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INTRODUCTION AND IMPORTANCE: Acute colonic pseudo-obstruction (ACPO) is an uncommon phenomenon that is especially rare in young patients and can result in bowl ischemia and perforation if left untreated. Furthermore, pneumoperitoneum is almost always a concerning imaging finding and in the context of recent colonic resection may be a sign of anastomotic leakage. CASE PRESENTATION: We describe a case of a young female patient with postpartum ACPO who subsequently underwent a hemicolectomy with colorectal anastomosis. The patient's hospital course was complicated by massive postoperative pneumoperitoneum that resulted in resection of the anastomosis and creation of an end colostomy. However, despite this measure, there was recurrent pneumoperitoneum on cross-sectional imaging 36 h later. This was treated non-operatively and the remainder of their hospital course was uneventful. CLINICAL DISCUSSION: A potential etiology for ACPO during pregnancy may be due to compression of parasympathetic plexus nerves by the gravid uterus. Idiopathic pneumoperitoneum has been documented on a number of occasions, though this is generally in older patients. It can present with signs of peritonitis or can be asymptomatic. Simultaneous pneumothorax and pneumoperitoneum is rare and may be due to the transmission of air from the peritoneum to the mediastinum and thorax. The pneumoperitoneum itself may be due the air leakage through the significantly distended colon into the peritoneum. CONCLUSION: The combination of ACPO following pregnancy and associated pneumothorax, pneumomediastinum, and recurrent pneumoperitoneum suggest a communicating defect between the thoracic, mediastinal, and peritoneal cavities. Furthermore, the possibility of underlying colonic dysmotility should be considered prior to the restoration of large bowel continuity.
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BACKGROUND: Blunt chest wall injury accounts for 15% of trauma admissions. Previous studies have shown that the number of rib fractures predicts inpatient opioid requirements, raising concerns for pharmacologic consequences, including hypotension, delirium, and opioid dependence. We hypothesized that intercostal injection of liposomal bupivacaine would reduce analgesia needs and improve spirometry metrics in trauma patients with rib fractures. METHODS: A prospective, double-blinded, randomized placebo-control study was conducted at a Level I trauma center as a Food and Drug Administration investigational new drug study. Enrollment criteria included patients 18 years or older admitted to the intensive care unit with blunt chest wall trauma who could not achieve greater than 50% goal inspiratory capacity. Patients were randomized to liposomal bupivacaine or saline injections in up to six intercostal spaces. Primary outcome was to examine pain scores and breakthrough pain medications for 96-hour duration. The secondary endpoint was to evaluate the effects of analgesia on pulmonary physiology. RESULTS: One hundred patients were enrolled, 50 per cohort, with similar demographics (Injury Severity Score, 17.9 bupivacaine 17.6 control) and comorbidities. Enrolled patients had a mean age of 60.5 years, and 47% were female. Rib fracture number, distribution, and targets for injection were similar between groups. While both groups displayed a decrease in opioid use over time, there was no change in mean daily pain scores. The bupivacaine group achieved higher incentive spirometry volumes over Days 1 and 2 (1095 mL, 1063 mL bupivacaine vs. 900 mL, 866 mL control). Hospital and intensive care unit lengths of stay were similar and there were no differences in postinjection pneumonia, use of epidural catheters or adverse events bet ween groups. CONCLUSION: While intercostal liposomal bupivacaine injection is a safe method for rib fracture-related analgesia, it was not effective in reducing pain scores, opioid requirements, or hospital length of stay. Bupivacaine injection transiently improved incentive spirometry volumes, but without a reduction in the development of pneumonia. LEVEL OF EVIDENCE: Therapeutic/care management, Level II.
