Gail A. Van Norman

Adverse cardiac outcomes after noncardiac surgery in patients with prior percutaneous transluminal coronary angioplasty.

UNLABELLED In this retrospective cohort study, we compared adverse cardiac outcomes after noncardiac surgery among patients with prior percutaneous transluminal coronary angioplasty (PTCA), patients with nonrevascularized coronary artery disease (CAD), and normal controls. Inpatient hospital discharge abstracts from all nonfederal acute care hospitals in Washington State linked to death certificates were evaluated. Patients > or =45 yr old with prior PTCA who underwent noncardiac surgery from 1987 to 1993 were matched by age, sex, surgery type, and discharge year to 686 patients with CAD and to 2155 normal controls (no CAD). We compared risk for adverse cardiac outcomes (death, myocardial infarction, angina, congestive heart failure, malignant dysrhythmia, cardiogenic shock, coronary artery bypass graft, or PTCA) within 30 days. Patients with PTCA had twice the risk of adverse cardiac outcome as normal controls (odds ratio [OR] 1.98; P < 0.001), with a higher risk of angina (OR 7.84), congestive heart failure (OR 2.06), and myocardial infarction (OR 3.86) but a lower risk of death (OR 0.46; P < 0.001). Patients with PTCA had half the risk of adverse cardiac outcome as patients with CAD (OR 0.50; P < 0.001), including less risk of angina (OR 0.51) and congestive heart failure (OR 0.40; P < 0.001), but no difference in myocardial infarction (P = 0.304) or death (P = 0.436). No difference was found between 142 patients with recent PTCA (< or =90 days before noncardiac surgery) matched to patients with CAD (OR 0.90; P = 0.396). Patients revascularized by PTCA >90 days before noncardiac surgery seem to have a lower risk of poor outcome than nonrevascularized patients, although not as low as normal controls. For recent PTCA patients, the lack of difference compared with CAD patient outcomes requires a larger sample size for verification. Present findings do not lend support to a role for prophylactic PTCA to improve noncardiac surgery outcomes. This investigation did not control for CAD severity, medical management, or comorbidities. Study of these factors is needed before the clinical implications of PTCA for noncardiac surgical risk can be completely assessed. IMPLICATIONS Hospital records showed patients with prior percutaneous transluminal coronary angioplasty were twice as likely as healthy patients to have an adverse cardiac outcome after noncardiac surgery, although their risk was reduced by half compared with patients with untreated coronary artery disease. Further study of the role of percutaneous transluminal coronary angioplasty in modulating noncardiac surgery risk is needed.

Propofol versus isoflurane for endoscopic sinus surgery

PURPOSE A previous retrospective study reported that propofol anesthesia decreased bleeding during endoscopic sinus surgery compared with isoflurane. We performed a prospective study to compare the effects of propofol versus isoflurane on measured blood loss and the surgeons subjective assessment of operating conditions during endoscopic sinus surgery. PATIENTS AND METHODS After receiving institutional review board approval and written informed consent, 56 patients undergoing endoscopic sinus surgery were randomly assigned to receive propofol (n = 30) or isoflurane (n = 26) supplemented with nitrous oxide-oxygen and alfentanil. Blood loss was calculated from the hemoglobin concentration in suction canisters. One surgeon, who was blinded to the anesthetic agent, performed every procedure and assessed bleeding as follows: 1, no bleeding; 2, modest bleeding; 3, bleeding interfering with operating conditions and cause for an agent switch; and 4, intolerable bleeding requiring a change in surgical plan. Results were compared in the two anesthetic groups using chi-squared test, unpaired t-test, Mann-Whitney Utest, and a permutation test. A P of .05 was considered significant. RESULTS Mean bleeding scores were less over time (P = .02) with propofol anesthesia, particularly in surgery in the ethmoid and sphenoid sinuses (P = .03), and the proportion of patients with a mean score >2 was less in the propofol group (30% v 54%; P = .033). Time until discharge to home or to a limited stay in a hospital bed was also less in the propofol group (183 v 243 minutes; P = .019). CONCLUSION In our study, surgical blood loss was the same for both anesthetic agents overall, but propofol appeared to offer an advantage in terms of subjective improvement in operating conditions, particularly in the ethmoid and sphenoid sinuses.

