516805 research-article2013
SCVXXX10.1177/1089253213516805Seminars in Cardiothoracic and Vascular AnesthesiaHilberath and Muehlschlegel
The Perioperative Year in Review-2013
Noteworthy Articles in 2013 for Cardiothoracic Anesthesiologists
Seminars in Cardiothoracic and Vascular Anesthesia 2014, Vol. 18(1) 6–11 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1089253213516805 scv.sagepub.com
Jan N. Hilberath, MD1 and J. Daniel Muehlschlegel, MD, MMSc1
Abstract In 2013, the field of cardiothoracic anesthesiology has continued to grow at the same astounding rate as in previous years. It has become increasingly difficult for practicing anesthesiologists to stay current on impactful publications related to our exciting subspecialty. The scientific output has expanded to such a great extent that following the literature in specialty journals barely scrapes the surface of available knowledge. With the recent emphasis on teamwork spanning multiple medical specialties in the care for complex patients, the door has opened for our research to be presented in nontraditional, nonanesthesiology venues. In this review, we have selected a small sample of noteworthy contributions to the field of cardiothoracic and vascular anesthesiology published in 2013 with potential impact on our clinical practice. Keywords cardiac anesthesia, cardiac surgery, cardiopulmonary bypass, cerebrovascular accidents, cognitive dysfunction, coronary artery bypass grafting, deep hypothermic circulatory arrest, mitral valve, outcome, therapeutic impact
Introduction This article is part of a new series in Seminars in Cardiothoracic and Vascular Anesthesia that covers annual publication highlights. The authors thank the editor-in-chief, Dr Weitzel, for the opportunity to discuss several noteworthy publications of 2013 that might be of interest to cardiothoracic and vascular anesthesiologists alike. We fully admit to the difficulties and biases related to selecting only a small sample from the large number of high-quality articles published. Therefore, our review does not strive to be all-inclusive or complete, and many outstanding contributions had to be left out. Moreover, the goal of this article is not so much the detailed discussion of each article but rather to sensitize the reader to the various topics and encourage further study of the individual references. Our medical community’s ongoing effort to overcome the “silo” mentality still engrained in various subspecialties is one of the great achievements of 2013. Devising treatment strategies for patients increasingly involves multiple disciplines, which benefits patients and providers alike. This new openness for cross-communication has already led to an improved interdisciplinary understanding and will continue to brighten the atmosphere at our work places, be it the operating rooms (ORs), cardiology labs, or the hybrid radiology suite. Multidisciplinary discussions before procedures on complex cardiothoracic patients will hopefully become the norm rather than the exception. And while anesthesiology continues to expand outside of the
OR to embrace its modern role of a more holistic perioperative specialty, our interdisciplinary networks will only grow stronger. Anesthesiologists as perioperative specialists will play an increasingly important role in the decision-making pertaining to postoperative patient care. More is asked of us today than to hand-off a well-resuscitated, pain-free patient in the recovery room or the intensive care unit: anesthesiologists are frequently consulted on the potential impact of intraoperative decision-making on long-term patient outcomes. To reflect this increasing perioperative orientation of our specialty, we primarily selected publications directly affecting our work as anesthesiologists in the OR while also influencing perioperative patient care. We showcase several representative references to cover the following areas: (1) Clinical Research including (a) patient safety, (b) perioperative patient management and outcomes, (c) biomarkers of disease, (d) transesophageal echocardiography (TEE); (2) Translational Research; and (3) Basic Sciences Research.
1
Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Corresponding Author: J. Daniel Muehlschlegel, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, CWN L1, Boston, MA 02115, USA. Email: [email protected]
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Hilberath and Muehlschlegel
Clinical Research Patient Safety The American Heart Association released a remarkable scientific statement on patient safety in the cardiac OR in conjunction with the Society of Cardiovascular Anesthesiologists, the Society of Thoracic Surgeons, the Association of periOperative Registered Nurses, the Human Factors and Ergonomics Society, and the American Society of Extracorporeal Technology.1 This collaborative work very much embodies the new spirit of multidisciplinary care for the cardiothoracic patient. We therefore present it here despite not being hypothesis-driven, original research. Up to one third of deaths associated with coronary artery bypass grafting (CABG) operations may be preventable and are due to human error. Despite significant advances in surgical technique and technology and better patient outcomes overall, little evidence exists of improvements in the reduction or prevention of human errors in the OR environment. One challenge of examining human factors, teamwork, and communication in the OR lies in the qualitative and descriptive nature of these variables. While technical skills can be measured, nontechnical skills require observational and seemingly subjective assessments by experts not feasible for traditional quantitative statistical analyses. This American Heart Association statement focuses primarily on communication skills, as communication failures are the leading root cause of the majority of sentinel events reported by the Joint Commission. Available data on factors affecting teamwork are discussed in depth, particularly on how care teams interact with each other in the cardiac OR. Also, the importance of nontechnical skill level influencing patient safety is stressed. The statement consists of 3 major chapters: Communication and Teamwork, Physical environment, and Safety Culture. 1. Communication and Teamwork: Communication skills have been repeatedly measured as the worst aspect of teamwork behavior in the OR. The critical elements of teamwork can be summarized by the 6 “Cs”: Communication, Cooperation, Coordination, Cognition, Conflict resolution, and Coaching. There are proven interventions and promising tools available to improve safety and patient outcomes in the OR, namely, teamwork training, simulation training, the adoption of Surgical Safety Checklists, and the utilization of preoperative team briefings and postoperative debriefings. The use of checklists, team training, and the implementation of formal hand-off protocols receive Class I, Level of Evidence B recommendations. Event scenario training including
the complete OR team appear reasonable on a regular basis while further studies on communication and teamwork are to be promoted. Both recommendations are graded Class IIa, Level of Evidence C. 2. Physical environment: Poor OR ergonomics contribute to human errors and safety hazards, whereas optimal OR design allows for standardization and better focus on the patient. Moreover, the reduction of noise levels and traffic in the OR has proven beneficial for patient outcomes and OR personnel. Future study of optimal OR design to avoid potential design errors and the investigation of alarmrelated distractions receive Class IIa, Level of Evidence C recommendations. 3. Safety Culture: The Joint Commission has implemented standards for the creation of a hospitalwide culture of safety and quality. Part of these standards is the formulation of a disruptive behavior policy and a formal process to manage unacceptable behavior. A tense emotional climate has been linked to team errors and worse patient outcomes. Also, the initiation of local, regional, or multicenter quality-improvement initiatives has beneficial effects on patient safety. Therefore, the institution of robust quality-improvement initiatives in every hospital center as well as local policies on disruptive behavior in medical professionals in all hospital settings should be implemented immediately (Class I, Level of Evidence C). In conclusion, this safety statement highlights that cardiac surgery remains a high-risk endeavor deserving an intense focus on patient safety, whereas sustainability requires a sincere culture of safety. Research on patient safety is a growing, yet underfunded field. The statement writing committee envisions that results of ongoing and future studies will lead to greater patient and employee satisfaction and better clinical outcomes.
