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  1. Byrne L, Obonyo NG, Diab SD, Dunster KR, Passmore MR, Boon AC, et al.
    Am J Respir Crit Care Med, 2018 10 15;198(8):1043-1054.
    PMID: 29882682 DOI: 10.1164/rccm.201801-0064OC
    RATIONALE: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question.

    OBJECTIVES: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia.

    METHODS: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.9% saline or commenced hemodynamic support with protocolized noradrenaline and vasopressin. Microdialysis catheters were inserted into the arterial circulation, heart, brain, kidney, and liver to monitor local metabolism. Blood samples were recovered to measure serum inflammatory cytokines, creatinine, troponin, atrial natriuretic peptide, brain natriuretic peptide, and hyaluronan. All animals were monitored and supported for 12 hours after fluid resuscitation.

    MEASUREMENTS AND MAIN RESULTS: After resuscitation, animals that received fluid resuscitation required significantly more noradrenaline to maintain the same mean arterial pressure in the subsequent 12 hours (68.9 mg vs. 39.6 mg; P = 0.04). Serum cytokines were similar between groups. Atrial natriuretic peptide increased significantly after fluid resuscitation compared with that observed in animals managed without fluid resuscitation (335 ng/ml [256-382] vs. 233 ng/ml [144-292]; P = 0.04). Cross-sectional time-series analysis showed that the rate of increase of the glycocalyx glycosaminoglycan hyaluronan was greater in the fluid-resuscitated group over the course of the study (P = 0.02).

    CONCLUSIONS: Fluid resuscitation resulted in a paradoxical increase in vasopressor requirement. Additionally, it did not result in improvements in any of the measured microcirculatory- or organ-specific markers measured. The increase in vasopressor requirement may have been due to endothelial/glycocalyx damage secondary to atrial natriuretic peptide-mediated glycocalyx shedding.

    Matched MeSH terms: Fluid Therapy/adverse effects*
  2. Naing CM, Win DK
    Trans R Soc Trop Med Hyg, 2010 May;104(5):311-2.
    PMID: 20206954 DOI: 10.1016/j.trstmh.2010.02.001
    Permanent neurological impairment or death arising from hospital-acquired hyponatremia in both children and adults is well documented. The choice of intravenous fluids for fluid resuscitation in critically ill patients is a top priority in evidence-based medicine. The question of whether colloids in comparison to crystalloids can improve mortality in such cases remains to be answered. Well powered, randomized clinical trials addressing the comparative efficacy of different types of intravenous fluids is a high priority as is the ethical justification for such trials. The understanding of the pathophysiological process serves important information on clinical practice.
    Matched MeSH terms: Fluid Therapy/adverse effects
  3. Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M
    JAMA, 2012 Oct 17;308(15):1566-72.
    PMID: 23073953 DOI: 10.1001/jama.2012.13356
    Administration of traditional chloride-liberal intravenous fluids may precipitate acute kidney injury (AKI).
    Matched MeSH terms: Fluid Therapy/adverse effects*
  4. Tan AH, Lim SY, Ng RX
    JAMA Neurol, 2018 07 01;75(7):888-889.
    PMID: 29799978 DOI: 10.1001/jamaneurol.2018.0983
    Matched MeSH terms: Fluid Therapy/adverse effects*
  5. Lai NM, Ahmad Kamar A, Choo YM, Kong JY, Ngim CF
    Cochrane Database Syst Rev, 2017 Aug 01;8(8):CD011891.
    PMID: 28762235 DOI: 10.1002/14651858.CD011891.pub2
    BACKGROUND: Neonatal hyperbilirubinaemia is a common problem which carries a risk of neurotoxicity. Certain infants who have hyperbilirubinaemia develop bilirubin encephalopathy and kernicterus which may lead to long-term disability. Phototherapy is currently the mainstay of treatment for neonatal hyperbilirubinaemia. Among the adjunctive measures to compliment the effects of phototherapy, fluid supplementation has been proposed to reduce serum bilirubin levels. The mechanism of action proposed includes direct dilutional effects of intravenous (IV) fluids, or enhancement of peristalsis to reduce enterohepatic circulation by oral fluid supplementation.

    OBJECTIVES: To assess the risks and benefits of fluid supplementation compared to standard fluid management in term and preterm newborn infants with unconjugated hyperbilirubinaemia who require phototherapy.

    SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE via PubMed (1966 to 7 June 2017), Embase (1980 to 7 June 2017), and CINAHL (1982 to 7 June 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.

    SELECTION CRITERIA: We included randomised controlled trials that compared fluid supplementation against no fluid supplementation, or one form of fluid supplementation against another.

    DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group using the Covidence platform. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using mean difference (MD), risk difference (RD), and risk ratio (RR) with 95% confidence intervals (CIs).

    MAIN RESULTS: Out of 1449 articles screened, seven studies were included. Three articles were awaiting classification, among them, two completed trials identified from the trial registry appeared to be unpublished so far.There were two major comparisons: IV fluid supplementation versus no fluid supplementation (six studies) and IV fluid supplementation versus oral fluid supplementation (one study). A total of 494 term, healthy newborn infants with unconjugated hyperbilirubinaemia were evaluated. All studies were at high risk of bias for blinding of care personnel, five studies had unclear risk of bias for blinding of outcome assessors, and most studies had unclear risk of bias in allocation concealment. There was low- to moderate-quality evidence for all major outcomes.In the comparison between IV fluid supplementation and no supplementation, no infant in either group developed bilirubin encephalopathy in the one study that reported this outcome. Serum bilirubin was lower at four hours postintervention for infants who received IV fluid supplementation (MD -34.00 μmol/L (-1.99 mg/dL), 95% CI -52.29 (3.06) to -15.71 (0.92); participants = 67, study = 1) (low quality of evidence, downgraded one level for indirectness and one level for suspected publication bias). Beyond eight hours postintervention, serum bilirubin was similar between the two groups. Duration of phototherapy was significantly shorter for fluid-supplemented infants, but the estimate was affected by heterogeneity which was not clearly explained (MD -10.70 hours, 95% CI -15.55 to -5.85; participants = 218; studies = 3; I² = 67%). Fluid-supplemented infants were less likely to require exchange transfusion (RR 0.39, 95% CI 0.21 to 0.71; RD -0.01, 95% CI -0.04 to 0.02; participants = 462; studies = 6; I² = 72%) (low quality of evidence, downgraded one level due to inconsistency, and another level due to suspected publication bias), and the estimate was similarly affected by unexplained heterogeneity. The frequencies of breastfeeding were similar between the fluid-supplemented and non-supplemented infants in days one to three based on one study (estimate on day three: MD 0.90 feeds, 95% CI -0.40 to 2.20; participants = 60) (moderate quality of evidence, downgraded one level for imprecision).One study contributed to all outcome data in the comparison of IV versus oral fluid supplementation. In this comparison, no infant in either group developed abnormal neurological signs. Serum bilirubin, as well as the rate of change of serum bilirubin, were similar between the two groups at four hours after phototherapy (serum bilirubin: MD 11.00 μmol/L (0.64 mg/dL), 95% CI -21.58 (-1.26) to 43.58 (2.55); rate of change of serum bilirubin: MD 0.80 μmol/L/hour (0.05 mg/dL/hour), 95% CI -2.55 (-0.15) to 4.15 (0.24); participants = 54 in both outcomes) (moderate quality of evidence for both outcomes, downgraded one level for indirectness). The number of infants who required exchange transfusion was similar between the two groups (RR 1.60, 95% CI 0.60 to 4.27; RD 0.11, 95% CI -0.12 to 0.34; participants = 54). No infant in either group developed adverse effects including vomiting or abdominal distension.

    AUTHORS' CONCLUSIONS: There is no evidence that IV fluid supplementation affects important clinical outcomes such as bilirubin encephalopathy, kernicterus, or cerebral palsy in healthy, term newborn infants with unconjugated hyperbilirubinaemia requiring phototherapy. In this review, no infant developed these bilirubin-associated clinical complications. Low- to moderate-quality evidence shows that there are differences in total serum bilirubin levels between fluid-supplemented and control groups at some time points but not at others, the clinical significance of which is uncertain. There is no evidence of a difference between the effectiveness of IV and oral fluid supplementations in reducing serum bilirubin. Similarly, no infant developed adverse events or complications from fluid supplementation such as vomiting or abdominal distension. This suggests a need for future research to focus on different population groups with possibly higher baseline risks of bilirubin-related neurological complications, such as preterm or low birthweight infants, infants with haemolytic hyperbilirubinaemia, as well as infants with dehydration for comparison of different fluid supplementation regimen.

    Matched MeSH terms: Fluid Therapy/adverse effects*
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