Fluid-refractory Septic Shock Research Articles

Comparison of efficacy of dopamine versus epinephrine infusion in fluid refractory septic shock in a tertiary care pediatric ICU.

Objective: To compare the effectiveness of dopamine versus epinephrine as 1st line vasoactive therapy among children aged 6 months to 12 years and presenting with fluid-refractory septic shock in pediatric intensive care unit (PICU). Study Design: Randomized Controlled Trial. Setting: Department of Medicine, The Children’s Hospital, Multan, Pakistan. Period: August 2022 to January 2023. Material & Methods: A total of 156 children aged between 6 months to 12 year presenting to PICU with fluid refractory shock. Children were randomized to either Group-A (epinephrine) or Group-B (dopamine) till end points of resolution of shock was achieved. When the maximum recommended dose of the study drugs was reached, open-label vasoactive was initiated. Frequency of resolution of shock within 1st hour of resuscitation was noted. Results: In a total of 156 children, there were 85 (54.5%) children between 7 to 12 years of age. There were 90 (57.7%) males and 66 (42.3%) females. The efficacy was observed in 41 (52.6%) children in Group-A (epinephrine) versus 18 (23.1%) in Group-B (dopamine), p=0.0001. Conclusion: The epinephrine was more effective than dopamine as first-line vasoactive therapy in fluid-refractory septic shock in children aged 6 months to 12 years presenting in PICU.

Alternatives to Hydrocortisone for Hemodynamic Support in Septic Shock Management Due to Medication Shortage.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Septic shock is when initial fluid resuscitation fails to increase the mean atrial pressure to greater than or equal to 65 mm Hg. The 2021 Surviving Sepsis Campaign guidelines recommend corticosteroids for vasopressor and fluid-refractory septic shock patients. Medication shortages can arise, and their etiologies include natural disasters, quality control issues, and manufacturing discontinuation. The U.S. Food and Drug Administration and the American Society of Health-System Pharmacists announced a shortage of IV hydrocortisone. Methylprednisolone and dexamethasone are considered therapeutic alternatives to hydrocortisone. This commentary aims to guide clinicians on the alternative to hydrocortisone among septic shock patients due to medication shortage.

Management of septic shock by pediatric residents: An area for quality improvement

BackgroundCompliance with sepsis guidelines has been shown to be linked to better outcomes in patients with septic shock; however, adherence to these guidelines is not consistent among pediatric healthcare providers. In Tunisia, the management of children with septic shock is initiated by the pediatric resident on call. MethodsThis study assessed the compliance of Tunisian pediatric residents with the 2020 “Surviving Sepsis Campaign” guidelines and identified factors that could improve compliance. We conducted a cross-sectional national study based on an online survey (SurveyMonkey) presenting a clinical pediatric case of septic shock. The survey was sent to the 200 residents registered in the Tunisian pediatric residency program. ResultsThe response rate was 72%, with 144 residents replying to the survey. Up to 72.9% of the residents had good compliance with the 1-h bundle: obtaining blood cultures prior to antibiotics, early administration of intravenous (IV) antibiotics, IV fluid expansion, and vasopressor for fluid-refractory septic shock. Factors independently associated with good compliance were a pediatric intensive care unit rotation (odds ratio [OR]: 5.17, 95% confidence interval [CI]: 1.44–18.58; p = 0.012), availability of a written protocol (OR: 9.09, 95% CI: 2.67–30.97; p<0.001), an on-call senior supervisor on site (OR: 6.76, 95% CI: 2.24–20.40; p = 0.001), and European Pediatric Advanced Life Support (EPALS) certification (OR: 13.47, 95% CI: 3.05–59.31; p = 0.001). ConclusionThese factors could be considered in the process of a quality improvement strategy that ultimately better promotes performance in pediatric sepsis management and may improve patient outcomes.