Perioperative Management and Outcomes We selected 2 articles in this category to be presented: 1. In their single-center, retrospective, nonrandomized cohort study, Ji et al investigated the influence of perioperative use of the α2-adrenoceptor agonist dexmedetomidine on variable outcomes after cardiac surgery.2 Dexmedetomidine has previously been shown to reduce mortality in patients with coronary artery disease undergoing noncardiac surgery and lead to cardiac risk reduction in vascular surgery. Moreover, antidelirium and anti-inflammatory
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Seminars in Cardiothoracic and Vascular Anesthesia 18(1) effects of this sympatholytic compound have been examined in prior trials. This is, however, the first report of a beneficial effect on major outcomes such as mortality associated with the perioperative use of dexmedetomidine in cardiac surgical patients.
The study population consisted of 1134 consecutive cardiac surgical patients of which 568 received dexmedetomidine and 566 did not. The operations were primarily CABG, or CABG surgery combined with valve or other procedures. Exclusion criteria consisted of emergency surgery, off-pump or robotic surgery, as well as procedures requiring deep hypothermic circulatory arrest or surgery on the thoracic aorta. Definitions of outcome parameters were based on the publicly available STS adult cardiac surgery database, a voluntary and strictly confidential reporting tool of the Society of Thoracic Surgery. Relatively low-dose dexmedetomidine infusions (0.24-0.6 µg kg−1 h−1) were initiated after separation from cardiopulmonary bypass and continued for less than 24 hours, postoperatively. The reported major outcomes parameters included in-hospital, 30-day, and 1-year all-cause mortality and a composite outcome of major adverse cardiocerebral events (MACEs; ie, stroke, delirium, sepsis, perioperative myocardial infarction, heart block, and cardiac arrest). Secondary outcomes included postoperative length of mechanical ventilation, kidney injury or new dialysis requirement, length of intensive care unit and hospital stay, and 30-day readmission. The investigators employed rigorous statistical measures in their quest to reduce bias. Propensity scores and risk adjustments were computed for both cohorts including patient demographics and clinical risk factors to allow group comparisons. No significant demographic differences were found between the 2 groups with respect to age, race, sex, body mass index, past medical history, and preoperative medical therapy. The major findings of the study were that perioperative infusion of dexmedetomidine was associated with significantly reduced in-hospital (1.23% vs 4.59%, P = .008), 30-day (1.76% vs 5.12%, P = .002), and 1-year mortality (3.17% vs 7.95%, P = .0004). The incidence of delirium and overall complications after cardiac surgery was also lower in the treatment group. Dexmedetomidine administration was, however, not found to influence the incidence of postoperative MACEs, sepsis, postoperative ventilation time, length of intensive care unit stay, or length of hospitalization. The authors’ call for dexmedetomidine to become an integral part of standard perioperative medication regimen in cardiac surgery patients is likely too strong at this time given the retrospective nature of this study. Also, it can be discussed if this investigation provides compelling evidence for a causal link between dexmedetomidine use and
survival benefit. At this point, it is unclear if the reduction in mortality is a result of a decrease in major cardiovascular complications (eg, stroke, sepsis, acute renal failure) or a direct effect of the well-proven benefits of α2-adrenergic agonists such as sympathiolysis and anti-inflammatory and antidelirium properties. However, this work opens the door for future prospective, hypothesis-driven, multicenter research, which is needed to further improve patient outcomes. 2. Multiple recent experimental studies have shown that myocardial injury and infarct size through ischemia and reperfusion can be mitigated by ischemic conditioning interventions. There are 3 types of ischemic conditioning: (a) Ischemic preconditioning, where coronary beds are directly subjected to intervals of ischemia and reperfusion prior to an ischemic insult. In human subjects, this has been examined primarily in the setting of coronary interventions in cardiology patients but is not clinically feasible so long as a definitive positive effect has not been proven. (b) Postconditioning, where after the onset of tissue reperfusion multiple reocclusion stimuli are administered to decrease reperfusion injury. This form of conditioning is clinically more applicable but involves further manipulation of the culprit lesion. Available human data also primarily pertain to the cardiac catheterization laboratory. (c) In remote ischemic preconditioning, not the culprit coronary lesion is manipulated but a remote area like an arm or leg and subjected to ischemia and reperfusion prior to the sentinel coronary insult. Remote preconditioning is the technique most amenable to clinical practice and the cardiac OR involving anesthesiologists in the setting of coronary revascularization. Thielmann and coworkers report the results of a prospective, randomized, double-blind, controlled trial enrolling 329 consecutive patients with multivessel coronary artery disease for elective first-time CABG.3 This study is the first to confirm in a large cohort the findings of previous work on remote ischemic preconditioning. The treatment group underwent 3 cycles of remote ischemic preconditioning through inflation of a cuff around the upper arm for 5 minutes followed by 5 minutes of reperfusion. The area under the curve for release of cardiac troponin I in the first 72 hours after revascularization was significantly lower than that in the control group (266 ng/mL, 95% confidence interval [CI] = 237-298, vs 321 ng/mL, 95% CI = 287-360; difference 17%, 95% CI = 3% to 30%). The striking finding of this study, however, was the improvement in longer-term clinical outcomes induced by remote ischemic conditioning: In this admittedly low-risk population, remote ischemic preconditioning was associated with reduced incidence of
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Hilberath and Muehlschlegel all-cause death (hazard ratio 0.27, 95% CI = 0.08-0.98, P = .046) and myocardial infarction (hazard ratio 0.35, 95% CI = 0.15-0.78, P = .011) at 1 year. Apart from myocardial protective effects, Thielmann and colleagues note that reduced release of cardiac troponin I was associated with improvements in mortality at 1 year, but not at 30 days. Additionally, the incidence of non-heart-related events, such as sepsis or stroke, was lower in the remote ischemic preconditioning group. These findings suggest that the effect on the heart might be only one aspect of a much wider effect and that remote preconditioning, unlike local conditioning, could lead to persistent organ protection. Thus, this simple method of inducing natural protection might prove to have substantial clinical benefits. One important limitation of the Thielmann study is that it was only powered adequately to analyze cardiac troponin I as single surrogate biomarker and the secondary endpoints were assessed only in view of the significant primary endpoint. Further research to elucidate the molecular mechanisms underlying ischemic preconditioning is needed, and several promising phase 3 trials (ERICCA and RIPHeart) are underway.
