Novel method to assess arterial insufficiency in rodent hind limb.

BACKGROUND: Lack of techniques to assess maximal blood flow capacity thwarts the use of rodent models of arterial insufficiency to evaluate therapies for intermittent claudication. We evaluated femoral vein outflow (VO) in combination with stimulated muscle contraction as a potential method to assess functional hind limb arterial reserve and therapeutic efficacy in a rodent model of subcritical limb ischemia. MATERIALS AND METHODS: VO was measured with perivascular flow probes at rest and during stimulated calf muscle contraction in young, healthy rats (Wistar Kyoto, WKY; lean Zucker rats, LZR) and rats with cardiovascular risk factors (spontaneously hypertensive [SHR]; obese Zucker rats [OZR]) with acute and/or chronic femoral arterial occlusion. Therapeutic efficacy was assessed by administration of Ramipril or Losartan to SHR after femoral artery excision. RESULTS: VO measurement in WKY demonstrated the utility of this method to assess hind limb perfusion at rest and during calf muscle contraction. Although application to diseased models (OZR and SHR) demonstrated normal resting perfusion compared with contralateral limbs, a significant reduction in reserve capacity was uncovered with muscle stimulation. Administration of Ramipril and Losartan demonstrated significant improvement in functional arterial reserve. CONCLUSIONS: The results demonstrate that this novel method to assess distal limb perfusion in small rodents with subcritical limb ischemia is sufficient to unmask perfusion deficits not apparent at rest, detect impaired compensation in diseased animal models with risk factors, and assess therapeutic efficacy. The approach provides a significant advance in methods to investigate potential mechanisms and novel therapies for subcritical limb ischemia in preclinical rodent models.

Perioperative Lidocaine Infusion Reduces Opioid Use in Enhanced Recovery After Surgery Patients Undergoing Laparoscopic Colectomy.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) programs have become a mainstay of modern surgical care, and efforts to decrease postoperative opioid consumption have been increasingly employed. A previous study from our institution demonstrated that ERAS protocols decreased opioid use in the first 48 hours after surgery by 61%. In the present study, a lidocaine infusion was added for postoperative pain control. The aim was to analyze the differences in opioid requirements with and without this infusion in the first 48 hours after laparoscopic colectomy in ERAS patients. METHODS: Retrospective review of patients was conducted at an academically affiliated tertiary care hospital. The population included patients undergoing elective laparoscopic colon surgery enrolled in the ERAS program with the implementation of a lidocaine drip from June 2019 to October 2019, and compared to a previous patient cohort of ERAS patients evaluated without the lidocaine drip from September 2015 to May 2018. RESULTS: The primary endpoint was postoperative opioid use in the first 48 hours based on IV morphine milligram equivalents (MME). Secondary measures included type of surgery, age, BMI, prior abdominal surgery, and prior opioid use. Median MMEs were 6.0 in the lidocaine infusion group and 12.5 in the group without lidocaine, representing a 52% reduction (p < 0.001). DISCUSSION: This study demonstrates a significant reduction in post-op opioid use in ERAS patients who receive a lidocaine infusion after laparoscopic colectomy. Further studies should focus on measures to limit the treatment side effects in order to maximize the opioid-sparing benefits of this intervention.

Can the American College of Surgeons National Surgical Quality Improvement Program Risk Calculator Predict Outcomes for Urgent Colectomies?

BACKGROUND: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Risk Calculator (RC) predicts postoperative outcomes using 19 risk factors, including operative acuity. Acuity is defined by the calculator as emergent or elective only. The objective of this study is to evaluate the RC's accuracy in urgent (nonelective/nonemergent) cases. METHODS: This is a retrospective review of the NSQIP data for patients who underwent urgent colectomies at a single tertiary care center over a 4-year period. Each urgent case was entered into the RC as both elective and emergent, and predicted outcomes were compared to actual postoperative outcomes. Receiver operating characteristic (ROC) curves were used when sufficient statistical power was present and the area under the curve (AUC) was calculated. RESULTS: A total of 301 urgent colectomy patients were evaluated, representing 19% of all colectomies performed at our institution during the study period. Of the 15 possible postoperative outcomes, the RC showed high predictive value only for mortality (AUC elective .8467; emergent .8451) and discharge to a nursing/rehabilitation facility (AUC elective .8089; emergent .8105). The RC showed no predictive value for 6 outcomes and the remainder lacked statistical power to draw conclusions. DISCUSSION: While the calculator predicted mortality and discharge to a nursing/rehabilitation facility, it did not accurately predict complications for urgent colectomies. Future versions of the calculator should focus on improving the predictive value by including urgent cases as a separate category.

Opioid Requirements in Laparoscopic Colectomies: Do Enhanced Recovery After Surgery Protocols Make a Difference?

