Rebecca A. Schroeder

Predictive Indices of Morbidity and Mortality After Liver Resection

Objective:To determine if use of Model for End-Stage Liver Disease (MELD) scores to elective resections accurately predicts short-term morbidity or mortality. Summary Background Data:MELD scores have been validated in the setting of end-stage liver disease for patients awaiting transplantation or undergoing transvenous intrahepatic portosystemic shunt procedures. Its use in predicting outcomes after elective hepatic resection has not been evaluated. Methods:Records of 587 patients who underwent elective hepatic resection and were included in the National Surgical Quality Improvement Program Database were reviewed. MELD score, CTP score, Charlson Index of Comorbidity, American Society of Anesthesiology classification, and age were evaluated for their ability to predict short-term morbidity and mortality. Morbidity was defined as the development of one or more of the following complications: pulmonary edema or embolism, myocardial infarction, stroke, renal failure or insufficiency, pneumonia, deep venous thrombosis, bleeding, deep wound infection, reoperation, or hyperbilirubinemia. The analysis was repeated with patients divided according to their procedure and their primary diagnosis. Parametric or nonparametric analyses were performed as appropriate. Also, a new index was developed by dividing the patients into a development and a validation cohort, to predict morbidity and mortality in patients undergoing elective hepatic resection. ROC curves were also constructed for each of the primary indices. Results:CTP and ASA scores were superior in predicting outcome. Also, patients undergoing resection of primary malignancies had a higher rate of mortality but no difference in morbidity. Conclusion:MELD scores should not be used to predict outcomes in the setting of elective hepatic resection.

The emerging multifaceted roles of nitric oxide

Nitric oxide (NO) is a highly reactive free radical with a multitude of organ specific regulatory functions. Since 1985. NO has been the subject of numerous research efforts and as a result, has been found to play a major role in the cardiovascular, pulmonary, gastrointestinal, immune, and central nervous systems. In addition, deranged NO synthesis is the basis for a number of pathophysiologic states, such as atherosclerosis, pulmonary hypertension, pyloric stenosis, and the hypertension associated with renal failure. Traditional NO donors such as sodium nitroprusside and new pharmacologic NO adducts such as S-nitrosothiols may serve as exogenous sources of NO for the treatment of NO-deficient pathologic states. This review is an attempt to acquaint the surgical community with the fundamentals of NO biochemistry and physiology. Increased knowledge of its functions in normal homeostasis and pathologic states will enable physicians to better understand these disease processes and utilize new pharmacologic therapies.

Coronary revascularization rather than cardiac transplantation for chronic ischemic cardiomyopathy.

Patients with very poor ventricular function have been thought to be highly vulnerable to elective myocardial revascularization. Ischemic cardiomyopathy is now the major indication for cardiac transplantation. The 2-year survival of medically treated patients with ejection fractions less than 20%, but who are not sufficiently symptomatic for cardiac transplantation, is less than 25%. At our institution we have taken an aggressive approach by using myocardial revascularization for chronic ischemic cardiomyopathy. Between 1983 and 1988, 39 patients with preoperative ejection fractions less than 20% underwent coronary artery bypass. Patients were excluded if they had valvular heart disease other than mild to moderate mitral regurgitation, required resection of a left ventricular aneurysm, or required emergency operation for acute coronary occlusion. Mean age was 63.3 years (range, 43 to 80 years) and 31 were men. Mean preoperative ejection fraction was 18.3% (range, 10% to 20%) and the mean preoperative left ventricular end diastolic pressure was 22 mm Hg (range, 8 mm Hg to 38 mm Hg). There was one operative death (2.6%). Mean follow-up was 21 months (range, 3 to 60 months) with eight late deaths (a total mortality rate of 21%). Seven deaths were due to arrhythmias. Three patients continued to have severe heart failure, one of whom underwent successful cardiac transplantation. By life table analysis, there was a 3-year survival rate of 83%. With the present shortage of cardiac transplant donors, myocardial revascularization for ischemic cardiomyopathy is a reasonably effective means for preserving residual ventricular function.

PORTOPULMONARY HYPERTENSION AND THE LIVER TRANSPLANT CANDIDATE

The management of the liver transplant (OLT) candidate with portopulmonary hypertension (PPHTN) has dramatically changed in the past 3 years. Careful preoperative evaluation with functional characterization of right ventricular function plays a critical role. The pulmonary vascular response to epoprostenol infusion serves as a deciding factor for OLT candidacy. Careful perioperative attention to avoid right ventricular failure from acutely elevated pulmonary artery pressures or sudden increases in right ventricular preload is a key physiologic tenet of management. With increased surgical expertise, anesthetic sophistication, and availability of epoprostenol, PPHTN is no longer considered an absolute contraindication for OLT.

Osteopontin Is a Negative Feedback Regulator of Nitric Oxide Synthesis in Murine Macrophages

In a system of endotoxin (LPS)-mediated NO production in ANA-1 murine macrophages, suppression subtractive hybridization was used to identify genes up-regulated by NO. Osteopontin (OPN), a secreted acidic phosphoprotein that binds to a cell surface RGD integrin-binding motif, was found to be differentially expressed in the presence of NO. OPN has been demonstrated to inhibit NO production in a variety of cell types. Northern blot and nuclear run-on analyses demonstrated that OPN mRNA levels and gene transcription were significantly increased in the presence of LPS-induced NO synthesis. Transient transfection of an OPN promoter-luciferase reporter plasmid construct showed that promoter activity is increased in the presence of LPS and NO. Immunoblot analysis showed that OPN protein is secreted into the extracellular fluid. Similar results were noted with an alternative cell system, RAW 264.7 macrophages, and alternative inducers of NO synthesis, IFN-γ and IL-1β. In the presence of GRGDSP, a hexapeptide that blocks binding of RGD-containing proteins to cell surface integrins, NO production is significantly increased in the presence of LPS stimulation. These data suggest a unique trans-regulatory mechanism in which LPS-induced NO synthesis feedback regulates itself through up-regulation of OPN promoter activity and gene transcription.

