Derek T. Woodrum

Laparoscopic Skills Are Improved With LapMentor™ Training: Results of a Randomized, Double-Blinded Study

Objective:To determine if prior training on the LapMentor™ laparoscopic simulator leads to improved performance of basic laparoscopic skills in the animate operating room environment. Summary Background Data:Numerous influences have led to the development of computer-aided laparoscopic simulators: a need for greater efficiency in training, the unique and complex nature of laparoscopic surgery, and the increasing demand that surgeons demonstrate competence before proceeding to the operating room. The LapMentor™ simulator is expensive, however, and its use must be validated and justified prior to implementation into surgical training programs. Methods:Nineteen surgical interns were randomized to training on the LapMentor™ laparoscopic simulator (n = 10) or to a control group (no simulator training, n = 9). Subjects randomized to the LapMentor™ trained to expert criterion levels 2 consecutive times on 6 designated basic skills modules. All subjects then completed a series of laparoscopic exercises in a live porcine model, and performance was assessed independently by 2 blinded reviewers. Time, accuracy rates, and global assessments of performance were recorded with an interrater reliability between reviewers of 0.99. Results:LapMentor™ trained interns completed the 30° camera navigation exercise in significantly less time than control interns (166 ± 52 vs. 220 ± 39 seconds, P < 0.05); they also achieved higher accuracy rates in identifying the required objects with the laparoscope (96% ± 8% vs. 82% ± 15%, P < 0.05). Similarly, on the two-handed object transfer exercise, task completion time for LapMentor™ trained versus control interns was 130 ± 23 versus 184 ± 43 seconds (P < 0.01) with an accuracy rate of 98% ± 5% versus 80% ± 13% (P < 0.001). Additionally, LapMentor™ trained interns outperformed control subjects with regard to camera navigation skills, efficiency of motion, optimal instrument handling, perceptual ability, and performance of safe electrocautery. Conclusions:This study demonstrates that prior training on the LapMentor™ laparoscopic simulator leads to improved resident performance of basic skills in the animate operating room environment. This work marks the first prospective, randomized evaluation of the LapMentor™ simulator, and provides evidence that LapMentor™ training may lead to improved operating room performance.

Neutrophil Depletion Inhibits Experimental Abdominal Aortic Aneurysm Formation

Background—Neutrophils may be an important source of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two matrix-degrading enzymes thought to be critical in the formation of an abdominal aortic aneurysm (AAA). The purpose of this investigation was to test the hypothesis that neutrophil depletion would limit experimental AAA formation by altering one or both of these enzymes. Methods and Results—Control, rabbit serum–treated (RS; n=27) or anti-neutrophil-antibody–treated (anti-PMN; n=25) C57BL/6 mice underwent aortic elastase perfusion to induce experimental aneurysms. Anti-PMN–treated mice became neutropenic (mean, 349 cells/&mgr;L), experiencing an 84% decrease in the circulating absolute neutrophil count (P<0.001) before elastase perfusion. Fourteen days after elastase perfusion, control mice exhibited a mean aortic diameter (AD) increase of 104±14% (P<0.0001), and 67% developed AAAs, whereas anti-PMN–treated mice exhibited a mean AD increase of 42±33%, with 8% developing AAAs. The control group also had increased tissue neutrophils (20.3 versus 8.6 cells per 5 high-powered fields [HPFs]; P=0.02) and macrophages (6.1 versus 2.1 cells per 5 HPFs, P=0.005) as compared with anti-PMN–treated mice. There were no differences in monocyte chemotactic protein-1 or macrophage inflammatory protein-1&agr; chemokine levels between groups by enzyme-linked immunosorbent assay. Neutrophil collagenase (MMP-8) expression was detected only in the 14-day control mice, with increased MMP-8 protein levels by Western blotting (P=0.017), and MMP-8–positive neutrophils were seen almost exclusively in this group. Conversely, there were no statistical differences in MMP-2 or MMP-9 mRNA expression, protein levels, enzyme activity, or immunostaining patterns between groups. When C57BL/6 wild-type (n=15) and MMP-8–deficient mice (n=17) were subjected to elastase perfusion, however, ADs at 14 days were no different in size (134±7.9% versus 154±9.9%; P=0.603), which suggests that MMP-8 serves only as a marker for the presence of neutrophils and is not critical for AAA formation. Conclusions—Circulating neutrophils are an important initial component of experimental AAA formation. Neutrophil depletion inhibits AAA development through a non–MMP-2/9–mediated mechanism associated with attenuated inflammatory cell recruitment.

