by near-infrared spectroscopy (NIRS) monitoring, and that this fluid restriction regimen would result in a reduction in postoperative morbidity when compared with standard monitoring and fluid therapy. The intent of this pilot study was to demonstrate the feasibility and ease of conduct of this study protocol before expanding to the multicenter pivotal trial. We performed a prospective, (2:1) randomized, pilot study at two centers. A total enrollment of 24 fully evaluable patients undergoing elective open colorectal surgery (16 restricted, 8 standard) was planned. After providing informed consent, patients were randomized to standard fluid resuscitation (500 LR induction bolus, then LR 7 mL/kg/h X 1 h, then 5 mL/kg/h) or restricted fluid resuscitation (no induction bolus, then LR 2 mL/kg/h). Subsequent fluid bolus infusions were guided by physiologic parameters (systolic blood pressure < 90 mm Hg, heart rate > 100 bpm, or oliguria) in the standard group, and by tissue oxygen saturation from NIRS (tissue oxygen saturation (StO2) < 75%, or 20% below baseline; or the same physiologic parameters) in the restricted group. Primary endpoints were major postoperative complications. A total of 27 patients were randomized (18 restricted, 9 standard). Age, gender, ethnicity, past medical history, and body mass index were similar. American Society of Anesthesiologists class was somewhat higher in the restricted group (American Society of Anesthesiologists class 3 in 77% of restricted vs 44% of standard patients; P = 0.194). Median total intraoperative fluids were less in the restricted group (1300 mL) when compared with the standard group (3014 mL) ( P = 0.021). Total fluids for the hospitalization were also statistically significantly decreased in the restricted group. Complications occurred in about two-thirds of patients, and complication rates were not statistically different between groups (1.6/restricted patient vs 2.1/standard patient; P = 0.333). Primary indications for boluses (n = 93) given to study patients were: hypotension (69%); oliguria (15%); and tachycardia (14%), with multiple indications per bolus. In only two instances did the StO2 drop to less than 75 per cent, or decrease by 20 per cent from baseline in the 3 minutes before bolus as an indication for fluid administration. Patients undergoing elective colorectal surgery with a fluid restricted strategy had only rare episodes of decreased StO2, suggesting that adequate tissue perfusion was maintained in this group. As a result, NIRS monitoring did not significantly influence intraoperative fluid management of patients undergoing colorectal surgery.

Patients with pulmonary hypertension who undergo anesthesia and surgery have high morbidity and mortality. Recent advances in our understanding of pulmonary hypertension and its therapy provide an opportunity to improve outcomes.Pulmonary hypertension can be classified into several subtypes, each with its own causes, pathophysiology, and therapy. Echocardiography remains a critical aspect of the evaluation of patients with pulmonary hypertension, but estimation of right ventricular systolic pressure is often inaccurate. Inhaled vasodilators can produce selective and potent pulmonary vasodilation.The cause of pulmonary hypertension should be defined in perioperative patients with pulmonary hypertension, and therapy should be optimized prior to anesthesia. Pulmonary artery catheterization may be required to confirm the presence of pulmonary hypertension and its severity. The focus of anesthetic management is to maintain right ventricular cardiac output and avoid systemic hypotension. Inhaled vasodilators such as nitric oxide and prostacyclin can be life-saving when perioperative right heart failure occurs due to exacerbation of pulmonary hypertension.

As residents work disparate schedules at multiple locations and because of workweek hour limits mandated by the ACGME, residents may be unable to attend lectures, seminars, or other activities that would enhance their skills. Further, the ACGME requires that residency programs document resident learning in six stated core competencies and provide proof of completion for various other requirements. LMS/LC is a promising technology to provide a means by which residency programs may overcome these obstacles. More studies are needed to show under what conditions an LMS/LC program actually enhances learning, and which elements are most useful to the new generation of learners comfortable with Web 2.0 technologies.

