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Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER-TBI and OzENTER-TBI): a prospective, multicentre, comparative effectiveness study.
Wiegers, EJA, Lingsma, HF, Huijben, JA, Cooper, DJ, Citerio, G, Frisvold, S, Helbok, R, Maas, AIR, Menon, DK, Moore, EM, et al
The Lancet. Neurology. 2021;(8):627-638
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Abstract
BACKGROUND Fluid therapy-the administration of fluids to maintain adequate organ tissue perfusion and oxygenation-is essential in patients admitted to the intensive care unit (ICU) with traumatic brain injury. We aimed to quantify the variability in fluid management policies in patients with traumatic brain injury and to study the effect of this variability on patients' outcomes. METHODS We did a prospective, multicentre, comparative effectiveness study of two observational cohorts: CENTER-TBI in Europe and OzENTER-TBI in Australia. Patients from 55 hospitals in 18 countries, aged 16 years or older with traumatic brain injury requiring a head CT, and admitted to the ICU were included in this analysis. We extracted data on demographics, injury, and clinical and treatment characteristics, and calculated the mean daily fluid balance (difference between fluid input and loss) and mean daily fluid input during ICU stay per patient. We analysed the association of fluid balance and input with ICU mortality and functional outcome at 6 months, measured by the Glasgow Outcome Scale Extended (GOSE). Patient-level analyses relied on adjustment for key characteristics per patient, whereas centre-level analyses used the centre as the instrumental variable. FINDINGS 2125 patients enrolled in CENTER-TBI and OzENTER-TBI between Dec 19, 2014, and Dec 17, 2017, were eligible for inclusion in this analysis. The median age was 50 years (IQR 31 to 66) and 1566 (74%) of patients were male. The median of the mean daily fluid input ranged from 1·48 L (IQR 1·12 to 2·09) to 4·23 L (3·78 to 4·94) across centres. The median of the mean daily fluid balance ranged from -0·85 L (IQR -1·51 to -0·49) to 1·13 L (0·99 to 1·37) across centres. In patient-level analyses, a mean positive daily fluid balance was associated with higher ICU mortality (odds ratio [OR] 1·10 [95% CI 1·07 to 1·12] per 0·1 L increase) and worse functional outcome (1·04 [1·02 to 1·05] per 0·1 L increase); higher mean daily fluid input was also associated with higher ICU mortality (1·05 [1·03 to 1·06] per 0·1 L increase) and worse functional outcome (1·04 [1·03 to 1·04] per 1-point decrease of the GOSE per 0·1 L increase). Centre-level analyses showed similar associations of higher fluid balance with ICU mortality (OR 1·17 [95% CI 1·05 to 1·29]) and worse functional outcome (1·07 [1·02 to 1·13]), but higher fluid input was not associated with ICU mortality (OR 0·95 [0·90 to 1·00]) or worse functional outcome (1·01 [0·98 to 1·03]). INTERPRETATION In critically ill patients with traumatic brain injury, there is significant variability in fluid management, with more positive fluid balances being associated with worse outcomes. These results, when added to previous evidence, suggest that aiming for neutral fluid balances, indicating a state of normovolaemia, contributes to improved outcome. FUNDING European Commission 7th Framework program and the Australian Health and Medical Research Council.
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Usefulness of chloride levels for fluid resuscitation in patients undergoing targeted temperature management after out-of-hospital cardiac arrest.
