Article

Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock

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Abstract

Objectives: The primary outcome was to compare the effects of dopamine or epinephrine in severe sepsis on 28-day mortality; secondary outcomes were the rate of healthcare-associated infection, the need for other vasoactive drugs, and the multiple organ dysfunction score. Design: Double-blind, prospective, randomized controlled trial from February 1, 2009, to July 31, 2013. Setting: PICU, Hospital Universitário da Universidade de São Paulo, Brazil. Patients: Consecutive children who are 1 month to 15 years old and met the clinical criteria for fluid-refractory septic shock. Exclusions were receiving vasoactive drug(s) prior to hospital admission, having known cardiac disease, having already participated in the trial during the same hospital stay, refusing to participate, or having do-not-resuscitate orders. Interventions: Patients were randomly assigned to receive either dopamine (5-10 μg/kg/min) or epinephrine (0.1-0.3 μg/kg/min) through a peripheral or intraosseous line. Patients not reaching predefined stabilization criteria after the maximum dose were classified as treatment failure, at which point the attending physician gradually stopped the study drug and started another catecholamine. Measurements and main results: Physiologic and laboratory data were recorded. Baseline characteristics were described as proportions and mean (± SD) and compared using appropriate statistical tests. Multiple regression analysis was performed, and statistical significance was defined as a p value of less than 0.05. Baseline characteristics and therapeutic interventions for the 120 children enrolled (63, dopamine; 57, epinephrine) were similar. There were 17 deaths (14.2%): 13 (20.6%) in the dopamine group and four (7%) in the epinephrine group (p = 0.033). Dopamine was associated with death (odds ratio, 6.5; 95% CI, 1.1-37.8; p = 0.037) and healthcare-associated infection (odds ratio, 67.7; 95% CI, 5.0-910.8; p = 0.001). The use of epinephrine was associated with a survival odds ratio of 6.49. Conclusions: Dopamine was associated with an increased risk of death and healthcare-associated infection. Early administration of peripheral or intraosseous epinephrine was associated with increased survival in this population. Limitations should be observed while interpreting these results.

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... After initial screening, a total of 45 studies were retrieved as complete articles. After exclusion of further 33 trials that did not met inclusion criteria, a total of 12 studies randomizing 1,227 patients were included in the analysis ( Fig. 1) (10,11,14,(22)(23)(24)(25)(26)(27)(28)(29)(30). Details of major exclusions and reason for exclusion are provided in the Supplementary Appendix (Supplemental Digital Content 1, http://links.lww.com/CCM/F177). ...
... The majority of trials were performed in septic shock (seven trials, 644 patients) (11, 23-25, 27-29) followed by cardiogenic shock (two trials, 87 patients) (10,22), cardiac surgery (26), mixed ICU patients (14), and major noncardiac surgery (30) (one trial each) settings. Two trials were performed in the pediatric setting (180 patients) (25,29). ...
... p = 0.27; I 2 = 0%; removing Annane et al (11) and highest RR = 0.99; 95% CI, 0.85-1.14; p = 0.87; I 2 = 0%; removing Ventura et al [29]). Selecting only low risk of bias trials did not change magnitude and direction of the results (98/190 [51.6%] in the epinephrine group vs 103/200 [51.6%] in the control group; RR = 1.00; 95% CI, 0.83-1.21; ...
Article
Objectives: Epinephrine is frequently used as an inotropic and vasopressor agent in critically ill patients requiring hemodynamic support. Data from observational trials suggested that epinephrine use is associated with a worse outcome as compared with other adrenergic and nonadrenergic vasoactive drugs. We performed a systematic review and meta-analysis of randomized controlled trials to investigate the effect of epinephrine administration on outcome of critically ill patients. Data sources: PubMed, EMBASE, and Cochrane central register were searched by two independent investigators up to March 2019. Study selection: Inclusion criteria were: administration of epinephrine as IV continuous infusion, patients admitted to an ICU or undergoing major surgery, and randomized controlled trials. Studies on epinephrine administration as bolus (e.g., during cardiopulmonary resuscitation), were excluded. The primary outcome was mortality at the longest follow-up available. Data extraction: Two independent investigators examined and extracted data from eligible trials. Data synthesis: A total of 5,249 studies were assessed, with a total of 12 studies (1,227 patients) finally included in the meta-analysis. The majority of the trials were performed in the setting of septic shock, and the most frequent comparator was a combination of norepinephrine plus dobutamine. We found no difference in all-cause mortality at the longest follow-up available (197/579 [34.0%] in the epinephrine group vs 219/648 [33.8%] in the control group; risk ratio = 0.95; 95% CI, 0.82-1.10; p = 0.49; I = 0%). No differences in the need for renal replacement therapy, occurrence rate of myocardial ischemia, occurrence rate of arrhythmias, and length of ICU stay were observed. Conclusions: Current randomized evidence showed that continuous IV administration of epinephrine as inotropic/vasopressor agent is not associated with a worse outcome in critically ill patients.
... Another study showed dopamine suppressed macrophage activation and Tlymphocyte function [4]. Clinical studies with humans have found a higher rate of infections in children with sepsis with dopamine use than with epinephrine use [6]. Furthermore, use of dopamine was reported to be a risk factor for infection in children after cardiac surgery [7]. ...
... However, dopamine is not usually recommended as a first line inotrope in adult and pediatric critical care fields [16]. In addition, the association between dopamine and infection has not been assessed in extremely preterm infants, although it has been assessed in infants with sepsis and after cardiac surgery [6,7]. Although dopamine can affect the production of both inflammatory and antiinflammatory mediators [3], our study suggested that a large amount of dopamine may suppress the immune system and contribute to development of many types of infections in extremely preterm infants. ...
... ] mg/kg; p = 0.001), use of systemic steroids (n = 68, 67.3% vs n = 65, 41.7%; p < 0.001), and CRIB score(10 [7-13] vs 7[4][5][6][7][8][9][10][11]; p < 0.001) were significantly higher in the infection group than in the non-infection group.Tables 2 (total amount model)and 3 (duration model) show the results of the Cox proportional hazards regression analysis for infection. Total amount and duration of dopamine or dobutamine were analyzed with different models because they had strong correlation (dopamine, the correlation coefficient was 0.934; dobutamine, 0.918 by Spearman's rank correlation test). ...
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This study aimed to assess the effect of dopamine on the development of infections after birth in extremely preterm infants. We retrospectively identified 258 extremely preterm infants (born at < 28 gestational weeks) between July 2009 and December 2018 in a tertiary neonatal intensive care unit (NICU). We extracted data on potential risk factors for infection, total amount of dopamine, and infection history during NICU stay for each infant. We compared the infection group with the non-infection group, and used the Cox proportional hazard regression analysis to identify risk factors for infection during NICU stay. After adjustment for all potential risk factors, factors that significantly affected development of infection were gestational age (hazard ratio [HR], 0.70; 95% confidence interval [CI] 0.55–0.89; p = 0.004) and total amount of dopamine (HR, 1.04; 95% CI 1.02–1.07; p = 0.002). The receiver operating characteristic curve of total amount of dopamine for infection suggested that total amount of dopamine greater than 7.271 mg/kg predicted infection development with 80.4% sensitivity and 41.7% specificity. Conclusion: A large amount of dopamine can increase infections in extremely preterm infants. We should avoid using a large amount of dopamine and remain aware of the potential development of infections in extremely preterm infants.What is Known: • Inotropes are often used for extremely preterm infants and dopamine is the most commonly used inotrope. • However, it is suggested that dopamine affects the immune system and related infections. What is New: • This is the first study of the association between the amount of dopamine and infection in extremely preterm infants. • We should avoid using a large amount of dopamine in extremely preterm infants.
... However, case series and case reports are at high risk for reporting bias [8], therefore the rate of adverse events associated with PIV vasopressor administration could not be estimated. In addition, larger cohort studies examining adverse events associated with PIV vasopressor administration in adults [2,3,[9][10][11] have since been published as well as multiple recent studies in the child population [12][13][14]. We used systematic review and meta-analysis methodology to examine the incidence of adverse events associated with vasopressor administration through PIVs in patients of any age cared for in any acute care setting. ...
... Detailed full text review of 1,033 studies (kappa = 0.92) resulted in 23 studies (all written in the English language) included in the final systematic review [2,3,[9][10][11][12][13][14][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37], and 15 of those in the meta-analysis [2,3,[9][10][11][12][13][30][31][32][33][34][35][36][37]. Studies excluded after full text review commonly did not report the route of vasopressor administration (n = 465, 46%), or did not employ the desired study design (n = 214, 21%). ...
... Studies excluded after full text review commonly did not report the route of vasopressor administration (n = 465, 46%), or did not employ the desired study design (n = 214, 21%). Of the eight articles excluded from the meta-analysis, the most common deficiency related to not clearly reporting the number of patients that received vasopressors through a PIV (n = 5) [14,[25][26][27][28]. Other reasons for exclusion from the meta-analysis were failure to clearly report the numbers of adverse events (n = 2) [23,29], and outdated PIV insertion technique (n = 1) [24]. ...
Article
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Background It is unclear whether vasopressors can be safely administered through a peripheral intravenous (PIV). Systematic review and meta-analysis methodology was used to examine the incidence of local anatomic adverse events associated with PIV vasopressor administration in patients of any age cared for in any acute care environment. Methods MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of controlled trials, and the Database of Abstracts of Reviews of Effects were searched without restriction from inception to October 2019. References of included studies and related reviews, as well as relevant conference proceedings were also searched. Studies were included if they were: (1) cohort, quasi-experimental, or randomized controlled trial study design; (2) conducted in humans of any age or clinical setting; and (3) reported on local anatomic adverse events associated with PIV vasopressor administration. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials or the Joanna Briggs Institute checklist for prevalence studies where appropriate. Incidence estimates were pooled using random effects meta-analysis. Subgroup analyses were used to explore sources of heterogeneity. Results Twenty-three studies were included in the systematic review, of which 16 and 7 described adults and children, respectively. Meta-analysis from 11 adult studies including 16,055 patients demonstrated a pooled incidence proportion of adverse events associated with PIV vasopressor administration as 1.8% (95% CI 0.1–4.8%, I ² = 93.7%). In children, meta-analysis from four studies and 388 patients demonstrated a pooled incidence proportion of adverse events as 3.3% (95% CI 0.0–10.1%, I ² = 82.4%). Subgroup analyses did not detect any statistically significant effects associated with stratification based on differences in clinical location, risk of bias or design between studies, PIV location and size, or vasopressor type or duration. Most studies had high or some concern for risk of bias. Conclusion The incidence of adverse events associated with PIV vasopressor administration is low. Additional research is required to examine the effects of PIV location and size, vasopressor type and dose, and patient characteristics on the safety of PIV vasopressor administration.
... Recently, several studies have investigated the efficacy of dopamine versus epinephrine for pediatric or neonatal septic shock, but the results are conflicting [15][16][17]. This systematic review and meta-analysis of RCTs aims to assess the efficacy and safety of dopamine versus epinephrine for pediatric or neonatal septic shock. ...
... Literature search, study characteristics and quality assessment Figure 1 shows the detail flowchart of the search and selection results. 234 potentially relevant articles are identified initially and three RCTs are finally included in the meta-analysis [15][16][17]. ...
... The methods of dopamine or epinephrine are various in each RCT. Two studies involve pediatric septic shock [16,17], and the remaining study involves neonatal septic shock [15]. ...
Article
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Introduction: The efficacy of dopamine versus epinephrine for pediatric or neonatal septic shock remains controversial. We conduct a meta-analysis to explore the influence of dopamine versus epinephrine on shock reversal for pediatric or neonatal septic shock. Methods: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through July 2019 for randomized controlled trials (RCTs) assessing the efficacy and safety of dopamine versus epinephrine for pediatric or neonatal septic shock. Results: Three RCTs are included in the meta-analysis. Overall for pediatric or neonatal septic shock, dopamine and epinephrine reveal comparable shock reversal within 1 h (risk ratios (RR) = 0.61; 95% CI = 0.16 to 2.31; P = 0.47), mortality (RR = 1.16; 95% CI = 0.87 to 1.55; P = 0.30), heart rate (standard mean differences (SMD) = 0.03; 95% CI = -0.28 to 0.34; P = 0.85), systolic blood pressure (SMD = -0.18; 95% CI = -0.69 to 0.33; P = 0.49), mean arterial pressure (SMD = -0.15; 95% CI = -1.64 to 1.34; P = 0.84) and adverse events (RR = 1.00; 95% CI = 0.94 to 1.07; P = 0.91). Conclusions: Dopamine and epinephrine show the comparable efficacy for the treatment of pediatric or neonatal septic shock.