Efficacy of dopamine, epinephrine and blood transfusion for treatment of fluid refractory shock in children with severe acute malnutrition or severe underweight and cholera or other dehydrating diarrhoeas: protocol for a randomised controlled clinical trial

IntroductionDiarrhoea is one of the leading causes of under-5 childhood mortality and accounts for 8% of 5.4 million global under-5 deaths. In severely malnourished children, diarrhoea progresses to shock, where...

A Randomized Controlled Trial of Norepinephrine Plus Dobutamine Versus Epinephrine As First-Line Vasoactive Agents in Children With Fluid Refractory Cold Septic Shock.

Open-label randomized controlled study. A single-center PICU from North India. Children 2 months to less than 18 years old with fluid refractory cold septic shock. In the intervention group, norepinephrine and dobutamine were started and in the control group, epinephrine was started as the first-line vasoactive agent. The primary outcome was the proportion attaining shock resolution (attaining all the therapeutic endpoints) at 1 hour of therapy. We enrolled 67 children: 34 in the norepinephrine plus dobutamine group (intervention) and 33 in the epinephrine group (control). There was no difference in shock resolution at 1 hour (17.6% vs 9%; risk ratio [RR], 2.0; 95% CI, 0.54-7.35; p = 0.25), 6 hours (76.4% vs 54.5%; RR, 1.69; 95% CI, 0.92-3.13; p = 0.06), and 24 hours between the intervention and control groups, respectively. Children in the norepinephrine plus dobutamine group attained shock resolution earlier (measured from starting of vasoactive agents to attaining all the therapeutic endpoints) (hazard ratio, 1.84 [1.1-3.08]). The difference in 28-day mortality was not significant (23.5% vs 39.3% in the intervention and control groups, respectively [RR, 0.59; 95% CI, 0.28-1.25]). In children with fluid refractory cold septic shock, with use of norepinephrine plus dobutamine as first-line agents, the difference in the proportion of children attaining shock resolution at 1 hour between the groups was inconclusive. However, the time to shock resolution was earlier in the norepinephrine plus dobutamine group. Also, fewer children in the intervention group were refractory to treatment. Further studies powered to detect (or exclude) an important difference would be required to test this intervention.

727: LONGITUDINAL STUDY OF THYROID PROFILE IN CHILDREN DURING SEPTIC SHOCK AND ITS IMPACT ON OUTCOMES

Introduction: Non-thyroidal illness syndrome (NTIS) is common in septic shock. Data on thyroid profile in pediatric patients from low- and middle-income countries (LMICs) are scarce, where undernutrition is common. Longitudinal behaviour of thyroid hormones during initial 7 days of septic shock and its association with clinical outcome in children from LMICs was studied. Methods: This prospective observational study was conducted in pediatric emergency room and pediatric intensive care unit in a tertiary care centre of a low-middle income country. Sixty-two patients (age, 6mo-12yrs) with fluid refractory septic shock at admission or developing it within 24hrs of admission were enrolled. Exclusions were history of CPR, chronic illness, endocrine disorders, and recent radio-contrast study. Serum levels of Thyroid Stimulating Hormone (TSH), T4 and T3 were measured on Day 1, 3 and 7. Correlation between thyroid hormones and severity of organ dysfunctions, outcomes and nutritional status were analysed. Results: TSH was low in 20% patients, which remained unaltered during 7 days. T4 and T3 levels were low in the majority (Day 1: 84% and 72%; Day 7: 68% and 59% respectively). Non-Survivors (n=24) have significantly lower TSH and T4 levels during 7 days compared to survivors (n=38) (p=0.045 and p=0.004 respectively). Non-survivors had significantly lower T3 on day 1 (p< 0.001), however it increased significantly over 7 days (p=0.05) to become similar to that among survivors. TSH, T4 and T3 levels were negatively correlated with admission pSOFA, maximum pSOFA and PRISM-III scores (p< 0.05). Children with VIS >40 had significantly lower T3 levels on day 1 and 3 (p=0.008 and p=0.034 respectively). Time to shock reversal was negatively correlated with T3 levels on day 3 (rho=-0.43, p=0.008). Children requiring ventilation had lower thyroid hormones on day 1 and 3. Their levels were positively correlated with ventilator-free days and acute care area free days. Nutritional status did not affect thyroid profile. Conclusions: Children with more severe disease had lower levels of all thyroid hormones on day 1 and 3. Non-survivors had significantly lower thyroid hormones on day 1, which mostly failed to increase during initial 7 days as compare to survivors. Nutritional status did not affect thyroid profile.

