MATERIALS AND METHODS: Twenty-one adult female sheep were randomly divided into no endotoxemia (n = 5) or endotoxemia groups (n = 16) with an escalating dose of lipopolysaccharide (LPS) up to 4 μg/kg/h administered to achieve a mean arterial pressure below 60 mmHg. Endotoxemia sheep received either no bolus fluid resuscitation (n = 8) or a 0.9% saline bolus (40 mL/kg over 60 min) (n = 8). No endotoxemia, saline only animals (n = 5) underwent fluid resuscitation with a 0.9% bolus of saline as detailed above. Hemodynamic support with vasopressors was initiated if needed, to maintain a mean arterial pressure (MAP) of 60-65 mm Hg in all the groups.
RESULTS: Rotational thromboelastometry (ROTEM®) and conventional coagulation biomarker tests demonstrated sepsis induced derangements to secondary haemostasis. This effect was exacerbated by saline fluid resuscitation, with low pH (p = 0.036), delayed clot initiation and formation together with deficiencies in naturally occurring anti-coagulants antithrombin (p = 0.027) and Protein C (p = 0.001).
CONCLUSIONS: Endotoxemia impairs secondary haemostasis and induces changes in the intrinsic, extrinsic and anti-coagulant pathways. These changes to haemostasis are exacerbated following resuscitation with 0.9% saline, a commonly used crystalloid in clinical settings.
Methods: Sixty-six severe TBI patients who required emergency craniotomy or craniectomy and were planned for post-operative ventilation were randomised into NS (n = 33) and BF therapy groups (n = 33). The calculation of maintenance fluid given was based on the Holliday-Segar method. The electrolytes and acid-base parameters were assessed at an 8 h interval for 24 h. The data were analysed using repeated measures ANOVA.
Results: The NS group showed a significant lower base excess (-3.20 versus -1.35, P = 0.049), lower bicarbonate level (22.03 versus 23.48 mmol/L, P = 0.031), and more hyperchloremia (115.12 versus 111.74 mmol/L, P < 0.001) and hypokalemia (3.36 versus 3.70 mmol/L, P < 0.001) than the BF group at 24 h of therapy. The BF group showed a significantly higher level of calcium (1.97 versus 1.79 mmol/L, P = 0.003) and magnesium (0.94 versus 0.80 mmol/L, P < 0.001) than the NS group at 24 h of fluid therapy. No significant differences were found in pH, pCO2, lactate, and sodium level.
Conclusion: BF therapy showed better effects in maintaining higher electrolyte parameters and reducing the trend toward hyperchloremic metabolic acidosis than the NS therapy during prolonged fluid therapy for postoperative TBI patients.
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.