Michael R. Mathis

Predictors and clinical outcomes from failed Laryngeal Mask Airway Unique™: a study of 15,795 patients.

Background: Although the estimated risk of life-threatening adverse respiratory events during supraglottic airway device use is rare, the reported rate of events leading to failure of the airway device is 0.2–8%. Little is known about the risk-adjusted prediction of Laryngeal Mask Airway failure requiring rescue tracheal intubation and its impact on patient outcomes. Methods: All adult patients in whom a laryngeal mask airway (LMA Unique™, uLMA™; LMA North America, Inc., San Diego, CA) was used in ambulatory and nonambulatory anesthesia settings were included. The primary outcome was uLMA™ failure, defined as an airway event requiring uLMA™ removal and tracheal intubation. The secondary outcomes were the incidence of difficult mask ventilation and unplanned hospital admissions. Results: Of the 15,795 cases included in our study, 170 (1.1%) experienced the primary outcome of uLMA™ failure. More than 60% of patients with uLMA™ failure experienced significant hypoxia, hypercapnia, or airway obstruction, whereas 42% presented with inadequate ventilation related to leak. Four independent risk factors for failed uLMA™ were identified: surgical table rotation, male sex, poor dentition, and increased body mass index. A 3-fold increased incidence of difficult mask ventilation was observed in patients with uLMA™ failure. Among outpatients with uLMA™ failure, 13.7% had unplanned hospital admission, 5.6% of whom needed intensive care for persistent hypoxemia. Conclusions: The study supports the use of the uLMA™ as an effective supraglottic airway device with a relatively low failure rate. However, there are clinically relevant consequences of uLMA™ failure, as evidenced by the high rate of acute respiratory events and need for unplanned hospital admissions.

Life-threatening critical respiratory events: a retrospective study of postoperative patients found unresponsive during analgesic therapy

STUDY OBJECTIVE To identify risk factors for life-threatening critical respiratory events occurring during parenteral analgesic therapy for acute postoperative pain. DESIGN Retrospective, observational, cohort study. SETTING University hospital. MEASUREMENTS The electronic records of patients with sudden-onset, life-threatening critical respiratory events during analgesic therapy for postoperative pain were studied. Critical respiratory event data were identified from the hospital risk management database between 8/1/2000 and 7/31//2007. Patients required rescue treatment with naloxone, endototracheal intubation, or cardiopulmonary resusucitation. Pediatric patients were excluded from the study. In addition to the event description (type of analgesia, opioid dose, patient monitoring data, time of day, and time from surgery), each patients record was reviewed to extract co-morbidities and outcome data. MAIN RESULTS Over the 6-year period, 32 patients experienced a postoperative critical respiratory event. Twenty-six events and three deaths occurred within the first 24 hours of opioid therapy. Four of 32 patients died. Congestive heart failure, postoperative acute renal failure, obstructive sleep apnea, cardiac dysrhythmia, diabetes mellitus, coronary artery disease, and hypertension were significant associations in adult patients. CONCLUSIONS The first 24 hours after commencing opioid-based analgesic therapy represents a high risk period. Obstructive sleep apnea, deep levels of sedation, nocturnal presentation, and postoperative acute renal failure were seen in patients who died as a result of these critical respiratory events.

Patient selection for day case-eligible surgery: identifying those at high risk for major complications.