L-Selectin-Mediated Neutrophil Recruitment in Experimental Rodent Aneurysm Formation

Background—This investigation tested the hypothesis that L-selectin is important in experimental abdominal aortic aneurysm (AAA) formation in rodents. Methods and Results—Rat abdominal aortas were perfused with saline (control) or porcine pancreatic elastase and studied on postperfusion days 1, 2, 4, 7, and 14 (n=5 per treatment group per day). Neutrophil (polymorphonucleur leukocyte, PMN) and macrophage counts per high-powered field (HPF) were performed on fixed sections. L-selectin expression and protein levels in aortic tissue were determined by polymerase chain reaction and Western blot, respectively. Elastase-perfused aortic diameters were significantly increased compared with control aortas at all time points except day 1 (P<0.05). PMN counts significantly increased in elastase-perfused aortas compared with control aortas at days 1, 2, and 4, reaching maximum levels at day 7 (40.8 versus 0.3 PMNs/HPF, P=0.001). L-selectin mRNA expression in elastase-perfused aortas was 18 (P=0.018), 17 (P<0.001), and 8 times (P=0.02) times greater than control aortas at days 1, 2, and 4, respectively. Western blot demonstrated a significant 69% increase in L-selectin protein at day 7 in elastase- as compared with saline-perfused aortas (P=0.005). Subsequent experiments involved similar studies on postperfusion days 4, 7, and 14 of aortas from C57BL/6 wild-type (WT) mice (n=21) and L-selectin–knockout (LKO) mice (n=19). LKO mice had significantly smaller aortic diameters at day 14 as compared with WT mice (88% versus 123%, P=0.02). PMN counts were significantly greater in elastase-perfused WT mouse aortas as compared with LKO mouse aortas at day 4 after perfusion (12.8 versus 4.8 PMNs/HPF, P=0.02). Macrophage counts were significantly greater at all time points after perfusion in elastase-perfused WT mouse aortas compared with elastase-perfused LKO mouse aortas, with a maximum difference at day 7 after perfusion (13.3 versus 0.5 macrophages/HPF, P<0.001). Conclusion—L-selectin–mediated neutrophil recruitment may be a critical early step in AAA formation.

Differential Regulation of Aortic Growth in Male and Female Rodents Is Associated With AAA Development

BACKGROUND The objective was to examine effects of gonadal hormone manipulation on aortic diameter and macrophage infiltration in rodents during abdominal aortic aneurysm (AAA) formation. METHODS Experiment 1: 17-beta estradiol and testosterone pellets were implanted in male (ME) and female (FT) rats. No pellet was implanted in shams (MES, FTS). Experiment 2: Testes and ovaries were removed from males (MO) and females (FO), respectively. No organs were removed from shams (MOS, FOS). Experiment 3: Male and female rats were orchiectomized and oophorectomized, respectively. Four weeks post-castration, testosterone (MOT) and 17-beta estradiol (FOE) pellets were implanted. Shams underwent castration, but no pellet was implanted (MOTS, FOES). All rats underwent infrarenal aortic infusion with elastase postimplantation/postcastration. Diameters were measured on postoperative d 14. Tissue was stained for macrophages by immunohistochemistry. RESULTS Diameter (P = 0.046) and macrophage counts (P = 0.014) decreased in ME compared with shams, but not in females treated with testosterone (FT). Diameter (P = 0.019) and macrophage infiltration (P = 0.024) decreased in MO compared with shams, but not in FO. Diameter increased in MOT compared with MOTS (P = 0.033), but decreased in FOE compared with FOES (P = 0.002). Macrophages decreased in FOE compared with FOES (P = 0.002). CONCLUSION This study documents a decrease in AAA diameter in males treated with estrogen or undergoing orchiectomy, but no changes in females treated with testosterone or undergoing oophorectomy; and an increase in diameter in MOT and a decrease in FOE. These data suggest that gonadal hormones differentially regulate AAA growth in association with changes in macrophages.

LapMentor metrics possess limited construct validity.

