O envelhecimento promove o aparecimento de doenças crônicodegenerativas, entre elas a osteoartrose. Artroplastia Total de Quadril (ATQ) tem sido procedimento comumente frequentemente com uso de cimento ósseo metilmetacrilato (MTC). Por outro lado, importantes alterações hemodinâmicas são descritas durante o procedimento de cimentação. A raquianestesia é um procedimento anestésico que produz menores efeitos hemodinâmicos e melhor analgesia pós-operatória em comparação a anestesia geral para a ATQ. Entretanto, especificamente neste procedimento cirúrgico tais alterações permanecem a ser investigadas. Buscamos avaliar os efeitos hemodinâmicos através da técnica de cardioimpedância em pacientes idosos submetidos à cirurgia de ATQ com o uso de MTC e raquianestesia. Utilizamos um estudo transversal, observacional, comparativo, inter-metodológico e com intervenção ativa. Método: Doze pacientes de ambos os sexos, > 65 anos, com indicação ortopédica para ATQ foram estudados. Os sujeitos receberam avaliação pré-anestésica e realizaram exames laboratoriais préoperatórios. Foram submetidos à cirurgia de ATQ com utilização de raquianestesia e implante de cimento de MTC. Os pacientes foram monitorados hemodinamicamente por meio da cardiografia de impedância, da saturação de oxigênio e pressão arterial, no intra-operatório, no momento acordado, durante a indução anestésica, na colocação do MTC e após este procedimento. Após a expansão volêmica observamos que houve aumento do DC quando comparado a raquianestesia, cimentação, inserção, redução da prótese e ao final da cirurgia (P<0,05). Tais resultados foram de certa forma, atenuados na presença de efedrina. No entanto, o VS sofreu alterações nos eventos supracitados na presença ou não da droga. Por outro lado, a FC, o IC e a RVS sofreu poucas alterações durante os eventos estudados. O DC, IC e o VS se correlacionaram com a massa corporal (r = 0,81, 0,60 e 0,67 respectivamente), o VS se correlacionou negativamente com a idade (r = -0.67), o IC se correlacionou negativamente com a classe funcional pela NYHA (r = -0,61) e o DC se correlacionou positivamente com a quantidade de efedrina administrada (r = 0,70). Conclusão: O procedimento cirúrgico de ATQ com MTC sob raquianestesia produz alterações hemodinâmicas e a cardioimpedância foi um instrumento útil para guiar os procedimentos e conduta do intraoperatório, configurando-se como uma técnica interessante para monitorização não invasiva. / Aging promotes the onset of chronic diseases, including osteoarthritis. Hip arthroplasty procedure has been commonly often the use of methylmethacrylate bone cement (MMA) has been used in the surgical procedure. On the other hand, significant hemodynamic changes are described in the cementation procedure. Spinal anesthesia is an anesthetic that produces less hemodynamic effects and better postoperative analgesia compared to general anesthesia for surgery arthroplasty. However, this particular surgical procedure (hip arthroplasty) such changes remain to be investigated. To evaluate the hemodynamic effects through cardioimpedance technique in elderly patients undergoing surgery for hip arthroplasty with the use of MMA for prosthetic hip and spinal. Twelve patients of both sexes, > 65 years, with orthopedic indication for hip arthroplasty were studied. The subjects received preanesthetic evaluation and underwent preoperative laboratory. From then underwent surgery for hip arthroplasty with use of spinal anesthesia and MMA cement. Patients were haemodynamically monitored by impedance cardiography, oxygen saturation and blood pressure intraoperative, when awake, during anesthesia induction, installing the MMA cement and after this procedure. After volume expansion, we observed that there was increase in CO when compared to spinal anesthesia, cementing, insertion, and reduction of the prosthesis at surgery (P<0.05). These results were somewhat attenuated in the presence of ephedrine. However, the SV underwent changes at aforementioned event on the presence or not of drugs. On the other hand, HR, CI and SVR has a few changed during the studied event. The CO, CI and the SV was correlated with body mass (r = 0.81, 0.60 and 0.67 respectively), SV was negatively correlated with age (r = -0.67), the CI was negatively correlated with NYHA functional class (r = -0.61) and CO was positively correlated with the amount of ephedrine administered (r = 0.70).Conclusion: The surgical procedure for hip arthroplasty under spinal anesthesia with MMA produces haemodynamic changes and cardioimpedance was a useful tool to guide the procedures and conduct of the intraoperative considering as interesting technique for noninvasive monitoring.

