numero rivista e pagine:
HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2012; 4(1): 5-9
A. Kurz*1,2, D. Sessler1,2
numero rivista e pagine: HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2012; 4(1): 5-9
Authors: A. Kurz*1,2, D. Sessler1,2
|Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic Foundation,|
* Corresponding author:
Andrea Kurz, M.D.
Department of Outcomes Research
Cleveland Clinic Foundation
9500 Euclid Avenue, Cleveland, Ohio 44195
Anesthesia clinical research has changed tremendously over the past years. While 20 years ago most anesthesia research focused on immediate perioperative outcomes, mainly testing safety of anesthetics, there is increasing evidence that intraoperative anesthetic management has long-term consequences, affecting patients months and years after surgery.
This is especially exciting considering that most patients are under our care only for a very restricted time period. It also highlights the importance of large, randomized, controlled trials, which are the gold standard for providing clinical evidence. outcomes research seeks to understand the end results of particular health care practices and interventions.
Outcomes include effects that people experience and care about, such as change in the ability to function. In particular, for individuals with chronic conditions - where cure is not always possible - end results include quality of life as well as mortality. By linking the care people get to end effects, outcomes research has become key to developing better ways to monitor and improve the quality of care.
Outcomes Research Consortium. The outcomes Research Consortium was formed in 1990 at the University of California in San francisco and is now a department of the Cleveland Clinic’s Anesthesiology Institute. We have two decades of experience with clinical research. The Consortium is not a society, foundation or company but rather an international academic collaboration of approximately 70 university-based investigators with a common interest in anesthesia- related clinical research. An advantage of this broad collaboration is that we have access to every surgical and critical care population. The Consortium is currently involved in more than 100 clinical studies, including large multicenter outcome trials.
The Consortium publishes about 50 full papers each year, and consortium papers are cited more than 1,100 times each year.
Members of the Consortium have trained more than 80 research fellows and dozens of medical and graduate students (each for at least a full year). Most fellows have graduated to positions in academic institutions and four subsequently chaired anesthesia departments.
Current Research Themes. Surgical treatment outcomes have improved considerably within the last decades in large part due to advances in anesthesia, surgical technique and perioperative care. More recently, dedicated anesthetic interventions were found to have a major impact on short-term and long-term patient out-come. our studies focus on generating evidence-based knowledge in regard to perioperative interventions likely to improve patient outcome.
Perioperative Inflammation. Surgery and the associated tissue injury evoke myriad endocrine and metabolic changes collectively considered the surgical stress response.
This systemic inflammatory response is associated with numerous systemic postoperative complications (cardio-pulmonary, neurological, gastro-intestinal), but also fatigue, mood disturbances, ileus, fever, hypercoagulability and hyperalgesia. Various perioperative interventions ameliorate the surgical stress response and might therefore improve patient outcome. Interventions currently under investigation by our group (in a number of studies in different patient populations) are perioperative tight glucose control (nCT 00524472), depth of anesthesia, alpha agonists (nCT 00561678) lidocaine (nCT 00840918) and steroid administration. outcomes of interest include 30-day postoperative morbidity, atrial fibrillation, myocardial ischemia, post- operative delirium and cognitive dysfunction, functional status and chronic pain.
Wound Complications. Complications associated with wound infection and inadequate healing are common and serious consequences of anesthesia and surgery. oxidative killing by neutrophils is the primary defense against surgical pathogens; good tissue oxygenation also improves scar formation. Treatments that increase tissue oxygen and perfusion might therefore reduce the risk of infection and related complications. Such treatments include normothermia, optimization of perioperative fluid management (to allow adequate perfusion of central and peripheral tissues) (nCT 00517127), hypercapnia (nCT 00273377), and prolonged postoperative supplemental oxygen administration. (nCT 00315822).
Cancer Recurrence. At least three perioperative factors shift the balance toward progression of residual disease after potentially curative cancer surgery:
1) Surgery per se depresses cell-mediated immunity, reduces concentration of tumor-related anti-angiogenic factors (e.g., angiostatin and endostatin), increases concentrations of pro-angiogenic factors such as VEGf, and releases growth factors that promote local and distant growth of malignant tissue.
2) Anesthesia impairs numerous immune functions, including those of neutrophils, macrophages, dendritic cells, T-cell and natural killer cells.
3) Opioid analgesics inhibit both cellular and humoral immunefunction in humans, increase angiogenesis and promote breast tumor growth in rodents.
Regional analgesia attenuates or prevents each of these adverse effects by largely preventing the neuroendocrine surgical stress response, eliminating or reducing the need for general anesthesia and minimizing opioid requirement. Animal and retrospective human studies suggest that regional analgesia may reduce the risk of cancer recurrence. We are thus currently conducting large outcome trials to test the hypothesis that regional analgesia reduces recurrence after breast (nCT 00418457), colon (nCT 00684229) and lung cancer surgery.