Vasoactive inotropic score as a predictor of mortality in neonatal septic shock.

Although many improvements in neonatal care have been achieved, mortality rates for sepsis and septic shock in newborns are still high. The vasoactive inotropic score (VIS) was designed and studied to predict mortality in different settings. There are currently no data on the predictive ability of the VIS for mortality in newborn patients with septic shock. Patients with late-onset neonatal sepsis who required inotropes because of fluid-refractory septic shock during the study period were included in the study. Four distinct VISvalues were calculated for each septic shock episode after inotropic treatment had begun, that is, at the initiation of inotropic treatment and at 24 and 48 h after inotropic treatment had begun, and the highest VIS (VISmax) at any time after initiation of inotropic agents. The 98 episodes studied were divided into two groups according to the outcomes of their sepsis episodes as survivors (n = 39) or nonsurvivors (n = 59). The areas under the curve of the VIS values for the prediction of mortality were the VISmax (0.819, p < 0.001), followed by the VIS48 (0.802, p < 0.001), VIS24 (0.762, p = 0.001) and VIS0 (0.699, p = 0.015). Patients with a VISmax of greater than 20 had significantly higher odds of mortality (p < 0.001, β = 14.7, 95% confidence interval [4.7-45.9]). We found that the VISmax was an easy-to-use and helpful tool for predicting a poor outcome in neonatal sepsis. Physicians should be aware that the prognosis is poor for any newborn with a VIS of 20 or greater at any point after the onset of sepsis.

O046 / #741: SUPERIOR VENACAVAL OXYGEN SATURATION MONITORING BASED GOAL DIRECTED THERAPY VS STANDARD CARE IN CHILDREN WITH SEPTIC SHOCK: AN OPEN LABEL RANDOMIZED CONTROL TRIAL

Aims & Objectives: Early goal directed therapy improves septic shock outcomes, however data from India is scarce. We studied feasibility of achieving and maintaining ScvO2 based goal directed therapy (GDT) versus prevalent practice Methods:Design: Randomized Control Trial Setting: Tertiary care teaching institute Participants: Children (6 month-12 years) with fluid refractory septic shock. Inotrope at arrival, chronic illnesses and contraindications for central line were exclusions Interventions: GDT group (n=46) received fluids, inotrope and packed red cells targeting ScvO2 of >70%. Standard therapy (ST) (n=46) group received usual care as per prevalent unit practice Main Outcome Measures: Mortality; shock endpoints and ScvO2 trend Results: Baseline characteristics were comparable in the two groups. However, children with baseline ScvO2 <70% were more in GDT arm compared to ST arm [21/42(50%) vs 4/14(28%), p=0.22]. More children attained endpoints within 5-day intervention period in the ST group vs GDT group[31(67%) vs 24(52%) (p=0.13)]. Endpoints were attained earlier in GDT arm vs ST arm [median(IQR) 9 hrs (6,21) vs 12 hours (6,24) (p=0.42)]. Significantly more children died in the GDT arm [35(76.1%) vs 21(45.7%); p=0.03]. Figure 1 shows outcome of GDT patients based on their baseline and subsequent ScvO2.Conclusions: GDT patients were relatively sicker. ScvO2 monitoring helped in identifying children with lower baseline ScvO2 and those with inability to attain ScvO2 >70%. The latter ones had higher mortality. The median duration to attain endpoints in the studied clinical setting seems to be delayed compared to high income countries probably due to limitation of material and human resources.

Clinical and Laboratory Parameters Associated with Septic Myocardial Dysfunction in Children with Septic Shock.