... 38,[64][65][66] Dopamina: de utilidad en situaciones de disminución moderada de la contractilidad y de las resistencias vasculares sistémicas (RVS), como sepsis, "shock" séptico resistente a volumen y estabilización posreanimación; sin embargo, nuevas evidencias y recomendaciones ubican como droga de primera elección frente al "shock" refractario a volumen la adrenalina. [67][68][69][70] Adrenalina: de elección en el tratamiento del "shock" séptico refractario a volumen, el PCR y el "shock" anafiláctico. [67][68][69][70] En dosis baja, en síndromes de bajo gasto cardíaco (BGC), sin respuesta a inodilatadores. ...
... [67][68][69][70] Adrenalina: de elección en el tratamiento del "shock" séptico refractario a volumen, el PCR y el "shock" anafiláctico. [67][68][69][70] En dosis baja, en síndromes de bajo gasto cardíaco (BGC), sin respuesta a inodilatadores. En dosis alta, en síndromes de bajo gasto con resistencias vasculares bajas. ...
... Dopamin uzun yıllar pediyatrik şokta ilk tercih edilen ilaç iken hem yetişkinlerde hem de çocuklarda yapılan çalışmalarla bu tercihten vazgeçilmiştir. [27][28][29] Yetişkinlerde dopamin ile norepinefrin karşılaştırıldığında, dopaminin kullanımı artmış mortalite ve aritmi oluşumu ile ilişkili bu-lunmuştır. 27 Son dönemlerde yapılan iki pediatrik çalışmada septik şokta dopamin ile epinefrin (adrenalin) kullanımı randomize edilmiştir. ...
... Her iki grupta SVK yerleştirilinceye kadar vazoaktif ilaçlar periferik IV yoldan verilmiştir. 28 Diğer çalışmada mortalite açısından bir fark gösterilememesine rağmen, epinefrin grubundaki çocukların daha hızlı şok tablosundan çıktığı ve daha az organ disfonksiyonu olduğu gösterilmiştir. 29 Amerikan yoğun bakım derneği kılavuzları, sıvıya dirençli soğuk şokta epinefrini birinci basamak tedavi olarak epinefrine ulaşılamadığı durumlarda ise dopamini (5-10 mcg/kg/dk) önerir. ...
Chapter
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Şok dolaşım sistemindeki yetersizlik sonucu dokuların gereksinimi olan oksijenin ve diğer besin maddelerinin karşılanamaması durumudur. Çocukluk yaş grubunda önemli mortalite ve morbidite nedenidir. Şok 4 gruba ayrılır; hipovolemik, distribütif, kardiyojenik ve obstrüktif. Fizik muayene, tıbbı özgeçmiş ve vital bulgulardaki anormalliklere bakılarak şokun erken tanınması sağlanabilir. Erken ve agresif tedavi organ disfonksiyonunu iyileştirir, morbidite ve mortaliteyi azaltır.
... La dopamina se asocia a mayor mortalidad en comparación con la adrenalina y la noradrenalina, y se la reserva como alternativa de segunda línea. [52][53][54][55][56] Otras drogas vasoactivas pueden incorporarse buscando efectos hemodinámicos concretos: inotrópicos, como milrinona para mejorar la contractilidad, o vasopresores, como vasopresina ante una vasodilatación no resuelta por la noradrenalina (Tablas 2 y 3). ...
Article
In 2016, the Surviving Sepsis Campaign and the National Institute for Health and Care Excellence (NICE) developed clinical practice guidelines for the management of pediatric septic shock. In 2017, the American College of Critical Care Medicine (ACCM) updated its recommendations for hemodynamic support of pediatric shock. Recognizing septic shock is critical, as well as an optimal, time-sensitive treatment. An adequate consultation with a pediatric specialist and/or a timely referral to a facility with a higher level of care are also critical for an appropriate outcome in the management of this condition. Here we analyze the bundles used in the management of these patients, which are essential to improve the quality of care. Sociedad Argentina de Pediatría.
... The second study 40 was a double-blind RCT that evaluated 120 children with refractory septic shock (despite the administration of 40 mL/kg of fluid). Randomization was to either dopamine or epinephrine, with the primary outcome of 28-day mortality and the secondary outcome of healthcare-associated infection. ...
Article
This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for pediatric life support is based on the most extensive evidence evaluation ever performed by the Pediatric Life Support Task Force. Three types of evidence evaluation were used in this review: systematic reviews, scoping reviews, and evidence updates. Per agreement with the evidence evaluation recommendations of the International Liaison Committee on Resuscitation, only systematic reviews could result in a new or revised treatment recommendation. Systematic reviews performed for this 2020 CoSTR for pediatric life support included the topics of sequencing of airway-breaths-compressions versus compressions-airway-breaths in the delivery of pediatric basic life support, the initial timing and dose intervals for epinephrine administration during resuscitation, and the targets for oxygen and carbon dioxide levels in pediatric patients after return of spontaneous circulation. The most controversial topics included the initial timing and dose intervals of epinephrine administration (new treatment recommendations were made) and the administration of fluid for infants and children with septic shock (this latter topic was evaluated by evidence update). All evidence reviews identified the paucity of pediatric data and the need for more research involving resuscitation of infants and children.
... Septic shock refers to sepsis with cardiovascular dysfunction. 13 An empyema refers to a pleural effusion with the macroscopic presence of pus, a positive Gram stain or culture of pleural fluid. ARDS was defined according to modified Berlin definition criteria. ...
Article
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Background/purpose: Despite the high prevalence of Mycoplasma pneumoniae infections, reports on severe life-threatening M. pneumoniae pneumonia (MPP) in children are limited. Methods: We retrospectively enrolled pediatric patients with PCR-positive MPP requiring ICU admission in a children's hospital in Taipei, Taiwan from Jun 2010 to October 2019. Clinical manifestations and laboratory data of severe MPP were analyzed. Macrolide susceptibility was determined by genotyping, and its relationship with clinical manifestations was also analyzed. Results: Approximately 5% (34/658) children hospitalized for MPP required ICU admission. Compared with non-ICU cases (n = 291), ICU cases (n = 34) were associated with more underlying conditions, more pleural effusion, longer fever duration, longer hospital stay, the requirement of second-line antibiotic treatment, and delayed effective and second-line antibiotic treatment. Macrolide resistance was similar in ICU and non-ICU groups (53% vs 53%; p = 0.986). In severe MPP, patients requiring endotracheal intubation were associated with more septic shock, empyema, ARDS, prolonged fever after effective antibiotic treatment, delayed second-line and effective antibiotic treatment. In 18 of the 22 patients with pleural fluid analysis, the pleural effusion was alkaline (pH > 7.7) and lymphocyte-predominant. Conclusion: M. pneumoniae infection can cause severe life-threatening pneumonia in children. Delayed effective and second-line antibiotic treatments are associated with severe life-threatening MPP.
... Epinephrine has been compared with dopamine in two RCTs in children with fluid-resistant septic shock. 159,160 Across both studies, epinephrine was associated with a lower risk of mortality (RR: 0.63; 95% CI: 0.40-0.99) and more organ failure-free days among survivors by day 28. ...
Article
After fluid administration for vasodilatory shock, vasopressors are commonly infused. Causes of vasodilatory shock include septic shock, post-cardiovascular surgery, post-acute myocardial infarction, postsurgery, other causes of an intense systemic inflammatory response, and drug -associated anaphylaxis. Therapeutic vasopressors are hormones that activate receptors—adrenergic: α1, α2, β1, β2; angiotensin II: AG1, AG2; vasopressin: AVPR1a, AVPR1B, AVPR2; dopamine: DA1, DA2. Vasopressor choice and dose vary widely because of patient and physician practice heterogeneity. Vasopressor adverse effects are excessive vasoconstriction causing organ ischemia/infarction, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. To date, no randomized controlled trial (RCT) of vasopressors has shown a decreased 28-day mortality rate. There is a need for evidence regarding alternative vasopressors as first-line vasopressors. We emphasize that vasopressors should be administered simultaneously with fluid replacement to prevent and decrease duration of hypotension in shock with vasodilation. Norepinephrine is the first-choice vasopressor in septic and vasodilatory shock. Interventions that decrease norepinephrine dose (vasopressin, angiotensin II) have not decreased 28-day mortality significantly. In patients not responsive to norepinephrine, vasopressin or epinephrine may be added. Angiotensin II may be useful for rapid resuscitation of profoundly hypotensive patients. Inotropic agent(s) (e.g., dobutamine) may be needed if vasopressors decrease ventricular contractility. Dopamine has fallen to almost no-use recommendation because of adverse effects; angiotensin II is available clinically; there are potent vasopressors with scant literature (e.g., methylene blue); and the novel V1a agonist selepressin missed on its pivotal RCT primary outcome. In pediatric septic shock, vasopressors, epinephrine, and norepinephrine are recommended equally because there is no clear evidence that supports the use of one vasoactive agent. Dopamine is recommended when epinephrine or norepinephrine is not available. New strategies include perhaps patients will be started on several vasopressors with complementary mechanisms of action, patients may be selected for particular vasopressors according to predictive biomarkers, and novel vasopressors may emerge with fewer adverse effects.
... In pediatric trials, epinephrine has been shown to be superior to dopamine with faster resolution of shock and lower mortality. 25,26 However, in neonatal trials, epinephrine and dopamine were comparable. 27,28 However, epinephrine was associated with more metabolic disturbances such as hyperglycemia and lactic acidosis. ...
Article
In persistent pulmonary hypertension of the newborn (PPHN), the ratio of pulmonary vascular resistance to systemic vascular resistance is increased. Extrapulmonary shunts (patent ductus arteriosus and patent foramen value) allow for right-to-left shunting and hypoxaemia. Systemic hypotension can occur in newborns with PPHN due to variety of reasons, such as enhanced peripheral vasodilation, impaired left ventricular function and decreased preload. Systemic hypotension can lead to end organ injury from poor perfusion and hypoxaemia in the newborn with PPHN. Thus, it must be managed swiftly. However, not all newborns with PPHN and systemic hypotension can be managed the same way. Individualised approach based on physiology and echocardiographic findings are necessary to improve perfusion to essential organs. Here we present a review of the physiology and mechanisms of systemic hypotension in PPHN, which can then guide treatment.
... The current study used dopamine as the first-line vasoactive-inotropic agents before 2018 based on the 2008 Surviving Sepsis Campaign International Guidelines [28]. In recent years, two randomized control trials demonstrated that epinephrine may be better than dopamine as the firstline vasoactive-inotropic agents in treating pediatric septic shock [29,30]. But these two studies did not analyze the pathophysiology to explain why epinephrine was better than dopamine in pediatric septic shock. ...
Article
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Persistent catecholamine-resistant shock in children causes severe morbidity and mortality. We aimed to analyze the association between hemodynamics and serum lactate at different time points and 28-day mortality in children with persistent catecholamine-resistant shock. Methods. Twenty-six children with persistent catecholamine-resistant shock were enrolled, and their hemodynamics were monitored using the pulse index continuous cardiac output. Serial cardiac index (CI), systemic vascular resistant index (SVRI), and vasoactive-inotropic score (VIS) were analyzed for the first 24 hours. Associations between hemodynamics, serum lactate, and 28-day mortality were analyzed. Results. The 28-day mortality rate was 53.8%. SVRI and VIS were independent predictors of 28-day mortality. The mortality group had lower serial SVRI and higher VIS than the survival group (p
... A 2020 ILCOR scoping review (PLS 1604) included two RCTs but did not find sufficient evidence to suggest a change in recommendation. 143,339,340 Both RCTs compared adrenaline and dopamine in paediatric septic patients with fluid-refractory shock. Both have several limitations making their usage for clinical guidelines development difficult. ...
Article
These European Resuscitation Council Paediatric Life Support (PLS) guidelines, are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidelines on the management of critically ill infants and children, before, during and after cardiac arrest.
... There are no studies to compare the effects of epinephrine and norepinephrine, but early administration of epinephrine was associated with increased survival when compared with dopamine. 12,64 Dopamine stimulates both dopaminergic and adrenergic receptors. The haemodynamic effect is dose dependent. ...