Information technology has been promoted as a way to improve patient care and outcomes. Whereas information technology systems for ancillary hospital services (e.g., radiology, pharmacy) are deployed commonly, it has been estimated that anesthesia information management systems (AIMS) are only installed in a small fraction of United States (US) operating rooms. In this study, we assessed the adoption of AIMS at academic anesthesia departments and explored the motivations for and resistance to AIMS adoption.Members of the Society of Academic Anesthesiology Chairs and the Association of Anesthesiology Program Directors were solicited by e-mail to participate in an online survey of AIMS adoption. Two months after closing the survey, another e-mail was sent with a single question asking for an update to their AIMS implementation status.Surveys were fully completed by 48 (34%) of the 140 Society of Academic Anesthesiology Chairs and Association of Anesthesiology Program Directors departments surveyed, with 72 (51%) providing AIMS status information. Twenty of these 72 departments have an AIMS installed, 12 are currently implementing, 11 have selected but not yet installed, and 18 are planning to purchase an AIMS in 2008 or 2009. Therefore, at least 61 (44%) of all 140 US academic anesthesia departments have committed to AIMS. This estimated adoption rate is conservative because the numerator equals the affirmative responses, whereas the denominator equals the total population of academic departments. Among adopters, the top ranked anticipated benefits from installing an AIMS included improved clinical documentation, improved data collection for clinical research, enhancement of quality improvement programs, and compliance with requirements of regulatory authorities. The hospital provided funding in almost all facilities (90%), with co-funding by the anesthesia group in 35%.At least 61 or 44% of the 140 US academic departments surveyed in this study have already implemented, are planning to acquire, or are currently searching for an AIMS. Adoption of AIMS technology appears to have reached sufficient momentum within academic anesthesiology departments to result in a fundamental change.

Background Although short-term findings after lung reperfusion have been extensively reported, in vivo animal studies have not described outcome beyond the immediate time period. Therefore, the authors evaluated lung injury 27 h after reperfusion. They also investigated whether attenuation of lung injury with the A3 adenosine receptor agonist MRS3558 was sustained beyond the immediate time period. Methods In intact-chest, spontaneously breathing cats in which the left lower lung lobe was isolated and subjected to 2 h of ischemia and 3 h of reperfusion, MRS3558 was administered before reperfusion. Animals were killed 3 or 27 h after reperfusion. Results When compared with 3 h of reperfusion, at 27 h the left lower lobe showed reduced apoptosis and no change in inflammation, but increased edema. Increased edema of the nonischemic right lung and hypoxemia were observed at 27 h after left lower lobe reperfusion. Increases in phosphorylated p38 levels were found at 3 h of reperfusion compared with control lung, with further increases at 27 h. The attenuation of injury observed with MRS3558 treatment at 3 h of reperfusion was sustained at 27 h. Conclusions Lung edema may worsen hours after the immediate postreperfusion period, even though lung apoptosis and inflammation are reduced or show no change, respectively. This was associated with further increases in phosphorylated p38 levels. The nonischemic lung may also be affected, suggesting a systemic response to reperfusion. In addition, early attenuation of injury is beneficial beyond the immediate period after reperfusion. Treatment aimed at inhibiting p38 activation, such as A3 receptor activation, should be further studied to explore its potential long-term beneficial effect.

Sepsis is a complex, incompletely understood and often fatal disorder,1 typically accompanied by hypotension,2 that is considered to represent a dysregulated host response to infection.3,4,5 Neurotensin (NT) is a 13-amino-acid peptide that, among its multiple effects, induces hypotension.6 We find that intraperitoneal and plasma concentrations of NT are increased in mice after severe caecal ligation and puncture (CLP), a model of sepsis, and that mice treated with a pharmacological antagonist of NT, or NT-deficient mice, exhibit reduced mortality during severe CLP. In mice, mast cells can degrade NT and reduce NT-induced hypotension and CLP-associated mortality, and optimal expression of these effects requires mast cell expression of neurotensin receptor 1 and neurolysin. These findings show that NT contributes to sepsis-related mortality in mice during severe CLP and that mast cells can lower NT concentrations, and suggest that mast cell-dependent reduction in NT levels contributes to the ability of mast cells to enhance survival after CLP.

