Initial resuscitation and management of pediatric septic shock.
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ABSTRACT:
SUBMITTER: Martin K
PROVIDER: S-EPMC4395852 | biostudies-literature | 2015 Apr
REPOSITORIES: biostudies-literature
Publications
Initial resuscitation and management of pediatric septic shock.
Minerva pediatrica 20150121 2
The pediatric sepsis syndrome remains a common cause of morbidity, mortality, and health care utilization costs worldwide. The initial resuscitation and management of pediatric sepsis is focused on 1) rapid recognition of abnormal tissue perfusion and restoration of adequate cardiovascular function; 2) eradication of the inciting invasive infection, including prompt administration of empiric broad-spectrum antimicrobial medications; and 3) supportive care of organ system dysfunction. Efforts to ...[more]
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Project description:Intravenous fluid resuscitation is recommended first-line treatment for sepsis-associated hypotension and/or hypoperfusion. The rationale is to restore circulating volume and optimize cardiac output in the setting of shock. Nonetheless, there is limited high-level evidence to support this practice. Over the past decade emerging evidence of harm associated with large volume fluid resuscitation among patients with septic shock has led to calls for a more conservative approach. Specifically, clinical trials undertaken in Africa have found harm associated with initial fluid resuscitation in the setting of infection and hypoperfusion. While translating these findings to practice in other settings is problematic, there has been a re-appraisal of current practice with some recommending earlier use of vasopressors rather than repeated fluid boluses as an alternative to restore perfusion in septic shock. There is consequently uncertainty and variation in practice. The question of fluids or vasopressors for initial resuscitation in septic shock is the subject of international multicentre clinical trials.
| S-EPMC9729725 | biostudies-literature
Project description:In an ongoing translational research program involving microarray-based expression profiles in pediatric septic shock, we have now conducted longitudinal studies focused on the temporal expression profiles of canonical signaling pathways and gene networks. Genome-level expression profiles were generated from whole blood-derived RNA samples of children with septic shock (n = 30 individual patients) corresponding to days 1 and 3 of admission to the pediatric intensive care unit. Based on sequential statistical and expression filters, day 1 and day 3 of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to normal control patients. Venn analysis demonstrated 239 unique genes in the day 1 data set, 598 unique genes in the day 3 data set, and 1,906 genes common to both data sets. Analyses targeted toward derivation of biological function from these data sets demonstrated time-dependent, differential regulation of genes involved in multiple canonical signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell- and MHC antigen-related biological processes were persistently downregulated from day 1 to day 3. Further analyses demonstrated large scale and persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock, which has undergone longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses that can be readily tested at both the experimental and translational levels. Keywords: Inflammation; sepsis; innate immunity; T cells; MHC antigen Keywords: to be updated
2007-06-14 | GSE8121 | GEO
Project description:BackgroundThe Surviving Sepsis Campaign and the American College of Critical Care Medicine guidelines have provided recommendations for the management of pediatric septic shock patients. We conducted a survey among the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) members to assess variations to these recommendations.MethodsA total of 114 pediatric intensive care physicians completed an electronic survey. The survey consisted of four standardized clinical cases exploring seven clinical scenarios.ResultsAmong the seven different clinical scenarios, the types of fluids were preferentially non-synthetic colloids (albumin) and crystalloids (isotonic saline) and volume expansion was not limited to 60 ml/kg. Early intubation for mechanical ventilation was used by 70% of the participants. Norepinephrine was stated to be used in 94% of the PICU physicians surveyed, although dopamine or epinephrine is recommended as first-line vasopressors in pediatric septic shock. When norepinephrine was used, the addition of another inotrope was frequent. Specific drugs such as vasopressin or enoximone were used in < 20%. Extracorporeal life support was used or considered by 91% of the physicians audited in certain specific situations, whereas the use of high-flow hemofiltration was considered for 44%.ConclusionsThis pediatric septic shock management survey outlined variability in the current clinician-reported practice of pediatric septic shock management. As most recommendations are not supported by evidence, these findings outline some limitation of existing pediatric guidelines in regard to context and patient's specificity.