Article
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Background: Septic shock is a common critical illness associated with high morbidity and mortality in children. This article provides an updated narrative review on the management of septic shock in paediatric practice. Methods: A PubMed search was performed using the following Medical Subject Headings: “sepsis”, “septic shock” and “systemic inflammatory response syndrome”. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies and reviews. The search was limited to the English literature and specific to children. Results: Septic shock is associated with high mortality and morbidity. The outcome can be improved if the diagnosis is made promptly and treatment initiated without delay. Early treatment with antimicrobial therapy, fluid therapy and vasoactive medications, and rapid recognition of the source of sepsis and control are the key recommendations from paediatric sepsis management guidelines. Conclusion: Most of the current paediatric sepsis guideline recommendations are based on the adult population; therefore, the research gaps in paediatric sepsis management should be addressed.
... There was no difference in the adverse event rate (16.1% versus 13.8%, P=0.8) and no difference in mortality, although this study was not powered for mortality. The second study 40 was a double-blind RCT that evaluated 120 children with refractory septic shock (despite the administration of 40 mL/kg of fluid). Randomization was to either dopamine or epinephrine, with the primary outcome of 28-day mortality and the secondary outcome of healthcare-associated infection. ...
Article
Full-text available
This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for pediatric life support is based on the most extensive evidence evaluation ever performed by the Pediatric Life Support Task Force. Three types of evidence evaluation were used in this review: systematic reviews, scoping reviews, and evidence updates. Per agreement with the evidence evaluation recommendations of the International Liaison Committee on Resuscitation, only systematic reviews could result in a new or revised treatment recommendation. Systematic reviews performed for this 2020 CoSTR for pediatric life support included the topics of sequencing of airway-breaths-compressions versus compressions-airway-breaths in the delivery of pediatric basic life support, the initial timing and dose intervals for epinephrine administration during resuscitation, and the targets for oxygen and carbon dioxide levels in pediatric patients after return of spontaneous circulation. The most controversial topics included the initial timing and dose intervals of epinephrine administration (new treatment recommendations were made) and the administration of fluid for infants and children with septic shock (this latter topic was evaluated by evidence update). All evidence reviews identified the paucity of pediatric data and the need for more research involving resuscitation of infants and children.
... Vasopressor selection is often debated, but inotropic support with epinephrine is a reasonable first choice. 9 Pediatric POCUS is an emerging modality that physicians are becoming more comfortable with implementing in their practice. Visualization with ultrasound is a fast and easy tool that can be used upon arrival before any laboratory tests have been released. ...
Article
Introduction: Pediatric myocarditis is a commonly missed diagnosis in the pediatric emergency department (ED) with high morbidity and mortality. The presentation of cardiogenic shock secondary to myocarditis and septic shock can be difficult to differentiate during initial resuscitation, and incorrect treatment can lead to poor prognosis. Early diagnosis may provide a better prognosis for this life-threatening condition. Case report: We report a case of a five-year-old female who presented to the ED with non-specific symptoms of myocarditis. Rapid point-of-care ultrasound led to early diagnosis, correct management, and great prognosis for the patient. Conclusion: Providers must maintain a high index of suspicion for cardiogenic shock in patients with nonspecific symptoms and fluid unresponsiveness. Point-of-care ultrasound can help in the identification of cardiac disorders and guide practitioners in their management plans.
... Based on randomised control trials which have concluded that there are increased adverse effects with the use of dopamine in comparison to epinephrine and norepinephrine, current practice has moved towards the use of epinephrine and norepinephrine as first line vasoactive agents, both of which have vasopressor as well as inotropic effects. 1,26,27 If there is a delay or difficulty in obtaining central access, vasoactive agents can be administered peripherally. 1,28 Epinephrine is the only vasoactive agent approved to run peripherally, though many practitioners will administer norepinephrine peripherally if necessary due to lack of central N Peshimam and S Nadel journals.sagepub.com/home/tai ...
Article
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Sepsis is a common, complex condition that requires early recognition and aggressive management to improve outcomes. There has been significant improvement in the management of sepsis and septic shock in the last decade; however, it continues to be a leading cause of mortality, morbidity and burden on healthcare services globally. Several guidelines with evidence-based recommendations for the management of children with septic shock and associated organ dysfunction have been produced with the objective of helping clinicians in various settings to provide standardised high-quality care. This article aims to increase awareness among all clinicians, including those working in emergency departments, general paediatric wards and primary care physicians, about the management of sepsis in children.
... [20] Two well-designed randomized controlled trials (RCTs) demonstrated benefit of epinephrine above dopamine as vasoactive infusion. [21,22] A 2020 ILCOR scoping review included above two RCTs but did not find sufficient evidence to suggest a change in recommendation. [23] The ERC 2021 writing group suggests starting with either noradrenaline or adrenaline, depending on local practices and infusing via either a central or a peripheral line. ...
Article
There is a lack of scientific data to use as local evidence on resuscitation science from the Indian subcontinent and other developing countries, making it difficult to develop regional guidelines and updates on practice of resuscitation based on the context, resources, infrastructure, geographical variabilities, values, and preferences. In this report, we try to identify key problem statements and plan to expand the list related to resuscitation practices primarily for in-hospital cardiac arrest (CA) in infants and children in India. To stimulate local research and data collection on resuscitation science and practices, Indian Resuscitation Council Federation proposes the concept of National CPR Registry and post-CA care bundle in the form of a checklist targeted for Indian settings.
... The search terminal date was 2019/4/22. Finally we found 2,517 articles, excluding 1,374 duplications, then we included 46 articles through reading the title and abstract, and 31 studies (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) were (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58) included by reading the whole articles ( Figure 1). ...
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Background: Septic shock is one of the major healthcare problems, affecting millions of people around the world every year. The object of this study is to find the best kind of regimen of vasopressors treatment in septic shock. Methods: The PubMed, and the Web of Science were used to find the included studies. Stata 15.1 was performed to this systemic review and network meta-analysis. Results: After searching and screening the articles, finally we included articles about 31 randomized controlled trials (RCTs), 11 arms (dopamine, dopexamine, epinephrine, norepinephrine, norepinephrine + dobutamine, norepinephrine + dopexamine, norepinephrine + epinephrine, norepinephrine + vasopressin, phenylephrine, terlipressin, vasopressin) and total 5,928 patients with septic shock. Compared with dopamine, the regimens (epinephrine, norepinephrine, norepinephrine + dobutamine, and vasopressin) have significantly lower 28-day mortality. Ranking the regimens in the order of estimated probabilities of each treatment by using the network meta-analysis for 28-day mortality, the result showed that norepinephrine + dopexamine was the best one (57.3%), followed by norepinephrine + epinephrine (14.8%), norepinephrine + dobutamine (10.9%), dopexamine (11.2%), terlipressin (9.8%), norepinephrine + vasopressin (2.4%), phenylephrine (1.2%), epinephrine (1.0%), vasopressin (0.5%), norepinephrine (0.0%), and dopamine (0.0%). In addition, for the results of arrhythmia and increased heart rate, the combination regimens groups did not showed inferiority to other single regimen groups. Conclusions: Single dopamine had significantly higher 28d mortality. Combination regimens of vasopressors accounted for the best three therapeutic regimens. In treating patients with septic shock, using combining regimens probably gets more benefits.
... With regard to the desirable effects of dopamine relative to adrenaline, the estimated effects of the length of stay in the pediatric ICU yielded a MD of 1.00 days shorter (95% CI: 3.95 shorter to 1.95 longer) (1 RCT, n = 60). 840 With regard to the undesirable effects of dopamine relative to adrenaline, the estimated effects for 28-day mortality yielded a RD of 136 more per 1,000 (95%CI: 61 fewer to 590 more) (2 RCTs, n = 180), 785,840 that for resolution of shock within 1 h yielded an RD of 286 fewer per 1,000 (95%CI: 368 fewer to 58 fewer) (1 RCT, n = 60), 784 that for vasoactive drug-free days yielded a MD of 4.80 days shorter (95%CI: 8.44 shorter to 1.16 shorter) (1 RCT, n = 120), 839 and that for serious adverse effects (healthcare-associated infections and ischemia) yielded an RD of 126 more per 1,000 (95% CI: 50 fewer to 764 more) (2 RCTs, n = 180). 784,839 Accordingly, the desirable effects of dopamine were deemed trivial, whereas the undesirable effects were deemed moderate. ...
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The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.
... However, we believe this is supported by a double-blind prospective randomized controlled trial conducted in Latin America that demonstrated that early administration of peripheral or intraosseous epinephrine in children with fluid-refractory septic shock was associated with longer survival (OR 6.49), when compared to dopamine. 54 Antimicrobial therapy is an important component in the treatment of sepsis as it directly targets the underlying cause of sepsis. The guideline of antibiotic administration within the first hour after the onset of shock is mainly derived from observational studies in which delayed administration is associated with greater mortality. ...
Article
Abstract Objective: to develop evidence-based recommendations for the diagnosis and treatment of sepsis in children in low- and middle-income countries (LMICs), more specifically, in Latin America. Design: a panel was formed consisting of 27 experts with experience in the treatment of pediatric sepsis, and two methodologists working in Latin American countries. The experts were organized into 10 nominal groups, each coordinated by a member. Methods: A formal consensus was formed based on the modified Delphi method, combining the opinions of nominal groups of experts with the interpretation of available scientific evidence, in a systematic process of consolidating a body of recommendations. The systematic search was performed by a specialized librarian and included specific algorithms for the Cochrane Specialized Register, PubMed, Lilacs and Scopus, as well as for OpenGrey databases for grey literature. The GRADEpro GDT guide was used to classify each of the selected articles. Special emphasis was placed on search engines that included original research conducted in LMICs. Studies in English, Spanish and Portuguese were covered. Through virtual meetings held between February 2020 and February 2021 and the entire group of experts reviewed the recommendations and suggestions. Result: At the end of the 12 months of work, the Consensus provided 62 recommendations for the diagnosis and treatment of pediatric sepsis in LMICs. Overall, 60 were strong recommendations; although, 56 of these had a low level of evidence. Conclusions: These are the first consensus recommendations for the diagnosis and management of pediatric sepsis focused on LMICs, more specifically, Latin American countries. The Consensus shows that, in these regions, where the burden of pediatric sepsis is greater than in high-income countries, there is little high-level evidence. Despite the limitations, this Consensus is an important step forward for the diagnosis and treatment of pediatric sepsis in Latin America. Key words: grading of recommendations, assessment, pediatrics, infection, septic shock, guidelines.
... However, we believe this is supported by a double-blind prospective randomized controlled trial conducted in Latin America that demonstrated that early administration of peripheral or intraosseous epinephrine in children with fluid-refractory septic shock was associated with longer survival (OR 6.49), when compared to dopamine. 54 Antimicrobial therapy is an important component in the treatment of sepsis as it directly targets the underlying cause of sepsis. The guideline of antibiotic administration within the first hour after the onset of shock is mainly derived from observational studies in which delayed administration is associated with greater mortality. ...
Article
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Objective The aim of this study was to develop evidence-based recommendations for the diagnosis and treatment of sepsis in children in low- and middle-income countries (LMICs), more specifically in Latin America. Design: A panel was formed consisting of 27 experts with experience in the treatment of pediatric sepsis and two methodologists working in Latin American countries. The experts were organized into 10 nominal groups, each coordinated by a member. Methods: A formal consensus was formed based on the modified Delphi method, combining the opinions of nominal groups of experts with the interpretation of available scientific evidence, in a systematic process of consolidating a body of recommendations. The systematic search was performed by a specialized librarian and included specific algorithms for the Cochrane Specialized Register, PubMed, Lilacs, and Scopus, as well as for OpenGrey databases for grey literature. The GRADEpro GDT guide was used to classify each of the selected articles. Special emphasis was placed on search engines that included original research conducted in LMICs. Studies in English, Spanish, and Portuguese were covered. Through virtual meetings held between February 2020 and February 2021, the entire group of experts reviewed the recommendations and suggestions. Result: At the end of the 12 months of work, the consensus provided 62 recommendations for the diagnosis and treatment of pediatric sepsis in LMICs. Overall, 60 were strong recommendations, although 56 of these had a low level of evidence. Conclusions: These are the first consensus recommendations for the diagnosis and management of pediatric sepsis focused on LMICs, more specifically in Latin American countries. The consensus shows that, in these regions, where the burden of pediatric sepsis is greater than in high-income countries, there is little high-level evidence. Despite the limitations, this consensus is an important step forward for the diagnosis and treatment of pediatric sepsis in Latin America.