To quantify the incidence of anemia and red blood cell (RBC) transfusion practice in critically ill patients and to examine the relationship of anemia and RBC transfusion to clinical outcomes.Prospective, multiple center, observational cohort study of intensive care unit (ICU) patients in the United States. Enrollment period was from August 2000 to April 2001. Patients were enrolled within 48 hrs of ICU admission. Patient follow-up was for 30 days, hospital discharge, or death, whichever occurred first.A total of 284 ICUs (medical, surgical, or medical-surgical) in 213 hospitals participated in the study.A total of 4,892 patients were enrolled in the study.The mean hemoglobin level at baseline was 11.0 +/- 2.4 g/dL. Hemoglobin level decreased throughout the duration of the study. Overall, 44% of patients received one or more RBC units while in the ICU (mean, 4.6 +/- 4.9 units). The mean pretransfusion hemoglobin was 8.6 +/- 1.7 g/dL. The mean time to first ICU transfusion was 2.3 +/- 3.7 days. More RBC transfusions were given in study week 1; however, in subsequent weeks, subjects received one to two RBC units per week while in the ICU. The number of RBC transfusions a patient received during the study was independently associated with longer ICU and hospital lengths of stay and an increase in mortality. Patients who received transfusions also had more total complications and were more likely to experience a complication. Baseline hemoglobin was related to the number of RBC transfusions, but it was not an independent predictor of length of stay or mortality. However, a nadir hemoglobin level of9 g/dL was a predictor of increased mortality and length of stay.Anemia is common in the critically ill and results in a large number of RBC transfusions. Transfusion practice has changed little during the past decade. The number of RBC units transfused is an independent predictor of worse clinical outcome.

Background: Anemia is a common occurrence in the intensive care unit (ICU). Although resuscitation, including the use of blood, is a mainstay of early treatment of trauma victims, the safety and efficacy of red blood cell(RBC) transfusion has come under scrutiny recently. The issue of blood use in critically injured patients requires evaluation. Methods: This was a post hoc analysis of a subset of trauma patients (≥18 years in age) from a prospective, multicenter, observational, cohort study in the United States. Patients were enrolled within 48 hours after ICU admission and followed for up to 30 days, or until hospital discharge or death. Results: Five hundred seventy-six patients from 111 ICUs in 100 hospitals were enrolled between August 2000 and April 2001. At baseline, mean age was 44.1 ′ 20.2 years, 73.6% were men, and mean APACHE II score was 16.9 ′ 8.2. Mean baseline hemoglobin was 11.1 ′ 2.4 g/dL and patients remained anemic throughout the study either with or without transfusion; 55.4% of patients were transfused (mean, 5.8 ′ 5.5 units) during the ICU stay and 43.8% of patients had an ICU length of stay ≥ 7 days. Mean pretransfusion hemoglobin was 8.9 ′ 1.8 g/dL. Mean age of RBCs transfused was 20.1 ′ 11.4 days. As compared with the full study population, patients in the trauma subset were more likely to be transfused and received an average of 1 additional unit of blood. Conclusion: Anemia is common in critically injured trauma patients and persists throughout the duration of critical illness. These patients receive a large number of RBC transfusions during their ICU course with aged blood.

Based on its pleiotropic effects, erythropoietin can decrease inflammation, oxidative stress, and apoptosis. Erythropoietin provides organ protection for the heart, brain, and kidney in diverse preclinical animal studies, especially models that include ischemia-reperfusion injury and/or inflammation. However, large clinical studies in coronary reperfusion, heart failure, stroke, acute kidney injury, and chronic renal disease have failed to demonstrate improved outcomes. A study in a previous issue of Critical Care examining the ability of erythropoietin to prevent or ameliorate acute kidney injury in patients undergoing complex valvular heart surgery is similarly negative. The failure of erythropoietin in clinical studies may be due to an inadequate dose, since the receptors responsible for organ protection may require higher concentrations than those responsible for erythropoiesis. However, as has occurred in studies in sepsis and acute respiratory distress syndrome, the negative studies probably reflect an inadequate understanding of the complexity of the underlying processes with multiple redundant and interacting pathways that may differ among the large number of different cell types involved. As tools to understand this complexity and integrate it on an organismal basis continue to evolve, we will develop the ability to use erythropoietin and related nonhematopoietic agents for organ protection.