Biomarkers of Disease The American Heart Association/American College of Cardiology perioperative evaluation guidelines highlight the patients’ functional status to decide on further preoperative cardiac testing and surgical risk assessment. Given the procedural and financial challenges of preoperative testing in the CABG population, the identification of a reliable biomarker like B-type natriuretic peptide (BNP) to identify subclinical heart failure or ischemia prior to heart surgery could affect perioperative risk stratification and patient optimization and ultimately improve outcomes. Several studies have shown that elevated BNP is associated with increased mortality and adverse cardiovascular events in noncardiac surgical patients. The existing literature on elevated preoperative BNP levels leading to worse outcomes in the cardiac surgery population includes primarily high-risk patients, and outcome data are therefore difficult to interpret. Fox and coworkers investigated the association between increased perioperative BNP and heart failure hospitalization or death after elective, nonemergency CABG surgery.4 The authors conducted a 2-institution, prospective, observational study including 1025 patients undergoing isolated primary CABG surgery and measured plasma BNP levels preoperatively and at various time points postoperatively. Primary outcome parameters were hospitalization or death from heart failure up to 5 years after CABG surgery. The investigators found that higher preoperative and peak postoperative BNP concentrations (postoperative days 1-5) each were independently associated with heart failure outcomes (log10 preoperative BNP hazard ratio = 1.93, 95%
CI = 1.30-2.88, P = .001; log10 peak postoperative BNP hazard ratio = 3.38, 95% CI = 1.45-7.65, P = .003). After adjusting for clinical risk factors such as low preoperative left ventricular ejection fraction, increased preoperative and peak postoperative BNP levels significantly shortened the time to first heart failure complication during the initial 5 years after CABG surgery. This research group had previously shown that elevated perioperative BNP leads to longer hospital stays, more postoperative ventricular dysfunction, and increased all-cause mortality, but all of these short-term adverse events lacked direct treatment options. In ambulatory heart failure patients, BNP is an established diagnostic and prognostic parameter, and interventions to lower BNP levels can reduce cardiovascular adverse events. It seems conceivable that the same holds true for CABG surgery patients when medical management is targeted toward identifying sources of increased BNP and subsequent treatment. Hence, the novelty of the present study is the potential for perioperative physicians to directly alter patient care and heart failure management based on BNP levels and thereby influence long-term outcomes. However, further research will need to determine how exactly BNP measurements in CABG patients can be used to prevent adverse long-term outcomes. Future studies will need to also validate these results in other settings and investigate if these findings are reproducible in cardiac valve surgery, and possibly even noncardiac surgery.
Transesophageal Echocardiography Mitral valve (MV) repair has become a therapeutic mainstay in the treatment of mitral regurgitation over the last 2 decades since patient outcomes seem favorable compared to MV replacements. One important concern during MV repair is the potential for acute, iatrogenic mitral stenosis. To assess for MV stenosis in the intraoperative setting, the estimation of diastolic pressure gradients across the MV derived from transmitral flow velocity spectral Doppler profiles using the simplified Bernoulli equation is considered a Level 1 recommendation. The available literature on intraoperative cutoff values for expected or acceptable transmitral pressure gradients after MV repair is sparse, and predicting the need for immediate reoperation for iatrogenic stenosis remains a difficult task even for experienced echocardiographers. In this study, the authors retrospectively analyzed TEE data of 552 consecutive patients undergoing MV repair at a single center over a 3-year period.5 This same patient cohort had previously led to the formulation of cutoff values that reproducibly predict the need for timely reoperation for iatrogenic postoperative mitral stenosis. In this second analysis, the investigators focused on 84 patients undergoing edge-toedge repair of the MV, also referred to as an “Alfieri stitch.” This repair technique was introduced in the 1990s
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Seminars in Cardiothoracic and Vascular Anesthesia 18(1)
and has since gained widespread acceptance in the treatment of various etiologies of mitral regurgitation. The anatomic and functional changes to the MV through the creation of a double-orifice valve have been well described previously. However, with the number of edge-to-edge repairs likely to increase due to the rising number of percutaneous MV procedures, little data are available to counsel anesthesiologists, surgeons, and cardiologists on intraoperative, echocardiographic decision-making. The authors reported significantly higher peak and mean Dopplerderived transmitral pressure gradients after edge-to-edge repair compared to conventional repair techniques (10.7 ± 0.5 mm Hg and 4.3 ± 0.2 mm Hg vs 7.1 ± 0.2 mm Hg and 2.8 ± 0.1 mm Hg, P < .0001). The addition of an annuloplasty system to the edge-to-edge repair did not affect transmitral pressure gradients compared to edge-to-edge repair alone, and likely has implications for durability of repair but not immediate gradients. The need for urgent reoperation due to iatrogenic MV stenosis after edge-toedge repair appeared higher (4.8%) compared to conventional repairs (1%), but the previously reported cutoff values of peak and mean gradients over 17 mm Hg and 7 mm Hg, respectively, remained valid. This is a first report describing mildly elevated average intraoperative transmitral pressure gradients as expected and allowable after edge-to-edge repair during cardiac surgery. These data could serve as helpful guidance to echocardiographers in the perioperative arena and improve communication between anesthesiologists and surgeons or cardiac interventionalists. Postoperative mean transmitral pressure gradients in the range between 5 and 7 mm Hg warrant a thorough interdisciplinary discussion to assess risks and benefits of surgical correction of this mild degree of MV stenosis, taking into account patient hemodynamics and cardiac output. Mean gradients exceeding 7 mm Hg almost uniformly require surgical management in this population.