Background: Many surgical training programs are introducing virtual-reality laparoscopic simulators into their curriculum. If a surgical simulator will be used to determine when a trainee has reached an “expert” level of performance, its evaluation metrics must accurately reflect varying levels of skill. The ability of a metric to differentiate novice from expert performance is referred to as construct validity. The present study was undertaken to determine whether the LapMentors metrics demonstrate construct validity. Methods: Medical students, residents and faculty laparoscopic surgeons (n = 5–14 per group) performed 5 consecutive repetitions of 6 laparoscopic skills tasks: 30° Camera Manipulation, Eye-Hand Coordination, Clipping/Grasping, Cutting, Electrocautery, and Translocation of Objects. The LapMentor measured performance in 4 to 12 parameters per task. Mean performance for each parameter was compared between subject groups for the first and fifth repetitions. Pairwise comparisons among the 3 groups were made by post hoc t-tests with Bonferroni technique. Significance was set at P < 0.05. Results: Of the 6 tasks evaluated, only the Eye-Hand Coordination task (3/12 parameters) and the Clipping and Grasping (1/7 parameters) had expert-level discrimination when performance was compared after completion of 1 repetition. Comparison of the fifth repetition performance (representing the plateau of the learning curves), demonstrated that the parameters Time and Score had expert level discrimination on the Eye-Hand Coordination task, and Time on the Cutting task. The remaining LapMentor tasks evaluated did not exhibit the ability to differentiate level of expertise based on the built-in metrics on either repetition 1 or 5. Conclusions: The majority of the LapMentor tasks’ metrics were unable to differentiate between laparoscopic experts and less skilled subjects. Therefore, performance on those tasks may not accurately reflect a subjects true level of ability. Feedback to the manufacturer about these findings may encourage the development of evaluation parameters with greater sensitivity.

Salvage of an unstable brain dead donor with prompt extracorporeal support

Maximizing the support of the marginal donor is an approach to optimizing the donor pool. Thirty-two percent of brain dead donors are hemodynamically unstable and 25% of donors under the age of 60 with traumatic brain injuries expire before organs can be procured (1, 2). When standard donor management protocols are insufficient to salvage a potential donor, aggressive attempts to save the organs can be considered. We present a case of an unstable brain dead donor who suffered premature cardiac death and the use of ECMO (extra-corporeal membrane oxygenation) perfusion in the successful salvage of organs for transplantation. Shortly after being declared brain dead, a 25-year-old patient became hypoxic and hemodynamically unstable. The patient’s family strongly desired organ donation. Despite hormonal replacement and three vasopressors, his mean arterial pressure (MAP) was less than 45 mm Hg. The situation was reviewed with the family, who gave consent for ECMO. The ECMO team was called for an emergent cannulation. The patient was placed on venous-arterial ECMO via cannula placement in the common femoral artery, the internal jugular vein, and the common femoral vein. The patient had a significant improvement in hemodynamics and resumed making urine (MAP 60 to 75). Approximately 75 min later and for unclear reasons, the patient had a cardiac arrest. The MAP was maintained at 53 via ECMO support following cessation of cardiac activity. The patient was transported to the operating room. ECMO flow was not interrupted during this transport. Shortly after arriving into the operating room, cold University of Wisconsin solution was infused through the ECMO circuit. The femoral venous cannula was cut and allowed to drain into a waste bucket. The abdomen was opened and cold slush was poured into the abdominal cavity. The perfusate return soon cleared and the kidneys were procured in the standard fashion. The kidneys were placed on pulsatile pump perfusion. Both kidneys were transplanted and functioned immediately. At our center, we have had success with a protocol using extracorporeal support for NHBDs (non-heart beating donors) (3). In our experience with NHBD, balloon aortic occlusion and a mean ECMO flow of 3.0 L/minute provides physiologic flow to the intra-abdominal organs. Failure of physiologic support to prevent early cardiac death was the second most frequent potentially remediable causes of procurement failure (4). Many potential donors who are unstable are not referred to the local organ procurement organization. In addition, patients who have been hemodynamically tenuous are frequently only kidney donors and the other organs are not procured. In this case, the use of ECMO salvaged the kidneys for donation. In addition, the circuit provided an expeditious means to perfuse with cold University of Wisconsin solution. Using ECMO to optimize brain dead donors is a novel strategy to increase the number of donors and the yield of organs per donor. Michael J. Englesbe Derek Woodrum Meelie Debroy Richard Chenault William Miller Judiann Miskulin Fresca Swaniker John C. Magee Juan D. Arenas Jeffery D. Punch Randall S. Sung Department of Surgery Division of Transplant Surgery and Surgical Critical Care University of Michigan Health System Ann Arbor, Michigan