BACKGROUND: With the growing opioid epidemic and recent focus on the quantity of opioids prescribed at discharge after surgery, enhanced recovery pathways provide another tool to counteract this epidemic. The aim of this current study is to analyze the differences in opioid requirements and pain scores in the immediate postoperative period for patients who underwent laparoscopic colectomies before and after the implementation of enhanced recovery after surgery (ERAS) protocols. MATERIALS AND METHODS: This study is a retrospective review of patients and was conducted at an academically affiliated tertiary care hospital. In patients undergoing elective laparoscopic colectomies before December 1, 2013-July 31, 2015 and after September 1, 2015-May 31, 2018, the implementation of enhanced recovery pathways was included. The primary end point was opioid consumption from the end of surgery until 48 hours after surgery. Secondary end points included pain scores, surgery length of time, and hospital length of stay after surgery. RESULTS: A total of 242 patients (122 pre- and 120 postimplementation) were analyzed. Patient characteristics were similar between groups. Pain scores were higher in the preimplementation patients for postoperative day (POD) 0 scores (P = .019). There was a decrease in the morphine milligram equivalents (MME) on POD 0-2 for the postimplementation patients. This decrease resulted in a 61% reduction in opioid requirements after implementation of ERAS protocols (32 vs. 12.5 MME, P < .0001). DISCUSSION: Enhanced recovery after surgery protocols can reduce opioid requirements after elective laparoscopic colectomies without negatively affecting pain scores.

Marvels, mysteries, and misconceptions of vascular compensation to peripheral artery occlusion.

Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation.

Risk factors for anastomotic leak and mortality in diabetic patients undergoing colectomy: analysis from a statewide surgical quality collaborative.

OBJECTIVES: To determine the risk factors in diabetic patients that are associated with increased postcolectomy mortality and anastomotic leak. DESIGN: A prospectively acquired statewide database of patients who underwent colectomy was reviewed. Primary risk factors were diabetes mellitus, hyperglycemia (glucose level ≥ 140 mg/dL), steroid use, and emergency surgery. Categorical analysis, univariate logistic regression, and multivariate regression were used to evaluate the effects of these risk factors on outcomes. SETTING: Participating hospitals within the Michigan Surgical Quality Collaborative. PATIENTS: Database review of patients from hospitals within the Michigan Surgical Quality Collaborative. MAIN OUTCOME MEASURES: Anastomotic leak and 30- day mortality rate. RESULTS: Of 5123 patients, 153 (3.0%) had leaks and 153 (3.0%) died. Preoperative hyperglycemia occurred in 15.6% of patients, only 54% of whom were known to have diabetes. Multivariate analysis showed that the risk of leak for patients with and without diabetes increased only by preoperative steroid use (P<.05). Mortality among diabetic patients was associated with emergency surgery (P<.01) and anastomotic leak (P<.05); it was not associated with hyperglycemia. Mortality among nondiabetic patients was associated with hyperglycemia (P<.005). The presence of an anastomotic leak was associated with increased mortality among diabetic patients (26.3% vs 4.5%; P<.001) compared with nondiabetic patients (6.0% vs 2.5%; P<.05). CONCLUSIONS: The presence of diabetes did not have an effect on the presence of an anastomotic leak, but diabetic patients who had a leak had more than a 4-fold higher mortality compared with nondiabetic patients. Preoperative steroid use led to increased rates of anastomotic leak in diabetic patients. Mortality was associated with hyperglycemia for nondiabetic patients only. Improved screening may identify high-risk patients who would benefit from perioperative intervention.

Suppressed hindlimb perfusion in Rac2-/- and Nox2-/- mice does not result from impaired collateral growth.

While tissue perfusion and angiogenesis subsequent to acute femoral artery occlusion are suppressed in NADPH oxidase 2 (Nox2)-null (Nox2(-/-)) mice, studies have not established the role of Nox2 in collateral artery enlargement. Rac2 is a small GTPase that binds Nox2 and activates Nox2-based NAD(P)H oxidase but, unlike Nox2, is primarily restricted to bone marrow-derived cells. In this study, we used Rac2-null (Rac2(-/-)) and Nox2(-/-) mice with a novel method of identifying primary hindlimb collaterals to investigate the hypothesis that collateral growth requires these molecules. When initial experiments performed with femoral ligation demonstrated similar perfusion and collateral growth in Rac2(-/-) and wild-type C57BL/6J (BL6) mice, subsequent experiments were performed with a more severe ischemia model, femoral artery excision. After femoral excision, tissue perfusion was suppressed in Rac2(-/-) mice relative to BL6 mice. Histological assessment of ischemic injury including necrotic and regenerated muscle fibers and lipid and collagen deposition demonstrated greater injury in Rac2(-/-) mice. The diameters of primary collaterals identified during Microfil injection with intravital microscopy were enlarged to a similar extent in BL6 and Rac2(-/-) mice. Intimal cells in collateral cross sections were increased in number in both strains and were CD31 positive and CD45 negative. Circulating leukocytes and CD11b(+) cells were increased more in Rac2(-/-) than BL6 animals. Experiments performed in Nox2(-/-) mice to verify that the unexpected results related to collateral growth were not unique to Rac2(-/-) mice gave equivalent results. The data demonstrate that, subsequent to acute femoral artery excision, perfusion recovery is impaired in Rac2(-/-) and Nox2(-/-) mice but that collateral luminal expansion and intimal cell recruitment/proliferation are normal. These novel results indicate that collateral luminal expansion and intimal cell recruitment/proliferation are not mediated by Rac2 and Nox2.