The authors' objective was to determine the association of clinical and laboratory parameters at admission with septic myocardial dysfunction (SMD) in children with septic shock. A chart review of children aged 3 mo-17 y with fluid refractory septic shock who underwent echocardiography within 3h of admission was undertaken (2015-2017). Univariate followed by multivariate analysis was performed to identify factors associated with SMD. Of the 95 children fulfilling the inclusion criteria, SMD was diagnosed in 44 (46%) children. Children 'with SMD' had longer capillary refill time (CRT), increased lactate, lower platelet count, increased blood urea, and increased alanine aminotransferase (ALT) (p < 0.05 for all) compared to those 'without SMD'. On multivariate analysis, none of these were significant. The mortality rate was higher in those 'with SMD' than 'without SMD' [36% vs. 20% (p = 0.07)]. Prolonged CRT, increased lactate, lower platelet count, increased blood urea and elevated liver enzymes at admission may be associated with SMD in children with septic shock and may warrant early assessment of cardiac function.

Part 4: Pediatric Basic and Advanced Life Support 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

1. High-quality cardiopulmonary resuscitation (CPR) is the foundation of resuscitation. New data reaffirm the key components of high-quality CPR: providing adequate chest compression rate and depth, minimizing interruptions in CPR, allowing full chest recoil between compressions, and avoiding excessive ventilation. 2. A respiratory rate of 20 to 30 breaths per minute is new for infants and children who are (a) receiving CPR with an advanced airway in place or (b) receiving rescue breathing and have a pulse. 3. For patients with nonshockable rhythms, the earlier epinephrine is administered after CPR initiation, the more likely the patient is to survive. 4. Using a cuffed endotracheal tube decreases the need for endotracheal tube changes. 5. The routine use of cricoid pressure does not reduce the risk ofd regurgitation during bag-mask ventilation and may impede intubation success. 6. For out-of-hospital cardiac arrest, bag-mask ventilation results in the same resuscitation outcomes as advanced airway interventions such as endotracheal intubation. 7. Resuscitation does not end with return of spontaneous circulation (ROSC). Excellent post–cardiac arrest care is critically important to achieving the best patient outcomes. For children who do not regain consciousness after ROSC, this care includes targeted temperature management and continuous electroencephalography monitoring. The prevention and/or treatment of hypotension, hyperoxia or hypoxia, and hypercapnia or hypocapnia is important. 8. After discharge from the hospital, cardiac arrest survivors can have physical, cognitive, and emotional challenges and may need ongoing therapies and interventions. 9. Naloxone can reverse respiratory arrest due to opioid overdose, but there is no evidence that it benefits patients in cardiac arrest. 10. Fluid resuscitation in sepsis is based on patient response and requires frequent reassessment. Balanced crystalloid, unbalanced crystalloid, and colloid fluids are all acceptable for sepsis resuscitation. Epinephrine or norepinephrine infusions are used for fluid-refractory septic shock. More than 20 000 infants and children have a cardiac arrest per year in the …

Thiamine Status in Children with Septic Shock from a Developing Country: A Prospective Case-Control Study.