... Ventura et al. tested the 2007 vasoactive drug recommendation in a randomized trial and found that the use of peripheral adrenaline infusion reduced mortality to 7% compared with 20% with use of peripheral dopamine infusion until central access was secured (32). ...
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The implementation of managed protocols contributes to a systematized approach to the patient and continuous evaluation of results, focusing on improving clinical practice, early diagnosis, treatment, and outcomes. Advantages to the adoption of a pediatric sepsis recognition and treatment protocol include: a reduction in time to start fluid and antibiotic administration, decreased kidney dysfunction and organ dysfunction, reduction in length of stay, and even a decrease on mortality. Barriers are: absence of a written protocol, parental knowledge, early diagnosis by healthcare professionals, venous access, availability of antimicrobials and vasoactive drugs, conditions of work, engagement of healthcare professionals. There are challenges in low-middle-income countries (LMIC). The causes of sepsis and resources differ from high-income countries. Viral agent such as dengue, malaria are common in LMIC and initial approach differ from bacterial infections. Some authors found increased or no impact in mortality or increased length of stay associated with the implementation of the SCC sepsis bundle which reinforces the importance of adapting it to most frequent diseases, disposable resources, and characteristics of healthcare professionals. Conclusions: (1) be simple; (2) be precise; (3) education; (5) improve communication; (5) work as a team; (6) share and celebrate results.
... No studies directly compare epinephrine with norepinephrine. However, epinephrine has been compared to dopamine in two RCTs in children with fluidrefractory septic shock(224,225). Across both studies, epinephrine was associated with a lower risk of mortality (RR 0.63, 95% CI 0.40, 0.99) and more organ failure-free days among survivors by day 28 (MD 4 more days, 95% CI 2.0 to 6.0) (SupplementalTable 10, SupplementalFigure 4). ...
Article
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Objectives To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. Design A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. Methods The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, “in our practice” statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. Results The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, “in our practice” statements were provided. In addition, 52 research priorities were identified. Conclusions A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.
Chapter
Shock is defined as an imbalance between oxygen delivery (DO2) and oxygen consumption (VO2). Oxygen demand greater than oxygen delivery leads to a severe decrease in tissue oxygenation, nutrient delivery, and eventually cell death. Shock can damage all tissues and quickly progress to multiorgan failure. This is why early identification and treatment of shock is critical to prevent irreversible cell death. This chapter provides an overview of the diagnosis and management of this complex entity.
Article
Objectives: Determine level of agreement among clinical signs of shock type, identify which signs clinicians prioritize to determine shock type and select vasoactive medications, and test the association of shock type-vasoactive mismatch with prolonged organ dysfunction or death (complicated course). Design: Retrospective observational study. Setting: Single large academic PICU. Patients: Patients less than 18 years treated on a critical care sepsis pathway between 2012 and 2016. Interventions: None. Measurements and main results: Agreement among clinical signs (extremity temperature, capillary refill, pulse strength, pulse pressure, and diastolic blood pressure) was measured using Fleiss and Cohen's κ. Association of clinical signs with shock type and shock type-vasoactive mismatch (e.g., cold shock treated with vasopressor rather than inotrope) with complicated course was determined using multivariable logistic regression. Of 469 patients, clinicians determined 307 (65%) had warm and 162 (35%) had cold shock. Agreement across all clinical signs was low (κ, 0.25; 95% CI, 0.20-0.30), although agreement between extremity temperature, capillary refill, and pulse strength was better than with pulse pressure and diastolic blood pressure. Only extremity temperature (adjusted odds ratio, 26.6; 95% CI, 15.5-45.8), capillary refill (adjusted odds ratio, 15.7; 95% CI, 7.9-31.3), and pulse strength (adjusted odds ratio, 21.3; 95% CI, 8.6-52.7) were associated with clinician-documented shock type. Of the 86 patients initiated on vasoactive medications during the pathway, shock type was discordant from vasoactive medication (κ, 0.14; 95% CI, -0.03 to 0.31) and shock type-vasoactive mismatch was not associated with complicated course (adjusted odds ratio, 0.3; 95% CI, 0.1-1.02). Conclusions: Agreement was low among common clinical signs used to characterize shock type, with clinicians prioritizing extremity temperature, capillary refill, and pulse strength. Although clinician-assigned shock type was often discordant with vasoactive choice, shock type-vasoactive mismatch was not associated with complicated course. Categorizing shock based on clinical signs should be done cautiously.
Article
Objectives: To assess the prevalence of immunocompromised diagnoses among children with severe sepsis and septic shock, and to determine the association between immunocompromised diagnoses and clinical outcomes after adjustment for demographics and illness severity. Design: Retrospective multicenter cohort study. Setting: Eighty-three centers in the Virtual Pediatric Systems database. Patients: Children with severe sepsis or septic shock admitted to a participating PICU between January 1, 2012, and December 31, 2016. Interventions: None. Measurements and main results: Across 83 centers, we identified 10,768 PICU admissions with an International Classification of Diseases, 9th Revision, Clinical Modification code for severe sepsis or septic shock; 3,021 of these patients (28%) had an immunocompromised diagnosis. To evaluate variation across centers and determine factors associated with PICU mortality, we used mixed-effect logistic regression models. Among patients without hematopoietic cell transplant, congenital immunodeficiency (adjusted odds ratio, 1.90; 95% CI, 1.24-2.92), multiple prior malignancies (adjusted odds ratio, 1.86; 95% CI, 1.15-2.99), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 3.09; 95% CI, 1.91-4.98) were associated with an increased odds of PICU mortality. Among patients with prior hematopoietic cell transplant, liquid malignancy (adjusted odds ratio, 3.15; 95% CI, 2.09-4.74), congenital immunodeficiency (adjusted odds ratio, 6.94; 95% CI, 3.84-12.53), multiple prior malignancies (adjusted odds ratio, 3.54; 95% CI, 1.80-6.95), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 2.79; 95% CI, 1.36-5.71) were associated with an increased odds of PICU mortality. PICU mortality varied significantly by center, and a higher mean number of sepsis patients per month in a center was associated with lower PICU mortality (adjusted odds ratio, 0.94; 95% CI, 0.90-0.98). PICU resource utilization varied by immunocompromised diagnosis and history of hematopoietic cell transplant, and among survivors immunocompromised patients have shorter median PICU length of stay compared with patients without immunocompromised diagnoses (p < 0.001). Conclusions: Immunocompromised diagnoses are present in 28% of children with severe sepsis or septic shock. Multiple prior malignancies, hemophagocytic lymphohistiocytosis, congenital immunodeficiency, and hematopoietic cell transplant are independently associated with an increased odds of PICU mortality in children with severe sepsis or septic shock. Significant variation exists in PICU mortality among centers despite adjustment for immunocompromised diagnoses, known risk factors for sepsis-related mortality, and center-level sepsis volume.
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Objective: To investigate the association between antibiotics administration timing with morbidity and mortality in children with severe sepsis and septic shock, presenting to a tertiary care center in a developing country. Methods: This is a retrospective study of children aged 14 years or younger diagnosed with severe sepsis or septic shock at a free-standing tertiary children's hospital in Saudi Arabia between April 2015 and February 2018. We investigated the association between antibiotic administration timing and pediatric intensive care unit (PICU) mortality, PICU length of stay (LOS), hospital LOS, and ventilation-free days after adjusting for confounders. Results: Among the 189 admissions, 77 patients were admitted with septic shock and 112 with severe sepsis. Overall, the mortality rate was 16.9%. The overall median time from sepsis recognition to antibiotic administration was 105 min (IQR: 65-185.5 min); for septic shock patients, it was 85 min (IQR: 55-148 min), and for severe sepsis, 130 min (IQR: 75.5-199 min). Delayed antibiotic administration (> 3 h) was associated with 3.85 times higher PICU mortality (95% confidence intervals 1.032-14.374) in children with septic shock than in children who receive antibiotics within 3 h, after controlling for severity of illness, age, comorbidities, and volume resuscitation. However, delayed antibiotics administration was not significantly associated with higher PICU mortality in children diagnosed with severe sepsis. Conclusions: Delayed antibiotics administration in children with septic shock admitted to a free-standing children's hospital in a developing country was associated with PICU mortality.
Chapter
Despite significant advances in many areas of care, the management of low blood pressure and circulatory compromise in the preterm infant continues to be based on quite limited evidence. Deciding when to intervene, and with what to intervene, remains a conundrum at the bedside. In this chapter we explore the aetiology of low blood pressure, we review assessment strategies including new monitoring modalities that may provide a better understanding of the underlying problem and hence direct more appropriate treatments. The evidence for current therapies is reviewed, including the newer inodilators. The future will see a paradigm shift in our current approach to haemodynamic instability and management.
Article
SEPSIS REMAINS one of the most common causes of childhood morbidity, mortality, and higher healthcare costs, with over 75,000 hospital admissions in the United States and an estimated 4 million cases worldwide per year. While standardized criteria to define sepsis are in flux, the general concept of sepsis is a severe infection that results in organ dysfunction. Although sepsis can affect previously healthy children, those with certain pre-existing comorbid conditions, including congenital and acquired heart disease, are at higher risk for both developing sepsis and having a poor outcome after sepsis. Multiple specialists including intensivists, cardiologists, surgeons, and anesthesiologists commonly contribute to the management and outcome of sepsis in children. In this article, the authors examine the evolving epidemiology of pediatric sepsis, including the subset of patients with underlying heart disease; contrast pediatric and adult sepsis; review the latest hemodynamic guidelines for management of pediatric septic shock and their application to children with heart disease; discuss the role of mechanical circulatory support; and review key aspects of anesthetic management for children with sepsis.
Article
Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. Methods: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. Results: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 49 research priorities were identified. Conclusions: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.
Article
Objective: Sepsis is one of the most urgent health care issues worldwide. Guidelines for early identification and treatment are essential to decrease sepsis-related mortality. Our aim was to collect data on the epidemiology of pediatric septic shock (PSS) from the emergency department (PED) and to assess adherence to recommendations for its management in the first hour. Methods: A multicenter, prospective, cross-sectional study was conducted evaluating children with PSS seen at the PED of 10 tertiary-care centers in Latin America. Adherence to guidelines was evaluated. Results: We included 219 patients (median age, 3.7 years); 43% had comorbidities, 31% risk factors for developing sepsis, 74% clinical signs of "cold shock," and 13% of "warm shock," 22% had hypotension on admission. Consciousness was impaired in 55%. A peripheral line was used as initial access in 78% (median placement time, 10 minutes). Fluid and antibiotics infusion was achieved within a median time of 30 minutes (interquartile range [IQR], 20-60 minutes) and 40 minutes (IQR, 20-60 minutes), respectively; 40% responded inadequately to fluids requiring vasoactive drugs (median time at initiation, 60 minutes; IQR, 30-135 minutes). Delay to vasoactive drug infusion was significantly longer when a central line was placed compared to a peripheral line (median time, 133 minutes [59-278 minutes] vs 42 minutes [30-70 minutes], respectively [P < 0.001]). Adherence to all treatment goals was achieved in 13%. Mortality was 10%. An association between mortality and hypotension on admission was found (26.1% with hypotension vs 4.9% without; P < 0.001). Conclusions: We found poor adherence to the international recommendations for the treatment of PSS in the first hour at the PED in third-level hospitals in Latin America.
Article
Objectives: To compare the prevalence of adverse events related to vasoactive drug infusions administered via a peripheral venous catheter versus a central venous or intraosseous catheter. Design: Retrospective observational study. Setting: A pediatric critical care transport team, and the PICUs and regional hospitals within the North Thames and East Anglia regions of the United Kingdom. Patients: Children (up to 18 yr old) transported by the Children's Acute Transport Service receiving an infusion of a vasoactive drug (epinephrine, dobutamine, dopamine, norepinephrine, and vasopressin). Interventions: None. Measurements and main results: The medical records of all children transported between April 2017 and May 2020 receiving a vasoactive drug infusion were reviewed and cross-referenced with the service critical incident database. The outcome measure was anatomic catheter-related adverse events (including extravasation) reported during transport or in the first 24 hours on the PICU. During the study period, the service undertook 3,836 transports. Vasoactive drugs were administered during 558 patient transports (14.5%). During 198 of 558 transports (35.5%), vasoactive drugs were administered via a peripheral venous catheter, with seven of 198 (3.5%) adverse events. One extravasation event resulted in tissue necrosis. The median time to injury after the infusion was commenced was 60 minutes (interquartile range, 30-60 min). During 360 of 558 transports (64.5%), vasoactive infusions were administered by central venous or intraosseous catheter, with nine of 360 (2.5%) adverse events. Conclusions: During pediatric critical care transport, we did not find a difference in prevalence of adverse events following the administration of vasoactive drugs via peripheral venous catheters or via central venous and intraosseous catheters.