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Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Manejo del Dolor/métodos , Fracturas de las Costillas/complicaciones , Analgésicos Opioides/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Inyecciones , Puntaje de Gravedad del Traumatismo , Unidades de Cuidados Intensivos , Tiempo de Internación/estadística & datos numéricos , Liposomas , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , EspirometríaRESUMEN
The impact of antithrombin III activity (AT-III) on prophylactic enoxaparin anti-factor Xa concentration (anti-Xa) is unknown in high-risk trauma patients. So too is the optimal anti-Xa-adjusted enoxaparin dosage. This prospective, randomized, pilot study sought to explore the association between AT-III and anti-Xa goal attainment and to preliminarily evaluate two enoxaparin dosage adjustment strategies in patients with subprophylactic anti-Xa. Adult trauma patients with Risk Assessment Profile (RAP) ≥ 5 prescribed enoxaparin 30 mg subcutaneously every 12 h were eligible. AT-III and anti-Xa were drawn 8 h after the third enoxaparin dose and compared between patients with anti-Xa ≥ 0.1 IU/mL (goal; control group) or anti-Xa < 0.1 IU/mL (subprophylactic; intervention group). The primary outcome was difference in baseline AT-III. Subsequently, intervention group patients underwent 1:1 randomization to either enoxaparin 40 mg every 12 h (up to 50 mg every 12 h if repeat anti-Xa < 0.1 IU/mL) (enox12) or enoxaparin 30 mg every 8 h (enox8) with repeat anti-Xa assessments. The proportion of patients achieving goal anti-Xa after dosage adjustment were compared. A total of 103 patients were included. Anti-Xa was subprophylactic in 50.5%. Baseline AT-III (median [IQR]) was 87% [80-98%] in control patients versus 82% [71-96%] in intervention patients (p = 0.092). Goal trough anti-Xa was achieved on first assessment in 38.1% enox12 versus 50% enox8 patients (p = 0.67), 84.6% versus 53.3% on second assessment (p = 0.11), and 100% vs. 54.5% on third trough assessment (p = 0.045). AT-III activity did not differ between high-risk trauma patients with goal and subprophylactic enoxaparin anti-Xa concentrations, although future investigation is warranted. Enoxaparin dose adjustment rather than frequency adjustment may be associated with a higher proportion of patients achieving goal anti-Xa over time.
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Enoxaparina/uso terapéutico , Tromboembolia Venosa , Adulto , Anticoagulantes/uso terapéutico , Antitrombina III , Enoxaparina/clasificación , Humanos , Proyectos Piloto , Estudios Prospectivos , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & controlRESUMEN
BACKGROUND: Interest in surgery has declined for two decades. This study aimed to evaluate the impact of one's interest in surgery on career choice. METHODS: Students who completed the surgical clerkship (2016-2017) were invited to complete surveys assessing rotation experience, learning style, burnout, and grit. Students were grouped according to interest or no interest in surgery after the clerkship. RESULTS: Surveys were completed by 62 students of whom 51.6% reported an interest in surgery. No minority students expressed interest compared with Caucasian (51.1%) and Asian (71.4%) students (pâ¯=â¯0.02). Disinterested students had higher emotional exhaustion (EE, 20 vs 25, pâ¯=â¯0.03). There was no difference in clerkship grade between groups (86.3% vs 85.3%, pâ¯=â¯0.56). Students who matched into surgery had lower EE and higher grit. CONCLUSIONS: Interest in surgery was not associated with improved clerkship performance. Disinterested students had higher EE, suggesting interest may play a role in adapting to clerkship challenges.