| S-EPMC6598895 | biostudies-literature
Project description:BackgroundLeft ventricular-arterial coupling (VAC), defined as the ratio of effective arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), has been extensively described as a key determinant of cardiovascular work efficacy. Previous studies indicated that left ventricular-arterial uncoupling was associated with worse tissue perfusion and increased mortality in shock patients. Therefore, this study aims to investigate whether a resuscitation algorithm based on optimizing left VAC during the initial resuscitation can improve prognosis in patients with septic shock.MethodsThis pilot study was conducted in an intensive care unit (ICU) of a tertiary teaching hospital in China. A total of 83 septic shock patients with left ventricular-arterial uncoupling (i.e., the Ea/Ees ratio ≥ 1.36) were randomly assigned to receive usual care (usual care group, n = 42) or an algorithm-based resuscitation that attempt to reduce the Ea/Ees ratio to 1 within the first 6 h after randomization (VAC-optimized group, n = 41). The left VAC was evaluated by transthoracic echocardiography every 2 h during the study period. The primary endpoint was 28-days mortality. The secondary endpoints included lactate clearance rate, length of ICU stay, and duration of invasive mechanical ventilation (IMV).ResultsEighty-two patients (98.8%) completed the study and were included in the final analysis. The Ea/Ees ratio was reduced in both groups, and the decrease in Ea/Ees ratio in the VAC-optimized group was significantly greater than that in the usual care group [median (interquartile range), 0.39 (0.26, 0.45) vs. 0.1 (0.06, 0.22); P < 0.001]. Compared with the usual care group, the VAC-optimized group likely exhibited the potential to reduce the 28-days mortality (33% vs. 50%; log-rank hazard ratio = 0.526, 95% confidence interval: 0.268 to 1.033). Moreover, the VAC-optimized group had a higher lactate clearance rate than the usual care group [27.7 (11.9, 45.7) % vs. 18.3 (- 5.7, 32.1) %; P = 0.038]. No significant difference was observed in terms of the length of ICU stay or duration of IMV.ConclusionsDuring the initial resuscitation of septic shock, optimizing left ventricular-arterial coupling was associated with improved lactate clearance, while likely having a beneficial effect on prognosis.Trial registrationChinese Clinical Trial Registry, ChiCTR1900024031 . Registered 23 June 2019 - Retrospectively registered.
| S-EPMC8781114 | biostudies-literature
Project description:BackgroundNew definitions for sepsis and septic shock (Sepsis-3) were published, but the strategy to adjust vasopressors after the initial guidelines is still unclear. We conducted a retrospective observational study to explore dosing strategy of norepinephrine (NE).MethodsA retrospective observational study in the 15-bed mixed intensive care unit of a tertiary care university hospital. The study was performed on septic shock patients after 30 mL/kg fluid resuscitation and mean arterial pressure (MAP) levels reached >65 mmHg requiring NE. We divided patients into NE dosage increase and decrease groups, and collected hemodynamic and tissue perfusion parameters before (T1) and after (T2) adjusting NE dosage.ResultsIn both NE increase and decrease groups, central venous pressure (CVP) and pressure difference between usual MAP and MAP (dMAP) at the T1 time point were associated with lactate clearance. In groups LC HM (CVP <10 mmHg, dMAP > 0 mmHg) and HC HM (CVP ≥ 10 mmHg, dMAP > 0 mmHg), decrease in NE dosage decreased lactate level, while in group HC LM (CVP ≥ 10 mmHg, dMAP ≤ 0 mmHg), both increase and decrease in NE dosage led to increase lactate level.ConclusionsAfter patients with septic shock (Sepsis-3) resuscitated to reach the initial recovery target goals, combination of CVP and MAP refer to usual levels can help doctors make the next decision to make the correct choice of increase NE dosage or decrease NE dosage.