Mitochondrial dysfunction is central to sepsis-induced multi-organ dysfunction. Thiamine deficiency may contribute to mitochondrial dysfunction and thus high mortality. Study was planned to assess thiamine status in children with septic shock in comparison to healthy controls from a developing country and to study the effect of thiamine levels on its outcome. A prospective case-control study (April 2017 to May 2018) enrolling consecutive children with septic shock as 'cases' (n = 76), their healthy siblings (n = 51) and apparently healthy children from immunization clinic (n = 35) as 'controls'. Whole blood total thiamine (WBTT) level was measured on days 1, 10 and 1-month post-discharge. Outcome parameters were acute care area free days on days 14 and 28, and mortality. WBTT [nMol/l; median (interquartile range, IQR)] was significantly lower on day 1 in cases compared with sibling controls [23.1 (21.8-26.3) vs. 36.9 (33.6-40.5); p < 0.001]. It fell further on day 10 [20.8 (18.1-21.1); p < 0.02]. Levels rose significantly 1-month post-discharge [35.5 (31.2-36.6)] and became comparable to sibling controls (p = 0.4). Immunization clinic controls also had lower WBTT [42.3 (40.1-45.9)], but was significantly higher than sibling controls and cases at 1-month post-discharge (p < 0.001). Survivors and non-survivors of septic shock were similar. WBTT levels did not correlate with any of the severity indicators of septic shock or its outcomes. WBTT was significantly low in all children, and fell further during septic shock. Observed severe deficiency might have precluded any further association of thiamine levels with severity of septic shock and its outcome. Data obtained may inform trials on metabolic resuscitation in paediatric septic shock in developing countries. Lay summaryThiamine deficiency may contribute to high mortality in paediatric septic shock as thiamine is an essential factor for functioning of mitochondria, the powerhouse of the cells. This prospective case-control study was conducted to assess thiamine status in children with septic shock in comparison with healthy controls in a developing country. Consecutive children with fluid-refractory septic shock were enrolled as 'cases'. Their apparently healthy siblings, and apparently healthy children from immunization clinic, were enrolled as 'controls'. The whole blood total thiamine (WBTT) level was measured on days 1, 10 and 1 month after hospital discharge. Seventy-six children were enrolled as cases, 51 children as sibling controls and 35 children as immunization clinic controls. WBTT was significantly lower on day 1 in cases as compared with their sibling controls. It fell further on day 10. The level rose significantly after a month of discharge and became comparable to sibling controls. Immunization clinic controls also had lower WBTT but was significantly higher compared with sibling controls and cases at 1-month post-discharge. Survivors and non-survivors of septic shock had similar WBTT levels. Observed severe deficiency might have precluded any further association of thiamine levels with septic shock outcome.

Use of Inotropics by Peripheral Vascular Line in the First Hour of Treatment of Pediatric Septic Shock: Experience at an Emergency Department.

Mortality in pediatric septic shock remains unacceptably high. Delays in vasopressor administration have been associated with an increased risk of mortality. Current treatment guidelines suggest the use of a peripheral vascular line (PVL) for inotropic administration in fluid-refractory septic shock when a central vascular line is not already in place. The aim of this study was to report local adverse effects associated with inotropic drug administration through a PVL at a pediatric emergency department setting in the first hour of treatment of septic shock. A prospective, descriptive, observational cohort study of patients with septic shock requiring PVL inotropic administration was conducted at the pediatric emergency department of a tertiary care pediatric hospital. For the infusion and postplacement care of the PVL for vasoactive drugs, an institutional nursing protocol was used. We included 49 patients; 51% had an underlying disease. Eighty-four percent of the children included had a clinical "cold shock." The most frequently used vasoactive drug was epinephrine (72%). One patient presented with local complications. At our center, infusion of vasoactive drugs through a PVL was shown to be safe and allowed for adherence to the current guidelines for pediatric septic shock.

Vasopressin in Conjunction With Norepinephrine in Septic Shock: A Retrospective Cohort Study From a Low Middle-Income Country.

Objectives:Guidelines recommend use of norepinephrine as the first-line treatment for fluid-refractory septic shock and if septic shock persists vasopressin may be initiated. Since there are limited data from low middle-income countries with high disease burden of sepsis, we aimed to compare the outcomes of using vasopressin adjunct to norepinephrine in comparison with norepinephrine alone.Design:Retrospective cohort study.Setting:Aga Khan University Hospital, Karachi, Pakistan.Patients:Six-hundred fifty-three patients diagnosed with septic shock from January 2019 to December 2019, with 498 given norepinephrine only and 155 given norepinephrine-vasopressin combination.Interventions:None.Measurements and Main Results:Primary outcome was in-hospital mortality. Secondary outcomes were duration of vasopressor used, length of hospital stay, length of ICU stay, and days on ventilatory support. After adjustment by multivariable logistic regression, it was found that mortality was not significantly associated with the norepinephrine-vasopressin combination (adjusted odds ratio, 0.633 [95% CI, 0.370–1.081]). However, Sequential Organ Failure Assessment score at admission (1.100 [1.014–1.193]), lactate at admission (1.167 [1.109–1.227]), duration of vasopressor used (1.481 [1.316–1.666]), and level of care (3.025 [1.682–5.441]) were found to be independently associated with the adjunct usage of norepinephrine and vasopressin.Conclusions:The use of norepinephrine-vasopressin combination has remained debatable in literature. Our study showed that although there was no difference in mortality between the two groups, admission Sequential Organ Failure Assessment scores and admission lactate levels were found to be significantly higher in the norepinephrine-vasopressin group. Hence, physicians from Pakistan used the norepinephrine-vasopressin combination in resistant septic shock patients who were sicker to begin with. Furthermore, duration of vasopressor therapy and ICU admission were also significantly higher in the combination group. Considering the recent hyperinflation of vasopressors costs and that most healthcare expenditure for patients in Pakistan is out-of-pocket, this can consequently lead to unwarranted financial burden for patients and their families.