Intraoperative bispectral index monitoring and time to extubation after cardiac surgery: secondary analysis of a randomized controlled trial

BackgroundFast track recovery is a care process goal after cardiac surgery. Intraoperative anesthetic depth may impact recovery, but the impact of brain monitoring on time to extubation and intensive care unit (ICU) length of stay after cardiac surgery has not been extensively studied. Our goal was to determine if BIS-guided anesthesia improves time to extubation compared to MAC-guided anesthesia in a cardiac surgery population.MethodsIn this secondary outcome analysis of a randomized controlled study, we analyzed 294 patients undergoing elective coronary bypass grafting, valve replacements, and bypass plus valve replacements at a single tertiary referral center between February 1, 2009 and April 30, 2010. We analyzed cardiac surgery patients that had been randomized to BIS-guided anesthesia alerts (n = 131) or MAC-guided anesthesia alerts (n = 163). The primary outcome measure was time to extubation in the BIS-guided and anesthetic concentration-guided groups. Secondary outcomes were length of stay in the ICU and total postoperative hospital length of stay.ResultsValid extubation time data were available for 247 of 294 patients. The median [IQR] time to extubation was 307 [215 to 771] minutes in the BIS group and 323 [196 to 730] minutes in the anesthetic concentration group (p = 0.61). The median [IQR] ICU length of stay was 54 [29 to 97] hours versus 70 [44 to 99] hours (p = 0.11). In terms of postoperative hospital length of stay, there was no difference between the groups with median [IQR] times of 6 [5-8] days (p = 0.69) in each group.ConclusionsThe use of intraoperative BIS monitoring during cardiac surgery did not change time to extubation, ICU length of stay or hospital length of stay. Data regarding BIS monitoring and recovery in an exclusively cardiac surgery population are consistent with recent effectiveness studies in the general surgical population.Trial registrationClinicalTrials.gov number NCT00689091.

Differential Effect of 17-ß-Estradiol on Smooth Muscle Cell and Aortic Explant MMP21

OBJECTIVE The present investigation tested the hypothesis that intrinsic gender-related differences exist in rat aortic smooth muscle cell matrix metalloproteinase 2 (MMP2). METHODS This investigation comprised 3 sets of experiments. Experiment I: Adult male and female rat aortic smooth muscle cells (RASMCs) at passages 4-8 were stimulated in serum-free media for 48 h with interleukin(IL)1beta at doses encountered in human abdominal aortic aneurysms (2 ng/mL). Messenger RNA was extracted from the RASMCs, and gene expression of MMP2 and tissue inhibitor of metalloproteinase 2 (TIMP2), a major MMP2 inhibitor, was measured by real-time polymerase chain reaction. MMP2 protein levels in conditioned media were measured by Western blotting, and MMP2 and TIMP2 activity quantified by standard and reverse gelatin zymography. Experiment II: Male and female RASMCs were incubated for 48 h in Dulbeccos modified Eaglers medium containing IL-1beta and 17-beta-estradiol at doses from 1x10(-10) to 1x10(-6) molar. MMP2 activity in the conditioned media was then determined. Experiment III: Male rats underwent sustained 17-beta-estradiol exposure for 21 d using extended-release, subcutaneously implanted pellets prior to sacrifice and aortic explantation. Aortas from males, females, and estradiol-treated males were stimulated with IL-1beta for 48-h, and MMP2 activity in the conditioned media was determined. RESULTS Experiment I: MMP2 gene expression was 3-fold higher in male compared with female IL-1beta stimulated RASMCs (P<0.0001). MMP2:TIMP2 gene expression ratio was 7.5-fold greater in male versus female RASMCs. MMP2 protein levels were 3-fold higher (2.68 versus 0.96 o.d./mg total protein, P=0.003) in male versus female RASMCs. Gelatinolytic activity was more than 6-fold higher (15,010 versus 2,472 o.d./mg total protein, P=0.002) in male versus female RASMCs. Experiment II: MMP2 activity in male and female RASMCs was not altered by a wide range of 17-beta-estradiol concentrations. Experiment III: When pretreated with 17-beta-estradiol, MMP2 activity in the media of male rat whole-aortic explants decreased 2-fold (P=0.002). This post-17-beta-estradiol treatment male level was not different than baseline female aortic explant MMP2 levels. CONCLUSIONS MMP2 is higher in male RASMCs compared to female RASMCs. Exogenous 17-beta-estradiol did not alter MMP2 activity in vitro, but in vivo 17-beta-estradiol exposure greatly decreased male aortic MMP2 production to levels seen in the female aorta. Gender differences in MMP2 are speculated to be associated with phenotypic differences in human abdominal aortic aneurysm formation.

