RESUMO
BACKGROUND: Resuscitation with racemic lactated Ringer's solution induces cellular apoptosis. This study was conducted to determine if the elimination of D-lactate isomer would attenuate apoptosis in the liver, and to investigate the possible mechanisms. STUDY DESIGN: Sprague Dawley rats (n=30, 5 per group) were subjected to modified volume-controlled hemorrhage and randomized to the following groups: no hemorrhage (sham); no resuscitation (NR); resuscitation with racemic lactated Ringer's (DL-LR); L-isomer LR (L-LR); ketone (beta-hydroxybuturate) Ringer's (KR); or pyruvate Ringer's (PR). Animals were sacrificed 2 hours later and expressions of proapoptotic proteins (BAD), antiapoptotic (bcl-2) proteins, and poly-ADP ribose polymerase (PARP) cleavage in liver were analyzed by Western blotting. Contribution of the phosphatidylinositol 3-kinase/serine/threonine kinase (PI3k/Akt) pathway was assessed by measuring total and phosphorylated PI3K, Akt, BAD, and endothelial nitric oxide synthase (eNOS) proteins. The terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay was used to detect the apoptotic cells. Liver ATP levels were measured using a luciferase reaction assay. RESULTS: Hemorrhage significantly decreased the hepatic ATP level and resuscitation improved it, but it returned to normal only in the L-isomer lactated Ringer's and ketone Ringer's groups. Expression of proapoptotic proteins was significantly lower in the pyruvate Ringer's and ketone Ringer's groups; L-isomer lactated Ringer's and pyruvate Ringer's resuscitation significantly increased bcl-2 expression. Poly-ADP ribose polymerase fragmentation and total number of apoptotic cells were significantly increased in the racemic lactated Ringer's group. There was no significant induction of Akt activity or changes in phosphorylated BAD, Akt, or eNOS levels. CONCLUSIONS: Resuscitation with racemic lactated Ringer's induces hepatic apoptosis, which is decreased if the D-isomer of lactate is eliminated. Apoptosis is reduced even more when lactate is substituted with beta-hydroxybutyrate or pyruvate. The beneficial effects are not through improvements in the energy status or activation of the PI3K/Akt pathway.
Assuntos
Apoptose/efeitos dos fármacos , Soluções Isotônicas/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Ressuscitação , Choque Hemorrágico/patologia , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose/metabolismo , Modelos Animais de Doenças , Soluções Isotônicas/química , Soluções Isotônicas/uso terapêutico , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Solução de Ringer , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , EstereoisomerismoRESUMO
BACKGROUND: Value-based analysis (VBA) is a management strategy used to determine changes in value (quality/cost) when a usual practice (UP) is replaced by a best practice (BP). Previously validated in clinical initiatives, its usefulness in complex systems is unknown. To answer this question, we used VBA to correct deficiencies in cardiac surgery at Memorial Healthcare System. STUDY DESIGN: Cardiac surgery is a complex surgical system that lends itself to VBA because outcomes metrics provided by the Society of Thoracic Surgeons provide an estimate of quality; cost is available from Centers for Medicare and Medicaid Services and other contemporary sources; the UP can be determined; and the best practice can be established. RESULTS: Analysis of the UP at Memorial Healthcare System revealed considerable deficiencies in selection of patients for surgery; the surgery itself, including choice of procedure and outcomes; after care; follow-up; and control of expenditures. To correct these deficiencies, each UP was replaced with a BP. Changes included replacement of most of the cardiac surgeons; conversion to an employed physician model; restructuring of a heart surgery unit; recruitment of cardiac anesthesiologists; introduction of an interactive educational program; eliminating unsafe practices; and reducing cost. CONCLUSIONS: There was a significant (p < 0.01) reduction in readmissions, complications, and mortality between 2009 and 2013. Memorial Healthcare System was only 1 of 17 (1.7%) database participants (n = 1,009) to achieve a Society of Thoracic Surgeons 3-star rating in all 3 measured categories. Despite substantial improvements in quality, the cost per case and the length of stay declined. These changes created a savings opportunity of $14 million, with actual savings of $10.4 million. These findings suggest that VBA can be a powerful tool to enhance value (quality/cost) in a complex surgical system.