| S-EPMC6511425 | biostudies-literature
Project description:BackgroundWe hypothesized that the cardiovascular responses to Surviving Sepsis Guidelines (SSG)-defined resuscitation are predictable based on the cardiovascular state.MethodsFifty-five septic patients treated by SSG were studied before and after volume expansion (VE), and if needed norepinephrine (NE) and dobutamine. We measured mean arterial pressure (MAP), cardiac index (CI), and right atrial pressure (Pra) and calculated pulse pressure and stroke volume variation (PPV and SVV), dynamic arterial elastance (Eadyn), arterial elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees), Ees/Ea (VAC), LV ejection efficiency (LVeff), mean systemic pressure analogue (Pmsa), venous return pressure gradient (Pvr), and cardiac performance (Eh), using standard formulae.ResultsAll patients were hypotensive (MAP 56.8 ± 3.1 mmHg) and tachycardic (113.1 ± 7.5 beat min-1), with increased lactate levels (lactate = 5.0 ± 4.2 mmol L-1) with a worsened VAC. CI was variable but > 2 L min-1 M-2 in 74%. Twenty-eight-day mortality was 48% and associated with admission lactate, blood urea nitrogen (BUN), and creatinine levels but not cardiovascular state. In all patients, both MAP and CI improved following VE, as well as cardiac contractility (Ees). Fluid administration improved Pra, Pmsa, and Pvr in all patients, whereas both HR and Ea decreased after VE, thus normalizing VAC. CI increases were proportional to baseline PPV and SVV. CI increases proportionally decreased PPV and SVV. VE increased MAP > 65 mmHg in 35/55 patients. MAP responders had higher PPV, SVV, and Eadyn than non-responders. NE was given to 20/55 patients in septic shock, but increased MAP > 65 mmHg in only 12. NE increased Ea, Eadyn, Pra, Pmsa, and VAC while decreasing HR, PPV, SVV, and LVeff. MAP responders had higher pre-NE Ees and lower VAC. Dobutamine was given to 6/8 patients who remained hypotensive following NE. It increased Ees, MAP, CI, and LVeff, while decreasing HR, Pra, and VAC. At all times and all steps of the protocol, CI changes were proportional to Pvr changes independent of treatment.ConclusionsThe cardiovascular response to SSG-based resuscitation is highly heterogeneous but predictable from pre-treatment measures of cardiovascular state.
| S-EPMC6466803 | biostudies-literature
Project description:BACKGROUND:Fluid resuscitation has become the cornerstone of early septic shock management, but the optimal fluid rate is still not well studied. The goal of this investigation is to examine the relationship between fluid resuscitation rate and septic shock resolution. METHOD:We retrospectively studied adult (≥ 18 years) patients with septic shock, defined based on sepsis III definition, from January 1, 2006, through May 31, 2018, in the medical intensive care unit (MICU) of Mayo Clinic Rochester. The fluid resuscitation time was defined as the time required to infuse the initial fluid bolus of 30 ml/kg, based on the recommendations of the 2016 surviving sepsis campaign. The cohort was divided into four groups based on the average fluid rate (group 1 ≥ 0.5, group 2 0.25-0.49, group 3 0.17-0.24, and group 4 < 0.17 ml/kg/min). The primary outcome was the time to shock reversal. Multivariable regression analyses were conducted to account for potential confounders. RESULT:A total of 1052 patients met eligibility criteria and were included in the analysis. The time-to-shock reversal was significantly different among the groups (P < .001). Patients in group 1 who received fluid resuscitation at a faster rate had a shorter time to shock reversal (HR = 0.78; 95% CI 0.66-0.91; P = .01) when compared with group 4 with a median (IQR) time-to-shock reversal of 1.7 (1.5, 2.0) vs. 2.8 (2.6, 3.3) days, respectively. Using 0.25 ml/kg/min as cutoff, the higher fluid infusion rate was associated with a shorter time to shock reversal (HR = 1.22; 95% CI 1.06-1.41; P = .004) and with decreased odds of 28-day mortality (HR = 0.71; 95% CI 0.60-0.85; P < .001). CONCLUSION:In septic shock patients, initial fluid resuscitation rate of 0.25-0.50 ml/kg/min (i.e., completion of the initial 30 ml/kg IV fluid resuscitation within the first 2 h), may be associated with early shock reversal and lower 28-day mortality compared with slower rates of infusion.