Can We Make Postoperative Patient Handovers Safer? A Systematic Review of the Literature

Postoperative patient handovers are fraught with technical and communication errors and may negatively impact patient safety. We systematically reviewed the literature on handover of care from the operating room to postanesthesia or intensive care units and summarized process and communication recommendations based on these findings. From >500 papers, we identified 31 dealing with postoperative handovers. Twenty-four included recommendations for structuring the handover process or information transfer. Several recommendations were broadly supported, including (1) standardize processes (e.g., through the use of checklists and protocols); (2) complete urgent clinical tasks before the information transfer; (3) allow only patient-specific discussions during verbal handovers; (4) require that all relevant team members be present; and (5) provide training in team skills and communication. Only 4 of the studies developed an intervention and formally assessed its impact on different process measures. All 4 interventions improved metrics of effectiveness, efficiency, and perceived teamwork. Most of the papers were cross-sectional studies that identified barriers to safe, effective postoperative handovers including the incomplete transfer of information and other communication issues, inconsistent or incomplete teams, absent or inefficient execution of clinical tasks, and poor standardization. An association between poor-quality handovers and adverse events was also demonstrated. More innovative research is needed to define optimal patient handovers and to determine the effect of handover quality on patient outcomes.

Nitric oxide: physiology and pharmacology.

T he relevance of the nitrogen oxides for clinical medicine has been recognized for over a century. Nitrous oxide (N,O) has been used safely and effectively for analgesia and anesthesia since the 18th century. Nitric oxide (NO) has emerged as a chemical messenger in a multitude of biologic systems having homeostatic activity in maintenance of cardiovascular tone, platelet regulation, and central nervous system signaling, as well as a role in gastrointestinal smooth muscle relaxation, immune regulation, and as a possible effector molecule for the volatile anesthetics. This review will discuss the biochemical basis of NO activity and examine the current clinical applications of NO, focusing primarily on the practice of anesthesia and critical care medicine.

Superoxide enhances interleukin 1β–mediated transcription of the hepatocyte-inducible nitric oxide synthase gene ☆ ☆☆

BACKGROUND & AIMS Exposure to oxidative stress, as in states of shock, ischemia-reperfusion injury, or sepsis, commonly initiates a complex cellular cascade of interlocking redox modulatory systems that detoxify electrophiles. In interleukin 1beta (IL-1beta)-treated rat hepatocytes, we have previously demonstrated that inducible nitric oxide synthase (iNOS) protein expression, steady-state iNOS messenger RNA (mRNA) levels, and NO synthesis are increased by oxidative stress induced by superoxide. The effect of hepatocellular redox state upon iNOS gene transcription has not been previously studied. METHODS Using rat hepatocytes in primary culture, iNOS gene transcription was induced by IL-1beta. Oxidative stress was mediated by 1,2,3-benzenetriol (BZT), an autocatalytic source of superoxide. Nuclear run-on assays and transient transfection assays using the rat hepatocyte iNOS full-length promoter and deletion constructs were designed to isolate a cis-acting regulatory element. Specificity was confirmed by site-directed mutagenesis. Gel shift analysis determined the presence of a corresponding trans-acting regulatory factor. RESULTS In IL-1beta-treated cells, BZT increased iNOS gene transcription without altering mRNA half-life. An antioxidant-responsive element (ARE) was found in the iNOS promoter at base pair -1347, which conferred redox sensitivity. Gel shift analysis identified a corresponding nuclear protein capable of binding to ARE in IL-1beta- and BZT-treated rat hepatocytes. CONCLUSIONS An ARE in the rat hepatocyte iNOS promoter confers redox sensitivity and augments IL-1beta-mediated iNOS gene and protein expression in the setting of superoxide treatment.

Differential effects of nitric oxide-mediated S-nitrosylation on p50 and c-jun DNA binding.

BACKGROUND Nitric oxide (NO) regulates a variety of cellular functions. One mechanism by which NO may exert its influence is through formation of S-nitrosothiols at critical thiol residues in protein-active sites, including those of nuclear protein transcription factors. METHODS NF-kappa B p50 and AP-1 c-jun were S-nitrosylated in the presence of acidic NaNO2. Wild-type protein and protein subjected to nitrosylating conditions in the absence of NaNO2 served as controls. Confirmatory evidence for S-nitrosothiol bond formation was obtained by ultraviolet-visible spectrophotometry with the absorption maximum for S-NO bonds at approximately 320 to 360 nm. With consensus oligonucleotide probes, gel-shift analysis was used to examine DNA binding characteristics. RESULTS In the case of NF-kappa B p50, S-nitrosylation resulted in significantly decreased DNA binding. In contrast, S-nitrosylation did not alter c-jun DNA binding. The S-nitrosylating conditions themselves did not alter p50 or c-jun DNA binding. Quantitative analysis was performed according to the Scatchard plot technique to generate the respective dissociation constants. S-nitrosylated p50 was associated with a fourfold greater dissociation constant than that of the wild-type p50. CONCLUSIONS S-nitrosylation of transcription factors may be one mechanism by which NO may selectively regulate gene transcription.

Intraoperative use of inhaled PGI2 for acute pulmonary hypertension and right ventricular failure

Inhaled prostacyclin (PGI(2)) can be used as an effective pulmonary vasodilator intraoperatively to treat pulmonary hypertension and impending right ventricular failure.