Postoperative Monitoring and Cardio-Vascular Events. Worldwide, more than 200 million noncardiac surgical procedures take place every year, and approximately 7% of patients might suffer a cardiovascular event (myocardial events and stroke) within 30 days.
Recent evidence suggests that intra and postoperative hypotension might be associated with these events. Despite the fact that blood pressure (BP) is tightly controlled during anesthesia and surgery, interim data from the VISIon Study, a large prospective, observational study evaluating the incidence of postoperatrive cardiovascular events after non-cardiac surgery, suggests that a large proportion of patients are exposed to perioperative hypotension and hypoxemia.
Given the potential impact of hypotension and hypoxemia on mortality and cardiovascular events, the limitations of current monitoring practice (especially on surgical floors), and the easy amenability to correction of hypotension and hypoxemia, there is great potential to improve patient safety and outcome by improving postoperative care. Currently anesthesiologists are not involved in patient management on the floor. However, as advances in technology continue to improve intraoperative care, new practice models will expand our influence on postoperative care as only anesthesiologists comprehend the full scope of perioperative medicine. An evaluation of the incidence and association between hypotension and hypoxemia with adverse outcomes after noncardiac surgery is an obvious initial step in this process. Therefore we currently obtain baseline patterns and frequencies of postoperative hypotension and hypoxemia based on various definitions. furthermore, we evaluate the independent relationships:
a) between postoperative hypotension and a composite binary endpoint comprised of mortality, nonfatal myocardial infarction, nonfatal cardiac arrest and nonfatal stroke at 30 days after;
b) between postoperative hypoxemia and the composite binary endpoint.
Chronic pain. A potential adverse outcome of surgery is the development of chronic pain. The incidence ranges from 10 to 50% depending on the type of surgery. Chronic post-surgical pain is defined aspain developing after a surgical procedure that lasts at least three months for which other causes (i.e., malignancy or chronic infection) have been excluded. There are number of factors involved in chronic pain formation, most importantly injury caused by surgery intraoperatively which produces intense pain signals. These signals are emitted from the peripheral nerves and tissues and sensitize the nociceptive pathways in the central nervous system (CnS) which leads to restructuring and central sensitization in the CnS - which is then amplified by ongoing peripheral input. once established persistent incisional pain is difficult to control or eliminate.
We currently perform several studies determining the risk of persistent incisional pain for a variety of surgical procedures; evaluating the association between neuraxial anesthesia and development of persistent incisional pain; and evaluating the associations between persistent incisional pain and perioperative use of nitrous oxide, central alpha-receptor agonists (clonidine or dexmedetomidine), and ACE inhibitors.
Comparative Effectiveness. While randomized trials remain the gold standard for clinical evidence, results obtained from such efficacy trials often generalize poorly. furthermore, conventional randomized trials are limited in that mortality and other serious complications are usually too rare to practically address. There is thus increasing interest in clinical effectiveness studies in which interventions are evaluated over an entire health care environment. The usual approach to effectiveness studies are historically controlled effectiveness approaches. Benefits are evaluated, if at all, bycomparing before-and-after results. Major difficulties with this approach include:
1) unrelated time-dependent practice changes that improve outcomes;
2) unrecognized confounding factors;
3) the Hawthorne effect. Before-and-after comparisons are therefore inherently weak - with the consequence that effectiveness interventions are rarely rigorously evaluated.
We are thus exploring innovative randomized effectiveness studies in which decision support systems, combined with electronic anesthesia records, will be used to randomize nearly all surgical patients at the Cleveland Clinic Main Campus to various interventions.
We have observed that patients who are sensitive to anesthesia do poorly. for example, the combination of low MAC and low MAP is a strong predictor for mortality. When combined with low BIS, mortality was even greater. The combination of low MAC, low MAP and low BIS is thus an ominous “Triple Low” that is associated with a tripled risk of mortality at 30 days and doubled risk of mortality at one year. This result is especially concerning since the average low values for each state were well within the range that many anesthesiologists tolerate routinely. our first randomized effectiveness trial thus tests the hypothesis that early intervention to maintain MAP reduces mortality.
Summary. In summary, outcomes research has become an important field in clinical anesthesia in the perioperative period. Anesthesia research nowadays evaluates numerous intermediate and long-term complications and thus emphasizes the importance of perioperative care. Many of the postoperative outcomes, though serious, are fairly rare and thus large studies are needed. This more and more shows the need for multi-center studies and national and international collaborations.