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Selección de Profesión , Prácticas Clínicas/organización & administración , Competencia Clínica , Educación de Pregrado en Medicina/organización & administración , Cirugía General/educación , Estudiantes de Medicina/psicología , Adaptación Psicológica , Adulto , Actitud del Personal de Salud , Femenino , Humanos , Masculino , Estudiantes de Medicina/estadística & datos numéricos , Encuestas y Cuestionarios , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
STUDY OBJECTIVE: To evaluate extended-infusion (EI) cefepime pharmacokinetics (PK) and pharmacodynamic target attainment in critically ill patients receiving continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD). DESIGN: Prospective, open-label, PK study. SETTING: Intensive care units at a large, academic, tertiary-care medical center. PATIENTS: Ten critically ill adults who were receiving cefepime 2 g intravenously every 8 hours as a 4-hour infusion while receiving CVVH (eight patients) or CVVHD (two patients). INTERVENTION: Two sets of five serum cefepime concentrations were collected for each patient to assess pharmacokinetics before and during presumed steady state. Concurrent serum and CRRT effluent samples were collected at hours 1, 2, 3, 4, and 8 after the first cefepime dose and after either the fourth, fifth, or sixth (steady-state) cefepime doses. MEASUREMENTS AND MAIN RESULTS: Reversed-phase high-performance liquid chromatography was used to determine free cefepime concentrations. PK analyses included CRRT clearance, half-life, and sieving coefficient or saturation coefficient. Cefepime peak (4 hrs) concentrations, trough (8 hrs) concentrations (Cmin ), and minimum inhibitory concentration breakpoint of 8 µg/ml for the pathogen (MIC8 ) were used to evaluate attainment of pharmacodynamic targets: 100% of the dosing interval that free drug remains above MIC8 (100% fT > MIC8 ), 100% fT > 4 × MIC8 (optimal), percentage of time fT > 4 × MIC8 (%fT > 4 × MIC8 ) at steady state, and ratio of Cmin to MIC8 (fCmin /MIC8 ). Total CRRT effluent flow rate was a mean ± SD of 30.1 ± 5.4 ml/kg/hr, CRRT clearance was 39.6 ± 9.9 ml/min, and half-life was 5.3 ± 1.7 hours. Sieving coefficient or saturation coefficient were 0.83 ± 0.13 and 0.69 ± 0.22, respectively. First and steady-state dose Cmin were 23.4 ± 10.1 µg/ml and 45.2 ± 14.6 µg/ml, respectively. All patients achieved 100% fT > MIC8 on first and steady-state doses. First and steady-state dose 100% fT > 4 × MIC8 were achieved in 22% (2/9 patients) and 87.5% (7/8 patients) of patients, respectively. The mean %fT > 4 × MIC8 at steady state was 97.5%. The fCmin /MIC8 was 2.92 ± 1.26 for the first dose and 5.65 ± 1.83 at steady state. CONCLUSION: Extended-infusion cefepime dosing in critically ill patients receiving CRRT successfully attained 100% fT > MIC8 in all patients and an appropriate fCmin /MIC8 for both first and steady-state doses. All but one patient achieved 100% fT > 4 × MIC8 at steady state. No significant differences were observed in PK properties between first and steady-state doses among or between patients. It may be reasonable to initiate an empiric or definitive regimen of EI cefepime in critically ill patients receiving concurrent CRRT who are at risk for resistant organisms. Further research is needed to identify the optimal dosing regimen of EI cefepime in this patient population.
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Antibacterianos/administración & dosificación , Cefepima/administración & dosificación , Terapia de Reemplazo Renal Continuo , Enfermedad Crítica/terapia , Adulto , Anciano , Antibacterianos/farmacocinética , Cefepima/farmacocinética , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Infusiones Intravenosas , Unidades de Cuidados Intensivos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVE: Increasing reports on resident burnout have resulted in efforts to improve trainee well-being. Medical student burnout, however, is not well understood. We set out to evaluate burnout among third-year medical students and explore its impact on clerkship performance. DESIGN: Analysis of prospectively-collected survey data from medical students on the third-year surgery clerkship was performed. Surveys included an institution-specific pre- and postclerkship survey, the 12-item Grit Scale, and the Maslach Burnout Inventory. SETTING: University of Cincinnati College of Medicine. PARTICIPANTS: Between 2016 and 2017, 166 students completed the surgery clerkship and were asked to complete the surveys. Sixty-two students (37.4%) completed all surveys and were included in this study. RESULTS: Among the third-year medical student participants, there was no difference in burnout before vs after the clerkship (22.6% vs 17.7%, pâ¯=â¯0.41). Students with burnout had significantly lower grit scores (3.10 ± 0.66) compared to those without burnout (3.63 ± 0.50, pâ¯=â¯0.01). Linear regression analysis demonstrated that increasing grit was associated with decreasing emotional exhaustion (pâ¯=â¯0.01), decreasing depersonalization (pâ¯=â¯0.04), and increasing personal achievement (pâ¯=â¯0.03). Finally, 75% of students with resolution of burnout developed an interest in surgery, whereas all students who developed burnout after the clerkship had no interest in surgery (pâ¯=â¯0.03). Upon completion of the rotation, burnout was not associated with poorer quality of clerkship experience or decreased clerkship performance (p > 0.05 for each). CONCLUSIONS: Although traditionally considered a difficult rotation, we found no increase in medical student burnout following the surgery clerkship. Higher grit scores were associated with decreased burnout, though burnout did not have a negative impact on student experience or performance. Clerkships should continue to set high expectations and maximize educational opportunities without significant apprehension that it may have a negative impact on students.