Is administration of enteric contrast material safe before abdominal CT in children who require sedation? Experience with chloral hydrate and pentobarbital.

OBJECTIVE: It has been common practice to administer enteric contrast material in preparation for abdominal CT in children who require sedation to be examined. At some institutions, the practice of administering an anesthetic or enteric contrast material before sedation is being challenged because it violates the "nothing by mouth" status that is otherwise strictly enforced before sedation. Our purpose was to review our safety record in administering enteric contrast material for CT before sedation. MATERIALS AND METHODS: Radiology reports, medical records, and department incident reports were reviewed for the past 5 years from all patients who required sedation for abdominal CT. Patient age and sex, type of sedation, and complications (defined as vomiting with aspiration) related to enteric contrast material before the sedation were recorded. For routine oral contrast material, diluted Hypaque (meglumine diatrizoate) was administered in an age-based amount 1-2 hr before scanning. For sedation, depending on the patient's age, either oral chloral hydrate (70-100 mg/kg) or IV pentobarbital (3 mg/kg with repeated doses of up to 7 mg/kg) was used. RESULTS: Three hundred sixty-seven patients who received oral contrast material before sedation for abdominal CT were identified (200 boys, 167 girls; age range, 1 month-19 years; mean age, 2.9 years). Chloral hydrate was used in 30 patients and IV pentobarbital in 337 patients. No complications related to the administration of oral contrast material before sedation were identified. CONCLUSION: The practice of administering oral contrast material in children before sedation for abdominal CT appears to be safe when using the sedation drugs and protocols in place at our institution. Further study of the safety of this practice should be undertaken.

Imaging findings in pediatric patients with persistent airway symptoms after surgery for double aortic arch.

OBJECTIVE: The purpose of this study was to review the imaging findings of children referred for cross-sectional imaging to evaluate persistent airway symptoms after surgical therapy for double aortic arch. CONCLUSION: Airway narrowing is clearly shown on cross-sectional imaging in patients with persistent airway symptoms after surgical therapy for double aortic arch. Two patterns of airway compression are typically seen: narrowing of the trachea at the level of the postsurgical arch and narrowing of the left main bronchus as a result of compression from a midline descending aorta. Both patterns may be seen in patients regardless of whether the left or the right arch has been ligated.

Aberrant subclavian arteries: cross-sectional imaging findings in infants and children referred for evaluation of extrinsic airway compression.

OBJECTIVE: The purpose of our study was to describe patterns of airway compression identified on cross-sectional imaging in infants and children with either right aortic arch and aberrant left subclavian artery or left aortic arch with aberrant right subclavian artery. MATERIALS AND METHODS: Data from MR imaging and CT performed to evaluate pediatric patients for extrinsic airway compression were reviewed for cases that revealed an aberrant right or left subclavian artery. Clinical, endoscopic, and imaging findings in identified cases were reviewed. Recurrent patterns of extrinsic compression were reviewed among cases. RESULTS: Twelve patients with right aortic arch with aberrant left subclavian artery and nine patients with left aortic arch and aberrant right subclavian artery were identified. All 12 with right aortic arch with aberrant left subclavian artery had airway compression shown, with multiple sites or diffuse compression in six. Of these 12 patients, nine had compression at the level of the arch and aberrant subclavian artery (10 had Kommerell's diverticulum), and nine had compression of the distal airway in association with a midline descending aorta. Five of the nine patients with left aortic arch and aberrant right subclavian artery had airway compression shown, all at the level of the arch and aberrant subclavian artery. None of these compressions was associated with either Kommerell's diverticulum or midline descending aorta. CONCLUSION: Both right and left aberrant subclavian arteries can be associated with symptomatic airway compression, but the patterns of compression are different. The airway compression in right aortic arch with aberrant left subclavian artery is often associated with either Kommerell's diverticulum or midline descending aorta, whereas compression associated with left aortic arch and aberrant right subclavian artery is not.