Article
Sepsis is a life-threatening response to infection that contributes significantly to neonatal and pediatric morbidity and mortality worldwide. The key tenets of care include early recognition of potential sepsis, rapid intervention with appropriate fluids to restore adequate tissue perfusion, and empiric antibiotics to cover likely pathogens. Vasoactive/inotropic agents are recommended if tissue perfusion and hemodynamics are inadequate following initial fluid resuscitation. Several adjunctive therapies have been suggested with theoretical benefit, though definitive recommendations are not yet supported by research reports. This review focuses on the recommendations for medication and fluid management of pediatric sepsis and septic shock, highlighting issues related to antibiotic choices and antimicrobial stewardship, selection of intravenous fluids for resuscitation, and selection and use of vasoactive/inotropic medications. Controversy remains regarding resuscitation fluid volume and type, antibiotic choices depending upon infectious risks in the patient's community, and adjunctive therapies such as vitamin C, corticosteroids, intravenous immunoglobulin, and methylene blue. We include best practice recommendations based on international guidelines, a review of primary literature, and a discussion of ongoing clinical trials and the nuances of therapeutic choices.
Article
In this educational article we summarize the changes in the new European Resuscitation Council guidelines for Pediatric Life Support, emphasizing the most important aspects for the anesthesiologist. Among these are: the use of two-thumb-encircling technique for thorax compressions in infants, 10 ml/kg as the standard volume fluid bolus and ventilation after intubation at an age-dependent rate. Using a fictitious case, we present a point-by-point summary of the changes and briefly mention some of the evidence behind them, referring the reader to the full guidelines for further evidence. We also give a summary of the incidence, causes, challenges, treatment and prognosis of pediatric cardiac arrest in the operating room.
Article
Purpose To summarize recently published research reports and practice guidelines deemed to be significantly impactful for pediatric pharmacy practice. Summary Our author group was composed of 8 board-certified pediatric pharmacists. Eight major themes were identified: critical care, hematology/oncology, medication safety, general pediatrics, infectious diseases, neurology/psychiatry, gastrointestinal/nutrition, and neonatology. The author group was assigned a specific theme(s) based on their practice expertise and were asked to identify articles using MEDLINE and/or searches of relevant journal articles pertaining to each theme that were published from January 2019 through December 2020 that they felt were “significant” for pediatric pharmacy practice. A final list of compiled articles was distributed to the authors, and an article was considered significant if it received a vote from 5 of the 8 authors. Thirty-two articles, including 16 clinical practice guidelines or position statements and 16 review or primary literature articles, were included in this review. For each of these articles, a narrative regarding its implications for pediatric pharmacy practice is provided. Conclusion Given the heterogeneity of pediatric patients, it is difficult for pediatric pharmacists to stay up to date with the most recent literature, especially in practice areas outside their main expertise. Over the last few years, there has been a significant number of publications impacting the practice of pediatric pharmacists. This review of articles that have significantly affected pediatric pharmacy practice may be helpful in staying up to date on key articles in the literature.
Article
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Sepsis remains a major cause of morbidity and mortality among children worldwide. Furthermore, refractory septic shock and multiple organ dysfunction syndrome are the most critical groups which account for a high mortality rate in pediatric sepsis, and their clinical course often deteriorates rapidly. Resuscitation based on hemodynamics can provide objective values for identifying the severity of sepsis and monitoring the treatment response. Hemodynamics in sepsis can be divided into two groups: basic and advanced hemodynamic parameters. Previous therapeutic guidance of early-goal directed therapy (EGDT), which resuscitated based on the basic hemodynamics (central venous pressure and central venous oxygen saturation (ScvO2)) has lost its advantage compared with “usual care”. Optimization of advanced hemodynamics, such as cardiac output and systemic vascular resistance, has now been endorsed as better therapeutic guidance for sepsis. Despite this, there are still some important hemodynamics associated with prognosis. In this article, we summarize the common techniques for hemodynamic monitoring, list important hemodynamic parameters related to outcomes, and update evidence-based therapeutic recommendations for optimizing resuscitation in pediatric septic shock.
Article
Vasopressors (synthetic catecholamines) play an important role in the management of hemodynamics and are being used by perioperative anaesthesiologists and intensive care physicians around the world on a daily basis. However, vasopressors require a cautious use and may inflict serious harm if applied in an inappropriate manner or in the wrong situation. Whether it is during a caesarean section in healthy young women, in multimorbid patients in the intensive care unit or in in the preclinical setting: Knowing the basics of pharmacodynamics and -kinetics of the commonly used vasopressors is crucial for the outcome of patients and is the focus of this article.
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The European Resuscitation Council (ERC) Paediatric Life Support (PLS) guidelines are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations of the International Liaison Committee on Resuscitation (ILCOR). This section provides guidelines on the management of critically ill or injured infants, children and adolescents before, during and after respiratory/cardiac arrest.
Chapter
Cardiovascular agents are utilized when myocardial and/or circulatory dysfunction persists despite optimization of volume status. They have potent activity on the biochemical and neurochemical pathways that maintain and regulate vascular tone, cardiac contractility, and heart rate.
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This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for pediatric life support is based on the most extensive evidence evaluation ever performed by the Pediatric Life Support Task Force. Three types of evidence evaluation were used in this review: systematic reviews, scoping reviews, and evidence updates. Per agreement with the evidence evaluation recommendations of the International Liaison Committee on Resuscitation, only systematic reviews could result in a new or revised treatment recommendation. Systematic reviews performed for this 2020 CoSTR for pediatric life support included the topics of sequencing of airway-breaths-compressions versus compressions-airway-breaths in the delivery of pediatric basic life support, the initial timing and dose intervals for epinephrine administration during resuscitation, and the targets for oxygen and carbon dioxide levels in pediatric patients after return of spontaneous circulation. The most controversial topics included the initial timing and dose intervals of epinephrine administration (new treatment recommendations were made) and the administration of fluid for infants and children with septic shock (this latter topic was evaluated by evidence update). All evidence reviews identified the paucity of pediatric data and the need for more research involving resuscitation of infants and children.
Chapter
Musculoskeletal infections may lead to sepsis, a systemic inflammatory response, which can cause cardiovascular compromise (septic shock) and multiple organ dysfunction. Early recognition and treatment of sepsis are crucial, with early administration of antibiotics associated with improved outcomes. Patients with sepsis and septic shock frequently require management in the intensive care unit and aggressive treatment with support for multi-organ dysfunction. This chapter details the pathophysiology of sepsis and septic shock along with the fundamentals of care for the critically ill patient with an underlying musculoskeletal infection. This chapter also provides additional information on special considerations regarding sepsis in low and middle income countries.
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OBJECTIVE: To analyze the clinical outcome of children with fluid-refractory septic shock initially treated with dopamine or epinephrine. METHODS: A 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. RESULTS: We 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). CONCLUSIONS: At 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.
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Few studies have demonstrated improvement in adherence to Pediatric Advanced Life Support guidelines for severe sepsis and septic shock. We sought to improve adherence to national guidelines for children with septic shock in a pediatric emergency department with poor guideline adherence. Prospective cohort study of children presenting to a tertiary care pediatric emergency department with septic shock. Quality improvement (QI) interventions, including repeated plan-do-study-act cycles, were used to improve adherence to a 5-component sepsis bundle, including timely (1) recognition of septic shock, (2) vascular access, (3) administration of intravenous (IV) fluid, (4) antibiotics, and (5) vasoactive agents. The intervention focused on IV fluid delivery as a key driver impacting bundle adherence, and adherence was measured using statistical process control methodology. Two-hundred forty-two patients were included: 126 subjects before the intervention (November 2009 to March 2011), and 116 patients during the QI intervention (October 2011 to May 2013). We achieved 100% adherence for all metrics, including (1) administration of 60 mL/kg IV fluid within 60 minutes (increased from baseline adherence rate of 37%), (2) administration of vasoactive agents within 60 minutes (baseline rate of 35%), and (3) 5-component bundle adherence (baseline rate of 19%). Improvement was sustained over 9 months. The number of septic shock cases between each death from this condition increased after implementation of the QI intervention. Using QI methodology, we have demonstrated improved adherence to national guidelines for severe sepsis and septic shock.
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The recognition, diagnosis, and management of sepsis remain among the greatest challenges in pediatric critical care medicine. Sepsis remains among the leading causes of death in both developed and underdeveloped countries and has an incidence that is predicted to increase each year. Unfortunately, promising therapies derived from preclinical models have universally failed to significantly reduce the substantial mortality and morbidity associated with sepsis. There are several key developmental differences in the host response to infection and therapy that clearly delineate pediatric sepsis as a separate, albeit related, entity from adult sepsis. Thus, there remains a critical need for well-designed epidemiologic and mechanistic studies of pediatric sepsis in order to gain a better understanding of these unique developmental differences so that we may provide the appropriate treatment. Herein, we will review the important differences in the pediatric host response to sepsis, highlighting key differences at the whole-organism level, organ system level, and cellular and molecular level.
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Unrecognized and undertreated septic shock increases morbidity and mortality. Septic shock in children is defined as sepsis and cardiovascular organ dysfunction, not necessarily with hypotension. Cases of unrecognized and undertreated septic shock in our emergency department (ED) were reviewed with a focus on (1) increased recognition at triage and (2) more aggressive treatment once recognized. We hypothesized that septic shock protocol and care guideline would expedite identification of septic shock, increase compliance with recommended therapy, and improve outcomes. We developed an ED septic shock protocol and care guideline to improve recognition beginning at triage and evaluated all eligible ED patients from January 2005 to December 2009. We identified 345 pediatric ED patients (49% male, median age: 5.6 years), and 297 (86.1%) met septic shock criteria at triage. One hundred ninety-six (56.8%) had ≥ 1 chronic complex condition. Hypotension was present in 34% (n = 120); the most common findings were tachycardia (n = 251 [73%]) and skin-color changes (n = 269 [78%]). The median hospital length of stay declined over the study period (median: 181-140 hours; P < .05); there was no change in mortality rate, which averaged 6.3% (22 of 345). The greatest gains in care included more complete recording of triage vital signs, timely fluid resuscitation and antibiotic administration, and serum lactate determination. Implementation of an ED septic shock protocol and care guideline improved compliance in delivery of rapid, aggressive fluid resuscitation and early antibiotic and oxygen administration and was associated with decreased length of stay.
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To audit current UK practice of the management of severe sepsis in children against the 2002 American College of Critical Care Medicine/Pediatric Advanced Life Support (ACCM-PALS) guideline. Prospective observational study. 17 UK paediatric intensive care units (PICUs) and two UK PICU transport services. 200 children accepted for PICU admission within 12 h of arrival in hospital, whether or not successfully transported to a PICU, with a discharge diagnosis of sepsis or suspected sepsis. Medical interventions, physiological and laboratory data to determine the presence or absence of shock, inter-hospital transfer times, predicted mortality (using the Paediatric Index of Mortality, version 2 (PIM2) scoring system) and observed mortality. 34/200 (17%) children died following referral. Although children defined as being in shock received significantly more fluid (p<0.001) than those who were not in shock, overall fluid and inotrope management suggested by the 2002 ACCM-PALS guideline was not followed in 62% of shocked children. Binary logistic regression analysis demonstrated that the odds ratio for death, if shock was present at PICU admission, was 3.8 (95% CI 1.4 to 10.2, p = 0.008). The presence of shock at PICU admission is associated with an increased risk of death. Despite clear consensus guidelines for the emergency management of children with severe sepsis and septic shock, most children received inadequate fluid resuscitation and inotropic support in the crucial few hours following presentation.