To determine whether the administration of recombinant human erythropoietin (rHuEPO) to critically ill patients in the intensive care unit (ICU) would reduce the number of red blood cell (RBC) transfusions required.A prospective, randomized, double-blind, placebo-controlled, multicenter trial.ICUs at three academic tertiary care medical centers.A total of 160 patients who were admitted to the ICU and met the eligibility criteria were enrolled in the study (80 into the rHuEPO group; 80 into the placebo group).Patients were randomized to receive either rHuEPO or placebo. The study drug (300 units/kg of rHuEPO or placebo) was administered by subcutaneous injection beginning ICU day 3 and continuing daily for a total of 5 days (until ICU day 7). The subsequent dosing schedule was every other day to achieve a hematocrit (Hct) concentration of38%. The study drug was given for a minimum of 2 wks or until ICU discharge (for subjects with ICU lengths of stay2 wks) up to a total of 6 wks (42 days) postrandomization.The cumulative number of units of RBCs transfused was significantly less in the rHuEPO group than in the placebo group (p.002, Kolmogorov-Smirnov test). The rHuEPO group was transfused with a total of 166 units of RBCs vs. 305 units of RBCs transfused in the placebo group. The final Hct concentration of the rHuEPO patients was significantly greater than the final Hct concentration of placebo patients (35.1+/-5.6 vs. 31.6+/-4.1; p.01, respectively). A total of 45% of patients in the rHuEPO group received a blood transfusion between days 8 and 42 or died before study day 42 compared with 55% of patients in the placebo group (relative risk, 0.8; 95% confidence interval, 0.6, 1.1). There were no significant differences between the two groups either in mortality or in the frequency of adverse events.The administration of rHuEPO to critically ill patients is effective in raising their Hct concentrations and in reducing the total number of units of RBCs they require.

This paper reports the effect of triptolide (a diterpenoid triepoxide) on the development of monocrotaline (MCT)-induced pulmonary hypertension in pneumonectomized rats. Male Sprague- Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Rats received therapy from Day 5 to 35 with triptolide (0.25 mg/kg intraperitoneally, every other day, n = 10), or vehicle (0.1 ml of ethanol/cremophor intraperitoneally, every other day, n = 10). By Day 35, triptolide-treated rats demonstrated lower mean pulmonary arterial pressure (mPAP) than vehicle-treated rats (mPAP 21 +/- 3 versus 42 +/- 5 mm Hg, p < 0.001). Triptolide-treated rats also had significantly less right ventricular hypertrophy (RVH) and pulmonary arterial neointimal formation. In a rescue experiment, rats initiated therapy on Day 21. At Day 35, vehicle-treated rats (n = 4) had higher mPAP (40 +/- 9 mm Hg), greater RVH, and more severe pulmonary arterial neointimal formation than rats that received triptolide (0.25 mg/kg every other day, n = 7, mPAP 30 +/- 4 mm Hg) and rats that received triptolide (0.2 mg/kg daily, n = 7, mPAP 25 +/- 5 mm Hg, p < 0.01). In pneumonectomized rats that receive MCT, triptolide attenuates the development of pulmonary hypertension and RVH, and promotes regression of pulmonary arterial neointimal formation.

E NDOTHELIUM-derived relaxing factor, der scribed in 1980, was subsequently identified as nitric oxide. Nitric oxide, previously considered only as an environmental contaminant and a toxic product of combustion, became an object of medical scientific attention. Since then, the synthesis of nitric oxide and its pathophysiological effects in all major organ systems have been desCribed. In the clinical arena, inhaled nitric oxide has been investigated for therapeutic use. Many recent publications have comprehensively summarized available data on nitric oxide.l-3 The following is a review of the physiology, mechanisms of action, and clinical applications of inhaled nitric oxide focusing on acute respiratory distress syndrome (ARDS), perioperative use, chronic pulmonary hypertension, hypoxemic respiratory failure of the newborn, sickle cell disease, and one-lung ventilation (OLV).

Objective To determine whether inhaled nitric oxide (IN0) and intravenous milrinone have additive pulmonary vasodilator effects in a rat model of pulmonary hypertension. Design Prospective, experimental study. Setting Animal laboratory of a university medical center. Subjects Male New Zealand White rabbits. Interventions Anesthetized rabbits were mechanically ventilated and instrumented for measurement of systemic mean arterial pressure (MAP), pulmonary artery pressure (PAP), left atrial pressure, and cardiac output (CO). After baseline measurements, the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg iv) was administered. Pulmonary hypertension was produced by the continuous infusion of U46619, a thromboxane A2 mimetic. INO (40 ppm) was added to the inspired gas, and hemodynamic measurements were obtained before and after INO. Milrinone was administered sequentially as a 30-mg/kg bolus followed by a 3-microg/kg/min infusion, a 100-mg/kg bolus followed by a 10-microg/kg/min infusion, and a 300-mg/kg bolus followed by a 30-microg/kg/min infusion (M3). Hemodynamic measurements were obtained with and without INO at each dose of milrinone. Measurements and main results During U46619-induced pulmonary hypertension, INO decreased PAP and pulmonary vascular resistance (PVR) but did not affect MAP, systemic vascular resistance (SVR), or CO. Milrinone dose dependently decreased PAP, PVR, MAP, and SVR and increased CO. At each dose of milrinone, INO further decreased PVR but not SVR. M3 decreased PVR 49%, and the addition of INO decreased PVR an additional 19% so that PAP and PVR decreased to baseline values. Conclusions Milrinone and INO both decrease pulmonary hypertension individually, and the combination produces additive effects. Combination therapy may produce potent and selective pulmonary vasodilation during the treatment of pulmonary hypertension.