Introduktion: CT-angiografi med kontrastinjektion kan ge en god visualisering av kroppens blodkärl. Även om CT har många fördelar i samband med avbildning, har det några nackdelar som bör uppmärksammas. Det finns forskning som visar hur optimering av kontrastmedelsanvändning kan minska stråldosen och samtidigt förbättra bildkvaliteten. Syfte: Syftet med denna studie är att undersöka hur kontrastmedelsanvändningen vid CT-angiografi kan optimeras utifrån faktorerna cardiac output, arm- och kroppspositionering samt val av injektionsplats. Material och metod: En systematisk litteraturöversikt genomfördes. Studierna som använts i litteraturstudien hämtades från tre olika databaser. Totalt valdes 16 studier ut för att besvara syftet. De inkluderade artiklarna publicerades på engelska mellan 2010–2019. Resultat: Resultatet visade att blodflödet beror på cardiac output och påverkar kontrastförstärkningen i kärlen. Den ventrala armpositionen bidrar till minst artefakter och förbättrad kontrastförstärkning. Den optimala kroppspositioneringen är den som följer blod- och kontrastflödet för att undvika artefakter. Resultatet visade även att injektion i höger arm gav bättre attenuering, mindre artefakter samt lägre stråldos. Slutsats: Resultatet från studien visade att de olika faktorerna hos patienten kan påverka kontrastförstärkningen i blodkärlen samtidigt som bildkvalitet förbättras och stråldosen reduceras.

Cardiac output, the volume of blood pumped by the heart over time, is a powerful clinical metric used by physicians to assess overall cardiac health and patient well-being. However, current cardiac output estimation methods are typically invasive, time-consuming, expensive, or some combination of all three. Patients that receive artificial cardiac pacemaker devices are particularly susceptible to cardiac dysfunction and often require long-term cardiac monitoring support. This thesis proposes a novel cardiac output monitoring solution which leverages an implantable intracardiac medical device. The principles of traditional impedance cardiography, an established cardiac output monitoring technique in practice for over fifty years, have been adapted to incorporate a leadless artificial cardiac pacemaker, an implantable medical device contained entirely within the heart. This novel method, colloquially referred to as Z-Cardio, monitors time-varying intracardiac impedance modulation to assess changes in cardiac output. In this study, technologies both old and new are synthesized to produce a novel and effective method of monitoring a critical metric of cardiac health.