Too much of a good thing is wonderful: observational data for perioperative research.

MANY of our clinical decisions are based on animal models, small in vivo studies, retrospective chart reviews, or tradition. As anesthetic safety has improved over the past few decades, the infrequent events that comprise current anesthesia morbidity are difficult to analyze using traditional research tools. Intraoperative blood pressure management research exemplifies this challenge. Although we measure, document, and treat blood pressure continuously during each case throughout our careers, systemic blood pressure remains one of the most understudied aspects of anesthetic care in vivo. In this issue of ANESTHESIOLOGY, Bijker et al. provide an important contribution to the perioperative medicine literature in this arena. Bijker et al. evaluate the relationship between intraoperative “hypotension” and 1-yr all-cause mortality. Unfortunately, because no standardized definition of hypotension has been adopted, the authors evaluated 48 different forms of hypotension for an outcome effect. Despite— or perhaps because of—this exhaustive search, the authors struggle to provide compelling evidence for an association between any definition of hypotension and mortality. Using traditional multivariate modeling techniques, they were unable to identify a relationship. However, classification and regression tree analysis demonstrated an association between mortality and mean arterial pressure hypotension less than 60 mmHg, independent of patient age or duration of surgery. Of note, it is unclear whether this analysis controlled for patient comorbidities. The analysis of Bijker et al. includes only 1,705 patients with 88 deaths at 1 yr—with 45 patients (52%) succumbing to cancer or unknown causes. The many independent variables to be considered—patient age, duration of surgery, surgical risk, comorbidities, and 48 definitions of hypotension— are modeled against only 88 outcome events, a challenge to any statistical technique. The work of Bijker et al. and similar studies hampered by small sample size highlight the current opportunity for large data set research and the need for and impact of multicenter perioperative outcomes databases. The challenge of small sample sizes combined with infrequent adverse events forces the anesthesia community to expand its research tool set. Just as the analysis by Lindenauer et al. of more than 700,000 patients complemented early small trials of perioperative blockade, we must use prospective, detailed, perioperative clinical data sets to investigate infrequent anesthetic adverse events. Investigators in the United States have begun to use large national data sets to evaluate fundamental perioperative outcomes: anesthetic-related mortality, stroke, and acute kidney injury. One major advantage of these data sets—the Multiple Cause of Death Public Use Data File, Nationwide Inpatient Sample, and National Surgical Quality Improvement Program Participant Use Data File—is the consistency of data collection and facile access to data. However, each data set has an alternate primary purpose—public health reporting, billing, or surgical outcomes research—and cannot be modified to evaluate specific anesthetic management questions. For example, it is impossible to identify patients who received epidural analgesia as an adjunct to a general anesthetic using the National Surgical Quality Improvement Program data set. The lack of detailed anesthetic intervention information limits these data sets to process-of-care or risk stratification research. Recognizing these limitations and the need for detailed perioperative clinical data, the American Society of Anesthesiologists established the Anesthesia Quality Institute in 2008. A not-for-profit corporation established with seed funds from the American Society of Anesthesiologists, the Anesthesia Quality Institute is the fruition of years of effort by quality improvement champions within our field. It has grown from initial work performed nearly a decade ago by the Committee on Performance and Outcomes Measurement, which defined the clinical outcomes of interest to providers and patients alike. The Anesthesia Quality Institute will house the National Anesthesia Clinical Outcomes Registry, a patient data registry that will be combined with other data sources to enable provider benchmarking, quality improvement, research, public reporting, credentialing, and maintenance of certification. Because the National Anesthesia Clinical Outcomes Registry will be designed and developed by anesthesiologists, it will contain anesthesia-specific data elements that are essential for comprehensive perioperative clinical research. It represents This Editorial View accompanies the following article: Bijker JB, van Klei WA, Vergouwe Y, Eleveld DJ, van Wolfswinkel L, Moons KGM, Kalkman CJ: Intraoperative hypotension and 1-year mortality after noncardiac surgery. ANESTHESIOLOGY 2009; 111:1217–26.