Early norepinephrine decreases fluid and ventilatory requirements in pediatric vasodilatory septic shock

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Abstract

Aims:

We previously reported that vasodilatation was common in pediatric septic shock, regardless of whether they were warm or cold, providing a rationale for early norepinephrine (NE) to increase venous return (VR) and arterial tone. Our primary aim was to evaluate the effect of smaller fluid bolus plus early-NE versus the American College of Critical Care Medicine (ACCM) approach to more liberal fluid boluses and vasoactive-inotropic agents on fluid balance, shock resolution, ventilator support and mortality in children with septic shock. Secondly, the impact of early NE on hemodynamic parameters, urine output and lactate levels was assessed using multimodality-monitoring.

Methods:

In keeping with the primary aim, the early NE group (N-27) received NE after 30ml/kg fluid, while the ACCM group (N-41) were a historical cohort managed as per the ACCM Guidelines, where after 40-60ml/kg fluid, patients received first line vasoactive-inotropic agents. The effect of early-NE was characterized by measuring stroke volume variation(SVV), systemic vascular resistance index (SVRI) and cardiac function before and after NE, which were monitored using ECHO + Ultrasound-Cardiac-Output-Monitor (USCOM) and lactates.

Results:

The 6-hr fluid requirement in the early-NE group (88.9+31.3 to 37.4+15.1ml/kg), and ventilated days [median 4 days (IQR 2.5-5.25) to 1day (IQR 1-1.7)] were significantly less as compared to the ACCM group. However, shock resolution and mortality rates were similar. In the early NE group, the overall SVRI was low (mean 679.7dynes/sec/cm5/m2, SD 204.5), and SVV decreased from 23.8±8.2 to 18.5±9.7, p=0.005 with NE infusion suggesting improved preload even without further fluid loading. Furthermore, lactate levels decreased and urine-output improved.

Conclusion:

Early-NE and fluid restriction may be of benefit in resolving shock with less fluid and ventilator support as compared to the ACCM approach.

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Most cited references 30

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Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares.

Paul E Marik, Michael Baram, Bobbak Vahid (2008)

Central venous pressure (CVP) is used almost universally to guide fluid therapy in hospitalized patients. Both historical and recent data suggest that this approach may be flawed. A systematic review of the literature to determine the following: (1) the relationship between CVP and blood volume, (2) the ability of CVP to predict fluid responsiveness, and (3) the ability of the change in CVP (DeltaCVP) to predict fluid responsiveness. MEDLINE, Embase, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. Reported clinical trials that evaluated either the relationship between CVP and blood volume or reported the associated between CVP/DeltaCVP and the change in stroke volume/cardiac index following a fluid challenge. From 213 articles screened, 24 studies met our inclusion criteria and were included for data extraction. The studies included human adult subjects, healthy control subjects, and ICU and operating room patients. Data were abstracted on study design, study size, study setting, patient population, correlation coefficient between CVP and blood volume, correlation coefficient (or receive operator characteristic [ROC]) between CVP/DeltaCVP and change in stroke index/cardiac index, percentage of patients who responded to a fluid challenge, and baseline CVP of the fluid responders and nonresponders. Metaanalytic techniques were used to pool data. The 24 studies included 803 patients; 5 studies compared CVP with measured circulating blood volume, while 19 studies determined the relationship between CVP/DeltaCVP and change in cardiac performance following a fluid challenge. The pooled correlation coefficient between CVP and measured blood volume was 0.16 (95% confidence interval [CI], 0.03 to 0.28). Overall, 56+/-16% of the patients included in this review responded to a fluid challenge. The pooled correlation coefficient between baseline CVP and change in stroke index/cardiac index was 0.18 (95% CI, 0.08 to 0.28). The pooled area under the ROC curve was 0.56 (95% CI, 0.51 to 0.61). The pooled correlation between DeltaCVP and change in stroke index/cardiac index was 0.11 (95% CI, 0.015 to 0.21). Baseline CVP was 8.7+/-2.32 mm Hg [mean+/-SD] in the responders as compared to 9.7+/-2.2 mm Hg in nonresponders (not significant). This systematic review demonstrated a very poor relationship between CVP and blood volume as well as the inability of CVP/DeltaCVP to predict the hemodynamic response to a fluid challenge. CVP should not be used to make clinical decisions regarding fluid management.

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Sepsis and the heart.