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To characterize the role of cardiac function in septic shock, serial radionuclide cineangiographic and hemodynamic evaluations were done on 20 patients with documented septic shock. Although all patients had a normal or elevated cardiac index, 10 patients had moderate to severe depression of their ejection fraction with values below 0.40. Thirteen of twenty patients survived their episode. Paradoxically, 10 of 13 survivors, but none of the 7 nonsurvivors, had an initial ejection fraction less than 0.40 (p less than 0.005). The mean initial ejection fraction for the survivors was 0.32 +/- 0.04, and their mean end systolic and end diastolic ventricular volumes were substantially increased with a normal stroke volume. The survivors' serial scans showed a gradual return to normal ejection fraction and ventricular volume by 10 days after the onset of shock. Nonsurvivors had normal initial ejection fractions and ventricular volumes that did not change during serial studies.
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It is apparent that delays and inadequate or inappropriate management occur frequently and may contribute to the continued high mortality seen in meningococcal disease. An attempt has been made to define the major sources of delay or inappropriate treatment. A prospective, descriptive study of children with meningococcal disease referred to a tertiary centre paediatric intensive care and infectious disease unit. Definitions of optimal care were established at three stages: parental; general practitioner (GP)/accident and emergency (A&E) department; and hospital. Duration of symptoms and management were recorded from direct questioning of parents and carers, and from hospital records. 54 consecutive children with meningococcal disease were recruited to the study. Delayed parental recognition occurred in 16 children. GPs correctly diagnosed 19 of 35 children. Delay of 2.5-21 hours occurred in those who were incorrectly diagnosed. Two of 15 children who presented to the A&E department with specific features were incorrectly diagnosed. Hospital treatment was suboptimal in 71%. Shock was not recognised or treated in 50%, 20% of children had unnecessary lumbar punctures. Time from illness onset to treatment was longer in fatal disease (median 18.3, range 8-24 hours), compared with survivors (median 12, range 2-48 hours; p < 0.01, Mann-Whitney U test). Suboptimal treatment in meningococcal disease is due to failure of parents, GPs, and hospital doctors to recognise specific features of the illness. Improvement by public education and better training of clinicians in recognition, resuscitation, and stabilisation of seriously ill children.
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Experimental and clinical studies of septic shock support the concept that early resuscitation with fluid and inotropic therapies improves survival in a time-dependent manner. The new American College of Critical Care Medicine-Pediatric Advanced Life Support (ACCM-PALS) Guidelines for hemodynamic support of newborns and children in septic shock recommend this therapeutic approach. The objective of this study was to determine whether early septic shock reversal and use of resuscitation practice consistent with the new ACCM-PALS Guidelines by community physicians is associated with improved outcome. A 9-year (January 1993-December 2001) retrospective cohort study was conducted of 91 infants and children who presented to local community hospitals with septic shock and required transport to Children's Hospital of Pittsburgh. Shock reversal (defined by return of normal systolic blood pressure and capillary refill time), resuscitation practice concurrence with ACCM-PALS Guidelines, and hospital mortality were measured. Overall, 26 (29%) patients died. Community physicians successfully achieved shock reversal in 24 (26%) patients at a median time of 75 minutes (when the transport team arrived at the patient's bedside), which was associated with 96% survival and >9-fold increased odds of survival (9.49 [1.07-83.89]). Each additional hour of persistent shock was associated with >2-fold increased odds of mortality (2.29 [1.19-4.44]). Nonsurvivors, compared with survivors, were treated with more inotropic therapies (dopamine/dobutamine [42% vs 20%] and epinephrine/norepinephrine [42% vs 6%]) but not increased fluid therapy (median volume; 32.9 mL/kg vs 20.0 mL/kg). Resuscitation practice was consistent with ACCM-PALS Guidelines in only 27 (30%) patients; however, when practice was in agreement with guideline recommendations, a lower mortality was observed (8% vs 38%). Early recognition and aggressive resuscitation of pediatric-neonatal septic shock by community physicians can save lives. Educational programs that promote ACCM-PALS recommended rapid, stepwise escalations in fluid as well as inotropic therapies may have value in improving outcomes in these children.
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Large quantitaties of inflammatory mediators are released during the course of endotoxaemia. These mediators in turn can stimulate the sympathetic nervous system (SNS) to release catecholamines, which ultimately regulate inflammation-associated impairment in tissue perfusion, myocardial impairment and vasodilatation. Treatment of sepsis is based on surgical and/or antibiotic therapy, appropriate fluid management and application of vasoactive catecholamines. With respect to the latter, discussions on the vasopressor of choice are still ongoing. Over the past decade dopamine has been considered the 'first line' vasopressor and is frequently used to improve organ perfusion and blood pressure. However, there is a growing body of evidence that dopamine has deleterious side effects; therefore, its clinical relevance seems to be more and more questionable. Nevertheless, it has not been convincingly demonstrated that other catecholamines are superior to dopamine in this respect. Apart from its haemodynamic action, dopamine can modulate immune responses by influencing the cytokine network. This leads to inhibition of expression of adhesion molecules, inhibition of cytokine and chemokine production, inhibition of neutrophil chemotaxis and disturbed T-cell proliferation. In the present review we summarize our knowledge of the immunomodulatory effects of dopamine, with an emphasis on the mechanisms by which these effects are mediated.
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To determine whether suboptimal management in hospital could contribute to poor outcome in children admitted with meningococcal disease. Case-control study of childhood deaths from meningococcal disease, comparing hospital care in fatal and non-fatal cases. National statistics and hospital records. All children under 17 years who died from meningococcal disease (cases) matched by age with three survivors (controls) from the same region of the country. Predefined criteria defined optimal management. A panel of paediatricians blinded to the outcome assessed case records using a standardised form and scored patients for suboptimal management. We identified 143 cases and 355 controls. Departures from optimal (per protocol) management occurred more frequently in the fatal cases than in the survivors. Multivariate analysis identified three factors independently associated with an increased risk of death: failure to be looked after by a paediatrician, failure of sufficient supervision of junior staff, and failure of staff to administer adequate inotropes. Failure to recognise complications of the disease was a significant risk factor for death, although not independently of absence of paediatric care (P = 0.002). The odds ratio for death was 8.7 (95% confidence interval 2.3 to 33) with two failures, increasing with multiple failures. Suboptimal healthcare delivery significantly reduces the likelihood of survival in children with meningococcal disease. Improved training of medical and nursing staff, adherence to published protocols, and increased supervision by consultants may improve the outcome for these children and also those with other life threatening illnesses.
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To compare the endocrine effects of dopamine and dobutamine in hypotensive very low birthweight (VLBW) infants. Non-blinded randomised prospective trial. Level III neonatal intensive care unit. 35 hypotensive VLBW infants who did not respond to volume loading, assigned to receive dopamine or dobutamine. Measurements: Haemodynamic variables and serum levels of thyroid stimulating hormone (TSH), total thyroxine (T(4)), prolactin (PRL) and growth hormone were assessed during the first 72 h of treatment and the first 72 h after stopping treatment. Demographic and clinical data did not significantly differ between the two groups. Necessary cumulative and mean drug doses and maximum infusion required to normalise blood pressure were significantly higher in the dobutamine than in the dopamine group (p<0.01). Suppression of TSH, T(4) and PRL was observed in dopamine-treated newborns from 12 h of treatment onwards, whereas levels of growth hormone reduced significantly only at 12 h and 36 h of treatment (p<0.01). TSH, T(4) and PRL rebound was observed from the first day onwards after stopping dopamine. Dobutamine administration did not alter the profile of any of the hormones and no rebound was observed after stopping treatment. Dopamine and dobutamine both increase the systemic blood pressure, though dopamine is more effective. Dopamine reduces serum levels of TSH, T(4) and PRL in VLBW infants but such suppression is quickly reversed after treatment is stopped. Further research is required to assess if short-term iatrogenic pituitary suppression has longer-term consequences.
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The goal was to report the 1- and 3-year outcomes of preterm infants with low systemic blood flow in the first day and the effect of dobutamine versus dopamine for treatment of low systemic blood flow. A cohort of 128 infants born at <30 weeks of gestation underwent echocardiographic measurement of superior vena cava flow at 3, 10, and 24 hours of age. Forty-two infants with low superior vena cava flow (<41 mL/kg per minute) were assigned randomly to dobutamine or dopamine. Surviving infants underwent blinded neurodevelopmental assessments at corrected ages of 1 and 3 years. Seventy-six of 87 surviving infants were seen at 1 year and 67 at 3 years. Forty-four infants had low superior vena cava flow. At 3 years, with adjustment for perinatal risk factors, death was predicted by low superior vena cava flow, lower gestational age, and low 5-minute Apgar score. Substantial reductions in the Griffiths General Quotient were associated with low superior vena cava flow and birth weight of <10th percentile. Infants with low flow had significant reductions in personal-social, hearing and speech, and performance subscales. Death or disability at 3 years was predicted by low superior vena cava flow and lower gestational age. For infants treated with inotropes, no significant differences were found in clinical outcomes, except for reduced rates of late severe periventricular/intraventricular hemorrhage in the dobutamine group. At 3 years, infants in the dopamine group had significantly more disability and a lower Griffiths General Quotient. At the latest time measured, however, combined rates of death or disability were similar. Early low superior vena cava flow was associated with substantial rates of death, morbidity, and developmental impairments. No difference was found in combined rates of death and disability for infants assigned randomly to dopamine or dobutamine.
Article
To analyze mortality rates of children with severe sepsis and septic shock in relation to time-sensitive fluid resuscitation and treatments received and to define barriers to the implementation of the American College of Critical Care Medicine/Pediatric Advanced Life Support guidelines in a pediatric intensive care unit in a developing country. Retrospective chart review and prospective analysis of septic shock treatment in a pediatric intensive care unit of a tertiary care teaching hospital. Ninety patients with severe sepsis or septic shock admitted between July 2002 and June 2003 were included in this study. Of the 90 patients, 83% had septic shock and 17% had severe sepsis; 80 patients had preexisting severe chronic diseases. Patients with septic shock who received less than a 20-mL/kg dose of resuscitation fluid in the first hour of treatment had a mortality rate of 73%, whereas patients who received more than a 40-mL/kg dose in the first hour of treatment had a mortality rate of 33% (P < 0.05). Patients treated less than 30 minutes after diagnosis of severe sepsis and septic shock had a significantly lower mortality rate (40%) than patients treated more than 60 minutes after diagnosis (P < 0.05). Controlling for the risk of mortality, early fluid resuscitation was associated with a 3-fold reduction in the odds of death (odds ratio, 0.33; 95% confidence interval, 0.13-0.85). The most important barriers to achieve adequate severe sepsis and septic shock treatment were lack of adequate vascular access, lack of recognition of early shock, shortage of health care providers, and nonuse of goals and treatment protocols. The mortality rate was higher for children older than 2 years, for those who received less than 40 mL/kg in the first hour, and for those whose treatment was not initiated in the first 30 minutes after the diagnosis of septic shock. The acknowledgment of existing barriers to a timely fluid administration and the establishment of objectives to overcome these barriers may lead to a more successful implementation of the American College of Critical Care Medicine guidelines and reduced mortality rates for children with septic shock in the developing world.
Article
Objective: To quantitate ventricular systolic mechanics in septic children. Design: Prospective wall-stress analysis was compared to standard ejection phase indices. Setting: University-based pediatric intensive care unit. Patients: Fifteen children with sepsis (hemodynamically stable, n = 5; in shock, n = 10). Measurements and Main Results: Left ventricular ejection phase indices: shortening fraction (shortening) and corrected mean velocity of circumferential shortening (velocity) were adjusted for end-systolic wall stress (stress). Ejection phase, performance (stress-shortening relation), contractility (stress-velocity relation), and afterload (stress) were indexed to age-corrected normal means, with variance of >=2 sd regarded as significant. Preload index represented variance between performance and contractility indices. All hemodynamically stable septic patients had normal performance, contractility, and preload. Afterload was increased in three of five patients. Of the patients with septic shock, six often had decreased performance (decreased contractility and increased afterload, n = 4; decreased afterload, n = 1; and severe preload deficit, n = 1). Despite aggressive volume resuscitation, six of ten children in septic shock had evidence of diminished preload. Follow-up studies in the septic shock patients demonstrated reversal of depressed ventricular contractility within 3 to 6 days in all four patients initially affected (p < .05). One patient developed late decreased performance and contractility in association with multiple organ failure. Ventricular loading abnormalities persisted in a follow-up study of these patients including a preload deficit in five of ten patients in shock. Conclusions: The frequency rate (40%) of reversible impaired ventricular contractility in children with septic shock is significant. Afterload is normal or increased in the majority of septic subjects, possibly due to acute ventricular dilation. Decreased preload contributes to altered ventricular performance in the majority of children with septic shock, persisting days after the initiation of therapy. Wall-stress analysis provided detailed information regarding ventricular mechanics that was not otherwise obtainable by standard ejection phase indices. (Crit Care Med 1994; 22:1647-1658) (C) Williams & Wilkins 1994. All Rights Reserved.