A Matter of Life and Death What Every Anesthesiologist Should Know about the Medical, Legal, and Ethical Aspects of Declaring Brain Death

Accurate criteria for death are increasingly important as it becomes more difficult for the public to distinguish between patients who are still alive from those who, through the aid of medical technology, merely look like they are alive even though they are dead. Patients and their families need to know that a clear line can be drawn between life and death, and that patients who are alive will not be unintentionally treated as though they are dead. For the public to trust the pronouncements of medical doctors as to whether a patient is dead or alive, the criteria must be unambiguous, understandable, and infallible. It is equally important to physicians that accurate, infallible criteria define death. Physicians need to know that a clear line can be drawn between life and death so that patients who are dead are not treated as though they are alive. Such criteria enable us to terminate expensive medical care to corpses. Clear criteria for death also allow us to ethically request the gift of vital organs. Clear, infallible criteria allow us to assure families and society that one living person will not be intentionally or unintentionally killed for the sake of another. The pressure of organ scarcity must not lead physicians to allow the criteria for life and death to become blurred because of the irreparable harm this would cause to the patient-physician relationship and the devastating impact it could have on organ transplantation. As the cases presented here illustrate, anesthesiologists have an important responsibility in the process of assuring that some living patients are not sacrificed to benefit others. Criteria for declaring death should be familiar to every anesthesiologist participating in organ retrieval. Before accepting the responsibility of maintaining a donor for vital organ collection, the anesthesiologist should review data supplied in the chart supporting the diagnosis of brain death and seriously question inconsistencies and inadequate testing conditions. Knowledge of brain death criteria and proper application of these criteria could have changed the course of each of the cases presented.

Another Matter of Life and Death What Every Anesthesiologist Should Know about the Ethical, Legal, and Policy Implications of the Non-Heart-beating Cadaver Organ Donor

Summary It remains to be seen whether the use of NHBCDs willsignificantly increase the number of organs available fortransplantation. Organ retrieval from such donors maybe ethical, provided that conflicts of interest amonghealthcare providers are defined and prevented, the ex-ploitation of vulnerable persons is avoided, the with-drawal of care is in accordance with accepted and ap-propriate medical standards, the inadvertent harvestingof vital organs from living patients does not occur, andthe humane treatment of dying patients and their fami-lies is safeguarded. Further, the process must not beimplemented in ways that cause distrust among dyingpatients that their medical and social needs will be putsecondary to those of patients needing transplantableorgans. It is arguable whether any existing protocolcompletely addresses all of these issues.Any anesthesiologist involved with either policies orcare of patients who will become NHBCDs should beeducated about the legal, ethical, and medical issuesinvolved and should not undertake such duties withoutadequate knowledge and training. Even when with-drawal of care is anticipated in an operating room set-ting, only physicians with appropriate knowledge, train-ing, and experience in the withdrawal of life support andcomfort care of the dying patient should be involvedwith the NHBCD. Such specialty expertise is not withinthe customary training and practice of most anesthesiol-ogists. The physician withdrawing life support should besomeone who has been involved with the patient andfamily throughout the decision-making process, so thatdeath does not become, as Renee Fox described it, a“desolate, profanely ‘high-tech’ death that the patientdies, beneath operating room lights, amid masked,gowned, and gloved strangers.”

Drugs and Devices: Comparison of European and U.S. Approval Processes

Summary The regulation of medical drugs and devices involves competing goals of assuring safety and efficacy while providing rapid movement of innovative therapies through the investigative and regulatory processes as quickly as possible. The United States and the European Union approach these challenges in different ways. Whereas the United States has always relied on a strictly centralized process through 1 agency, the Food and Drug Administration (FDA), the European Commission synchronized the regulations of 28 different countries as they combined to create the European Union. The FDA historically developed as a consumer protection agency, whereas the regulations from the European Commission arose out of a need to harmonize inter-state commercial interests while preserving national “autonomy.” Thus, whereas the FDA has the advantages of centralization and common rules, the European Union regulates medical drug and device approvals through a network of centralized and decentralized agencies throughout its member states. This study explores some of the similarities and differences in European and U.S. regulation of drugs and devices, and discusses challenges facing each.

Indicators of fibrinolysis during cardiopulmonary bypass after exogenous antithrombin-III administration for acquired antithrombin III deficiency