Translational Research A significant body of literature in 2013 has focused on the perioperative changes to cognition after cardiothoracic and vascular surgery. Approximately one third of patients demonstrate cognitive deficits 6 weeks after cardiac surgery. Despite the relatively long duration, the functional neurocognitive decline seems to be transient rather than longterm. Neurocognitive decline is associated with cerebral (air) embolism, perioperative hypoperfusion, valve surgery, systemic inflammatory states, cell salvage, hyperglycemia, hyperthermia, hemodilution, transcerebral platelet and leukocyte activation, and genetic predisposition. Magnesium, an abundant intracellular cation, has previously been reported to exert neuroprotective functions through various mechanisms. Despite encouraging data
from various preliminary human studies supporting its neuroprotective properties, beneficial effects of magnesium could not be reproduced in several trials investigating brain injury beyond hospital discharge to date. In their study, Mathew and coworkers for the Neurologic Outcome Research Group of the Duke Heart Center investigated the effects of intraoperative administration of intravenous magnesium on postoperative cognition and neurologic dysfunction.6 A total of 389 patients were enrolled in this prospective, randomized, single-center, placebo-controlled, double-blind trial. The operations consisted of isolated CABG surgery, valve surgery, or combined valve and CABG surgery. Significant alcohol use, operations requiring circulatory arrest, a history of cerebrovascular disease, and renal and liver dysfunction were among the exclusion criteria as were poor preoperative neurocognitive test scores. Subjects were randomized to receive either magnesium as a 50 mg/kg bolus followed by a 50 mg/kg infusion over 3 hours after induction of anesthesia (100 mg/kg total) or administration of placebo. Neurocognitive testing was performed by blinded psychometricians 1 day before and 6 weeks after the operation using 5 different cognitive tests. To evaluate platelet and leukocyte activation, patient whole blood samples drawn at various perioperative time points were analyzed in a laboratory with specific antibody assays. The demographic and clinical data between both groups were similar, and neurocognitive deficits at 6 weeks after surgery were present in approximately 44% of patients in the treatment and placebo groups (P = .93). There was also no significant difference between groups in platelet and leukocyte activation or in platelet–leukocyte binding. The incidence of overall adverse events was also similar between cohorts. Here, in this largest perioperative trial of magnesium, the authors failed to demonstrate beneficial effects to magnesium administration. Magnesium did not improve neurocognitive function after cardiac surgery nor did it decrease platelet and leukocyte activation previously associated with cognitive decline. There was a weak interaction between higher patient weights and less cognitive impairment in the magnesium group after multivariate analysis (P = .06), potentially reflecting a dose-related or pharmacokinetic phenomenon. Further research is warranted to elucidate the underlying molecular mechanisms of postoperative cerebral impairment and to evaluate alternative preventative treatment modalities.
Basic Sciences Research Cardiovascular surgery requiring deep hypothermic circulatory arrest (DHCA) is associated with significant morbidity and mortality. The systemic inflammatory changes are more pronounced after DHCA than from exposure to cardiopulmonary bypass circuit alone. The pathophysiology of this
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Hilberath and Muehlschlegel response remains poorly understood and its progression to multisystem organ dysfunction is difficult to predict. However, the small intestine constitutes an anatomic region of special interest to systemic changes with ischemia and reperfusion and has been the focus of several prior investigations of systemic inflammation after cardiovascular surgery. Hypoperfusion during cardiac surgery has been associated with bacterial translocation as well as neutrophil invasion leading to subsequent breakdown of intestinal barrier function. The literature suggests that mast cells play a crucial part in the context of gut ischemia and reperfusion injury in their function as immune sentinel cells located at the host–environment interface as first responders to stress mediators and invading pathogens. Mast cells have been shown to translate hypoperfusion signals into immune-inflammatory events in various experimental settings of ischemia and are associated not only with local injury but also distal organ effects. In their study, Karhausen et al investigated mechanisms of intestinal ischemia and reperfusion injury in the setting of DHCA in a technically challenging in vivo rat model.7 The group performed molecular as well as functional studies to help define the underlying mechanisms resulting in intestinal injury after DHCA. The authors showed that DHCA mimics intestinal ischemia and reperfusion injury primarily centered in the terminal ileum, which leads to barrier dysfunction in the gut while sparing other vital organs such as kidneys and lungs. The physiologic luminal hypoxemia and the steep oxygen gradient across the intestinal mucosa seem to make this epithelial monolayer exquisitely susceptible to hypoxemic insults. Based on previous findings on the role of immune cells in ischemia and reperfusion injury, the investigators went on to study the functional contribution of mast cells to intestinal injury from DHCA. Their findings suggest that mast cells specifically influence 2 crucial aspects of the body’s response to DHCA: tissue injury and the systemic inflammatory response. Pharmacologic blockade of mast cell activation maintained better barrier integrity and highlighted their role in this intestinal injury pattern. Karhausen et al highlight intestinal ischemia and reperfusion injury as a direct result of DHCA and provide initial evidence for the role of mast cells in the initiation of local and systemic inflammation. Hereby, this study serves as promising starting point for future research on mast cell stabilization as potential treatment option to prevent systemic inflammatory responses after DHCA.
Conclusion
amount of research was dedicated to the increasingly interdisciplinary nature of our subspecialty and to patient outcomes. Nonetheless, a lot remains to be learned about the molecular mechanisms of what we do (well) every day. This year once again has fueled our optimism that cardiothoracic patient care will become an even safer endeavor in the future and that the cardiothoracic anesthesiologist plays a major role not only in the clinical care of this highrisk group of patients but also in advancing research in this exciting subspecialty. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work was supported by the National Institute of Health (Bethesda, MD) grant R01HL118266 and the American Heart Association (both JDM).
References 1. Wahr JA, Prager RL, Abernathy JH 3rd, et al. Patient safety in the cardiac operating room: human factors and teamwork: a scientific statement from the American Heart Association. Circulation. 2013;128:1139-1169. 2. Ji F, Li Z, Nguyen H, et al. Perioperative dexmedetomidine improves outcomes of cardiac surgery. Circulation. 2013;127:1576-1584. 3. Thielmann M, Kottenberg E, Kleinbongard P, et al. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet. 2013;382:597-604. 4. Fox AA, Nascimben L, Body SC, et al. Increased perioperative b-type natriuretic peptide associates with heart failure hospitalization or heart failure death after coronary artery bypass graft surgery. Anesthesiology. 2013;119:284-294. 5. Hilberath JN, Eltzschig HK, Shernan SK, Worthington AH, Aranki SF, Nowak-Machen M. Intraoperative evaluation of transmitral pressure gradients after edge-to-edge mitral valve repair. PLoS One. 2013;8:e73617. 6. Mathew JP, White WD, Schinderle DB, et al. Intraoperative magnesium administration does not improve neurocognitive function after cardiac surgery. Stroke. 2013;44:3407-3413. 7. Karhausen J, Qing M, Gibson A, et al. Intestinal mast cells mediate gut injury and systemic inflammation in a rat model of deep hypothermic circulatory arrest. Crit Care Med. 2013;41:e200-e210.