Article
To evaluate the prevalence and significance of myocardial dysfunction in children with septic shock. Thirty patients with septic shock were evaluated by transthoracic echocardiography within 24 hours of admission to a pediatric critical care unit. Transthoracic echocardiography evaluation included left ventricular (LV) size and function, mitral valve inflow velocities in early and late diastole, mitral valve annular velocities in systole and early and late diastole, and LV myocardial performance index. LV systolic dysfunction was defined as an ejection fraction or shortening fraction z-score <-2, and LV diastolic dysfunction was defined as a mitral valve inflow velocity/annular velocity in early diastole ratio z-score >2. Secondary outcomes included troponin I concentration, acute kidney injury, and 28-day mechanical ventilation-free duration. Mortality for the 30 patients (mean age, 9.5 ± 7 years) was 7%. The prevalence of LV systolic and/or diastolic dysfunction was 53% (16 of 30). Eleven patients (37%) had systolic dysfunction, 10 (33%) had diastolic dysfunction, and 5 (17%) had both. Systolic and/or diastolic dysfunction was significantly associated with troponin I level (P = .007) and acute kidney injury (P = .02), but not with ventilation-free duration (P = .12). Kaplan-Meier analyses for pediatric critical care unit and hospital length of stay identified no differences between patients with and those without myocardial dysfunction. Myocardial dysfunction occurs frequently in children with septic shock but might not affect hospital length of stay.
Article
In the past decade, guidelines have been developed for the early detection and management of severe sepsis in children and neonates. However, severe sepsis continues to be a significant U.S. healthcare problem, accounting for over 720,000 annual hospitalizations. Large-scale epidemiologic studies of severe sepsis continue to be limited, particularly in children. We present data from 1995, 2000, and 2005 in seven U.S. states, examining how case mix, outcome, and resource use for pediatric severe sepsis have changed over time. We constructed a database including all acute-care hospitalizations for children in the seven states. For each case, we extracted data on demographic characteristics; the principal diagnosis, up to six secondary diagnoses, and six procedures as classified by the International Classification of Diseases, 9th Revision, Clinical Modification codes; and in-hospital fatality. We identified patients with severe sepsis using International Classification of Diseases, 9th Revision, Clinical Modification codes for both infection and acute organ failure. Retrospective observational cohort dataset from seven U.S. states from 1995, 2000, and 2005. Children in the U.S. aged 0 -19 years old. None. In 2005, 17,542 children were hospitalized with severe sepsis in the seven states; there was an 81% increase in pediatric severe sepsis cases since 1995 and a 45% increase since 2000. This corresponded to an increase in prevalence from 0.56 to 0.89 cases per 1,000 pediatric population. Between 1995 and 2005, the prevalence of severe sepsis in newborns more than doubled, from 4.5 to 9.7 cases per 1,000 births. The most common infecting organisms in all 3 years were Staphylococcus species. From 1995 to 2005, the case-fatality rate decreased from 10.7% to 8.9%. Case fatality associated with Staphylococcus aureus increased, whereas fatality associated with Streptococcus pneumoniae decreased by 75%. Nationally, there were 75,255 pediatric hospitalizations in 2005 involving severe sepsis, with an associated cost of $4.8 billion. Between 1995 and 2005, the prevalence of severe sepsis in U.S. children steadily rose, due to a significant increase in the prevalence of severe sepsis in newborns.
Article
Objectives: Dopamine, a natural catecholamine with hypophysiotropic properties, is used as a first choice drug for inotropic and vasoactive support in pediatric intensive care. In infants and children, the pituitary gland plays a crucial role as a regulator of growth, metabolism, maturation and, possibly, immune function. We evaluated the effect of dopamine infusion (5 [mu]g/kg/min iv) on the dynamics of prolactin, growth hormone, and thyrotropin secretion and on the thyroid axis in critically ill infants and children. Design: Prospective, randomized, controlled, open-labeled, clinical study. Setting: Intensive care unit of a university hospital over a 9-month period. Patients and Methods: The study population consisted of infants and children recovering from cardiovascular surgery. The group was stratified into two age groups (infants aged 12 to 90 days [n = 18] and children aged 0.3 to 6.7 yrs [n = 15]) and was studied dynamically (blood sampling every 20 mins for 3 hrs) on two consecutive days, after randomization for dopamine with-drawal on the first or the second day. Serum prolactin, growth hormone, insulin-like growth factor-1, thyrotropin, thyroxine (T4), triiodothyronine (T3), and reverse triiodothyronine (reverse T3) concentrations were measured. Measurements and Main Results: In the newborns, dopamine was found to suppress prolactin, growth hormone, and thyrotropin secretion consistently, rebound releases starting within 20 mins after dopamine withdrawal. One day later, prolactin concentrations were ten times higher, pulsatile growth hormone secretion was augmented, thyrotropin was unchanged, but T3 was increased by 30% and the T3/reverse T3 ratio was inverted. In the children, dopamine suppressed prolactin and thyrotropin (but not growth hormone) secretion, rebound releases starting within 20 mins after dopamine withdrawal. One day later, prolactin concentrations were at least twice as high, thyrotropin was increased ten-fold, T4 was augmented by 14%, T3 by 30% and the T3/reverse T3 ratio had doubled. Neither in newborns nor in children did dopamine withdrawal appear to affect the low serum insulin-like growth factor-1 concentrations. Conclusions: The data indicate that dopamine infusion induces or aggravates partial hypopituitarism and the euthyroid sick syndrome in critically ill infants and children. (Crit Care Med 1994; 22:1747-1753) (C) Williams & Wilkins 1994. All Rights Reserved.
Article
: In 2002, the Surviving Sepsis Campaign pointed out the need to recognize sepsis as an important cause of death and high economic and social costs. There are few epidemiologic studies of this disease in pediatrics and none in Colombia. The objective of this study was to describe the sociodemographic and clinical characteristics of patients with sepsis who were admitted at participating pediatric intensive care units. : Prospective study. : A Web site, http://www.sepsisencolombia.com, was created, in which 19 pediatric intensive care units from the ten principal cities in the country reported epidemiologic data about patients with sepsis between March 1, 2009, and February 28, 2010. : None. : There were 1,051 patients. Of these, 55% were male. Fifty-six percent came from urban areas. Fifty-six percent were <2 yrs of age. Seventy-six percent belonged to a low socioeconomic strata and 44% received government-subsidized health insurance. Forty-eight percent of patients had septic shock, 25% severe sepsis, and 27% sepsis. Forty-three percent were diagnosed with multiple organ dysfunction syndrome. In 54%, the infection was of respiratory origin followed by the abdomen as the site of origin in 18% of the patients. In almost 50%, the etiological agent was detected with Gram-negative bacteria being the most frequent and of highest mortality. Fifty percent had some type of relevant pathologic antecedent. Eleven percent had an invasive device on admission. Sixty-eight percent of the patients required mechanical ventilation. Mortality rate was 18%. The most important risk factors for mortality were age under 2 yrs, presence of shock or multiple organ dysfunction syndrome, and presence of Gram-negative bacteria. : Sepsis is common in Colombian pediatric intensive care units. Clear risk factors for getting sick and dying from this disease were identified. Mortality resulting from this disease is considerable for a developing society like ours.
Article
There has long-been controversy about the possible superiority of norepinephrine compared to dopamine in the treatment of shock. The objective was to evaluate the effects of norepinephrine and dopamine on outcome and adverse events in patients with septic shock. A systematic search of the MEDLINE, Embase, Scopus, and CENTRAL databases, and of Google Scholar, up to June 30, 2011. All studies providing information on the outcome of patients with septic shock treated with dopamine compared to norepinephrine were included. Observational and randomized trials were analyzed separately. Because time of outcome assessment varied among trials, we evaluated 28-day mortality or closest estimate. Heterogeneity among trials was assessed using the Cochrane Q homogeneity test. A Forest plot was constructed and the aggregate relative risk of death was computed. Potential publication bias was evaluated using funnel plots. We retrieved five observational (1,360 patients) and six randomized (1,408 patients) trials, totaling 2,768 patients (1,474 who received norepinephrine and 1,294 who received dopamine). In observational studies, among which there was significant heterogeneity (p < .001), there was no difference in mortality (relative risk, 1.09; confidence interval, 0.84-1.41; p = .72). A sensitivity analysis identified one trial as being responsible for the heterogeneity; after exclusion of that trial, no heterogeneity was observed and dopamine administration was associated with an increased risk of death (relative risk, 1.23; confidence interval, 1.05-1.43; p < .01). In randomized trials, for which no heterogeneity or publication bias was detected (p = .77), dopamine was associated with an increased risk of death (relative risk, 1.12; confidence interval, 1.01-1.20; p = .035). In the two trials that reported arrhythmias, these were more frequent with dopamine than with norepinephrine (relative risk, 2.34; confidence interval, 1.46-3.77; p = .001). In patients with septic shock, dopamine administration is associated with greater mortality and a higher incidence of arrhythmic events compared to norepinephrine administration.
Article
The Institute of Medicine calls for the use of clinical guidelines and practice parameters to promote "best practices" and to improve patient outcomes. 2007 update of the 2002 American College of Critical Care Medicine Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock. Society of Critical Care Medicine members with special interest in neonatal and pediatric septic shock were identified from general solicitation at the Society of Critical Care Medicine Educational and Scientific Symposia (2001-2006). The Pubmed/MEDLINE literature database (1966-2006) was searched using the keywords and phrases: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation (ECMO), and American College of Critical Care Medicine guidelines. Best practice centers that reported best outcomes were identified and their practices examined as models of care. Using a modified Delphi method, 30 experts graded new literature. Over 30 additional experts then reviewed the updated recommendations. The document was subsequently modified until there was greater than 90% expert consensus. The 2002 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and AHA sanctioned recommendations. Centers that implemented the 2002 guidelines reported best practice outcomes (hospital mortality 1%-3% in previously healthy, and 7%-10% in chronically ill children). Early use of 2002 guidelines was associated with improved outcome in the community hospital emergency department (number needed to treat = 3.3) and tertiary pediatric intensive care setting (number needed to treat = 3.6); every hour that went by without guideline adherence was associated with a 1.4-fold increased mortality risk. The updated 2007 guidelines continue to recognize an increased likelihood that children with septic shock, compared with adults, require 1) proportionally larger quantities of fluid, 2) inotrope and vasodilator therapies, 3) hydrocortisone for absolute adrenal insufficiency, and 4) ECMO for refractory shock. The major new recommendation in the 2007 update is earlier use of inotrope support through peripheral access until central access is attained. The 2007 update continues to emphasize early use of age-specific therapies to attain time-sensitive goals, specifically recommending 1) first hour fluid resuscitation and inotrope therapy directed to goals of threshold heart rates, normal blood pressure, and capillary refill <or=2 secs, and 2) subsequent intensive care unit hemodynamic support directed to goals of central venous oxygen saturation >70% and cardiac index 3.3-6.0 L/min/m.
Article
To determine whether ultrasound (US) increases successful central venous catheter (CVC) placement, decreases site attempts, and decreases CVC placement complications. A prospective observational cohort study evaluating a transition by the Pediatric Critical Care Medicine service to US-guided CVC placement. Medical and surgical patients in a 21-bed quaternary multidisciplinary pediatric intensive care unit had CVCs placed by attendings, fellows, residents, and a nurse practitioner. Ninety-three patients were prospectively enrolled into the landmark (LM) group and 119 into the US group. : After collection of prospective LM data, training with US guidance was provided. CVCs were subsequently placed with US guidance. Operator information, disease process, emergent/routine, sites attempted, and complications were recorded. Procedure time was from initial skin puncture to guidewire placement. There was no difference overall in success rates (88.2% LM vs. 90.8% US, p = 0.54) or time to successful placement (median seconds 269 LM vs. 150 US, p = 0.14) between the two groups. Median number of attempts were fewer with US for all CVCs attempted (3 vs. 1, p < 0.001) as were attempts at >1 anatomical site (20.7% LM vs. 5.9% US, p = 0.001). Use of US was associated with fewer inadvertent artery punctures (8.5% vs. 19.4%, p = 0.03). Time to successful placement by residents was decreased with US (median 919 seconds vs. 405 seconds, p = 0.02). More internal jugular CVCs were placed during the US period than during the LM period (13.4% vs. 2.1%). US-guided CVC placement in children is associated with decreased number of anatomical sites attempted and decreased number of attempts to gain placement. Time to placement by residents was decreased with US, but not the time to placement by other operators. US guidance increased the use of internal jugular catheter placement and decreased artery punctures. US guidance did not improve success rates.
