Doxycycline improves traumatic brain injury outcomes in a murine survival model.

BACKGROUND: Traumatic brain injury (TBI) has significant morbidity and cost implications. Primary treatment modalities aim to decrease intracranial pressure; however, therapies targeting the underlying pathophysiology of a TBI are limited. The TBI-induced microvascular leak and secondary injury are largely due to proteolysis of the blood-brain barrier (BBB) by matrix metalloproteinase-9. We previously observed doxycycline's inhibitory affinity on matrix metalloproteinase-9 resulting in preserved BBB integrity in nonsurvival murine studies. This study sought to determine the effect of doxycycline on functional motor and behavioral outcomes in the setting of a TBI murine survival model. METHODS: C57BL/6J mice were assigned to a sham, TBI, or TBI with doxycycline arm. A moderate TBI was induced utilizing a controlled cortical impactor. The TBI with doxycycline cohort received a dose of doxycycline (20 mg/kg) 2 hours after injury and every 12 hours until postoperative day (POD) 6. All mice underwent preoperative testing for weight, modified neurological severity score, wire grip, and ataxia analysis (DigiGait). Postoperative testing was performed on POD 1, POD 3, and POD 6 for the same measures. SAS 9.4 was used for comparative analysis. RESULTS: Fifteen sham mice, 15 TBI mice, and 10 TBI with doxycycline mice were studied. Mice treated with doxycycline had significantly improved modified neurological severity score and wire grip scores at POD 1 (all p < 0.05). Mice treated with doxycycline had significantly improved ataxia scores by POD 3 and POD 6 (all p < 0.05). There was no significant difference in rate of weight change between the three groups. CONCLUSION: Mice treated with doxycycline following TBI demonstrated improved behavioral and motor function suggesting doxycycline's role in preserving murine BBB integrity. Examining the role of doxycycline in human TBIs is warranted given the relative universal accessibility, affordability, and safety profile of doxycycline.

Postoperative Opioid Prescription Reduction Strategy in a Regional Healthcare System.

BACKGROUND: The CDC reported in 2017 that the largest increments in probability of continued use were observed after days 5 and 31 on opioid therapy. This study demonstrates the correlation between a system-wide pain management and opioid stewardship effort with reductions in discharge prescriptions for elective surgical patients. STUDY DESIGN: Discharge prescriptions were monitored through the electronic health record. Baseline prescribing patterns were established for the first quarter of 2018, preceding the first intervention in the multipronged opioid reduction initiative. Beginning in the second quarter of 2018, a series of pain management and opioid stewardship educational conferences were provided. Enhanced Recovery after Surgery protocols were simultaneously implemented system-wide. In the third quarter of 2018, a quality metric linked to compensation rewarded surgeons for limiting postoperative discharge prescriptions to 5 or fewer days. Opioid prescriptions were compared by quarter from January 2018 to March 2019 using chi-square and Kruskal-Wallis test with significance of p < 0.05. RESULTS: There were 31,814 patients who underwent elective surgical procedures during the study period. At baseline, the rate of postoperative opioid prescriptions of 5 or fewer days was 81%. This rate increased to 82%, 86%, 89%, and 92% in each successive quarter (p < 0.0001 for quarters 3 to 5). CONCLUSIONS: A system-wide, multipronged pain management and opioid reduction program significantly reduced opioid discharge prescriptions written for more than 5 days. This approach can serve as a model for other healthcare systems attempting to reduce opioid prescribing and combat the opioid crisis in the US.

Preoperative Frailty and Surgical Outcomes Across Diverse Surgical Subspecialties in a Large Health Care System.