Background:Due to economic pressures and improvements in perioperative care, outpatient surgical procedures have become commonplace. However, risk factors for outpatient surgical morbidity and mortality remain unclear. There are no multicenter clinical data guiding patient selection for outpatient surgery. The authors hypothesize that specific risk factors increase the likelihood of day case-eligible surgical morbidity or mortality. Methods:The authors analyzed adults undergoing common day case-eligible surgical procedures by using the American College of Surgeons’ National Surgical Quality Improvement Program database from 2005 to 2010. Common day case-eligible surgical procedures were identified as the most common outpatient surgical Current Procedural Terminology codes provided by Blue Cross Blue Shield of Michigan and Medicare publications. Study variables included anthropometric data and relevant medical comorbidities. The primary outcome was morbidity or mortality within 72 h. Intraoperative complications included adverse cardiovascular events; postoperative complications included surgical, anesthetic, and medical adverse events. Results:Of 244,397 surgeries studied, 232 (0.1%) experienced early perioperative morbidity or mortality. Seven independent risk factors were identified while controlling for surgical complexity: overweight body mass index, obese body mass index, chronic obstructive pulmonary disease, history of transient ischemic attack/stroke, hypertension, previous cardiac surgical intervention, and prolonged operative time. Conclusions:The demonstrated low rate of perioperative morbidity and mortality confirms the safety of current day case-eligible surgeries. The authors obtained the first prospectively collected data identifying risk factors for morbidity and mortality with day case-eligible surgery. The results of the study provide new data to advance patient-selection processes for outpatient surgery.

Failure of the laryngeal mask airway unique™ and classic™ in the pediatric surgical patient: A study of clinical predictors and outcomes

Background:Although predictors of laryngeal mask airway failure in adults have been elucidated, there remains a paucity of data regarding laryngeal mask airway failure in children. Methods:The authors performed a retrospective database review of all pediatric patients who received a laryngeal mask anesthetic at their institution from 2006 to 2010. Device brands were restricted to LMA Unique™ (Cardinal Health, Dublin, OH) and LMA Classic™ (LMA North America, San Diego, CA), and primary outcome was laryngeal mask failure, defined as any airway event requiring device removal and tracheal intubation. Potential risk factors were analyzed with both univariate and multivariate techniques and included medical history, physical examination, surgical, and anesthetic characteristics. Results:Of the 11,910 anesthesia cases performed in the study, 102 cases (0.86%) experienced laryngeal mask failure. Common presenting features of laryngeal mask failures included leak (25%), obstruction (48%), and patient intolerance such as intractable coughing/bucking (11%). Failures occurred before incision in 57% of cases and after incision in 43%. Independent clinical associations included ear/nose/throat surgical procedure, nonoutpatient admission status, prolonged surgical duration, congenital/acquired airway abnormality, and patient transport. Conclusions:The findings of the study support the use of the LMA Unique™ and LMA Classic™ as reliable pediatric supraglottic airway devices, demonstrating relatively low failure rates. Predictors of laryngeal mask airway failure in the pediatric surgical population do not overlap with those in the adult population and should therefore be independently considered.

Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve

Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy and aortopathy. Here we report a genome-wide association scan of 466 BAV cases and 4,660 age, sex and ethnicity-matched controls with replication in up to 1,326 cases and 8,103 controls. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4. GATA4 was interrupted by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors. The disruption of GATA4 significantly impaired the transition from endothelial cells into mesenchymal cells, a critical step in heart valve development.

Complications, Risk Factors, and Staffing Patterns for Noncardiac Surgery in Patients with Left Ventricular Assist Devices

Background: Patients with left ventricular assist devices presenting for noncardiac surgery are increasingly commonplace; however, little is known about their outcomes. Accordingly, the authors sought to determine the frequency of complications, risk factors, and staffing patterns. Methods: The authors performed a retrospective study at their academic tertiary care center, investigating all adult left ventricular assist device patients undergoing noncardiac surgery from 2006 to 2015. The authors described perioperative profiles of noncardiac surgery cases, including patient, left ventricular assist device, surgical case, and anesthetic characteristics, as well as staffing by cardiac/noncardiac anesthesiologists. Through univariate and multivariable analyses, the authors studied acute kidney injury as a primary outcome; secondary outcomes included elevated serum lactate dehydrogenase suggestive of left ventricular assist device thrombosis, intraoperative bleeding complication, and intraoperative hypotension. The authors additionally studied major perioperative complications and mortality. Results: Two hundred and forty-six patients underwent 702 procedures. Of 607 index cases, 110 (18%) experienced postoperative acute kidney injury, and 16 (2.6%) had elevated lactate dehydrogenase. Of cases with complete blood pressure data, 176 (27%) experienced intraoperative hypotension. Bleeding complications occurred in 45 cases (6.4%). Thirteen (5.3%) patients died within 30 days of surgery. Independent risk factors associated with acute kidney injury included major surgical procedures (adjusted odds ratio, 4.4; 95% CI, 1.1 to 17.3; P = 0.03) and cases prompting invasive arterial line monitoring (adjusted odds ratio, 3.6; 95% CI, 1.3 to 10.3; P = 0.02) or preoperative fresh frozen plasma transfusion (adjusted odds ratio, 1.7; 95% CI, 1.1 to 2.8; P = 0.02). Conclusions: Intraoperative hypotension and acute kidney injury were the most common complications in left ventricular assist device patients presenting for noncardiac surgery; perioperative management remains a challenge.