Article
Guidelines for the adrenergic support of septic shock are controversial. In patients with community-acquired septic shock, we assessed the impact of the choice of vasopressor support on mortality. Cohort, multiple center, observational study. Seventeen Portuguese intensive care units (ICUs). All adult patients admitted to a participating ICU between December 2004 and November 2005. None. Patients were followed up during the first five ICU days, the day of discharge or death, and hospital outcome. Eight hundred ninety-seven consecutive patients with community-acquired sepsis (median age, 63 years; 577 men; and hospital mortality, 38%) were studied. Of the 458 patients with septic shock, 73% received norepinephrine and 50.5% dopamine. The norepinephrine group had a higher hospital mortality (52% vs. 38.5%, p = 0.002). A Kaplan-Meier survival curve showed diminished 28-day survival in the norepinephrine group (log-rank = 22.6, p < 0.001). A Cox proportional hazard analysis revealed that the administration of norepinephrine was associated with an increased risk of death (adjusted hazard ratio, 2.501; 95% confidence interval, 1.413-4.425; p = 0.002). In a multivariate analysis with ICU mortality as the dependent factor, Simplified Acute Physiology Score II and norepinephrine administration were independent risk factors for ICU mortality in patients with septic shock. In patients with community-acquired septic shock, our data suggest that norepinephrine administration could be associated with worse outcome.
Article
We report that the pediatric cardiogenic shock and septic shock populations show similar hemodynamic and oxygen utilization physiologic relationships during aggressive intensive care therapy. We examined the mathematical relationships between vascular tone and flow, and oxygen utilization and oxygen delivery (DO2) in the early and middle stages of cardiogenic and septic shock. The fitted curves between cardiac index and systemic vascular resistance, and oxygen consumption (VO2) and DO2 were clinically and statistically similar in both shock populations. We found no evidence for decreased oxygen extraction in sepsis as compared to the cardiogenic shock population. In addition, it appears that the major determinant of VO2 in these populations is DO2, not oxygen extraction. We suggest that patients with cardiogenic or septic shock can be treated according to similar physiologic principles.
Article
The neurological morbidity associated with prolonged periods of circulatory arrest has led some cardiac surgical teams to promote continuous low-flow cardiopulmonary bypass as an alternative strategy. The nonneurological postoperative effects of both techniques have been previously studied only in a limited fashion. We compared the hemodynamic profile (cardiac index and systemic and pulmonary vascular resistances), intraoperative and postoperative fluid balance, and perioperative course after deep hypothermia and support consisting predominantly of total circulatory arrest or low-flow cardiopulmonary bypass in a randomized, single-center trial. Eligibility criteria included a diagnosis of transposition of the great arteries and a planned arterial switch operation before the age of 3 months. Of the 171 patients, 129 (66 assigned to circulatory arrest and 63 to low-flow bypass) had an intact ventricular septum and 42 (21 assigned to circulatory arrest and 21 to low-flow bypass) had an associated ventricular septal defect. There were 3 (1.8%) hospital deaths. Patients assigned to low-flow bypass had significantly greater weight gain and positive fluid balance compared with patients assigned to circulatory arrest. Despite the increased weight gain in the infants assigned to low-flow bypass, the duration of mechanical ventilation, stay in the intensive care unit, and hospital stay were similar in both groups. Hemodynamic measurements were made in 122 patients. During the first postoperative night, the cardiac index decreased (32.1 +/- 15.4%, mean +/- SD), while pulmonary and systemic vascular resistance increased. The measured cardiac index was < 2.0 L.min-1.m-2 in 23.8% of the patients, with the lowest measurement typically occurring 9 to 12 hours after surgery. Perfusion strategy assignment was not associated with postoperative hemodynamics or other nonneurological postoperative events. After heart surgery in neonates and infants, both low-flow bypass and circulatory arrest perfusion strategies have comparable effects on the nonneurological postoperative course and hemodynamic profile.
Article
To determine the hemodynamic responses to dopamine and epinephrine infusions in newborn piglets during normoxia and hypoxia. Prospective, randomized, blind cross-over study. Newborn piglets (n = 7). Animals were acutely instrumented for measurements of cardiac output, pulmonary and systemic pressures, carotid and coronary artery blood flow, and coronary artery oxygen consumption. Dopamine at infusion rates of 2 to 16 micrograms/kg/min and epinephrine 0.2 to 1.6 micrograms/kg/min were administered during normoxia. Six piglets were similarly prepared and were then made hypoxic to an arterial O2 saturation of 45% to 50%. Epinephrine at infusion rates of 0.2 to 3.2 micrograms/kg/min and dopamine at rates of 2 to 32 micrograms/kg/min were administered in random order during hypoxia. During normoxia, cardiac output increased similarly with both drugs and was significantly increased by > or = 0.2 micrograms/kg/min of epinephrine and significantly increased by 8 or 16 micrograms/kg/min of dopamine. Mean arterial blood pressure was not affected by dopamine but was significantly increased by epinephrine at a rate of 1.6 micrograms/kg/min. The relative effects of the drugs on pulmonary and systemic vascular resistance differed, the pulmonary/systemic vascular resistance ratio was reduced at the higher doses of epinephrine (i.e., 0.8 and 1.6 micrograms/kg/min) and was unaffected by dopamine. Coronary artery oxygen consumption and coronary blood flow increased significantly with both medications at rates > 0.4 and 4 micrograms/kg/min, respectively. Increases of both variables were greater with epinephrine than with dopamine. Myocardial extraction ratio was unaffected by dopamine and reduced at 0.2 and 1.6 micrograms/kg/min of epinephrine. Hypoxia caused significant increases in cardiac index, systemic blood pressure, pulmonary arterial pressure, carotid artery blood flow, coronary artery blood flow, coronary oxygen consumption, coronary oxygen extraction ratio, and the pulmonary/systemic vascular resistance ratio. Mean systemic arterial blood pressure increased significantly with 1.6 and 3.2 micrograms/kg/min of epinephrine, but was not significantly affected by dopamine at any infusion rate. Cardiac index was not affected significantly by either of the medications. Thus, there was a significant increase in the calculated systemic vascular resistance index with the highest dose of epinephrine, in contrast to the slight, statistically significant, decrease in calculated systemic vascular resistance index with the highest dose of dopamine. Epinephrine significantly reduced pulmonary arterial pressures at 0.2, 0.4, and 0.8 microgram/kg/min. Dopamine had no effect on this variable. The pulmonary/systemic vascular resistance ratio was significantly reduced by epinephrine at doses of 0.2 and 3.2 micrograms/kg/min, whereas the highest dose of dopamine caused a significant increase in the pulmonary/systemic vascular resistance ratio. Epinephrine infusion during normoxia increases systemic pressure more than pulmonary arterial pressure at doses > or = 8 micrograms/kg/min, and furthermore, produces a more appropriate hemodynamic profile in the presence of hypoxic pulmonary hypertension than dopamine infusion, in the acutely operated anesthetized piglet.
Article
To quantitate ventricular systolic mechanics in septic children. Prospective wall-stress analysis was compared to standard ejection phase indices. University-based pediatric intensive care unit. Fifteen children with sepsis (hemodynamically stable, n = 5; in shock, n = 10). Left ventricular ejection phase indices: shortening fraction (shortening) and corrected mean velocity of circumferential shortening (velocity) were adjusted for end-systolic wall stress (stress). Ejection phase, performance (stress-shortening relation), contractility (stress-velocity relation), and afterload (stress) were indexed to age-corrected normal means, with variance of > or = 2 SD regarded as significant. Preload index represented variance between performance and contractility indices. All hemodynamically stable septic patients had normal performance, contractility, and preload. Afterload was increased in three of five patients. Of the patients with septic shock, six of ten had decreased performance (decreased contractility and increased afterload, n = 4; decreased afterload, n = 1; and severe preload deficit, n = 1). Despite aggressive volume resuscitation, six of ten children in septic shock had evidence of diminished preload. Follow-up studies in the septic shock patients demonstrated reversal of depressed ventricular contractility within 3 to 6 days in all four patients initially affected (p < .05). One patient developed late decreased performance and contractility in association with multiple organ failure. Ventricular loading abnormalities persisted in a follow-up study of these patients including a preload deficit in five of ten patients in shock. The frequency rate (40%) of reversible impaired ventricular contractility in children with septic shock is significant. Afterload is normal or increased in the majority of septic subjects, possibly due to acute ventricular dilation. Decreased preload contributes to altered ventricular performance in the majority of children with septic shock, persisting days after the initiation of therapy. Wall-stress analysis provided detailed information regarding ventricular mechanics that was not otherwise obtainable by standard ejection phase indices.
Article
This study evaluated the extent of the collagen network in neonatal heart muscle and whether the type I/type III collagen ratio is the same as in the adult heart. The functional integrity and the stress-strain relation of heart muscle depends largely on the extracellular collagen matrix. The question therefore arises whether the altered compliance of the neonatal heart could relate to the developmental state of collagen and, in particular, the distribution of types I and III collagen. Type I collagen mainly provides rigidity and type III collagen elasticity. Specimens from the left lateral wall of the left ventricle of human hearts (immature to full term, n = 23; 3 weeks to 12 years, n = 17) were used to determine the total collagen amount, using the hydroxyproline assay. Similar left ventricular specimens of human hearts (fetal to mature, n = 20; 2 months to 1.5 years, n = 6) were fixed in formalin, paraffin embedded and stained with Sirius red F3BA for total collagen. The ratio of total collagen to total protein was quantified spectrophotometrically. Frozen sections of left ventricular myocardium (immature to mature, n = 17; 4 months to 12 years, n = 10) were stained with antibodies raised against types I and III collagen. Antibody titration was done on human leiomyoma tissue with a known type I/type III collagen ratio. The endomysial collagen types were quantified using a spectrophotometer and expressed as a ratio. Adult human myocardium (n = 10) was used as reference. The study showed that the total amount of collagen increases with age. However, the ratio of total collagen to total protein and the ratio of type I to type III collagen were very high in hearts of the very young. During development, a gradual decrease occurred, with the total collagen/total protein ratio reaching normal levels at approximately 5 months after birth and the type I/type III collagen ratio stabilizing at a much later age. These findings suggest that the relative high content of collagen, related to the myocytes, and the high ratio of type I to type III collagen provide the substrate for a rigid, less compliant heart in neonates.
Article
Adrenaline is used increasingly in the management of septic shock, but its efficacy and safety are uncertain. In an open, randomised, crossover study we compared the effects of stepped doses of adrenaline 0.1 to 0.5 microgram/kg per min and dopamine 2.5 to 10 micrograms/kg per min on the haemodynamic and acid-base status of 23 patients critically ill with severe sepsis (n = 10) or severe malaria (n = 13). All patients completed the dopamine study whereas in 16 (84%) patients the adrenaline infusion had to be terminated before reaching, or during, the maximum dose because of lactic acidosis (p < 0.0002). Adrenaline was associated with a mean (95% CI) increase in plasma lactate of 3.2 (2.6 to 3.8) mmol/L, and mean falls in arterial pH of 0.052 (0.035-0.068) pH units and base excess of 3.8 (2.8-4.7) mmol/L. The geometric mean (95% CI) lactate increment per unit adrenaline dose was 8.2 (5.8-10.5) mmol/L per microgram/kg per min. In contrast dopamine was associated with a fall in lactate of 1.0 (0.4-1.5) mmol/L, a rise in base excess of 1.4 (0.7 to 2.0) mmol/L (p < 0.0001 in each case), and no effect on arterial pH. Both drugs induced significant increases in cardiac index and oxygen delivery with smaller increases in oxygen consumption and falls in systemic vascular resistance which were similar in severe malaria and severe sepsis (p > 0.1 in each case) [corrected]. Infusion of inotropic doses of adrenaline in severe infections causes lactic acidosis.