Clinical outcome of children with fluid-refractory septic shock treated with dopamine or epinephrine. A retrospective study at a pediatric emergency department in Argentina.

ObjectiveTo analyze the clinical outcome of children with fluid-refractory septic shock initially treated with dopamine or epinephrine.MethodsA retrospective cohort study was conducted at a pediatric emergency department of a tertiary hospital. Population: children admitted because of fluid-refractory septic shock. Clinical outcome was compared between two groups: Dopamine and Epinephrine. Variables evaluated were use of invasive mechanical ventilation, days of inotropic therapy, length of hospital stay, intensive care stay, and mortality. For numerical and categorical variables, we used measures of central tendency. They were compared by the Mann-Whitney U-test and the (2 test.ResultsWe included 118 patients. A total of 58.5% received dopamine and 41.5% received epinephrine. The rate of invasive mechanical ventilation was 38.8% for epinephrine versus 40.6% for dopamine (p = 0.84), with a median of 4 days for the Epinephrine Group and 5.5 for the Dopamine Group (p = 0.104). Median time of inotropic therapy was 2 days for both groups (p = 0.714). Median hospital stay was 11 and 13 days for the Epinephrine and Dopamine groups, respectively (p = 0.554), and median stay in intensive care was 4 days (0 - 81 days) in both groups (p = 0.748). Mortality was 5% for the Epinephrine Group versus 9% for the Dopamine Group (p = 0.64).ConclusionsAt our center, no differences in use of invasive mechanical ventilation, time of inotropic therapy, length of hospital stay, length of intensive care unit stay, or mortality were observed in children admitted to the pediatric emergency department with a diagnosis of fluid-refractory septic shock initially treated with dopamine versus epinephrine.

Respiratory variation of inferior vena cava diameter and central venous pressure in ventilated and non-ventilated children in fluid refractory septic shock: an observational study

Background: Ultrasound guided fluid assessment in management of septic shock has come up as an adjunct to the current gold standard Central Venous Pressure monitoring. This study was designed to observe the respiro-phasic variation of IVC diameter (RV-IVCD) in invasively mechanically ventilated and spontaneously breathing paediatric patients of fluid refractory septic shock.Methods: This was a prospective observational study done at Paediatric intensive Care Unit (PICU) in Paediatric ward of Jawaharlal Nehru Medical College and Hospital (JNMCH) from February 2016 to June 2017. 107 consecutive patients between 1 year to 16 years age who were in shock despite 40ml/kg of fluid administration were included. Inferior Vena Cava (IVC) diameters were measured at end-expiration and end inspiration and the IVC collapsibility index was calculated. Simultaneously Central Venous Pressure (CVP) was recorded. Both values were obtained in ventilated and non-ventilated patients. Data was analysed to determine to look for the profile of RV-IVCD and CVP in ventilated and non-ventilated cases.Results: Out of 107 patients, 91 were on invasive mechanical ventilation and 16 patients were spontaneously breathing. There was a strong negative correlation between central venous pressure (CVP) and inferior vena cava collapsibility (RV-IVCD) in both spontaneously breathing (-0.810) and mechanically ventilated patients (-0.700). Negative correlation was significant in both study groups in CVP &lt;8 mmHg and only in spontaneously breathing patients in CVP 8-12 mmHg range. IVC collapsibility showed a decreasing trend with rising CVP in both spontaneously breathing and mechanically ventilated patients.Conclusion: Ultrasonography guided IVCCI appears to be a valuable index in assessing fluid status in both spontaneously breathing and mechanically ventilated septic shock patients. However, more data is required from the paediatric population so as to define it as standard of practice.