| S-EPMC7140334 | biostudies-literature
Project description:PurposeInternational clinical practice guidelines call for initial volume resuscitation of at least 30 mL/kg body weight for patients with sepsis-induced hypotension or shock. Although not considered in the guidelines, preexisting cardiac dysfunction may be an important factor clinicians weigh in deciding the quantity of volume resuscitation for patients with septic shock.MethodsWe conducted a multicenter survey of clinicians who routinely treat patients with sepsis to evaluate their beliefs, behaviors, knowledge, and perceived structural barriers regarding initial volume resuscitation for patients with sepsis and concomitant heart failure with reduced ejection fraction (HFrEF) <40%. Initial volume resuscitation preferences were captured as ordinal values, and additional testing for volume resuscitation preferences was performed using McNemar and Wilcoxon signed rank tests as indicated. Univariable logistic regression models were used to identify significant predictors of ≥30 mL/kg fluid administration.ResultsA total of 317 clinicians at 9 US hospitals completed the survey (response rate 47.3%). Most respondents were specialists in either internal medicine or emergency medicine. Substantial heterogeneity was found regarding sepsis resuscitation preferences for patients with concomitant HFrEF. The belief that patients with septic shock and HFrEF should be exempt from current sepsis bundle initiatives was shared by 39.4% of respondents. A minimum fluid challenge of ∼30 mL/kg or more was deemed appropriate in septic shock by only 56.4% of respondents for patients with concomitant HFrEF, compared to 89.1% of respondents for patients without HFrEF (P < .01). Emergency medicine physicians were most likely to feel that <30 mL/kg was most appropriate in patients with septic shock and HFrEF.ConclusionsClinical equipoise exists regarding initial volume resuscitation for patients with sepsis-induced hypotension or shock and concomitant HFrEF. Future studies and clinical practice guidelines should explicitly address resuscitation in this subpopulation.
| S-EPMC7039763 | biostudies-literature
Project description:Background/aimsMaintaining a mean arterial pressure (MAP) ≥ 65 mmHg during septic shock should be based on individual circumstances, but specific target is poorly understood. We investigated associations between time-weighted average (TWA) hemodynamic parameters during the initial resuscitative period and 28-day mortality.MethodsProspectively collected data were obtained from a septic shock patient registry, according to the Sepsis-3 definition, between 2016 and 2018. The TWA systolic blood pressure, diastolic blood pressure, MAP, shock index, and pulse pressure (PP) during the first 6 hours after shock recognition were compared. Multivariable regression analysis was performed to assess associations between these parameters and 28-day mortality.ResultsOf 340 patients with septic shock, 92 died. Only the median TWA PP differed between the survivors and non-survivors (39.2 mmHg vs. 43.0 mmHg, p = 0.020), whereas the other indexes did not. When PP was divided into quartiles (< 34, 34 to 40, 40 to 48, and > 48 mmHg), the mortality rate was higher in the highest quartile (41.2%). Multivariable logistic analysis revealed that PP (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.012 to 1.622; p = 0.039) and PP of > 48 mmHg (OR, 2.25; 95% CI, 1.272 to 3.981; p = 0.005) were independently associated with 28-day mortality.ConclusionPP was significantly associated with 28-day mortality in patients with septic shock and MAP maintained at > 65 mmHg during the first 6 hours. Further studies are warranted to optimize strategies for maintaining PP and MAP at > 65 mmHg during the early resuscitative period.
| S-EPMC8273825 | biostudies-literature
Project description:ObjectivesPediatric septic shock continues to be an important public health problem. Several investigative groups have applied genetic and genomic approaches as a means of identifying novel pathways and therapeutic targets, discovery of sepsis-related biomarkers, and identification of septic shock subclasses. This review will highlight studies in pediatric sepsis with a focus on gene association studies and genome-wide expression profiling.Data sourcesA summary of published literature involving gene association and expression profiling studies specifically involving pediatric sepsis and septic shock.SummarySeveral polymorphisms of genes broadly involved in inflammation, immunity, and coagulation have been linked with susceptibility to sepsis, or outcome of sepsis in children. Many of these studies involve meningococcemia, and the strongest association involves a functional polymorphism of the plasminogen activator inhibitor-1 promoter region and meningococcal sepsis. Expression profiling studies in pediatric septic shock have identified zinc supplementation and inhibition of matrix metalloproteinase-8 activity as potential, novel therapeutic approaches in sepsis. Studies focused on discovery of sepsis-related biomarkers have identified interleukin-8 as a robust outcome biomarker in pediatric septic shock. Additional studies have demonstrated the feasibility and clinical relevance of gene expression-based subclassification of pediatric septic shock.ConclusionsPediatric sepsis and septic shock are increasingly being studied by genetic and genomic approaches and the accumulating data hold the promise of enhancing our future approach to this ongoing clinical problem.
| S-EPMC3329642 | biostudies-literature