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Agotamiento Profesional/psicología , Prácticas Clínicas/normas , Competencia Clínica , Cirugía General/educación , Estudiantes de Medicina/psicología , Rendimiento Laboral , Humanos , Estudios ProspectivosRESUMEN
INTRODUCTION: Acute hemorrhage remains the leading cause of death in potentially survivable injuries. The use of topical hemostatic agents has increased over the last two decades with the evolution of damage control surgery. By 2008, the military widely adopted Combat Gauze as the hemostatic dressing of choice for compressible hemorrhage. The goal of this study was to compare the performance of a novel fibrin sealant patch to Combat Gauze in two clinically relevant models of hemorrhage. MATERIALS AND METHODS: Yorkshire swine underwent unilateral femoral artery puncture or a grade V liver laceration with timed free bleeding then received either the fibrin patch or Combat Gauze packing with 3 minutes of standardized pressure. Animals were then resuscitated to maintain a mean arterial pressure of 60 mmHg for 4 hours. Hemostasis, blood loss, resuscitation volume, survival, vessel patency, and hematologic parameters were evaluated. RESULTS: Hemostasis was equivalent in both groups after hepatic and vascular injury. Survival was 80% in the fibrin patch vascular injury group and 100% in all other groups. Hematologic parameters were not significantly different between treatment groups. Femoral artery patency was 80% in both groups after vascular injury. With simulated ambulation after vessel injury, 60% of the Combat Gauze group and 80% of the fibrin patch group remained hemostatic (p > 0.05). In simulated re-exploration with packing removal, all animals rebled after hemostatic product removal. CONCLUSION: There was no significant difference in hemostasis between a novel fibrin patch and Combat Gauze after extremity arterial or hepatic injury. This novel fibrin patch may have a clinical advantage over the Combat Gauze, as it can be left in the body, thereby limiting the potential need for reoperation.
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Adhesivo de Tejido de Fibrina/normas , Hemorragia/terapia , Animales , Vendajes/normas , Vendajes/estadística & datos numéricos , Modelos Animales de Enfermedad , Adhesivo de Tejido de Fibrina/uso terapéutico , Hemorragia/prevención & control , Hemostáticos/normas , Hemostáticos/uso terapéutico , Hígado/lesiones , Hígado/cirugía , Hepatopatías/prevención & control , Hepatopatías/terapia , Porcinos/lesiones , Porcinos/cirugía , Lesiones del Sistema Vascular/prevención & control , Lesiones del Sistema Vascular/terapiaRESUMEN
INTRODUCTION: Predictors of student performance on clerkship rotations are limited. In this study, we aim to identify predictors of success on the surgery clerkship. METHODS: 62 third-year medical students completed an institution-specific clerkship survey. Students were grouped according to clerkship grade of honors (HG) versus high-pass or pass (PG). Statistical analyses were performed using Student's t-test, Pearson's Chi-square/Fisher's exact test, and linear regression analysis. Multivariate logistic regression was performed to identify predictors of achieving an honors on the clerkship. RESULTS: HG students were more likely to be individual-based learners with higher grit and USMLE Step 1 scores compared with PG students. Moreover, USMLE Step 1 score was associated with quiz, shelf examination, and final clerkship grades, but not clinical evaluations. There were few differences with regard to preferred learning modalities, but overall, medical students favored active learning activities. CONCLUSIONS: We found that higher USMLE Step 1 score, higher grit score, and an individual-based learning style were associated with a higher grade on the surgery clerkship. However, these factors may not fully capture the less objective components of high performance. Additional methods by which educators can measure students' clinical competency are needed.