M Merx, C. Weber (2007)

Sepsis is generally viewed as a disease aggravated by an inappropriate immune response encountered in the afflicted individual. As an important organ system frequently compromised by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades. Although a number of mediators and pathways have been shown to be associated with myocardial depression in sepsis, the precise cause remains unclear to date. There is currently no evidence supporting global ischemia as an underlying cause of myocardial dysfunction in sepsis; however, in septic patients with coexistent and possibly undiagnosed coronary artery disease, regional myocardial ischemia or infarction secondary to coronary artery disease may certainly occur. A circulating myocardial depressant factor in septic shock has long been proposed, and potential candidates for a myocardial depressant factor include cytokines, prostanoids, and nitric oxide, among others. Endothelial activation and induction of the coagulatory system also contribute to the pathophysiology in sepsis. Prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious focus, if indicated and feasible, is the mainstay and also the only strictly causal line of therapy. In the presence of severe sepsis and septic shock, supportive treatment in addition to causal therapy is mandatory. The purpose of this review is to delineate some characteristics of septic myocardial dysfunction, to assess the most commonly cited and reported underlying mechanisms of cardiac dysfunction in sepsis, and to briefly outline current therapeutic strategies and possible future approaches.

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Fluid overload is associated with impaired oxygenation and morbidity in critically ill children.

Michael Zappitelli, Angela Jefferson, A Arikan … (2012)

Fluid overload is common in the critically ill and is thought to contribute to oxygenation failure and mortality. Since increasing disease severity often requires more fluid for resuscitation, it is unclear whether fluid overload is a causative factor in morbidity or is simply an indicator of disease severity. Investigate the association between fluid overload and oxygenation while controlling for severity of illness by daily Pediatric Logistic Organ Dysfunction scores. Retrospective chart review, tertiary children's hospital. The oxygenation index, fluid overload percent, and daily Pediatric Logistic Organ Dysfunction scores were obtained in a retrospective chart review of 80 patients (mean age 58.7 ± 73.0 months) with respiratory failure. Univariate and multivariate approaches were used to assess the independent relation between fluid overload percent and duration of stay and ventilation. None. Higher peak fluid overload percent predicted higher peak oxygenation index, independent of age, gender, and Pediatric Logistic Organ Dysfunction (p = .009). Fluid overload percent ≥15% on any given day was also independently associated with that day's oxygenation index, controlled for age, gender, and Pediatric Logistic Organ Dysfunction (p < .05). Peak fluid overload percent and severe fluid overload percent (≥15%) were both independently associated with longer duration of ventilation (p = .004, p = .01), and pediatric intensive care unit (p = .008, p = .01) and hospital length of stay (p = .02, p = .04), controlled for age, gender, Pediatric Logistic Organ Dysfunction, and in the case of ventilation, respiratory admission. This is the first study to report that positive fluid balance adversely affected the pediatric intensive care unit course in children who did not receive renal replacement therapy. While timely administration of fluids is lifesaving, positive fluid balance after hemodynamic stabilization may impact organ function and negatively influence important outcomes in critically ill patients.

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Author and article information

Journal

Journal ID (nlm-ta): Indian J Crit Care Med

Journal ID (iso-abbrev): Indian J Crit Care Med

Journal ID (publisher-id): IJCCM

Title: Indian Journal of Critical Care Medicine : Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 0972-5229

ISSN (Electronic): 1998-359X

Publication date (Print): October 2016

Volume: 20

Issue: 10

Pages: 561-569

Affiliations

[1] From: Pediatric Intensive Care Unit, Apollo Children's Hospital, Chennai, Tamil Nadu, India

[1 ]Department of Pediatrics and Emergency Medicine, BC Children's Hospital, Sunny Hill Health Centre for Children, University of British Columbia, BC V6H 3V4, Canada

[2 ]Department of Medical Education, Apollo Hospitals, Chennai, Tamil Nadu, India

[3 ]Department of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, VA 23507, USA

Author notes

Correspondence: Dr. Suchitra Ranjit, Pediatric Intensive Care and Emergency Services, Apollo Children's Hospital, Greams Road, Chennai - 600 006, Tamil Nadu, India. E-mail: suchitraranjit@ 123456yahoo.co.in

Article

Publisher ID: IJCCM-20-561

DOI: 10.4103/0972-5229.192036

PMC ID: 5073769

PubMed ID: 27829710

SO-VID: 36bdaef0-60a4-4181-a8cf-430e492f8327

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This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Early norepinephrine decreases fluid and ventilatory requirements in pediatric vasodilatory septic shock

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Pediatric Pulse: Advancing Neonatal and Child Health

Most cited references 30

Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares.

Sepsis and the heart.

Fluid overload is associated with impaired oxygenation and morbidity in critically ill children.

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