Aims To investigate whether there is evidence for distinct cardiac output (CO) based phenotypes in patients with chronic right heart failure associated with severe tricuspid regurgitation (TR) and to characterize their impact on TR treatment and outcome. Methods and results A total of 132 patients underwent isolated transcatheter tricuspid valve repair (TTVR) for functional TR at two centres. Patients were clustered according to k-means clustering into low [cardiac index (CI) < 1.7 L/min/m2], intermediate (CI 1.7–2.6 L/min/m2) and high CO (CI > 2.6 L/min/m2) clusters. All-cause mortality and clinical characteristics during follow-up were compared among different CO clusters. Mortality rates were highest for patients in a low (24%) and high CO state (42%, log-rank P < 0.001). High CO state patients were characterized by larger inferior vena cava diameters (P = 0.003), reduced liver function, higher incidence of ascites (P = 0.006) and markedly reduced systemic vascular resistance (P < 0.001) as compared to TTVR patients in other CO states. Despite comparable procedural success rates, the extent of changes in right atrial pressures (P = 0.01) and right ventricular dimensions (P < 0.001) per decrease in regurgitant volume following TTVR was less pronounced in high CO state patients as compared to other CO states. Successful TTVR was associated with the smallest prognostic benefit among low and high CO state patients. Conclusions Patients with chronic right heart failure and severe TR display distinct CO states. The high CO state is characterized by advanced congestive hepatopathy, a substantial decrease in peripheral vascular tone, a lack of response of central venous pressures to TR reduction, and worse prognosis. These data are relevant to the pathophysiological understanding and management of this important clinical syndrome. Graphical Abstract Proposed mechanism of hypercirculatory tricuspid regurgitation. Tricuspid regurgitation related backward failure causes liver congestion and dysfunction with portal hypertension and reduced washout of vasoactive substances. Consequent splanchnic and peripheral vasodilatation alongside with reduced renal blood flow results in renin–angiotensin–aldosterone system (RAAS) activation and sympathetic overactivation. The sympathetic drive and volume retention lead to further capacitance depletion and volume overload, eventually resulting in a high cardiac output state, with limited preload reduction and prognostic benefit following transcatheter tricuspid valve repair. The alterations in the graph should be interpreted as simultaneous interaction rather than a timeline. Continuous lines indicate findings in the present study. Dashed lines express currently accepted mechanistical considerations. AP, alkaline phosphatase; γGT, gamma-glutamyl-transferase; RA, right atrium; RV, right ventricle.

<p><strong>Abstract:</strong><strong> </strong></p> <p><em>Introduction:</em></p> <p>Because the relationship between pulmonary function and exercise tolerance is highly variable in COPD, other contributing factors were investigated. Physiological factors that contribute to exercise tolerance must contribute to the symptoms limiting exercise, thus the symptoms limiting exercise in COPD and their contributing factors were explored, including an investigation of novel mechanisms to explore the reported tiotropium bromide-mediated improvement in exercise tolerance in COPD.</p> <p><em>Methods:</em></p> <p>We conducted a retrospective, cross-sectional analysis of 4,424 COPD patients and 4,221 healthy subjects; referred to McMaster University Medical Center for exercise testing. Multiple linear regression, ridge regression, and MANOVA were utilized to determine the factors contributing to exercise tolerance, important symptoms limiting exercise, and factors contributing to dyspnea.</p> <p>A randomized, double-blind, placebo-controlled, crossover study of 20 COPD subjects was performed. Repeated measures ANOVA was utilized to determine effects of 3 weeks tiotropium bromide vs. 3 weeks placebo on cardiac output and efficiency of gas exchange during exercise.</p> <p><em> </em></p> <p><em>Results:</em></p> <p>MBC, DL_CO, and quadriceps strength were the three major, independent, contributors to exercise capacity (MPO = -206.3 + 5.1*Quadriceps Strength + 1.8*MBC + 10.0*DL_CO, r² = 0.677). MANOVA further illustrated this.