Objective.We describe a new technology for measuring artery mechanical properties, called Sonic Vibrational Analysis (SVA).We utilize SVA to study the changes in radial artery smooth muscle tone caused by intravenous infusion of vasoactive agents. Methods.Six healthy volunteers were monitored with a radial intra-arterial catheter and an SVA sensor during progressively increasing doses of nitroglycerin (NTG), phenylephrine, sodium nitroprusside (SNP),dobutamine, and nicardipine. In SVA, the propagation velocity of an audio-frequency vibration is measured over a short segment of the radial artery. The measurement has sufficient temporal resolution to track the continuous changes in arterial properties that occur due to the natural blood pressure pulse. Results.Coupled with the measurement of radial blood pressure, SVA allowed determination of the physiological/mechanical state of the artery within a single cardiac cycle. NTG, SNP, and phenylephrine caused significant changes in both blood pressure and the physiological state of the radial artery. Nicardipine and dobutamine altered blood pressure without change in the state of the radial artery. Conclusions.The current results are consistent with previous studies of the effects of vasoactive agents on the radial artery. SVA is non-invasive, continuous, localized to a well-defined section of artery, and suitable for the collection of large volumes of time-resolved data in a laboratory or clinical setting.

Inhaled nitric oxide is a ubiquitous molecule which is produced endogenously and is also found in air pollution and in cigarette smoke. After describing the chemistry of NO, we review its history from the first description in 1980 to the current clinical indications. The biosynthesis of NO, its effects on pulmonary vasoreactivity, and the administration of inhaled NO will be described. The indications, uses, and side effects of inhaled NO are discussed with an emphasis on withdrawal of NO therapy, specifically the “rebound” phenomenon. Possible drug interactions are listed. Inhaled nitric oxide is here to stay, and future studies will provide more information on its therapeutic dose, duration and potential toxicity.

Autopsy findings indicate that 73% of pulmonary emboli diagnosed at autopsy were not detected clinically. 70 The clinical diagnosis of venous thromboembolism is unreliable, and the first manifestation of the disease may be fatal pulmonary embolism. Patients may be totally asymptomatic, or they may have symptoms such as dyspnea, tachypnea, or chest pain, which may be dull and centrally located or pleuritic in nature. Patients often will have hypoxemia, and may initially also have hypocapnia secondary to hyperventilation. Wheezing may occur as a result of the release of emboli-associated inflammatory mediators such as serotonin. Patients may also have nonspecific signs, such as tachycardia or signs of right ventricular strain on ECG or on echocardiogram. The chest radiograph is often normal. At the other end of the spectrum is the patient who presents with sudden-onset cardiovascular collapse and pulseless electrical activity. It is well known that surgery predisposes patients to venous thromboembolism. Less appreciated is the fact that they are at risk, not only in the immediate postoperative period, but even as late as 1 month postoperatively. 11,55 Deep vein thrombosis (DVT) and pulmonary embolism represent two aspects of the same disease process. Treatment and duration of treatment are usually the same in both instances. Because diagnosis and treatment both confer significant risks to the patient, there has been an ongoing search to determine the optimal strategy for confirming, or excluding the diagnosis. Several factors have to be considered in the diagnostic work-up, such as the role of history and physical examination, and how it influences the final diagnosis. Laboratory data and other diagnostic tests should be evaluated for their sensitivity and specificity, cost-effectiveness, availability, expertise required in their interpretation, ease of performing, and patient comfort. Advances have occurred in the field of anticoagulation with the introduction of low molecular weight heparins (LMWHs). Anticoagulation carries significant risks. The low therapeutic index of oral anticoagulants requires careful long-term monitoring, which in itself poses problems, and results in significant costs and inconvenience to patients. The role of inferior vena caval filters and surgical intervention also have associated significant costs and risks. The identification and stratification of patients at risk for venous thromboembolism is of paramount importance in order to institute effective prophylaxis and treatment. Most patients who die from pulmonary embolism do so within 30 minutes of the acute event—too soon for anticoagulation to be effective. 27 Despite numerous studies attesting to the efficacy and safety of prophylaxis, it is still underused. 16