BACKGROUND: Frailty is an emerging risk factor for surgical outcomes; however, its application across large populations is not well defined. We hypothesized that frailty affects postoperative outcomes in a large health care system. STUDY DESIGN: Frailty was prospectively measured in elective surgery patients (January 2016 to June 2017) in a health care system (4 hospitals/901 beds). Frailty classifications-low (0), intermediate (1 to 2), high (3 to 5)-were assigned based on the modified Hopkins score. Operations were classified as inpatient (IP) vs outpatient (OP). Outcomes measured (30-day) included major morbidity, discharge location, emergency department (ED) visit, readmission, length of stay (LOS), mortality, and direct-cost/patient. RESULTS: There were 14,530 elective surgery patients (68.1% outpatient, 31.9% inpatient) preoperatively assessed (cardiothoracic 4%, colorectal 4%, general 29%, oral maxillofacial 2%, otolaryngology 8%, plastic surgery 13%, podiatry 6%, surgical oncology 5%, transplant 3%, urology 24%, vascular 2%). High frailty was found in 3.4% of patients (5.3% IP, 2.5% OP). Incidence of major morbidity, readmission, and mortality correlated with frailty classification in all patients (p < 0.05). In the IP cohort, length of stay in days (low 1.6, intermediate 2.3, high 4.1, p < 0.0001) and discharge to facility increased with frailty (p < 0.05). In the OP cohort, ED visits increased with frailty (p < 0.05). Frailty was associated with increased direct-cost in the IP cohort (low, $7,045; intermediate, $7,995; high, $8,599; p < 0.05). CONCLUSIONS: Frailty affects morbidity, mortality, and health care resource use in both IP and OP operations. Additionally, IP cost increased with frailty. The broad applicability of frailty (across surgical specialties) represents an opportunity for risk stratification and patient optimization across a large health care system.

Surgical Site Infection after Primary Closure of High-Risk Surgical Wounds in Emergency General Surgery Laparotomy and Closed Negative-Pressure Wound Therapy.

BACKGROUND: We hypothesized that the universal adoption of closed wounds with negative pressure wound therapy (NPWT) in emergency general surgery patients would result in low superficial surgical infection (SSI) rates. STUDY DESIGN: We performed a retrospective observational study using primary wound closure with external NPWT, from May 2017 to May 2018. Patients with active soft tissue infection of the abdominal wall were excluded. Data were analyzed by Fisher's exact tests and Wilcoxon-Mann-Whitney tests, with significance is set at a value of p < 0.05. RESULTS: Eighty-five patients (53% female) with a median age of 65 years (range 19 to 98 years) underwent laparotomies. Four patients were excluded for active soft tissue infection. Wounds were classified as dirty (n = 18), contaminated (n = 52), and clean contaminated (n = 11). Median BMI was 27 kg/m2 (interquartile range [IQR] 23.4 to 33.0 kg/m2). Median antibiotic therapy was 4 days (IQR 1 to 7 days). Twenty-six patients had open abdomen management. Patient follow-up was a median of 20 days (range 14 to 120 days). Six patients (7%) developed superficial SSI requiring conversion to open wound management. No patients developed fascial dehiscence. There were no statistically significant associations between SSI and wound class (p = 0.072), antibiotic duration (p = 0.702), open abdomen management, or preoperative risk factors (p < 0.1). Overall morbidity was 38% and mortality was 6%. CONCLUSIONS: Primary closure of high risk incisions combined with NPWT is associated with acceptably low SSI rates. Due to the low morbidity and decreased cost associated with this technique, primary closure with NPWT should replace open wound management in the emergency general surgery population.

Quetiapine protects the blood-brain barrier in traumatic brain injury.

BACKGROUND: The integrity of the blood-brain barrier (BBB) is paramount in limiting vasogenic edema following traumatic brain injury (TBI). The purpose of this study was to ascertain if quetiapine, an atypical antipsychotic commonly used in trauma/critical care for delirium, protects the BBB and attenuates hyperpermeability in TBI. METHODS: The effect of quetiapine on hyperpermeability was examined through molecular modeling, cellular models in vitro and small animal models in vivo. Molecular docking was performed with AutoDock Vina to matrix metalloproteinase-9. Rat brain microvascular endothelial cells (BMECs) were pretreated with quetiapine (20 µM; 1 hour) followed by an inflammatory activator (20 µg/mL chitosan; 2 hours) and compared to controls. Immunofluorescence localization for tight junction proteins zonula occludens-1 and adherens junction protein ß-catenin was performed. Human BMECs were grown as a monolayer and pretreated with quetiapine (20 µM; 1 hour) followed by chitosan (20 µg/mL; 2 hours), and transendothelial electrical resistance was measured. C57BL/6 mice (n = 5/group) underwent mild to moderate TBI (controlled cortical impactor) or sham craniotomy. The treatment group was given 10 mg/kg quetiapine intravenously 10 minutes after TBI. The difference in fluorescence intensity between intravascular and interstitium (ΔI) represented BBB hyperpermeability. A matrix metalloproteinase-9 activity assay was performed in brain tissue from animals in the experimental groups ex vivo. RESULTS: In silico studies showed quetiapine thermodynamically favorable binding to MMP-9. Junctional localization of zonula occludens-1 and ß-catenin showed retained integrity in quetiapine-treated cells as compared with the chitosan group in rat BMECs. Quetiapine attenuated monolayer permeability compared with chitosan group (p < 0.05) in human BMECs. In the animal studies, there was a significant decrease in BBB hyperpermeability and MMP-9 activity when compared between the TBI and TBI plus quetiapine groups (p < 0.05). CONCLUSION: Quetiapine treatment may have novel anti-inflammatory properties to provide protection to the BBB by preserving tight junction integrity. LEVEL OF EVIDENCE: level IV.