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Rendimiento Académico , Prácticas Clínicas , Competencia Clínica , Cirugía General/educación , Adulto , Femenino , Humanos , Aprendizaje , Masculino , MotivaciónRESUMEN
BACKGROUND: Preoperative exposure to narcotics has recently been associated with poor outcomes after elective major surgery, but little is known as to how preoperative opioid use impacts outcomes after common, emergency general surgical procedures (EGS). METHODS: A high-volume, single-center analysis was performed on patients who underwent EGS from 2012 to 2013. EGS was defined as the seven emergent operations that account for 80% of the national burden. Preoperative opioid use was defined as having an active opioid prescription within 7 days prior to surgery. Chronic opioid use was defined as having an opioid prescription concurrent with 90 days after discharge. RESULTS: A total of 377 patients underwent EGS during the study period. Preoperative opioid use was present in 84 patients (22.3%). Preoperative opioid users had longer hospital LOS (10.5 vs 6 days), higher costs of care ($25,331 vs $11,454), and higher 30-day readmission rates (22.6 vs 8.2%) compared with opioid-naïve patients (p < 0.001 each). After covariate adjustment, preoperative opioid use was predictive of LOS (RR 1.19 [1.01-1.41]) and 30-day hospital readmission (OR 2.69 [1.25-5.75]) (p < 0.05 each). Total direct cost was not different after modeling. Preoperative opioid users required more narcotic refills compared with opioid-naïve patients (5 vs 0 refills, p < 0.001). After discharge, 15.4% of opioid-naïve patients met criteria for chronic opioid use, vs 77.4% in preoperative opioid users (p < 0.001). CONCLUSIONS: Preoperative opioid use is associated with greater resource utilization after emergency general surgery, as well as vastly different postoperative opioid prescription patterns. These findings may help to inform the impact of preoperative opioid use on patient care, and its implications on hospital and societal cost.
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Analgésicos Opioides/uso terapéutico , Costos Directos de Servicios , Prescripciones de Medicamentos/estadística & datos numéricos , Procedimientos Quirúrgicos Operativos , Adulto , Urgencias Médicas , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Periodo Posoperatorio , Periodo Preoperatorio , Estudios RetrospectivosRESUMEN
In this article we propose a practical approach to the use of prone therapy for acute respiratory distress syndrome (ARDS). We have attempted to provide information to improve the understanding and implementation of prone therapy based on the literature available and our own experience. We review the basic physiology behind ARDS and the theoretical mechanism by which prone therapy can be of benefit. The findings of the most significant studies regarding prone therapy in ARDS as they pertain to its implementation are summarized. Also provided is a discussion of the nuances of utilizing prone therapy, including potential pitfalls, complications, and contraindications. The specific considerations of prone therapy in open abdomens and traumatic brain injuries are discussed as well. Finally, we supply suggested protocols for the implementation of prone therapy discussing criteria for initiation and cessation of therapy as well as addressing issues such as the use of neuromuscular blockade and nutritional supplementation.