Kong, T, Chung, YE, Lee, HS, You, JS, Chung, HS, Park, I, Chung, SP
The American journal of emergency medicine. 2021;:69-76
Abstract
OBJECTIVE Chloride is an important electrolyte in the body. In this study, we aimed to evaluate the associations between chloride levels on emergency department (ED) admission and neurologic outcomes by stratifying patients undergoing targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) into three groups (hyper/normo/hypochloremia); we also assessed the effect of changes in chloride levels from baseline over time on outcomes. METHODS This retrospective, observational cohort study of 346 patients was conducted between 2011 and 2019. The chloride levels were categorized as hypochloremia, normochloremia, and hyperchloremia by predetermined definitions. The primary endpoint was poor neurologic outcomes after hospital discharge. We evaluated the associations between chloride levels on ED admission and neurologic outcomes and assess the effect of changes in chloride levels over time on clinical outcomes. RESULTS On ED admission, compared with normochloremia, hypochloremia was significantly associated with unfavorable neurologic outcomes (OR, 2.668; 95% CI, 1.217-5.850, P = 0.014). Over time, unfavorable neurologic outcomes were significantly associated with increases in chloride levels in the hyperchloremia and normochloremia groups after ED admission. The rates of poor neurologic outcomes in the hyperchloremia and normochloremia groups were increased by 14.2% at Time-12, 20.1% at Time-24, and 9.3% at Time-48 with a 1-mEq/L increase in chloride levels. CONCLUSION In clinical practice, chloride levels can be routinely and serially measured cost-effectively. Thus, baseline chloride levels may be a promising tool for rapid risk stratification of patients after OHCA. For fluid resuscitation after cardiac arrest, a chloride-restricted solution may be an early therapeutic strategy.
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Association of Positive Fluid Balance at Discharge After Sepsis Management With 30-Day Readmission.
Yoo, MS, Zhu, S, Lu, Y, Greene, JD, Hammer, HL, Iberti, CT, Nemazie, S, Ananias, MP, McCarthy, CM, O'Malley, RM, et al
JAMA network open. 2021;(6):e216105
Abstract
IMPORTANCE Although early fluid administration has been shown to lower sepsis mortality, positive fluid balance has been associated with adverse outcomes. Little is known about associations in non-intensive care unit settings, with growing concern about readmission from excess fluid accumulation in patients with sepsis. OBJECTIVE To evaluate whether positive fluid balance among non-critically ill patients with sepsis was associated with increased readmission risk, including readmission for heart failure. DESIGN, SETTING, AND PARTICIPANTS This multicenter retrospective cohort study was conducted between January 1, 2012, and December 31, 2017, among 57 032 non-critically ill adults hospitalized for sepsis at 21 hospitals across Northern California. Kaiser Permanente Northern California is an integrated health care system with a community-based population of more than 4.4 million members. Statistical analysis was performed from January 1 to December 31, 2019. EXPOSURES Intake and output net fluid balance (I/O) measured daily and cumulatively at discharge (positive vs negative). MAIN OUTCOMES AND MEASURES The primary outcome was 30-day readmission. The secondary outcomes were readmission stratified by category and mortality after living discharge. RESULTS The cohort included 57 032 patients who were hospitalized for sepsis (28 779 women [50.5%]; mean [SD] age, 73.7 [15.5] years). Compared with patients with positive I/O (40 940 [71.8%]), those with negative I/O (16 092 [28.2%]) were older, with increased comorbidity, acute illness severity, preexisting heart failure or chronic kidney disease, diuretic use, and decreased fluid administration volume. During 30-day follow-up, 8719 patients (15.3%) were readmitted and 3639 patients (6.4%) died. There was no difference in readmission between patients with positive vs negative I/O (HR, 1.00; 95% CI, 0.95-1.05). No association was detected between readmission and I/O using continuous, splined, and quadratic function transformations. Positive I/O was associated with decreased heart failure-related readmission (HR, 0.80 [95% CI, 0.71-0.91]) and increased 30-day mortality (HR, 1.23 [95% CI, 1.15-1.31]). CONCLUSIONS AND RELEVANCE In this large observational study of non-critically ill patients hospitalized with sepsis, there was no association between positive fluid balance at the time of discharge and readmission. However, these findings may have been limited by variable recording and documentation of fluid intake and output; additional studies are needed to examine the association of fluid status with outcomes in patients with sepsis to reduce readmission risk.
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Weight-Based Assessment of Fluid Overload in Patients with Acute Kidney Injury.