Open vs Closed Negative Pressure Wound Therapy for Contaminated and Dirty Surgical Wounds: A Prospective Randomized Comparison.

BACKGROUND: A new proprietary negative pressure wound device has been developed to apply negative pressure therapy to closed wounds (closed-NPWT). We postulated that closed-NPWT management of contaminated and dirty wounds would lead to faster wound healing and no significant difference in wound complications. STUDY DESIGN: An IRB approved, prospective randomized trial was performed. Patients were consented preoperatively, but not entered nor assigned treatment until intraoperative findings were known. Patients were randomly assigned to either open-NPWT or a wound closed with skin staples and external closed-NPWT. Primary outcome was time to complete wound healing, defined as complete epithelization of the wound. Secondary outcomes were wound complications including wound infection, seroma, and dehiscence. Statistical analysis was performed using chi-square test, Fisher exact test, t-test, and Wilcoxon Rank-Sum test with significance of p < 0.05. RESULTS: Twenty-five closed-NPWT and 24 open-NPWT patients were analyzed. There were no significant differences in sex, mean age, BMI, smoking history, steroid use, comorbidities, or indication for surgery in the 2 groups. One patient in the open-NPWT group and 2 patients in the closed-NPWT group developed a wound infection (p = 1.0). Four open-NPWT and 3 closed-NPWT patients died from complications unrelated to the wound. Wound healing occurred at a median of 48 days (range 6 to 126 days) for the open-NPWT group vs a median of 7 days (range 6 to 12 days) for the closed-NPWT group (p < 0.0001). CONCLUSIONS: Wound healing was significantly faster in contaminated and dirty wounds when managed with closed-NPWT. There was no difference in wound complications between the 2 treatment groups. This approach shows promise for closed management of contaminated and dirty wounds and warrants additional prospective studies with larger patient groups.

Impact of complications on length of stay in elective laparoscopic colectomies.

BACKGROUND: Length of hospital stay (LOS) is an indirect measure of surgical quality and a surrogate for cost. The impact of postoperative complications on LOS following elective colorectal surgery is not well defined. The purpose of this study is to determine the contribution of specific complications towards LOS in elective laparoscopic colectomy patients. MATERIALS AND METHODS: American College of Surgeon's National Surgical Quality Improvement Program database (2011-2014) was queried for patients undergoing elective laparoscopic partial colectomy with primary anastomosis. Demographics, specific 30 d postoperative complications and LOS, were evaluated. A negative binomial regression adjusting for demographic variables and complications was performed to explore the impact of individual complications on LOS, significance set at P < 0.05. RESULTS: A total of 42,365 patients were evaluated, with an overall median LOS 4.0 d (interquartile range, 3.0-5.0). Unplanned reoperation and pneumonia each increase LOS by 50%; superficial surgical site infections (SSIs), organ space SSI sepsis, urinary tract infection, ventilation >48 h, pulmonary embolism, and myocardial infarction each increase LOS by at least 25% (P < 0.0001). When accounting for additional LOS and rate of complications, unplanned reoperation, bleeding requiring transfusion within 72 h, and superficial SSIs were the highest impact complications. CONCLUSIONS: In laparoscopic colectomy, each complication uniquely impacts LOS, and therefore cost. Utilizing this model, individual hospitals can implement pathways targeting specific complication profiles to improve care and minimize health care cost.

NSQIP-Based Quality Improvement Curriculum for Surgical Residents.