First line vasoactive therapy after fluid resuscitation in pediatric septic shock – Dopamine, Adrenaline or Noradrenaline?

Severe sepsis and septic shock are the leading cause of morbidity and mortality in children all over the world, in both developed and developing nations. Surviving Sepsis Guidelines 2016 have recommended norepinephrine as the first choice of vasoactive agent in adult septic shock flowed by adrenaline or vasopressin in cases who do not respond to norepinephrine. In this article we have reviewed the literature and compared noradrenaline and adrenaline as first line vasoactive drug in children with fluid refractory septic shock. We have also discussed the change in the paradigm -use of dopamine as alternative instead of first line vasoactive agent

Prehospital Care and Emergency Department Door-to-Antibiotic Time in Sepsis.

Early antibiotics improve outcomes for patients with sepsis. Factors influencing antibiotic timing in emergency department (ED) sepsis remain unclear. Determine the relationship between prehospital level of care of patients with sepsis and ED door-to-antibiotic time. This retrospective cohort study comprised patients admitted from the community to an academic ED June 2009 to February 2015 with fluid-refractory sepsis or septic shock. Transfer patients and those whose antibiotics began before ED arrival or after ED discharge were excluded. We used multivariable regression to evaluate the association between the time from ED arrival to antibiotic initiation and prehospital level of care, defined as the highest level of emergency medical services received: none, basic life support (BLS) ambulance, or advanced life support (ALS) ambulance. We measured variation in this association when hypotension was or was not present by ED arrival. Among 361 community-dwelling patients with sepsis, the level of prehospital care correlated with illness severity. ALS-treated patients received antibiotics faster than patients who did not receive prehospital care (median, 103 [interquartile range, 75 to 135] vs. 144 [98 to 251] minutes, respectively) or BLS-only patients (168 [100-250] minutes; P < 0.001 for each pairwise comparison with ALS). This pattern persisted after multivariable adjustment, where ALS care (-43 min; 95% confidence interval [CI], -84 to -2; P = 0.033) but not BLS-only care (-4 min; 95% CI, -41 to +34; P = 0.97) was associated with less antibiotic delay compared with no prehospital care. ALS-treated patients more frequently received antibiotics within 3 hours of ED arrival (91%) compared with walk-in patients (62%; adjusted odds ratio, 3.11; 95% CI, 1.20 to 8.03; P = 0.015) or BLS-treated patients (56%; adjusted odds ratio, 4.51; 95% CI, 1.89 to 11.35; P < 0.001). ALS-treated patients started antibiotics faster than walk-in patients in the absence of hypotension by ED arrival (-41 min; 95% CI, -110 to -13; P = 0.009) but not when hypotension was present (+25 min; 95% CI, -43 to +92; P = 0.66). Prehospital ALS but not BLS-only care was associated with faster antibiotic initiation for patients with sepsis without hypotension. Process redesign for non-ALS patients may improve antibiotic timeliness for ED sepsis.

Oxygen Delivery and Oxygen Consumption in Pediatric Fluid Refractory Septic Shock During the First 42 h of Therapy and Their Relationship to 28-Day Outcome.