Assuntos
Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Atenção à Saúde/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Redução de Custos , Custos Hospitalares/estatística & dados numéricos , Mortalidade Hospitalar/tendências , Humanos , Tempo de Internação/estatística & dados numéricos , Medicaid/economia , Medicare/economia , Estados UnidosRESUMO
BACKGROUND: Resuscitative fluids induce distinctive changes in leukocyte functions: incubation with colloid Dextran increases production of reactive oxygen species and adhesion, whereas exposure to hypertonic saline (HTS) inhibits "oxidative burst" and phagocytosis. In hypertonic saline Dextran (HTD), the hypertonic component determines the leukocyte functional behavior and subsequently activation response. We investigated whether leukocyte gene expression is analogously affected. METHODS: Whole blood from eight volunteers was diluted and incubated for 30 min at 37(o)C in 6.0% Dextran-70, 7.5% HTS, and 7.5% HTD. Total leukocyte RNA was extracted and used to synthesize biotinylated cDNA probes. Each probe was individually hybridized to a cDNA array to simultaneously measure the expression of 23 genes involved in inflammation, cell migration, and apoptosis. RESULTS: Leukocytes incubated with Dextran-70 demonstrated greater than a 6-fold (p < 0.05) increase in the expression of interleukin-8, growth-regulated oncogenes alpha and beta, L-selectin, superoxide dismutase, tumor necrosis factor-alpha (TNF-alpha), and mitogen-activated protein kinase 3. The expression profile induced by HTS was not significantly different from that of unstimulated blood, except for prominent induction of only three genes. HTD attenuated the expression of Dextran-70 upregulated genes, although the level of their expression was higher than in HTS-treated leukocytes. CONCLUSIONS: Hypertonic resuscitation fluids diminish the expression of immune activation-associated genes. Hypertonic component of HTD determines the leukocyte gene expression profile.
Assuntos
Impressões Digitais de DNA/métodos , DNA Complementar/genética , Dextranos/farmacologia , Leucócitos/efeitos dos fármacos , Soluções para Reidratação/farmacologia , Solução Salina Hipertônica/farmacologia , Transcrição Gênica/efeitos dos fármacos , Adulto , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Humanos , Inflamação/genética , Inflamação/fisiopatologia , Leucócitos/metabolismo , Transcrição Gênica/genéticaRESUMO
Many algorithms have been developed for patients with acute lower gastrointestinal hemorrhage (ALGIH). Their clinical usefulness is not readily apparent. It is important first to observe patterns in admission, triage, and management to formulate hypotheses as to how outcomes might be affected. We reviewed patient charts with the diagnosis of gastrointestinal hemorrhage from June 1998 to January 2001. Patients with ALGIH were entered into a database. We defined patients as having ALGIH if presentation included melena or hematochezia. Patients with hematemesis, bloody nasogastric aspirate, or occult fecal blood were excluded. Observations were made on 420 patients. Seventy-six per cent of patients were admitted to the medical service. Lower endoscopy was the first diagnostic method in 33 per cent. Medical management comprised 52 per cent of first management strategies. Surgeons used angiography (3% vs 1%) or surgery (25% vs 5%) more than other services. Fourteen per cent of patients managed with endoscopy, 16 per cent medically, 17 per cent with surgery, and 67 per cent with interventional radiology required two or more subsequent packed red blood cell transfusions. Mean admission Acute Physiology and Chronic Health Evaluation II score was 9.2 whereas that for those with mortality was 13.5. We conclude that the construction of a database will allow for formation and testing of hypotheses in managing ALGIH.
Assuntos
Algoritmos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Melena/diagnóstico , Melena/terapia , Admissão do Paciente/estatística & dados numéricos , Triagem/métodos , APACHE , Doença Aguda , Idoso , Angiografia , Transfusão de Sangue , Colectomia , Colonoscopia , District of Columbia/epidemiologia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/mortalidade , Hospitais de Ensino , Humanos , Melena/etiologia , Melena/mortalidade , Valor Preditivo dos Testes , Prognóstico , Radiologia Intervencionista , Ressuscitação , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Triagem/normasRESUMO
OBJECTIVE: Rising costs and lowered reimbursements make value essential if laparoscopic cholecystectomy (LC) is to be offered to patients without condemning providers to financial loss. We hypothesize that our protocol increases this value. Once practiced, operative time, complications, and patient satisfaction compare with those of the typical method. METHODS: We prospectively randomized 50 consecutive patients equally to control or experimental LC according to our protocol. Equipment costs, operative time, conversions, complications, pain, and return to work were compared. The student's t test was used for comparisons. RESULTS: Mean disposable equipment costs were 173.00 dollars +/- 43.45 dollars and 434.42 dollars +/- 50.54 dollars for the study and control groups, respectively (P < .0001). Mean operative times were 67.26 +/- 15 and 70.60 +/- 19 minutes, respectively. CONCLUSIONS: The "bare bones" protocol is safe. It has a short learning curve, demonstrates a cost advantage over the common method, and requires no additional operative time. Pain, time to return to work, and satisfaction are equivalent.
