Noradrenaline use for septic shock in children: doses, routes of administration and complications

Lampin, Marie Emilie; Rousseaux, J.; Botte, A.; Ardıç, Sadık; Cremer, R.; Leclerc, F.

doi:10.1111/j.1651-2227.2012.02725.x

Cited by 53 publications

(33 citation statements)

References 23 publications

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“…Indeed, our results suggest using higher dosing regimens at the initiation of norepinephrine in the most critically ill and youngest children. These findings are in keeping with observational data reported by Lampin et al [3] who highlighted the use of higher doses of norepinephrine in septic children (0.5 ± 0.4 μg kg −1 min −1 starting dose up to 2.5 ± 2.2 μg kg −1 min −1 maximum dose) than those typically recommended in the literature which suggest a starting dose at 0.3 μg kg −1 min −1 [1,2]. However, this latter starting dose may be insufficient for certain patients and thus our model could help clinicians to reach the target MAP more quickly.…”

Section: Figuresupporting

confidence: 94%

“…Norepinephrine is currently administered to patients with hypotensive distributive shock . In children, it has supplanted dopamine over the past few years as the preferred drug for sustaining and increasing systemic arterial pressure, although evidenced‐based data are poor . The amplitude of the haemodynamic response, which is primarily dependent on norepinephrine concentrations, is difficult to predict given the multitude of factors involved and clinical experience suggests broad between‐subject variability .…”

Section: Introductionmentioning

confidence: 99%

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Population pharmacokinetics and haemodynamic effects of norepinephrine in hypotensive critically ill children

Oualha

Tréluyer

Lesage

et al. 2014

Brit J Clinical Pharma

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AIMThe aim of the study was to investigate the pharmacokinetics and pharmacodynamics of norepinephrine in hypotensive critically ill children, including associated variability factors. METHODSThis was a prospective study in an 18-bed neonatal and paediatric intensive care unit. All children were aged less than 18 years, weighed more than 1500 g and required norepinephrine for systemic arterial hypotension. The pharmacokinetics and haemodynamic effects were described using the non-linear mixed effect modelling software MONOLIX. RESULTSNorepinephrine dosing infusions ranging from 0.05 to 2 μg kg −1 min −1 were administered to 38 children whose weight ranged from 2 to 85 kg. A one compartment open model with linear elimination adequately described the norepinephrine concentration-time courses. Bodyweight (BW) was the main covariate influencing norepinephrine clearance (CL) and endogenous norepinephrine production rate (q0) via an allometric relationship: CL(BWi) = θCL × (BWi) 3/4 and q0(BWi) = θq0 × (BWi) 3/4 . The increase in mean arterial pressure (MAP) as a function of norepinephrine concentration was well described using an Emax model. The effects of post-conceptional age (PCA) and number of organ dysfunctions were significant on basal MAP level (MAP0i = MAP0 × PCA/9i 0.166 ) and on the maximal increase in MAP (32 mmHg and 12 mmHg for a number of organ dysfunctions ≤3 and ≥4, respectively). CONCLUSIONThe pharmacokinetics and haemodynamic effects of norepinephrine in hypotensive critically ill children highlight the between-subject variability which is related to the substantial role of age, BW and severity of illness. Taking into account these individual characteristics may help clinicians in determining an appropriate initial a priori dosing regimen. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Haemodynamic response to norepinephrine is variable and unpredictable.• The pharmacokinetics and pharmacodynamics of norepinephrine in adults are well described by a one compartment model with a first order elimination and Emax model, respectively. Clearance is influenced by the severity of illness.• Norepinephrine kinetics and dynamics in children are unknown. WHAT THIS STUDY ADDS• In children, the pharmacokinetics and pharmacodynamics of norepinephrine on between-subject variability are related to age, bodyweight and severity of illness.• The lower the age, the higher the number of organ dysfunctions and the lower the amplitude of the increase in mean arterial pressure.