The year 2013 has seen further progression in various fields of cardiothoracic anesthesia research. A significant
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SCVXXX10.1177/1089253213516805Seminars in Cardiothoracic and Vascular AnesthesiaHilberath and Muehlschlegel
The Perioperative Year in Review-2013
Noteworthy Articles in 2013 for Cardiothoracic Anesthesiologists
Seminars in Cardiothoracic and Vascular Anesthesia 2014, Vol. 18(1) 6–11 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1089253213516805 scv.sagepub.com
Jan N. Hilberath, MD1 and J. Daniel Muehlschlegel, MD, MMSc1
Abstract In 2013, the field of cardiothoracic anesthesiology has continued to grow at the same astounding rate as in previous years. It has become increasingly difficult for practicing anesthesiologists to stay current on impactful publications related to our exciting subspecialty. The scientific output has expanded to such a great extent that following the literature in specialty journals barely scrapes the surface of available knowledge. With the recent emphasis on teamwork spanning multiple medical specialties in the care for complex patients, the door has opened for our research to be presented in nontraditional, nonanesthesiology venues. In this review, we have selected a small sample of noteworthy contributions to the field of cardiothoracic and vascular anesthesiology published in 2013 with potential impact on our clinical practice. Keywords cardiac anesthesia, cardiac surgery, cardiopulmonary bypass, cerebrovascular accidents, cognitive dysfunction, coronary artery bypass grafting, deep hypothermic circulatory arrest, mitral valve, outcome, therapeutic impact
Introduction This article is part of a new series in Seminars in Cardiothoracic and Vascular Anesthesia that covers annual publication highlights. The authors thank the editor-in-chief, Dr Weitzel, for the opportunity to discuss several noteworthy publications of 2013 that might be of interest to cardiothoracic and vascular anesthesiologists alike. We fully admit to the difficulties and biases related to selecting only a small sample from the large number of high-quality articles published. Therefore, our review does not strive to be all-inclusive or complete, and many outstanding contributions had to be left out. Moreover, the goal of this article is not so much the detailed discussion of each article but rather to sensitize the reader to the various topics and encourage further study of the individual references. Our medical community’s ongoing effort to overcome the “silo” mentality still engrained in various subspecialties is one of the great achievements of 2013. Devising treatment strategies for patients increasingly involves multiple disciplines, which benefits patients and providers alike. This new openness for cross-communication has already led to an improved interdisciplinary understanding and will continue to brighten the atmosphere at our work places, be it the operating rooms (ORs), cardiology labs, or the hybrid radiology suite. Multidisciplinary discussions before procedures on complex cardiothoracic patients will hopefully become the norm rather than the exception. And while anesthesiology continues to expand outside of the
OR to embrace its modern role of a more holistic perioperative specialty, our interdisciplinary networks will only grow stronger. Anesthesiologists as perioperative specialists will play an increasingly important role in the decision-making pertaining to postoperative patient care. More is asked of us today than to hand-off a well-resuscitated, pain-free patient in the recovery room or the intensive care unit: anesthesiologists are frequently consulted on the potential impact of intraoperative decision-making on long-term patient outcomes. To reflect this increasing perioperative orientation of our specialty, we primarily selected publications directly affecting our work as anesthesiologists in the OR while also influencing perioperative patient care. We showcase several representative references to cover the following areas: (1) Clinical Research including (a) patient safety, (b) perioperative patient management and outcomes, (c) biomarkers of disease, (d) transesophageal echocardiography (TEE); (2) Translational Research; and (3) Basic Sciences Research.
1
Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Corresponding Author: J. Daniel Muehlschlegel, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, CWN L1, Boston, MA 02115, USA. Email: [email protected]
Downloaded from scv.sagepub.com at ORILLIA CAMPUS LRC on March 18, 2015
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Hilberath and Muehlschlegel
Clinical Research Patient Safety The American Heart Association released a remarkable scientific statement on patient safety in the cardiac OR in conjunction with the Society of Cardiovascular Anesthesiologists, the Society of Thoracic Surgeons, the Association of periOperative Registered Nurses, the Human Factors and Ergonomics Society, and the American Society of Extracorporeal Technology.1 This collaborative work very much embodies the new spirit of multidisciplinary care for the cardiothoracic patient. We therefore present it here despite not being hypothesis-driven, original research. Up to one third of deaths associated with coronary artery bypass grafting (CABG) operations may be preventable and are due to human error. Despite significant advances in surgical technique and technology and better patient outcomes overall, little evidence exists of improvements in the reduction or prevention of human errors in the OR environment. One challenge of examining human factors, teamwork, and communication in the OR lies in the qualitative and descriptive nature of these variables. While technical skills can be measured, nontechnical skills require observational and seemingly subjective assessments by experts not feasible for traditional quantitative statistical analyses. This American Heart Association statement focuses primarily on communication skills, as communication failures are the leading root cause of the majority of sentinel events reported by the Joint Commission. Available data on factors affecting teamwork are discussed in depth, particularly on how care teams interact with each other in the cardiac OR. Also, the importance of nontechnical skill level influencing patient safety is stressed. The statement consists of 3 major chapters: Communication and Teamwork, Physical environment, and Safety Culture. 1. Communication and Teamwork: Communication skills have been repeatedly measured as the worst aspect of teamwork behavior in the OR. The critical elements of teamwork can be summarized by the 6 “Cs”: Communication, Cooperation, Coordination, Cognition, Conflict resolution, and Coaching. There are proven interventions and promising tools available to improve safety and patient outcomes in the OR, namely, teamwork training, simulation training, the adoption of Surgical Safety Checklists, and the utilization of preoperative team briefings and postoperative debriefings. The use of checklists, team training, and the implementation of formal hand-off protocols receive Class I, Level of Evidence B recommendations. Event scenario training including
the complete OR team appear reasonable on a regular basis while further studies on communication and teamwork are to be promoted. Both recommendations are graded Class IIa, Level of Evidence C. 2. Physical environment: Poor OR ergonomics contribute to human errors and safety hazards, whereas optimal OR design allows for standardization and better focus on the patient. Moreover, the reduction of noise levels and traffic in the OR has proven beneficial for patient outcomes and OR personnel. Future study of optimal OR design to avoid potential design errors and the investigation of alarmrelated distractions receive Class IIa, Level of Evidence C recommendations. 3. Safety Culture: The Joint Commission has implemented standards for the creation of a hospitalwide culture of safety and quality. Part of these standards is the formulation of a disruptive behavior policy and a formal process to manage unacceptable behavior. A tense emotional climate has been linked to team errors and worse patient outcomes. Also, the initiation of local, regional, or multicenter quality-improvement initiatives has beneficial effects on patient safety. Therefore, the institution of robust quality-improvement initiatives in every hospital center as well as local policies on disruptive behavior in medical professionals in all hospital settings should be implemented immediately (Class I, Level of Evidence C). In conclusion, this safety statement highlights that cardiac surgery remains a high-risk endeavor deserving an intense focus on patient safety, whereas sustainability requires a sincere culture of safety. Research on patient safety is a growing, yet underfunded field. The statement writing committee envisions that results of ongoing and future studies will lead to greater patient and employee satisfaction and better clinical outcomes.