</p> <p>Dyspnea, alone or in equal combination with leg effort, was the most important symptom limiting exercise in COPD. V_E and MBC were the two major, independent, contributors to dyspnea (Dyspnea = 0.95 + 0.08*V_E + -0.01*MBC, r² = 0.457). The increase in dyspnea with V_E was much greater than the decrease with MBC.</p> <p>Tiotropium bromide did not significantly (p = 0.72) improve the efficiency of gas exchange for oxygen, significantly worsened (p = 0.005) the efficiency of gas exchange for carbon dioxide, and did not improve cardiac output.</p> <p><em>Conclusion:</em></p> <p>We concluded the reported tiotropium bromide-mediated improvement in exercise tolerance in COPD is not mediated through improvements in gas exchange efficiency and/or cardiac output.</p> <p><strong><br /></strong></p> / Doctor of Philosophy (Medical Science)

Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) is a breathing disorder characterized by recurrent episodes of upper airway collapse during sleep. Measuring cardiac function in OSAHS patients may provide information to help delineate not only chronic effects of autonomic imbalance and ventricular loading in the diseases state, but also possible beneficial effects of clinical treatments. Objectives (Study 1): The aim of this study was to determine the reproducibility of select cardiac variables when monitoring a simulated sleep apnea event using a new improved bioimpedance cardiography system. Methods: Fifteen apparently healthy males were tested on three different days in a protocol requiring their performance of two 15 sec and two 30 sec forced and sustained inspiratory efforts against a closed epiglottis (Müeller Maneuver-MM). Results: Changes in cardiac output (CO), heart rate (HR), stroke volume (SV), myocardial contractility index (MCI) and systemic vascular resistance (SVR) were similar during 15 sec and 30 sec MM in all three days. During 30 sec MM, these changes in cardiac function were pronounced in comparison to the minimal variations observed for the 15 sec MM challenge test. Objectives (Study 2): The aim of this study was to characterize the cardiac responses to negative intrathoracic pressure in OSAHS patients with and without hypertension versus healthy subjects. Methods: Two groups of 10 OSAHS patients, one without HTN and one with HTN were compared with a control group. Each subject underwent two 30 sec (MM) as previously described. Results: During MM, there were similar changes in SV, HR and SVR in all three groups. CO was lower during MM in controls compared to OSAHS groups, whereas MCI decreased during MM in both controls and OSAHS+HTN groups (-7.5% and -1.7%, respectively) compared with an increase in OSAHS group (11.8%). During a Post-MM, both OSAHS groups showed return of cardiac responses toward their pre-MM baseline within 30 sec. Conclusions: The new bioimpedance cardiograph evaluated in this study was found to be reliable for measuring acute changes in cardiac responses to this breathing challenge test. OSAHS may cause acute changes in selected cardiac parameters during and immediately after a breathing challenge test. / Ph. D.

Background: In the past 37 years, increased efforts have been directed toward a better understanding of the importance of Hcy in disease and it has now become clear that hyperhomocysteinemia is a major independent risk factor for CVD. Extensive research on the influence of vitamin supplementation leading to reductions in Hcy levels and improvements in cardiovascular function has been done. The importance of exercise in the lowering of cardiovascular risk factors, as well as its favourable influence on cardiovascular function has also been indicated in several studies, however, the limited number of studies investigating the effect of exercise on Hcy concentrations revealed contradicting results. Furthermore, a relationship between Hcy concentration and cardiovascular function with the intervention of an exercise training and a vitamin supplementation programme respectively has also not been investigated. Objective: The objective of this study was to examine the effect of a 12-week exercise training and a 12-week vitamin supplementation intervention respectively on tHcy concentrations and cardiovascular function, and whether the change in tHcy concentration within the different interventions correlated with the change in cardiovascular function. Methods: In a randomised controlled cross-over intervention study, 52 men matched for age, cardiorespiratory fitness levels and cardiovascular risk factors were randomly