Genome-wide association study of 1 million people identifies 111 loci for atrial fibrillation

To understand the genetic variation underlying atrial fibrillation (AF), the most common cardiac arrhythmia, we performed a genome-wide association study (GWAS) of > 1 million people, including 60,620 AF cases and 970,216 controls. We identified 163 independent risk variants at 111 loci and prioritized 165 candidate genes likely to be involved in AF. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans or mice (MYH6, NKX2-5, PITX2, TBC1D32, TBX5),1,2 or near genes important for striated muscle function and integrity (e.g. MYH7, PKP2, SSPN, SGCA). Experiments in rabbits with heart failure and left atrial dilation identified a heterogeneous distributed molecular switch from MYH6 to MYH7 in the left atrium, which resulted in contractile and functional heterogeneity and may predispose to initiation and maintenance of atrial arrhythmia.

Arterial Pressure Variation in Elective Noncardiac Surgery: Identifying Reference Distributions and Modifying Factors

Background: Assessment of need for intravascular volume resuscitation remains challenging for anesthesiologists. Dynamic waveform indices, including systolic and pulse pressure variation, are demonstrated as reliable measures of fluid responsiveness for mechanically ventilated patients. Despite widespread use, real-world reference distributions for systolic and pulse pressure variation values have not been established for euvolemic intraoperative patients. The authors sought to establish systolic and pulse pressure variation reference distributions and assess the impact of modifying factors. Methods: The authors evaluated adult patients undergoing general anesthetics for elective noncardiac surgery. Median systolic and pulse pressure variations during a 50-min postinduction period were noted for each case. Modifying factors including body mass index, age, ventilator settings, positioning, and hemodynamic management were studied via univariate and multivariable analyses. For systolic pressure variation values, effects of data entry method (manually entered vs. automated recorded) were similarly studied. Results: Among 1,791 cases, per-case median systolic and pulse pressure variation values formed nonparametric distributions. For each distribution, median values, interquartile ranges, and reference intervals (2.5th to 97.5th percentile) were, respectively, noted: these included manually entered systolic pressure variation (6.0, 5.0 to 7.0, and 3.0 to 11.0 mmHg), automated systolic pressure variation (4.7, 3.9 to 6.0, and 2.2 to 10.4 mmHg), and automated pulse pressure variation (7.0, 5.0 to 9.0, and 2.0 to 16.0%). Nonsupine positioning and preoperative &bgr; blocker were independently associated with altered systolic and pulse pressure variations, whereas ventilator tidal volume more than 8 ml/kg ideal body weight and peak inspiratory pressure more than 16 cm H2O demonstrated independent associations for systolic pressure variation only. Conclusions: This study establishes real-world systolic and pulse pressure variation reference distributions absent in the current literature. Through a consideration of reference distributions and modifying factors, the authors’ study provides further evidence for assessing intraoperative volume status and fluid management therapies.