Perioperative Management and Outcomes We selected 2 articles in this category to be presented: 1. In their single-center, retrospective, nonrandomized cohort study, Ji et al investigated the influence of perioperative use of the α2-adrenoceptor agonist dexmedetomidine on variable outcomes after cardiac surgery.2 Dexmedetomidine has previously been shown to reduce mortality in patients with coronary artery disease undergoing noncardiac surgery and lead to cardiac risk reduction in vascular surgery. Moreover, antidelirium and anti-inflammatory
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Seminars in Cardiothoracic and Vascular Anesthesia 18(1) effects of this sympatholytic compound have been examined in prior trials. This is, however, the first report of a beneficial effect on major outcomes such as mortality associated with the perioperative use of dexmedetomidine in cardiac surgical patients.
The study population consisted of 1134 consecutive cardiac surgical patients of which 568 received dexmedetomidine and 566 did not. The operations were primarily CABG, or CABG surgery combined with valve or other procedures. Exclusion criteria consisted of emergency surgery, off-pump or robotic surgery, as well as procedures requiring deep hypothermic circulatory arrest or surgery on the thoracic aorta. Definitions of outcome parameters were based on the publicly available STS adult cardiac surgery database, a voluntary and strictly confidential reporting tool of the Society of Thoracic Surgery. Relatively low-dose dexmedetomidine infusions (0.24-0.6 µg kg−1 h−1) were initiated after separation from cardiopulmonary bypass and continued for less than 24 hours, postoperatively. The reported major outcomes parameters included in-hospital, 30-day, and 1-year all-cause mortality and a composite outcome of major adverse cardiocerebral events (MACEs; ie, stroke, delirium, sepsis, perioperative myocardial infarction, heart block, and cardiac arrest). Secondary outcomes included postoperative length of mechanical ventilation, kidney injury or new dialysis requirement, length of intensive care unit and hospital stay, and 30-day readmission. The investigators employed rigorous statistical measures in their quest to reduce bias. Propensity scores and risk adjustments were computed for both cohorts including patient demographics and clinical risk factors to allow group comparisons. No significant demographic differences were found between the 2 groups with respect to age, race, sex, body mass index, past medical history, and preoperative medical therapy. The major findings of the study were that perioperative infusion of dexmedetomidine was associated with significantly reduced in-hospital (1.23% vs 4.59%, P = .008), 30-day (1.76% vs 5.12%, P = .002), and 1-year mortality (3.17% vs 7.95%, P = .0004). The incidence of delirium and overall complications after cardiac surgery was also lower in the treatment group. Dexmedetomidine administration was, however, not found to influence the incidence of postoperative MACEs, sepsis, postoperative ventilation time, length of intensive care unit stay, or length of hospitalization. The authors’ call for dexmedetomidine to become an integral part of standard perioperative medication regimen in cardiac surgery patients is likely too strong at this time given the retrospective nature of this study. Also, it can be discussed if this investigation provides compelling evidence for a causal link between dexmedetomidine use and
survival benefit. At this point, it is unclear if the reduction in mortality is a result of a decrease in major cardiovascular complications (eg, stroke, sepsis, acute renal failure) or a direct effect of the well-proven benefits of α2-adrenergic agonists such as sympathiolysis and anti-inflammatory and antidelirium properties. However, this work opens the door for future prospective, hypothesis-driven, multicenter research, which is needed to further improve patient outcomes. 2. Multiple recent experimental studies have shown that myocardial injury and infarct size through ischemia and reperfusion can be mitigated by ischemic conditioning interventions. There are 3 types of ischemic conditioning: (a) Ischemic preconditioning, where coronary beds are directly subjected to intervals of ischemia and reperfusion prior to an ischemic insult. In human subjects, this has been examined primarily in the setting of coronary interventions in cardiology patients but is not clinically feasible so long as a definitive positive effect has not been proven. (b) Postconditioning, where after the onset of tissue reperfusion multiple reocclusion stimuli are administered to decrease reperfusion injury. This form of conditioning is clinically more applicable but involves further manipulation of the culprit lesion. Available human data also primarily pertain to the cardiac catheterization laboratory. (c) In remote ischemic preconditioning, not the culprit coronary lesion is manipulated but a remote area like an arm or leg and subjected to ischemia and reperfusion prior to the sentinel coronary insult. Remote preconditioning is the technique most amenable to clinical practice and the cardiac OR involving anesthesiologists in the setting of coronary revascularization. Thielmann and coworkers report the results of a prospective, randomized, double-blind, controlled trial enrolling 329 consecutive patients with multivessel coronary artery disease for elective first-time CABG.3 This study is the first to confirm in a large cohort the findings of previous work on remote ischemic preconditioning. The treatment group underwent 3 cycles of remote ischemic preconditioning through inflation of a cuff around the upper arm for 5 minutes followed by 5 minutes of reperfusion. The area under the curve for release of cardiac troponin I in the first 72 hours after revascularization was significantly lower than that in the control group (266 ng/mL, 95% confidence interval [CI] = 237-298, vs 321 ng/mL, 95% CI = 287-360; difference 17%, 95% CI = 3% to 30%). The striking finding of this study, however, was the improvement in longer-term clinical outcomes induced by remote ischemic conditioning: In this admittedly low-risk population, remote ischemic preconditioning was associated with reduced incidence of
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Hilberath and Muehlschlegel all-cause death (hazard ratio 0.27, 95% CI = 0.08-0.98, P = .046) and myocardial infarction (hazard ratio 0.35, 95% CI = 0.15-0.78, P = .011) at 1 year. Apart from myocardial protective effects, Thielmann and colleagues note that reduced release of cardiac troponin I was associated with improvements in mortality at 1 year, but not at 30 days. Additionally, the incidence of non-heart-related events, such as sepsis or stroke, was lower in the remote ischemic preconditioning group. These findings suggest that the effect on the heart might be only one aspect of a much wider effect and that remote preconditioning, unlike local conditioning, could lead to persistent organ protection. Thus, this simple method of inducing natural protection might prove to have substantial clinical benefits. One important limitation of the Thielmann study is that it was only powered adequately to analyze cardiac troponin I as single surrogate biomarker and the secondary endpoints were assessed only in view of the significant primary endpoint. Further research to elucidate the molecular mechanisms underlying ischemic preconditioning is needed, and several promising phase 3 trials (ERICCA and RIPHeart) are underway.