Both inhaled nitric oxide (NO) and IV vasodilators decrease pulmonary hypertension, but the effects of combination therapy are unknown.We studied the response to inhaled NO (100 ppm) alone, IV vasodilator alone, and combined therapy during acute (U46619-induced) and chronic (monocrotaline-induced) pulmonary hypertension in the pentobarbital-anesthetized rat. Vasodilator doses were 1.0, 3.2, 10, and 32 [micro sign]g [middle dot] kg-1 [middle dot] min-1 sodium nitroprusside (SNP); 50, 100, 150, 200, and 300 [micro sign]g [middle dot] kg-1 [middle dot] min-1 adenosine; or 25, 50, 150, 200, and 300 ng [middle dot] kg-1 [middle dot] min-1 prostacyclin. In the absence of IV vasodilator therapy, inhaled NO decreased mean pulmonary artery pressure without decreasing mean systemic arterial pressure. In both acute and chronic pulmonary hypertension, the addition of inhaled NO to the largest dose of adenosine or prostacyclin, but not of SNP, decreased pulmonary artery pressure. Because inhaled NO and SNP activate guanylyl cyclase and adenosine and prostacyclin activate adenylyl cyclase, the results suggest that adding inhaled NO to a vasodilator not dependent on guanylyl cyclase may produce additional selective pulmonary vasodilation. Implications: In therapy of pulmonary hypertension, inhaled nitric oxide should produce additional selective pulmonary vasodilation when combined with a vasodilator whose mechanism of action is not dependent on cyclic guanosine 3[prime],5[prime]-monophosphate. (Anesth Analg 1999;89:152-8)

Inhaled nitric oxide (NO) and inhaled prostacyclin (PGI2) produce selective reductions in pulmonary vascular resistance (PVR) through differing mechanisms. NO decreases PVR via cGMP, and PGI2 produces pulmonary vasodilation via cAMP. As a general pharmacological principle, two drugs that produce similar effects via different mechanisms should have additive or synergistic effects when combined. We designed this study to investigate whether combined inhaled NO and PGI2 therapy results in additive effects during chronic pulmonary hypertension in the rat. Monocrotaline injected 4 wk before study produced pulmonary hypertension in all animals. Inhaled NO (20 parts/million) reversibly and selectively decreased pulmonary artery pressure (Ppa) with a mean reduction of 18%. Four concentrations of PGI2were administered via inhalation (5, 10, 20, and 80 μg/ml), both alone and combined with inhaled NO. Inhaled PGI2 alone decreased Ppa in a dose-dependent manner with no change in mean systemic arterial pressure. Combined inhaled NO and PGI2 selectively and significantly decreased Ppa more did than either drug alone. The effects were additive at the lower concentrations of PGI2 (5, 10, and 20 μg/ml). The combination of inhaled NO and inhaled PGI2 may be useful in the management of pulmonary hypertension.

P atients with pulmonary hypertension have markedly increased morbidity and mortality with anesthesia and surgery (1,2). For patients with Eisenmenger’s syndrome undergoing cesarean section, mortality is 46%70”/0 (3). The risks associated with primary pulmonary hypertension (PPH) seem to be even more frequent than those related to secondary pulmonary hypertension (4). Reports of successful outcomes of surgery in patients with primary pulmonary hypertension include curative procedures such as lung or heart-lung transplantation, cesarean section (2,3), and relatively brief procedures with minor blood loss and fluid shifts (lung biopsy, cholecystectomy, femoral artery repair, and laparoscopic tubal ligation) (5-9). The following case report describes a patient with PPH who successfully underwent combined abdominal aortic aneurysmectomy and hysterectomy. This case report emphasizes the value of preoperative pulmonary vasodilator testing to determine the risks of anesthesia and surgery and to provide a therapeutic option in the perioperative period. In this case report, we also discuss an approach to postoperative management of these patients.