BACKGROUND: General surgery training has historically lacked a standardized approach to resident quality improvement (QI) education aside from traditional morbidity and mortality conference. In 2013, the ACGME formalized QI as a component of residency training. Our residency chose the NSQIP Quality In-Training Initiative (QITI) as the foundation for our QI training. We hypothesized that a focused curriculum based on outcomes would produce change in culture and improve the quality of patient care. STUDY DESIGN: Quality improvement curriculum design and implementation were retrospectively reviewed. Institutional NSQIP data pre-, during, and post-curriculum implementation were reviewed for improvement. RESULTS: A QITI project committee designed a 2-year curriculum, with 3 parts: didactics, focused on methods of data collection, QI processes, and techniques; review of current institutional performance, practice, and complication rates; and QI breakout groups tasked with creating "best practice" guidelines addressing common complications in our NSQIP semi-annual reports. Educational presentations were given to the surgical department addressing reduction of cardiac complications, pneumonia, surgical site infections (SSIs), and urinary tract infections (UTIs). Twenty-four residents completed both years of the QITI curriculum. National NSQIP decile ranks improved in known high outlier areas: cardiac complications, ninth to fourth decile; pneumonia, eighth to first decile; SSIs, tenth to second decile; and UTIs, eighth to third decile. Pneumonia and SSI rates demonstrated statistical improvement after curriculum implementation (p < 0.003). CONCLUSIONS: Implementing a QITI curriculum with a full resident complement is feasible and can positively affect surgical morbidity and nationally benchmarked performance. Resident QI education is essential to future success in delivering high quality surgical care.

Protocol-Driven Management of Suspected Common Duct Stones.

BACKGROUND: Common duct stones can be diagnosed by magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS)/ERCP, and intraoperative cholangiogram (IOC). In 2015, our group adopted a standard approach of preoperative EUS/ERCP followed by laparoscopic cholecystectomy for patients with an admission bilirubin >4.0 mg/dL. For bilirubin <4.0 mg/dL, laparoscopic cholecystectomy with IOC was the initial procedure. Postoperative EUS/ERCP with endoscopic sphincterotomy was pursued for positive IOC. Exclusions included clinical suspicion of malignancy and surgically altered anatomy making endoscopic management impractical. STUDY DESIGN: A retrospective comparison of protocol and pre-protocol (baseline) patients was performed, looking at patient demographics, presence of pancreatitis, common duct stone risk factors, comorbidities, length of hospitalization, and postoperative morbidity. Statistical analysis was performed with t-test, chi-square, and Wilcoxon rank-sum test with significance at p < 0.05. RESULTS: There were 56 patients in each group, with a mean ± SD age of 50.5 ± 20.88 years and 49.3 ± 20.92 years, respectively (p = NS). There were no significant differences between baseline and protocol patients with respect to individual and cumulative preoperative comorbidities, pancreatitis, elevation of liver function tests, bilirubin, common duct size, and postoperative morbidity. There were fewer endoscopies (22 vs 35; p = 0.014), and shorter length of stay in protocol patients (2.8 days vs 3.8 days; p = 0.025). CONCLUSIONS: Protocol-driven management of patients with suspected common duct stones reduced the number of endoscopies and length of hospitalization, with no change in postoperative morbidity. This approach has the potential to decrease endoscopy-related morbidity and overall cost without affecting quality of care.

Characterizing End-of-Life Care after Geriatric Burns at a Verified Level I Burn Center.

BACKGROUND: End-of-life (EoL) care after geriatric burns (geri-burns) is understudied. OBJECTIVE: To examine the practices of burn surgeons for initiating EoL discussions and the impact of decisions made on the courses of geri-burn patients who died after injury. METHODS: This retrospective cohort study examined all subjects ≥65 years who died on our Level I burn service from April 1, 2009, to December 31, 2014. Measurements obtained were timing of first EoL discussion (EARLY <24 hours post-admission; LATE ≥24 hours post-admission), decisions made, age, total body surface area burned, and calculated probability of death at admission. RESULTS: The cohort consisted of 57 subjects, of whom 54 had at least one documented EoL care discussion between a burn physician and the patient/surrogate. No differences were seen between groups for the likelihood of an immediate decision for comfort care after the first discussion (p = 0.73) or the mean number of total discussions (p = 0.07). EARLY group subjects (n = 38) had significantly greater magnitudes of injury (p = 0.002), calculated probabilities of death at admission (p ≤ 0.001), shorter times to death (p ≤ 0.001), and fewer trips to the operating theater for burn excision and skin grafting (p ≤ 0.001) than LATE subjects (n = 16). LATE subjects' first discussion occurred at a mean of 9.3 ± 10.0 days. DISCUSSION: The vast majority of geri-burn deaths on our burn service occur after a discussion about EoL care. The timing of these discussions is driven by magnitude of injury, and it does not lead to higher proportions of an immediate decision for comfort care. The presence and timing of EoL discussions bears further study as a quality metric for geri-burn EoL care.