assigned to one of 3 groups (Group A = exercise training programme, 20-30min. at 70-80% of HRmax; Group B = 400 g folic acid and 25 g vitamin B12 supplement; Group C = control). Group A and B were crossed over for phase 11, and Group C remained the control. The questionnaires were completed, and the body composition variables (BMI, WHR and body fat percentage), cardiovascular function (Finometer), tHcy concentrations and VO2max, were measured before and after each 12-week intervention period. A 6-week washout period separated the crossovers. Results: The ANCOVA, adjusted for age and BMI, showed that the percentage change from baseline to end, corrected for baseline of the tHcy concentration increased significantly (p ≤ .05) by 9.7% with the exercise training intervention and decreased significantly (p ≤ .05) by 12.9%, with the vitamin supplementation intervention. The ANCOVA of the percentage change from baseline to end in cardiovascular function showed that the vitamin supplementation intervention resulted in improvements in cardiovascular function (decreased resting MAP, TPR and increased resting SV, CO, Cw) in comparison to the impairment in cardiovascular function with the exercise training intervention (increased resting DBP, MAP and TPR). The relationship between the tHcy concentration and cardiovascular function at baseline and within each of the different interventions were assessed by partial correlations adjusted for age, BMI and VO2max. Significant (p ≤ .05) relationships only occurred within the vitamin supplementation intervention, where decreased percentage change in tHcy concentration significantly correlated with increased percentage change of resting SV and CO and decreased percentage change of resting TPR. Conclusion: The general conclusion that can be drawn is that a 12-week vitamin supplementation intervention showed increased health related results, e.g. a significant reduction in tHcy concentration, an improvement in cardiovascular function and a significant positive relationship between these b o factors, in comparison to the 12-week exercise training intervention that significantly increased the tHcy concentration and did not show increased health related results. Due to inadequate compliance to the exercise training intervention, no conclusion can be drawn with regard to the effect of exercise training on tHcy concentrations and cardiovascular function. / Thesis (M.Sc. (Human Movement Science))--North-West University, Potchefstroom Campus, 2007

Fundamento: Na descompensação da insuficiência cardíaca, pode ocorrer o baixo débito cardíaco, nessa situação o uso de inotrópico pode ser necessário. Se o acesso venoso for periférico, a infusão venosa prolongada de inotrópicos pode levar à flebite. Por outro lado, o acesso venoso central pode apresentar complicações. O Cateter Central de Inserção Periférica (PICC) pode ser uma opção nessa situação. O objetivo do presente estudo foi avaliar a incidência de flebite com o uso do PICC em comparação ao acesso venoso periférico. Métodos: em estudo clínico randomizado foram selecionados pacientes com insuficiência cardíaca congestiva avançada, em uso de inotrópico endovenoso; plaquetas >= 50.000/mm3 e fração de ejeção do ventrículo esquerdo (FEVE) < 0,45. Os pacientes foram randomizados para receberem o PICC ou manter o acesso venoso periférico. O desfecho principal foi à ocorrência de flebite. Os dados foram analisados pela regressão logística. Resultados: Foram incluídos 40 pacientes no Grupo PICC e 40 pacientes no grupo controle. A mediana da idade foi de 61,5 (IQR=16) anos, a FEVE foi de 24,0 (IQR= 10) % e a dose da dobutamina foi de 7,73 (IQR = 5,3) mcg/kg*min. No Grupo PICC a ocorrência de flebite foi de 2,5 % (1 paciente) enquanto no grupo controle foi de 95% (38 pacientes), com razão dos riscos (HR) de 0,1% (IC 95%: 0,0 a 1,6%, P < 0,001). Conclusões: O uso de PICC foi associado a redução da incidência de flebite durante a infusão endovenosa contínua de dobutamina em pacientes com baixo débito cardíaco durante internação por insuficiência cardíaca descompensada / Background: During decompensated heart failure, the use of intravenous inotropes can be necessary. With peripheral venous access, prolonged infusions can cause phlebitis. However, traditional central venous catheters have possible complications. Peripherally inserted central catheters (PICCs) may be an alternative to traditional catheters. Our objective was to compare the incidence of phlebitis