Biomarkers of Disease The American Heart Association/American College of Cardiology perioperative evaluation guidelines highlight the patients’ functional status to decide on further preoperative cardiac testing and surgical risk assessment. Given the procedural and financial challenges of preoperative testing in the CABG population, the identification of a reliable biomarker like B-type natriuretic peptide (BNP) to identify subclinical heart failure or ischemia prior to heart surgery could affect perioperative risk stratification and patient optimization and ultimately improve outcomes. Several studies have shown that elevated BNP is associated with increased mortality and adverse cardiovascular events in noncardiac surgical patients. The existing literature on elevated preoperative BNP levels leading to worse outcomes in the cardiac surgery population includes primarily high-risk patients, and outcome data are therefore difficult to interpret. Fox and coworkers investigated the association between increased perioperative BNP and heart failure hospitalization or death after elective, nonemergency CABG surgery.4 The authors conducted a 2-institution, prospective, observational study including 1025 patients undergoing isolated primary CABG surgery and measured plasma BNP levels preoperatively and at various time points postoperatively. Primary outcome parameters were hospitalization or death from heart failure up to 5 years after CABG surgery. The investigators found that higher preoperative and peak postoperative BNP concentrations (postoperative days 1-5) each were independently associated with heart failure outcomes (log10 preoperative BNP hazard ratio = 1.93, 95%
CI = 1.30-2.88, P = .001; log10 peak postoperative BNP hazard ratio = 3.38, 95% CI = 1.45-7.65, P = .003). After adjusting for clinical risk factors such as low preoperative left ventricular ejection fraction, increased preoperative and peak postoperative BNP levels significantly shortened the time to first heart failure complication during the initial 5 years after CABG surgery. This research group had previously shown that elevated perioperative BNP leads to longer hospital stays, more postoperative ventricular dysfunction, and increased all-cause mortality, but all of these short-term adverse events lacked direct treatment options. In ambulatory heart failure patients, BNP is an established diagnostic and prognostic parameter, and interventions to lower BNP levels can reduce cardiovascular adverse events. It seems conceivable that the same holds true for CABG surgery patients when medical management is targeted toward identifying sources of increased BNP and subsequent treatment. Hence, the novelty of the present study is the potential for perioperative physicians to directly alter patient care and heart failure management based on BNP levels and thereby influence long-term outcomes. However, further research will need to determine how exactly BNP measurements in CABG patients can be used to prevent adverse long-term outcomes. Future studies will need to also validate these results in other settings and investigate if these findings are reproducible in cardiac valve surgery, and possibly even noncardiac surgery.
Transesophageal Echocardiography Mitral valve (MV) repair has become a therapeutic mainstay in the treatment of mitral regurgitation over the last 2 decades since patient outcomes seem favorable compared to MV replacements. One important concern during MV repair is the potential for acute, iatrogenic mitral stenosis. To assess for MV stenosis in the intraoperative setting, the estimation of diastolic pressure gradients across the MV derived from transmitral flow velocity spectral Doppler profiles using the simplified Bernoulli equation is considered a Level 1 recommendation. The available literature on intraoperative cutoff values for expected or acceptable transmitral pressure gradients after MV repair is sparse, and predicting the need for immediate reoperation for iatrogenic stenosis remains a difficult task even for experienced echocardiographers. In this study, the authors retrospectively analyzed TEE data of 552 consecutive patients undergoing MV repair at a single center over a 3-year period.5 This same patient cohort had previously led to the formulation of cutoff values that reproducibly predict the need for timely reoperation for iatrogenic postoperative mitral stenosis. In this second analysis, the investigators focused on 84 patients undergoing edge-toedge repair of the MV, also referred to as an “Alfieri stitch.” This repair technique was introduced in the 1990s
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Seminars in Cardiothoracic and Vascular Anesthesia 18(1)
and has since gained widespread acceptance in the treatment of various etiologies of mitral regurgitation. The anatomic and functional changes to the MV through the creation of a double-orifice valve have been well described previously. However, with the number of edge-to-edge repairs likely to increase due to the rising number of percutaneous MV procedures, little data are available to counsel anesthesiologists, surgeons, and cardiologists on intraoperative, echocardiographic decision-making. The authors reported significantly higher peak and mean Dopplerderived transmitral pressure gradients after edge-to-edge repair compared to conventional repair techniques (10.7 ± 0.5 mm Hg and 4.3 ± 0.2 mm Hg vs 7.1 ± 0.2 mm Hg and 2.8 ± 0.1 mm Hg, P < .0001). The addition of an annuloplasty system to the edge-to-edge repair did not affect transmitral pressure gradients compared to edge-to-edge repair alone, and likely has implications for durability of repair but not immediate gradients. The need for urgent reoperation due to iatrogenic MV stenosis after edge-toedge repair appeared higher (4.8%) compared to conventional repairs (1%), but the previously reported cutoff values of peak and mean gradients over 17 mm Hg and 7 mm Hg, respectively, remained valid. This is a first report describing mildly elevated average intraoperative transmitral pressure gradients as expected and allowable after edge-to-edge repair during cardiac surgery. These data could serve as helpful guidance to echocardiographers in the perioperative arena and improve communication between anesthesiologists and surgeons or cardiac interventionalists. Postoperative mean transmitral pressure gradients in the range between 5 and 7 mm Hg warrant a thorough interdisciplinary discussion to assess risks and benefits of surgical correction of this mild degree of MV stenosis, taking into account patient hemodynamics and cardiac output. Mean gradients exceeding 7 mm Hg almost uniformly require surgical management in this population.