Outpatient Laparoscopic Appendectomy: Is It Time to End the Discussion?

BACKGROUND: Laparoscopic appendectomy is typically associated with inpatient hospitalization averaging between 1 and 2 days. In July 2010, a prospective protocol for outpatient laparoscopic appendectomy was adopted at our institution. Patients were dismissed from the post-anesthesia recovery room or day surgery if they met certain predefined criteria. Patients admitted to a hospital room as either full admission or observation status were considered failures of outpatient management. STUDY DESIGN: An IRB-approved, retrospective review of a prospective database was performed on all patients having laparoscopic appendectomy for uncomplicated appendicitis from July 2010 through December 2014. Study exclusions included age younger than 17 years, pregnancy, interval appendectomy, and gangrenous or perforated appendicitis. Patient demographics, success with outpatient management, morbidity, and readmissions were analyzed. RESULTS: Five hundred and sixty-three patients underwent laparoscopic appendectomy for uncomplicated appendicitis during this time frame. There were 281 men and 282 women, with a mean age of 35.5 years. Four hundred and eighty-four patients (86%) were managed as outpatients. Seventy-nine patients were admitted for pre-existing conditions (32 patients), postoperative morbidity (10 patients), physician discretion (6 patients), or lack of transportation or support at home (31 patients). Thirty-eight patients (6.7%) experienced postoperative morbidity. Seven patients (1.2%) were readmitted after outpatient management for transient fever, nausea/vomiting, migraine headache, urinary tract infection, partial small bowel obstruction, and deep venous thrombosis. There were no mortalities or reoperations. Including the readmissions, overall success with outpatient management was 85%. CONCLUSIONS: Outpatient laparoscopic appendectomy can be performed with a high rate of success, low morbidity, and low readmission rate. This protocol has withstood the test of time. Widespread adoption has the potential for substantial health care savings.

Acute blood loss during burn and soft tissue excisions: An observational study of blood product resuscitation practices and focused review.

BACKGROUND: Many military and civilian centers have shifted to a damage-control resuscitation approach, focused on providing oxygen-carrying capacity while simultaneously mitigating coagulopathy with a balanced ratio of platelets and plasma to red blood cells. It is unclear to what degree this strategy is used during burn or soft tissue excision. Here, we characterized blood product transfusion during burn and soft tissue surgery and reviewed the published literature regarding intraoperative coagulation changes. We hypothesized that blood product resuscitation during burn and soft tissue excision is not hemostatic and would be insufficient to address hemorrhage-induced coagulopathy. METHODS: Consented adult patients were enrolled into an institutional review board-approved prospective observational study. Number, component type, volume, and age of the blood products transfused were recorded during burn excision/grafting or soft tissue debridement. Component bags (packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate) were collected, and the remaining sample was harvested from the bag and tubing. Aliquots of 1/1,000th the original volume of each blood product were obtained and combined, producing an amalgam sample containing the same ratio of product transfused. Platelet count, rotational thromboelastometry, and impedance aggregometry were measured. Significance was set at p < 0.05. RESULTS: Amalgamated transfusate samples produced abnormally weak clots (p ≤ 0.001) particularly if they did not contain platelets. Clot strength (48.8 [2.6] mm; reference range, 49-71 mm) for platelet-containing amalgams was below the lower limit of the reference range despite platelet-red blood cell ratios greater than 1:1. Platelet aggregation was abnormally low; transfused platelets were functionally inferior to native platelets. CONCLUSION: Our study and focused review demonstrate that further work is needed to fully understand the needs of patients undergoing tissue excision. The three studies reviewed and the results of our observational work suggest that coagulopathy and thrombocytopenia may contribute to intraoperative hemorrhage. Blood product resuscitation during burn and soft tissue excision is not hemostatic. LEVEL OF EVIDENCE: Epidemiologic study, level V.