METHODS: A randomized controlled study was carried out in the neonatal intensive care unit (NICU) of Hospital Universiti Kebangsaan Malaysia over a 12-month period. Fifty-four healthy term infants with severe hyperbilirubinemia were randomized to receive either solely enteral feeds (n = 27) or both enteral and intravenous (n = 27) fluid during phototherapy.
RESULTS: There were no significant differences in the mean birthweight, mean gestational age, ethnic distribution, gender distribution, modes of delivery and types of feeding between the two groups. Similarly, there was no significant difference in the mean indirect serum bilirubin (iSB) level at the time of admission to the NICU between the enteral (359 +/- 69 micromol/L [mean +/- SD]) and intravenous group (372 +/- 59 micromol/L; P = 0.4). The mean rates of decrease in iSB during the first 4 h of phototherapy were also not significantly different between the enteral group (10.4 +/- 4.9 micromol/L per h) and intravenous group (11.2 +/- 7.4 micromol/L per h; P = 0.6). There was no significant difference in the proportion of infants requiring exchange transfusion (P = 0.3) nor in the median duration of hospitalization (P = 0.7) between the two groups. No infant developed vomiting or abdominal distension during the study period.
CONCLUSION: Severely jaundiced healthy term infants had similar rates of decrease in iSB levels during the first 4 h of intensive phototherapy, irrespective of whether they received oral or intravenous fluid supplementation. However, using the oral route avoided the need for intravenous cannulae and their attendant complications.
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.
METHODS: Thirty consented adult patients who underwent craniotomy were randomly allocated into two groups of 15 patients each. The non-balanced group received 0.9% normal saline while the balanced group received Sterofundin®ISO as the intraoperative fluid for maintenance. Biochemical indices for acid-base balance and serum electrolytes were analyzed periodically.
RESULTS: In the non-balanced group, significant changes were noted in the pH, base excess and bicarbonate values over time compared to its respective baseline values (P<0.01). Four patients (27.7%) also developed a pH<7.35 and 5 patients (33.3%) developed marked acidosis with base excess fluid maintenance and replacement during elective neurosurgery.
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.
Materials and methods: RaFTA is a prospective, observational study in Asian intensive care unit (ICU) patients focusing on fluid therapy and related outcomes. Logistic regression was performed to identify risk factors for increased 90-day mortality and acute kidney injury (AKI).
Results: Twenty-four study centers joined the RaFTA registry and collected 3,187 patient data sets from November 2011 to September 2012. A follow-up was done 90 days after ICU admission. For 90-day mortality, significant risk factors in the overall population were sepsis at admission (OR 2.185 [1.799; 2.654], p < 0.001), cumulative fluid balance (OR 1.032 [1.018; 1.047], p < 0.001), and the use of vasopressors (OR 3.409 [2.694; 4.312], p < 0.001). The use of colloids was associated with a reduced risk of 90-day mortality (OR 0.655 [0.478; 0.900], p = 0.009). The initial colloid dose was not associated with an increased risk for AKI (OR 1.094 [0.754; 1.588], p = 0.635).
Conclusion: RaFTA adds the important finding that colloid use was not associated with increased 90-day mortality or AKI after adjustment for baseline patient condition.
Clinical significance: Early resuscitation with colloids showed potential mortality benefit in the present analysis. Elucidating these findings may be an approach for future research.
How to cite this article: Jacob M, Sahu S, Singh YP, Mehta Y, Yang K-Y, Kuo S-W, et al. A Prospective Observational Study of Rational Fluid Therapy in Asian Intensive Care Units: Another Puzzle Piece in Fluid Therapy. Indian J Crit Care Med 2020;24(11):1028-1036.
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.