Background: In septic shock, both oxygen delivery (DO2) and oxygen consumption (VO2) are dysfunctional. The current therapeutic regimens are geared to normalize global oxygen delivery (DO2) to tissues via goal directed therapies but mortality remains high at 10–20%.Methods: We studied cardiac index (CI), systemic vascular resistance index (SVRI), central venous oxygen saturation (ScvO2), central venous pressure (CVP), peripheral oxygen saturation (SpO2), mean blood pressure (MBP), body temperature, blood lactate, base excess and hemoglobin concentration (Hb) in a cohort of children admitted in “fluid-refractory” severe septic shock to pediatric intensive care, over 4.5-years. We calculated their 6 h global oxygen delivery (DO2) and global oxygen consumption (VO2) over the first 42 h and looked at factors associated with VO2/DO2 ratio (i.e., global oxygen extraction, gO2ER) and 28-day mortality.Results: Sixty-two children mean age (SD) 7.19 (5.44) years were studied. Fifty-seven (93%) children were sedated and mechanically ventilated and all received adrenaline or noradrenaline or both and added milrinone in 6 (9.6%). At 28 days, 9 (14.5%) were dead. The global oxygen extraction ratio (gO2ER) was consistently lower amongst the survivors and independently predicted mortality (ROC AUC = 0.75). A lactate level of 4 mmol/l or above, when associated with a concurrent metabolic acidosis predicted mortality with a sensitivity of 100% (95% CI 90.5–100) and a specificity of 67.7% (95% CI 62.2–72.9). A gO2ER of 0.48 or above on admission to the PICU was associated with death with a 66.7% sensitivity (95%CI 29.9–92.5) and 90.5% specificity (95%CI 79.3–96.8). A global O2ER of >0.48 combined with a concurrent blood lactate >4.0 mmol/l at any time within the first 42 h of therapy predicted death with a sensitivity of 63.9% (95% CI, 46.2–79.1) and specificity of 97.8% (95% CI, 95.7–99.0). A radar plot identified MBP-CVP difference, and CI as additional goals of therapy that may offer a survival benefit.Conclusions: Global O2ER of >0.48 with a concurrent blood lactate >4.0 mmol/l in children with metabolic acidosis was an independent factor associated with death in fluid resistant septic shock. Trends of gO2ER seem useful to recognize survivors and non-survivors early in the illness.

The glucocorticoid receptor and cortisol levels in pediatric septic shock

BackgroundThere is controversy around the prescription of adjunct corticosteroids in patients with fluid-refractory septic shock, and studies provide mixed results, showing benefit, no benefit, and harm. Traditional means for evaluating whether a patient receives corticosteroids relied on anecdotal experience or measurement of serum cortisol production following stimulation. We set out to measure both serum cortisol and the intracellular signaling receptor for cortisol, the glucocorticoid receptor (GCR), in this group of patients.MethodsWe enrolled pediatric patients admitted to the pediatric intensive care unit with a diagnosis of systemic inflammatory response syndrome (SIRS), sepsis, or septic shock as well as healthy controls. We measured serum cortisol concentration and GCR expression by flow cytometry in peripheral blood leukocytes on the day of admission and day 3.ResultsWe enrolled 164 patients for analysis. There was no difference between GCR expression comparing SIRS, sepsis, and septic shock. When all patients with septic shock were compared, those patients with a complicated course, defined as two or more organ failures at day 7 or death by day 28, had lower expression of GCR in all peripheral blood leukocytes. Further analysis suggested that patients with the combination of low GCR and high serum cortisol had higher rates of complicated course (75%) compared with the other three possible combinations of GCR and cortisol levels: low GCR and low cortisol (33%), high GCR and high cortisol (33%), and high GCR and low cortisol (13%; P <0.05).ConclusionsWe show that decreased expression of the GCR correlated with poor outcome from septic shock, particularly in those patients with high serum cortisol. This is consistent with findings from transcriptional studies showing that downregulation of GCR signaling genes portends worse outcome.

Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock.

There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock. Prospective cohort study. PICU of a tertiary care hospital. All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014. Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury. Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52-6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3-99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury. Manifestations of sepsis-associated acute kidney injury often occur early after PICU admission and is associated with increased morbidity and mortality. There is a need to develop a predictive model in septic shock which could facilitate early detection of acute kidney injury.