Chow, BL, Poh, CB, Chionh, CY
Nephron. 2020;(6):281-289
Abstract
INTRODUCTION Acute kidney injury (AKI) with fluid overload is associated with poor outcomes. While percentage fluid overload (PFO) using intake/output charts (PFOi/o) has been validated as a marker of overload, accurate PFOi/o measurements may not be possible in a general ward. We propose an alternative weight-based PFO calculation: PFOw = [(maximum weight - baseline weight) ÷ baseline weight] × 100%. METHODS This is a prospective, observational pilot study on general ward inpatients with AKI who were referred for nephrology consult. PFOw was compared with PFOi/o, and both were evaluated for associations with dialysis requirement, AKI stage 2 or 3, and 90-day mortality. RESULTS Fifty-eight patients with a median age of 67.5 years (interquartile range 18.0) were recruited. Of which, 33 (56.9%) were males and 41 (70.7%) had preexisting CKD 3 or higher. We found no correlation between PFOi/o and PFOw (R2 = 0.015, p = 0.531). A higher PFOw was observed in AKI stage 2 or 3 (p = 0.005) and in patients requiring dialysis (p = 0.001). On multivariate analysis, each percentage increase in PFOw was associated with increased odds of AKI stage 2 or 3 (odds ratio 1.37 [95% CI 1.05-1.78], p = 0.020) and dialysis need (odds ratio 1.69 [95% CI 1.20-2.39], p = 0.003). Twenty-nine patients had complete quantitative data to calculate PFOi/o. Multivariate analysis of these 29 patients showed that PFOw correlated with AKI stage 2 or 3 and dialysis requirement, while PFOi/o had no correlation with these events. The area under the curve receiver operating characteristics of PFOw was 0.706 for AKI stage 2 or 3 and 0.819 for AKI requiring dialysis. The optimal PFOw cutoff was determined at ≥1%. Three deaths occurred within 90 days, and all had PFOw ≥ 1%, although the log-rank test did not achieve statistical significance (p = 0.050). CONCLUSION The proposed PFOw is a potential prognostic indicator for general ward patients with AKI. PFOw ≥ 1% is associated with poor renal outcomes.
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[Risk factors for the development of early hyponatraemia in the premature infant. A review of the practice of giving sodium in the first days of life].
Pérez-Piaya Moreno, MR, Miranda Alcalde, B, Cárdenas Rebollo, JM, Riaza Gómez, M, Carnicer, H, Romera Modamio, G
Anales de pediatria. 2020;(6):359-364
Abstract
INTRODUCTION A retrospective study was conducted in the Neonatal Intensive Care Unit of a tertiary hospital to determine the incidence of early hyponatraemia (first 48hours of life) in preterm infants. Risk and protection factors in this condition were also examined as a starting point for a change in the medical action when prescribing intravenous fluids. MATERIAL AND METHODS The study included a sample of 256 premature babies (gestational age: 235-366) admitted to the Neonatal Intensive Care Unit of a tertiary hospital between January 2016 and June 2018. The number of patients receiving intravenous sodium in different intervals during the first 48hours of life was determined, as well as the number of those with hyponatraemia of any type (<135mmol / l), and moderate-severe (<130mmol / l). An analysis was made of the relationship between early hyponatraemia and weight / gestational age, antenatal steroids exposure, respiratory pathology, early sepsis, and perinatal asphyxia. RESULTS Hyponatraemia occurred in 81 patients, 31.64% of the total (up to 50% in<30 weeks of gestational age), and was moderate-severe (<130mmol / l) in 17.3% of the cases. The period of time with the most cases of hyponatraemia was in the first 12hours of life (22.64%). Weight (P=.034), gestational age (P<.001) and respiratory disease (P<.001) were found to be risk factors and, in a multivariate analysis, the latter was independently related to early hyponatremia (P<.01, OR=5.24, 95% CI: 2.79-9.84). Antenatal betamethasone exposure did not show to be a protection factor. CONCLUSION According to the results of this study, it is considered an advantage to provide sodium in the intravenous fluids prescribed during the first days of life, particularly in preterm infants of lower gestational age and with respiratory disease involvement.