between PICCs and catheters used to achieve peripheral venous access. Methods: In a randomized clinical trial, 40 patients were randomized to the PICC group and 40 patients were randomized to thecontrol group. The inclusion criteria were advanced heart failure, ejection fraction < 0.45, and platelets > 50,000/mm3. The patients were randomly assigned to receivea PICC or keep their peripheral venous access. The primary endpoint was the occurrence of phlebitis. Results: We included 40 patients in the PICC group and 40 patients in the control group. The median age was 61.5 (interquartile range [IQR]=16) years, the ejection fraction was 0.24 (IQR=0.10), and the dobutamine dose was 7.73 (IQR=5.3) mcg/kg*min. Phlebitis occurred in 1 patient (2.5%) in the PICC group and in 38 patients (95.0%) in the control group, with a hazard ratio of 0.1% (95% confidence interval [CI]: 0.0%-1.6%, P < 0.001). Conclusion: PICCs were associated with a lower incidence of phlebitis in patients hospitalized for decompensated heart failure with low cardiac output during intravenous dobutamine infusions

Introdução: O fluxograma de tratamento ACCM/PALS objetiva a reversão precoce do choque séptico pediátrico utilizando medidas convencionais. Na evolução destas recomendações, foram adicionadas medidas indiretas do equilíbrio entre oferta e demanda de oxigênio utilizando saturação venosa central de oxigênio (ScvO2 70%), dentro de uma abordagem direcionada a metas. Entretanto, enquanto que estas recomendações adicionadas baseiam-se em evidências de estudos em adultos, a extrapolação para o paciente pediátrico permanece sem validação. Objetivo: O objetivo deste estudo é comparar o fluxograma ACCM/PALS com ou sem terapia guiada pela ScvO2 sobre a morbidade e a mortalidade de crianças com sepse grave e choque séptico. MÉTODOS: Crianças e adolescentes com sepse grave ou choque séptico refratário a volume foram randomizados para receber o tratamento ACCM/PALS com ou sem ressuscitação guiada pela ScvO2. Mortalidade em vinte e oito dias foi o desfecho primário. Resultados: Dos 102 paciente incluídos, 51 receberam tratamento ACCM/PALS guiado pela ScvO2 e 51 receberam tratamento ACCM/PALS sem orientação pela ScvO2. Tratamento guiado pela ScvO2 resultou em menor mortalidade (11,8% vs. 39,2%, p = 0,002), e menor incidência de disfunções orgânicas (p = 0,03). O tratamento guiado pela ScvO2 resultou em mais cristalóide (28 [20-40] vs. 5 [0-20] mL/kg, p < 0,0001), transfusões de hemáceas (45,1% vs. 15,7%, p = 0,002) e suporte inotrópico (29,4% vs. 7,8%, p = 0,01) nas primeiras seis horas. Conclusões: Este estudo reforça o fluxograma ACCM/PALS. Tratamento guiado pela ScvO2 70% possui impacto significativo e aditivo sobre o prognóstico de crianças e adolescentes com choque séptico. / Introduction: ACCM/PALS guidelines address early correction of pediatric septic shock using conventional measures. In the evolution of these recommendations indirect measures of the balance between systemic oxygen delivery and demands using central venous or superior vena cava oxygen saturation (ScvO2 70%) in a goal directed approach have been added. However, while these additional goal-directed endpoints are based on evidenced based adult studies, the extrapolation to the pediatric patient remains unvalidated. Objective: The purpose of this study is to compare ACCM/PALS guidelines performed with and without ScvO2 goal-directed therapy on the morbidity and mortality rate of children with severe sepsis and septic shock. Methods: Children and adolescents with severe sepsis or fluid-refractory septic shock were randomly assigned to ACCM/PALS with, or without ScvO2 goal directed resuscitation. Twenty-eight day mortality was the primary endpoint. Results: Of the 102 enrolled patients, 51 received ACCM/PALS with ScvO2 goal directed therapy and 51 received ACCM/PALS without ScvO2 goal directed therapy. ScvO2 goal directed therapy resulted in less mortality (28-day 11.8 vs. 39.2 percent, p = 0.002), and fewer new organ dysfunctions (p = 0.03). ScvO2 goal directed therapy resulted in more crystalloid (28 [20-40] vs. 5 [0-20] mL/kg, p < 0.0001), blood transfusion (45.1 vs. 15.7 percent, p = 0.002) and inotropic support (29.4 vs. 7.8 percent, p = 0.01) in the first 6 hours. Conclusions: This study supports the current ACCM/PALS guidelines. Goal directed therapy using the endpoint of a ScvO2 70% provides significant and additive impact on the outcome of children and adolescents with septic shock.