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Section: Figuresupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics and haemodynamic effects of norepinephrine in hypotensive critically ill children

Oualha

Tréluyer

Lesage

et al. 2014

Brit J Clinical Pharma

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“…Norepinephrine and epinephrine are suggested for patients in dopamine-refractory shock depending on their vascular physiology at that time [6]. However, our data suggest a trend toward the use of norepinephrine as a first line vasopressor in pediatric septic shock patients in our study; this also was reported by Matt et al [14] and Lampin et al [15] The explanation of this trend is not clear but is likely due in part to a higher number of adverse events with dopamine than with norepinephrine [16]. …”

Section: Discussionsupporting

confidence: 63%

Management of children with sepsis and septic shock: a survey among pediatric intensivists of the Réseau Mère-Enfant de la Francophonie

Santschi

Leclerc

2013

Ann Intensive Care

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BackgroundPediatric sepsis represents an important cause of mortality in pediatric intensive care units (PICU). Although adherence to published guidelines for the management of severe sepsis patients is known to lower mortality, actual adherence to these recommendations is low. The aim of this study was to describe the initial management of pediatric patients with severe sepsis, as well as to describe the main barriers to the adherence to current guidelines on management of these patients.MethodsA survey using a case scenario to assess the management of a child with severe sepsis was designed and sent out to all PICU medical directors of the 20 institutions member of the “Réseau Mère- Enfant de la Francophonie”. Participants were asked to describe in detail the usual management of these patients in their institution with regard to investigations, fluid and catecholamine management, intubation, and specific treatments. Participants were also asked to identify the main barriers to the application of the Surviving Sepsis Campaign guidelines in their center.ResultsTwelve PICU medical directors answered the survey. Only two elements of the severe sepsis bundles had a low stated compliance rate: “maintain adequate central venous pressure” and “glycemic control” had a stated compliance of 8% and 25% respectively. All other elements of the bundles had a reported compliance of over 90%. Furthermore, the most important barriers to the adherence to Surviving Sepsis Campaign guidelines were the unavailability of continuous central venous oxygen saturation (ScvO2) monitoring and the absence of a locally written protocol.ConclusionsIn this survey, pediatric intensivists reported high adherence to the current recommendations in the management of pediatric severe sepsis regarding antibiotic administration, rapid fluid resuscitation, and administration of catecholamines and steroids, if needed. Technical difficulties in obtaining continuous ScvO2 monitoring and absence of a locally written protocol were the main barriers to the uniform application of current guidelines. We believe that the development of locally written protocols and of specialized teams could add to the achievement of the goal that every child in sepsis should be treated according to the latest evidence to heighten his chances of survival.

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“…All vasoactive agents, including norepinephrine, may be initiated through peripheral venous (or intraosseous, if in place) access if central venous access is not readily available to avoid delays in therapy [227,228]. However, central venous access should be obtained as soon as reasonably practicable.…”

Section: Vasoactive Medicationsmentioning

confidence: 99%

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

et al. 2020

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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 The Society of Critical Care Medicine guidelines are intended for general information only, are not medical advice, and do not replace professional advice, which should be sought for any medical condition. The full disclaimer for guidelines can be accessed at https ://www.sccm.org/Resea rch/Guide lines /Guide lines . 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. S14 the group heads, panel members, and methodologists. Searches utilized ...

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Noradrenaline use for septic shock in children: doses, routes of administration and complications

Abstract: Higher doses of noradrenaline than those suggested in the literature may be necessary to reverse hypotension and hypoperfusion. The use of noradrenaline through peripheral venous access or intra-osseous route was safe, without any adverse effects.

Cited by 53 publications

References 23 publications

Population pharmacokinetics and haemodynamic effects of norepinephrine in hypotensive critically ill children

Population pharmacokinetics and haemodynamic effects of norepinephrine in hypotensive critically ill children

Management of children with sepsis and septic shock: a survey among pediatric intensivists of the Réseau Mère-Enfant de la Francophonie

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

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