Assuntos
Colecistectomia Laparoscópica/economia , Equipamentos Descartáveis/economia , Adulto , Colecistectomia Laparoscópica/métodos , Redução de Custos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: Value is an economic utility defined by quality and cost, with the maximum benefit achieved by improving quality and reducing cost simultaneously. Health care systems are using value-based analysis to identify the best practices (BPs) that accomplish this goal. STUDY DESIGN: We chose a clinical condition, deep venous thrombophlebitis (DVT) to test this hypothesis by identifying the BPs available in the literature; determining the usual practice for DVT prophylaxis at each of 8 hospitals (ie, community, tertiary, and a university hospital) in an integrated system; measuring clinical outcomes (mortality and morbidity) for each hospital; determining cost for each treatment algorithm in each hospital; and measuring the savings opportunity if a single BP was used by all of the hospitals. RESULTS: The literature suggests that the BPs for DVT prophylaxis consist of sequential compression devices for short-stay procedures; unfractionated heparin for inpatient procedures, and low molecular weight heparin for thrombotic events. Four of the hospitals were using these BPs; the others relied on sequential compression devices and low molecular weight heparin for prophylaxis. Outcomes were identical and value-based analysis suggested a savings opportunity of nearly $4 million if a single BP was adopted. CONCLUSIONS: There were substantial variations in the type of DVT prophylaxis used by the hospitals with no difference in outcomes. A single BP increased value and resulted in savings of $1.5 million, with a savings opportunity of nearly $4 million.
Assuntos
Benchmarking , Análise Custo-Benefício , Procedimentos Cirúrgicos Vasculares/economia , Trombose Venosa/economia , Trombose Venosa/prevenção & controle , Feminino , Humanos , MasculinoRESUMO
It has been proposed that thiamine deficiency after gastric bypass surgery in obese patients results from prolonged nausea and emesis. We hypothesized that thiamine deficiency is induced by altered gut ecology. This report includes 2 retrospective studies of obese patients who underwent Roux-en-Y gastric bypass surgery at our institution from 1999 to 2005. In the first study, 80 patients (52 women and 28 men) had measurement of whole-blood thiamine diphosphate level and serum folate level. In these 80 patients, 39 (49%) had thiamine diphosphate levels less than the lower limit of the reference range, and 28 (72%) of the 39 had folate levels higher than the upper limit of the reference range, an indicator of small intestinal bacterial overgrowth. In 41 patients with normal thiamine levels, only 14 (34%) had folate levels higher than the upper limit of the reference range (chi(2) test, P < .01). In the second study, 21 patients (17 women and 4 men) had thiamine diphosphate levels less than the lower limit of the reference range and abnormal glucose-hydrogen breath tests, consistent with small intestinal bacterial overgrowth. Fifteen patients received oral thiamine supplements, but repeated thiamine levels remained low in all 15. Nine of these patients then received oral antibiotic therapy; repeated thiamine levels were found to be normal in all 9 patients. These results support the hypothesis that small intestinal bacterial overgrowth results from altered gut ecology and induces thiamine deficiency after gastric bypass surgery in obese patients.