elapsed time for the heparin boluses and ACT testing was 30 minutes. A presumptive diagnosis of AT-III deficiency was made, and 2,500 U of pooled AT III was administered. The dose was based on the assumption that the patients circulating AT-III activity was decreased by approximately 50%, and that adding 2,500 U of AT llI to his circulating volume would bring AT-III activity back to 100%. The ACT rose to 635 seconds, and cardiopulmonary bypass (CPB) was immediately initiated. CPB lasted 59 minutes, and no further heparin was required. After CPB, protamine sulfate, 200 rag, was administered IV, and the resulting ACT was 119 seconds. Postoperatively, the thromboelastogram was normal. The patient received 450 mL of autologous blood that had been withdrawn at the start of the case for the purpose of euvolemic hemodilution, and he received no other blood products. His postoperative course was uneventful, and he was discharged on the 5th postoperative day. When it was determined during the case that the patient was heparin resistant, blood samples were withdrawn from his autologous blood unit for baseline studies. This unit had been stored at 34°C for 30 minutes before sampling. Additional samples were drawn from the patient after the second and third boluses of heparin, after AT-Ill administration just before initiation of CPB, 30 minutes after initiation of CPB, and after administration of protamine at the end of CPB. The patients temperature, as recorded by simultaneous esophageal/urinary temperature probes, was 35.5°/35.9°C, 35.1/35.7°C, 36.2/ 35.6°C, 36.1/37°C, and 36.1/36.8°C, respectively. Blood samples, including the sample withdrawn from the autologous unit, were placed on ice for transport to the clinical laboratory. Blood was anticoagulated by addition of 4.5 mL of whole blood to 0.5 mL of 130 mmol/L sodium citrate. All samples were centrifuged for 10 minutes at 2,500g at room temperature. Citrated plasma was frozen at -80°C. The patients permission was obtained to run the blood samples for determination of F1 + 2, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator antigen (TPA Ag), and AT III activity levels. RESULTS

Blood ionized magnesium concentrations during cardiopulmonary bypass and their correlation with other circulating cations

Abstract Background and aim: The recent introduction of new measurement technology (using ion specific electrodes) makes intraoperative evaluation of blood ionized magnesium (Mg2+, or iMg)–the bioactive fraction of circulating magnesium–possible. The goals of this study were: (1) to examine the longitudinal pattern(s) of change in blood iMg during cardiopulmonary bypass (CPB); and (2) to determine the relationship of iMg to Ca2+ (iCa), K, pH, Na, and hematocrit (Hct) during CPB. Methods: Blood was collected serially before, during, and after CPB on 30 patients undergoing elective coronary artery bypass graft procedures and the iMg was measured with an AVL Scientific Corp., model 988–4 instrument. Results: Overall, 73% of iMg results were abnormally low, 50% during CPB. Some cases had both hypo‐ and hyperionized magnesemic episodes. There were low iCa during CPB in 97% of cases. Using Spearmans rank order correlations and p < 0.05, iMg and K were directly correlated before, during, and after bypass, suggesting their parallel movement between tissue and blood. iMg and iCa were directly correlated before, and inversely correlated after, CPB, but unassociated during bypass. iMg and Na were inversely correlated after bypass in all cases. iMg was inversely correlated to pH and positively correlated to Hct during CPB only, and only in patients with concurrent association of iMg and iCa. Conclusions: Blood iMg depletion occurs frequently in CPB patients. iMg changes are not readily predictable. The association of intraoperative iMg depletion with postsurgical atrial fibrillation–reported to have a hypomagnesemic connection–should be investigated.

Drugs, Devices, and the FDA: Part 1: An Overview of Approval Processes for Drugs

Summary Over the last 150 years, the U.S. Food and Drug Administration (FDA) has evolved from a small division of the U.S. Patent Office to 1 of the largest consumer protection agencies in the world. Its mission includes ensuring that new medical treatments reach the public as quickly as possible while simultaneously ensuring that new treatments are both safe and effective. In the face of urgent consumer need, the FDA has faced criticism that its processes are too lengthy and costly and that the time to new drug release is significantly longer in the United States than in other Western countries. Calls from the public to loosen FDA regulations to facilitate more rapid approval of drugs and devices have been countered by the occurrence of patient harm and deaths after some approved drugs have reached the marketplace. New drug and device approval in the United States take an average of 12 and 7 years, respectively, from pre-clinical testing to approval. Costs for development of medical devices run into millions of dollars, and a recent study suggests that the entire cost for a new drug is in excess of

Coronary stenting or percutaneous transluminal coronary angioplasty prior to noncardiac surgery increases adverse perioperative cardiac events: the evidence is mounting

1 billion. For investigators seeking approval for new drugs and devices, FDA processes can be formidable. This 2-part series is intended to provide an overview of the steps involved in bringing new drugs and devices through the FDA process. Part 1 concerns the process of new drug approvals. Part 2 continues with approval of medical devices.

Hemodynamic and metabolic effects of aortic unclamping following emergency surgery for traumatic thoracic aortic tear in shunted and unshunted patients

The findings of Kalusa et al. [(1)][1] support previous evidence that coronary manipulation <90 days before noncardiac surgery (NCS) does not benefit, and may actually harm, patients with coronary disease. In 1997, the American College of Physicians concluded that prophylactic coronary