Newer isn’t always better: comparative effectiveness of sevoflurane and isoflurane in cardiac surgery

In this issue of the Journal, Jones et al. present a comparative effectiveness trial showing no difference in clinically relevant outcomes between sevoflurane and isoflurane when used for anesthetic maintenance during cardiac surgery. Specifically, the authors showed that sevoflurane is non-inferior to isoflurane based on a primary outcome composite measure of prolonged intensive care unit (ICU) length of stay (LOS) and all-cause 30-day mortality. Furthermore, the authors found that sevoflurane is not superior to isoflurane on any other clinically important outcome. The direct ramifications of this study are interesting. For instance, the authors suggest potentially saving millions of healthcare dollars per year if anesthesiologists opt to use isoflurane rather than sevoflurane during cardiac surgery. Of greater interest, however, is the fact that this study was just now performed, despite both anesthetics being available for over 20 years in the context of clinical equipoise. This work highlights that scientific research should not only strive to push the bounds of basic knowledge but also welcome pragmatic studies performed in real-world settings to address daily clinical conundrums. Consider recent research in our field comparing isoflurane with sevoflurane. This work includes a study in a rodent model assessing electroencephalographic activity as well as a study assessing aminotransferase levels during hepatic ischemia-reperfusion injury in a similar animal model. Although this type of comparative basic science research yields valuable and often mechanistic findings, which should be commended and selectively encouraged, it should not be at the exclusion of pragmatic clinical trials such as that performed by Jones et al. Their comparative effectiveness study achieves its value by answering a common clinical question with an easily graspable healthcare impact, all the while engaging patients as participants in the progress of science. Indeed, the value of these trials has been previously shown and promoted among healthcare policy-makers who esteem ‘‘the art of the possible’’. To continue increasing its impact on science, the field of anesthesiology must complement and expand on its historical strengths in basic science and patient safety research with the expansion of comparative effectiveness research. Beyond an admirably practical study design, the work of Jones et al. sheds new light on a topic particularly germane to cardiac anesthesia. Among studies of volatile anesthetics used in cardiac surgery, meta-analyses have previously shown cardioprotective effects of volatile agents when compared with intravenous anesthetics. Comparing the differential effects of volatile anesthetics, studies have shown relatively less depressed systolic and diastolic function and smaller increases in heart rate in subjects receiving sevoflurane compared with isoflurane; however, these studies were limited by a lack of long-term outcomes and real-world applicability. Although these prior studies suggest that sevoflurane may provide a smoother set of hemodynamic dots and dashes on an anesthetic record, the impact this may have on any meaningful measure of healthcare is less apparent. Like many areas currently in medicine, this knowledge gap can often be bridged most effectively by a pragmatic trial. Through their work, Jones et al. make progress in rigorously evaluating (and dispelling) perceived differences between sevoflurane and M. R. Mathis, MD (&) S. Kheterpal, MD, MBA Department of Anesthesiology, University of Michigan Health System, 1H247 UH, SPC 5048, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5048, USA e-mail: mathism@med.umich.edu

Extended Case Duration and Hypotension Are Associated With Higher-grade Postoperative Complications After Urinary Diversion for Non-oncological Disease

OBJECTIVE To report survival for patients who undergo urinary diversion for benign indications and to identify risk factors for morbidity at 90 days. METHODS This is a retrospective review of consecutive urinary diversions with or without cystectomy for non-oncological indications at a single institution. The indication for diversion was intractable incontinence, upper tract deterioration, urinary fistula, and unmanageable bladder pain. Patients were categorized according to their most severe complication within 90 days of surgery, using the Clavien-Dindo system. Multivariable analysis was performed to identify factors associated with high-grade complications. Survival analysis was performed. RESULTS Between 2007 and 2014, 141 patients underwent urinary diversion for non-oncological indications. The postoperative rate of high-grade adverse events (class III or greater) was 28%. Risk factors for class III or greater complications at 90 days included prolonged intraoperative mean arterial pressure below 75% of baseline, operative duration greater than 343 minutes, and postoperative vasopressor requirement. Kaplan-Meier survival analysis demonstrated a 1- and 5-year survival of 88.4% and 77.2%, respectively. The long-term survival of patients who experienced higher-grade complications was not statistically different from the survival of the rest of the group. The study was limited by a retrospective design and sample size in identifying additional variables associated with increased risk of long-term mortality. CONCLUSION Urinary diversion for non-oncological conditions has a good 5-year survival in this cohort. Extended case duration and hemodynamic instability during or immediately after urinary diversion are associated with a high-grade complication within 90 days of the procedure.