Assuntos
Testes Respiratórios/métodos , Derivação Gástrica , Intestino Delgado/microbiologia , Obesidade/cirurgia , Complicações Pós-Operatórias/microbiologia , Deficiência de Tiamina/etiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Distribuição de Qui-Quadrado , Suplementos Nutricionais , Feminino , Ácido Fólico/sangue , Humanos , Intestino Delgado/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Estudos Retrospectivos , Tiamina/sangue , Tiamina/uso terapêutico , Deficiência de Tiamina/tratamento farmacológico , Adulto JovemRESUMO
UNLABELLED: Resuscitation with racemic lactated Ringer's solution (containing equal amounts of D and L isomers of lactate) has been shown to induce pulmonary apoptosis. Substitution of DL-isomer lactate with ketone bodies (beta-hydroxybutyrate, BHB), sodium pyruvate, or L-isomer of lactate decrease this injury without changing the energy status of the tissues or the expression of apoptotic genes. These modified solutions however alter the function of apoptotic proteins through an unknown mechanism. We postulated that DL-LR induces apoptosis by restricting the phosphorylation of key apoptotic proteins. METHODS: Male Sprague Dawley rats (n = 30, 5/group) were subjected to a three stage, volume-controlled hemorrhage and randomized to the following groups. 1) No hemorrhage (Sham); 2) Hemorrhage and no resuscitation (NR); 3) Resuscitation with 3x shed blood volume of racemic LR (DL-LR); 4) Resuscitation with 3x shed blood volume of LR containing only the L-isomer of lactate (L-LR); 5) Resuscitation with 3s shed blood volume of pyruvate Ringer's (PR); 6) Resuscitation with 3s shed blood volume of ketone Ringer's (KR). The modified Ringer's solutions were identical to racemic LR except for equimolar substitution of DL-lactate for L-lactate, pyruvate and BHB respectively. Lung tissue was obtained 2 hours later and subjected to Western Blotting. The levels of Akt, Bad, and eNOS (total and phosphorylated) proteins were measured. Finally, the expression of gene coding for protein 14-3-3 was measured using RT-PCR. RESULTS: Resuscitation with DL-LR caused a significant (p < 0.05) increase in the total Bad and a decrease in phosphorylated Bad protein expression in the lung. It also caused an increase in the phosphorylated Akt levels and a decrease in gene coding for protein 14-3-3. These changes were consistent with signaling imbalances that favor apoptosis. Modified LR solutions, on the other hand, did not cause these alterations. Phosphorylation pattern of eNOS supported the involvement of PI3K/Akt pathway in this process. CONCLUSION: Racemic lactate plays a role in the induction of pulmonary apoptosis by restricting phosphorylation of Bad and eNOS proteins.
Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Transporte/efeitos dos fármacos , Modelos Animais de Doenças , Soluções Isotônicas/uso terapêutico , Pulmão , Óxido Nítrico Sintase/efeitos dos fármacos , Choque Hemorrágico , Proteínas 14-3-3 , Animais , Apoptose/genética , Western Blotting , Proteínas de Transporte/metabolismo , Química Farmacêutica , Avaliação Pré-Clínica de Medicamentos , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Infusões Intravenosas , Soluções Isotônicas/química , Soluções Isotônicas/metabolismo , Soluções Isotônicas/farmacologia , Pulmão/química , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo III , Fosforilação , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ressuscitação/métodos , Lactato de Ringer , Solução de Ringer , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Tirosina 3-Mono-Oxigenase/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/genética , Proteína de Morte Celular Associada a bclRESUMO
BACKGROUND: Resuscitation from hemorrhagic shock causes profound immunologic changes. The tonicity of fluids used for resuscitation clearly influences the immune response. Our study was designed to determine whether isotonic and hypertonic fluids exert their differential effects on immune response by altering the cytokine gene profile of human leukocytes. The cDNA array method was used to profile transcriptional responses after exposure to hypertonic and isotonic fluids. METHODS: Blood from seven healthy volunteers was incubated for 30 minutes with isotonic (10% dextran-40 and lactated Ringer's [LR] solution) and hypertonic (7.5% hypertonic saline and hypertonic dextran [HTD]) fluids. The volumes of isotonic fluids used were equal to the volume of blood, whereas the volumes of hypertonic fluids were adjusted to keep the salt load identical to the LR group. The cDNA array technique was used to measure the gene expression of 23 common cytokines. RESULTS: Increased gene transcription of proinflammatory cytokines (interleukin [IL]-1alpha, IL-6, IL-10, and tumor necrosis factor-alpha) as well as others (IL-5, IL-7, and IL-16) was found after incubation with resuscitation fluids. Variances were noted depending on the type of fluid: HTD and LR solution did not induce expression of IL-5, and HTD also did not induce IL-1beta expression. Genes encoding IL-1alpha, IL-6, IL-9, and tumor necrosis factor-alpha had low level baseline expression in leukocytes isolated from unstimulated blood, and their expression increased markedly after exposure to resuscitation fluids. The inducible transcripts included IL-1beta, IL-7, IL-10, and IL-16. However, there was no difference in cytokine expression profile between isotonic and hypertonic fluids. CONCLUSION: Exposure of human leukocytes to resuscitation fluids causes an increase in cytokine gene expressions compared with undiluted blood. This expression profile is largely independent of the type of fluid used.