Introdução: O fluxograma de tratamento ACCM/PALS objetiva a reversão precoce do choque séptico pediátrico utilizando medidas convencionais. Na evolução destas recomendações, foram adicionadas medidas indiretas do equilíbrio entre oferta e demanda de oxigênio utilizando saturação venosa central de oxigênio (ScvO2 70%), dentro de uma abordagem direcionada a metas. Entretanto, enquanto que estas recomendações adicionadas baseiam-se em evidências de estudos em adultos, a extrapolação para o paciente pediátrico permanece sem validação. Objetivo: O objetivo deste estudo é comparar o fluxograma ACCM/PALS com ou sem terapia guiada pela ScvO2 sobre a morbidade e a mortalidade de crianças com sepse grave e choque séptico. MÉTODOS: Crianças e adolescentes com sepse grave ou choque séptico refratário a volume foram randomizados para receber o tratamento ACCM/PALS com ou sem ressuscitação guiada pela ScvO2. Mortalidade em vinte e oito dias foi o desfecho primário. Resultados: Dos 102 paciente incluídos, 51 receberam tratamento ACCM/PALS guiado pela ScvO2 e 51 receberam tratamento ACCM/PALS sem orientação pela ScvO2. Tratamento guiado pela ScvO2 resultou em menor mortalidade (11,8% vs. 39,2%, p = 0,002), e menor incidência de disfunções orgânicas (p = 0,03). O tratamento guiado pela ScvO2 resultou em mais cristalóide (28 [20-40] vs. 5 [0-20] mL/kg, p < 0,0001), transfusões de hemáceas (45,1% vs. 15,7%, p = 0,002) e suporte inotrópico (29,4% vs. 7,8%, p = 0,01) nas primeiras seis horas. Conclusões: Este estudo reforça o fluxograma ACCM/PALS. Tratamento guiado pela ScvO2 70% possui impacto significativo e aditivo sobre o prognóstico de crianças e adolescentes com choque séptico. / Introduction: ACCM/PALS guidelines address early correction of pediatric septic shock using conventional measures. In the evolution of these recommendations indirect measures of the balance between systemic oxygen delivery and demands using central venous or superior vena cava oxygen saturation (ScvO2 70%) in a goal directed approach have been added. However, while these additional goal-directed endpoints are based on evidenced based adult studies, the extrapolation to the pediatric patient remains unvalidated. Objective: The purpose of this study is to compare ACCM/PALS guidelines performed with and without ScvO2 goal-directed therapy on the morbidity and mortality rate of children with severe sepsis and septic shock. Methods: Children and adolescents with severe sepsis or fluid-refractory septic shock were randomly assigned to ACCM/PALS with, or without ScvO2 goal directed resuscitation. Twenty-eight day mortality was the primary endpoint. Results: Of the 102 enrolled patients, 51 received ACCM/PALS with ScvO2 goal directed therapy and 51 received ACCM/PALS without ScvO2 goal directed therapy. ScvO2 goal directed therapy resulted in less mortality (28-day 11.8 vs. 39.2 percent, p = 0.002), and fewer new organ dysfunctions (p = 0.03). ScvO2 goal directed therapy resulted in more crystalloid (28 [20-40] vs. 5 [0-20] mL/kg, p < 0.0001), blood transfusion (45.1 vs. 15.7 percent, p = 0.002) and inotropic support (29.4 vs. 7.8 percent, p = 0.01) in the first 6 hours. Conclusions: This study supports the current ACCM/PALS guidelines. Goal directed therapy using the endpoint of a ScvO2 70% provides significant and additive impact on the outcome of children and adolescents with septic shock.