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Posición Prona , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/terapia , Humanos , Respiración Artificial/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Low anti-factor Xa (anti-Xa) concentrations with twice-daily enoxaparin are associated with venous thromboembolism (VTE) in high-risk trauma patients. Concerns have been raised with once-daily dalteparin regarding effectiveness and achievable anti-Xa concentrations. The purpose of this before-and-after study was to evaluate the effectiveness of a VTE prophylaxis protocol using anti-Xa concentrations and associated dalteparin dose adjustment in high-risk trauma patients. METHODS: Adult trauma patients receiving VTE chemoprophylaxis and hospitalized for at least 3 days were prospectively followed during two 6-month epochs before (PRE) and after (POST) implementation of anti-Xa monitoring. In both groups, high-risk patients received dalteparin 5,000 U subcutaneously once daily; low-risk patients received subcutaneous unfractionated heparin. High-risk POST patients with anti-Xa less than 0.1 IU/mL 12 hours after initial dalteparin dose received dalteparin every 12 hours. All patients underwent routine VTE ultrasound surveillance of the lower extremities. The primary outcome was incidence of VTE. RESULTS: A total of 785 patients (PRE, n = 428; POST, n = 357) were included. Demographics, injury patterns, Injury Severity Score (ISS), red blood cell transfusions, intensive care unit and hospital stays, and mortality did not differ between groups. Overall, POST patients had lower VTE (7.0% vs. 13%, p = 0.009) including acute VTE (6.4% vs. 12%, p = 0.01) and proximal deep vein thromboembolism (2.2% vs. 5.7%, p = 0.019). Between high-risk patients, VTE occurred in 53 (16.3%) PRE compared with 24 (9.0%) POST patients (p = 0.01); there was no difference in VTE between low-risk patients (PRE, 2.0% vs. POST, 1.1%; p = 0.86). Among 190 high-risk POST patients with anti-Xa, 97 (51%) were less than 0.1 IU/mL. Patients with low anti-Xa had higher rates of VTE (14.0% vs. 5.4%, p = 0.05) and deep vein thromboembolism (14.4% vs. 3.2%, p = 0.01). Younger age (odds ratio, 0.97; 95% confidence interval, 0.95-0.99) and greater weight (odds ratio, 1.02; 95% confidence interval, 1.00-1.03) predicted low anti-Xa on multivariate regression. CONCLUSION: A VTE prophylaxis protocol using anti-Xa-based dalteparin dosage adjustment in high-risk trauma patients was associated with decreased VTE. Once-daily dalteparin 12-hour anti-Xa concentrations are suboptimal in a majority of patients and associated with VTE. LEVEL OF EVIDENCE: Therapeutic study, level IV.
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Dalteparina/administración & dosificación , Factor Xa/efectos de los fármacos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/prevención & control , Heridas y Lesiones/tratamiento farmacológico , Adulto , Anciano , Anticoagulantes/administración & dosificación , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Factor Xa/análisis , Femenino , Estudios de Seguimiento , Heparina de Bajo-Peso-Molecular/administración & dosificación , Humanos , Incidencia , Inyecciones Subcutáneas , Puntaje de Gravedad del Traumatismo , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Estudios Prospectivos , Valores de Referencia , Medición de Riesgo , Factores de Tiempo , Centros Traumatológicos , Resultado del Tratamiento , Tromboembolia Venosa/tratamiento farmacológico , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Positive surgical role models influence medical students to pursue a career in surgery. However, the perception by role models of their own effectiveness has yet to be examined. In this study, we evaluated the influence of surgical role models on medical student career choice, and how these role models perceive themselves. METHODS: We distributed a voluntary and anonymous survey to third-year medical students, general surgery resident applicants, general surgery residents, and attending surgery faculty during the 2010-2011 academic year. We performed statistical analysis using the chi-square and Cochran-Mantel-Haenszel tests (P < 0.05 was significant). RESULTS: Medical students and resident applicants agreed that faculty and residents are important in shaping the career paths of students. The applicants were more likely to agree than were students that clerkship role models (P = 0.0049) and mentors (P = 0.0035) affected their interest in surgery. The applicants were also more likely to agree than the students that attending surgeons (P = 0.0004), senior (P = 0.0019) and junior (P = 0.0028) surgery residents served as positive role models. Although the surgical faculty and residents agreed with the students that each level of the surgical team served as positive role models, they did not agree as strongly with the students that they have an important role in shaping students' career path (P < 0.0001). CONCLUSIONS: Surgical faculty and residents serve as positive role models for medical students. They have an essential role in shaping students' career paths and should be more cognizant of their influence, which may draw a student toward or lead them away from the field of surgery.