Translational Research A significant body of literature in 2013 has focused on the perioperative changes to cognition after cardiothoracic and vascular surgery. Approximately one third of patients demonstrate cognitive deficits 6 weeks after cardiac surgery. Despite the relatively long duration, the functional neurocognitive decline seems to be transient rather than longterm. Neurocognitive decline is associated with cerebral (air) embolism, perioperative hypoperfusion, valve surgery, systemic inflammatory states, cell salvage, hyperglycemia, hyperthermia, hemodilution, transcerebral platelet and leukocyte activation, and genetic predisposition. Magnesium, an abundant intracellular cation, has previously been reported to exert neuroprotective functions through various mechanisms. Despite encouraging data
from various preliminary human studies supporting its neuroprotective properties, beneficial effects of magnesium could not be reproduced in several trials investigating brain injury beyond hospital discharge to date. In their study, Mathew and coworkers for the Neurologic Outcome Research Group of the Duke Heart Center investigated the effects of intraoperative administration of intravenous magnesium on postoperative cognition and neurologic dysfunction.6 A total of 389 patients were enrolled in this prospective, randomized, single-center, placebo-controlled, double-blind trial. The operations consisted of isolated CABG surgery, valve surgery, or combined valve and CABG surgery. Significant alcohol use, operations requiring circulatory arrest, a history of cerebrovascular disease, and renal and liver dysfunction were among the exclusion criteria as were poor preoperative neurocognitive test scores. Subjects were randomized to receive either magnesium as a 50 mg/kg bolus followed by a 50 mg/kg infusion over 3 hours after induction of anesthesia (100 mg/kg total) or administration of placebo. Neurocognitive testing was performed by blinded psychometricians 1 day before and 6 weeks after the operation using 5 different cognitive tests. To evaluate platelet and leukocyte activation, patient whole blood samples drawn at various perioperative time points were analyzed in a laboratory with specific antibody assays. The demographic and clinical data between both groups were similar, and neurocognitive deficits at 6 weeks after surgery were present in approximately 44% of patients in the treatment and placebo groups (P = .93). There was also no significant difference between groups in platelet and leukocyte activation or in platelet–leukocyte binding. The incidence of overall adverse events was also similar between cohorts. Here, in this largest perioperative trial of magnesium, the authors failed to demonstrate beneficial effects to magnesium administration. Magnesium did not improve neurocognitive function after cardiac surgery nor did it decrease platelet and leukocyte activation previously associated with cognitive decline. There was a weak interaction between higher patient weights and less cognitive impairment in the magnesium group after multivariate analysis (P = .06), potentially reflecting a dose-related or pharmacokinetic phenomenon. Further research is warranted to elucidate the underlying molecular mechanisms of postoperative cerebral impairment and to evaluate alternative preventative treatment modalities.
Basic Sciences Research Cardiovascular surgery requiring deep hypothermic circulatory arrest (DHCA) is associated with significant morbidity and mortality. The systemic inflammatory changes are more pronounced after DHCA than from exposure to cardiopulmonary bypass circuit alone. The pathophysiology of this
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Hilberath and Muehlschlegel response remains poorly understood and its progression to multisystem organ dysfunction is difficult to predict. However, the small intestine constitutes an anatomic region of special interest to systemic changes with ischemia and reperfusion and has been the focus of several prior investigations of systemic inflammation after cardiovascular surgery. Hypoperfusion during cardiac surgery has been associated with bacterial translocation as well as neutrophil invasion leading to subsequent breakdown of intestinal barrier function. The literature suggests that mast cells play a crucial part in the context of gut ischemia and reperfusion injury in their function as immune sentinel cells located at the host–environment interface as first responders to stress mediators and invading pathogens. Mast cells have been shown to translate hypoperfusion signals into immune-inflammatory events in various experimental settings of ischemia and are associated not only with local injury but also distal organ effects. In their study, Karhausen et al investigated mechanisms of intestinal ischemia and reperfusion injury in the setting of DHCA in a technically challenging in vivo rat model.7 The group performed molecular as well as functional studies to help define the underlying mechanisms resulting in intestinal injury after DHCA. The authors showed that DHCA mimics intestinal ischemia and reperfusion injury primarily centered in the terminal ileum, which leads to barrier dysfunction in the gut while sparing other vital organs such as kidneys and lungs. The physiologic luminal hypoxemia and the steep oxygen gradient across the intestinal mucosa seem to make this epithelial monolayer exquisitely susceptible to hypoxemic insults. Based on previous findings on the role of immune cells in ischemia and reperfusion injury, the investigators went on to study the functional contribution of mast cells to intestinal injury from DHCA. Their findings suggest that mast cells specifically influence 2 crucial aspects of the body’s response to DHCA: tissue injury and the systemic inflammatory response. Pharmacologic blockade of mast cell activation maintained better barrier integrity and highlighted their role in this intestinal injury pattern. Karhausen et al highlight intestinal ischemia and reperfusion injury as a direct result of DHCA and provide initial evidence for the role of mast cells in the initiation of local and systemic inflammation. Hereby, this study serves as promising starting point for future research on mast cell stabilization as potential treatment option to prevent systemic inflammatory responses after DHCA.
Conclusion
amount of research was dedicated to the increasingly interdisciplinary nature of our subspecialty and to patient outcomes. Nonetheless, a lot remains to be learned about the molecular mechanisms of what we do (well) every day. This year once again has fueled our optimism that cardiothoracic patient care will become an even safer endeavor in the future and that the cardiothoracic anesthesiologist plays a major role not only in the clinical care of this highrisk group of patients but also in advancing research in this exciting subspecialty. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work was supported by the National Institute of Health (Bethesda, MD) grant R01HL118266 and the American Heart Association (both JDM).
References 1. Wahr JA, Prager RL, Abernathy JH 3rd, et al. Patient safety in the cardiac operating room: human factors and teamwork: a scientific statement from the American Heart Association. Circulation. 2013;128:1139-1169. 2. Ji F, Li Z, Nguyen H, et al. Perioperative dexmedetomidine improves outcomes of cardiac surgery. Circulation. 2013;127:1576-1584. 3. Thielmann M, Kottenberg E, Kleinbongard P, et al. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet. 2013;382:597-604. 4. Fox AA, Nascimben L, Body SC, et al. Increased perioperative b-type natriuretic peptide associates with heart failure hospitalization or heart failure death after coronary artery bypass graft surgery. Anesthesiology. 2013;119:284-294. 5. Hilberath JN, Eltzschig HK, Shernan SK, Worthington AH, Aranki SF, Nowak-Machen M. Intraoperative evaluation of transmitral pressure gradients after edge-to-edge mitral valve repair. PLoS One. 2013;8:e73617. 6. Mathew JP, White WD, Schinderle DB, et al. Intraoperative magnesium administration does not improve neurocognitive function after cardiac surgery. Stroke. 2013;44:3407-3413. 7. Karhausen J, Qing M, Gibson A, et al. Intestinal mast cells mediate gut injury and systemic inflammation in a rat model of deep hypothermic circulatory arrest. Crit Care Med. 2013;41:e200-e210.
The year 2013 has seen further progression in various fields of cardiothoracic anesthesia research. A significant
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