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Selección de Profesión , Mentores , Especialidades Quirúrgicas , Adulto , Femenino , Humanos , Internado y Residencia , Masculino , Estudiantes de Medicina/estadística & datos numéricos , Adulto JovenRESUMEN
PURPOSE OF REVIEW: Although drug therapy is most commonly delivered via the intravenous route, novel inhaled agents have been introduced for use in the ICU. Additionally, drugs previously delivered intravenously are now being delivered via the respiratory tract in an effort to reduce systemic toxicity and maximize effectiveness. RECENT FINDINGS: Aerosolized antibiotics have seen increased use in an effort to reduce systemic effects, reduce ventilator-associated pneumonia, and direct high drug concentrations at the site of infection. Drug-resistant pneumonia has also been effectively treated with aerosolized antibiotics. Secretion management includes a host of devices, therapies, and drugs, but the evidence for these is scant. Cardiac drugs via the endotracheal route should be used only when intravenous access is delayed. Inhaled nitric oxide has a defined role in care of infants, although new indications have limited and conflicting data. The use of helium-oxygen mixtures provides symptom relief in a wide variety of scenarios associated with turbulent flow in large airways. SUMMARY: Inhaled nitric oxide has an established role in neonatal intensive care and a limited role in adult intensive care. Heliox provides symptom relief, but at present cannot be considered routine as a consequence of the multiple technological challenges. Inhaled antimicrobials appear to provide a therapeutic advantage in select individuals with pneumonia. Secretion management is best achieved by adequate humidification and as needed suctioning. The role of inhaled carbon monoxide in critical care holds significant promise, but is currently in early clinical trials.
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Unidades de Cuidados Intensivos , Terapia Respiratoria/métodos , HumanosRESUMEN
BACKGROUND: Vascular endothelial growth factor (VEGF)-165 promotes cardiomyogenesis in chronic myocardial ischemia and nonreperfused myocardial infarction (MI). It is unknown whether this effect is present in reperfused MI. We sought to investigate the effect of VEGF-165 gene therapy on cardiomyogenesis after reperfused MI. METHODS AND RESULTS: Twenty-four Yucatan minipigs underwent thoracotomy and a vascular clamp was placed in the left circumflex artery. Reperfusion was reestablished after 90 minutes, and VEGF-165 gene therapy or placebo was administered. A replication-deficient recombinant human adenovirus serotype 5 was used for gene transfer (Ad5-VEGF165). The same viral vector devoid of VEGF gene (Ad5-beta-galactosidase) was used as placebo. Two administration routes were tested, intramyocardial (IM) injection and circumflex intracoronary (IC) infusion. The pigs were assigned to one of the following groups: IM Ad5-VEGF165 (n = 6), IM Ad5-betaGal (n = 6), IC Ad5-VEGF165 (n = 6), and IC Ad5-betaGal (n = 6). All pigs received 5-bromo-2'-deoxyuridine (BrdU) 250 mg IV twice a week to label cells undergoing DNA replication. The hearts were explanted at 4 weeks. BrdU-labeled cardiomyocytes in the peri-infarct area were counted by a pathologist blinded to group assignment. The number of BrdU-labeled cardiomyocytes per million cells was 4-fold higher in the group receiving IM VEGF-165 (64 +/- 11.4) vs. IM placebo (16 +/- 10.6), P = 0.034. No difference in infarct size or ventricular function was observed between the groups. CONCLUSIONS: IM VEGF-165 gene therapy promotes cardiomyogenesis in reperfused MI. However, no benefit in infarct size or cardiac function was observed at 4 weeks. The origin of these cells remains unknown and needs to be determined.