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Fluid Intake But Not Fluid Balance Is Associated With Poor Outcome in Nontraumatic Subarachnoid Hemorrhage Patients.
Rass, V, Gaasch, M, Kofler, M, Schiefecker, AJ, Ianosi, BA, Steinkohl, F, Beer, R, Pfausler, B, Gizewski, ER, Thomé, C, et al
Critical care medicine. 2019;(7):e555-e562
Abstract
OBJECTIVES Optimal fluid management is important in patients with acute brain injury, including subarachnoid hemorrhage. We aimed to examine the relationship between daily fluid intake and fluid balance with hospital complications and functional outcome. DESIGN Retrospective observational cohort study. SETTING Neurocritical care unit at a tertiary academic medical center. PATIENTS Two-hundred thirty-seven consecutive nontraumatic subarachnoid hemorrhage patients admitted to the neurologic ICU between 2010 and 2016. INTERVENTIONS Total daily amount of fluids and fluid balance were calculated over 15 days. Using multivariate generalized estimating equation models the association of daily fluid intake and fluid balance with disease severity, hospital complications and poor functional outcome (3-mo modified Rankin Score ≥ 3) was investigated. Additionally, we described the composition of fluids given. MEASUREMENTS AND MAIN RESULTS Patients presented with a median admission Hunt and Hess grade of 3 (interquartile range, 1-5) and were 57 years old (interquartile range, 47-67 yr old). A higher daily fluid intake was associated with higher admission Hunt and Hess grade (odds ratio, 1.61; 95% CI, 1.47-1.76; p < 0.001), increased pulmonary fluid accumulation (adjusted odds ratio, 1.11; 95% CI, 1.01-1.21; p = 0.033), prolonged mechanical ventilation (Wald statistic = 20.08; degrees of freedom = 1; p < 0.001), higher daily Subarachnoid hemorrhage Early Brain Edema Score (adjusted odds ratio, 1.11; 95% CI, 1.01-1.22; p = 0.034), occurrence of anemia (adjusted odds ratio, 1.36; 95% CI, 1.20-1.54; p < 0.001), delayed cerebral ischemia (adjusted odds ratio, 1.31; 95% CI, 1.14-1.51; p < 0.001), and poor functional outcome (adjusted odds ratio, 1.25; 95% CI, 1.10-1.41; p < 0.001). Daily fluid balance was associated with higher admission Hunt and Hess grade (odds ratio, 1.09; 95% CI, 1.05-1.13; p < 0.001) and anemia (adjusted odds ratio, 1.17; 95% CI, 1.03-1.33; p = 0.019). The main contributors to fluids were nutritional compounds (31%), IV drugs (30%), and volume substitution (17%). CONCLUSIONS Our study demonstrates a significant association of fluid intake but not fluid balance with hospital complications and poor functional outcome in subarachnoid hemorrhage patients. A larger prospective study is needed to confirm our results.
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Prophylaxis in High-Risk Patients With eGFR < 30 mL/min/1.73 m2: Get the Balance Right.
Nijssen, EC, Nelemans, PJ, Rennenberg, RJ, Theunissen, RA, van Ommen, V, Wildberger, JE
Investigative radiology. 2019;(9):580-588
Abstract
OBJECTIVES Clinical guidelines recommend prophylactic intravenous fluids for patients with estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m to prevent adverse postcontrast outcomes. These patients represent a small minority of the population receiving intravascular iodinated contrast material, and data are not readily available. The current study aim is to gain insight into positive and negative effects of prophylaxis by comparing postcontrast outcomes in high-risk patients who did and did not receive prophylaxis. MATERIALS AND METHODS Observational data were gathered over 4 years. Inclusion criteria were age 18 years or older, eGFR less than 30 mL/min/1.73 m, and elective intravascular iodinated contrast administration. Exclusion criteria were dialysis and nonstandard periprocedural prophylaxis. Primary outcome was postcontrast acute kidney injury (>25% or >44 μmol/L serum creatinine increase within 2-5 days). Secondary outcomes were change in eGFR, 5 mL/min/1.73 m or greater eGFR decline, dialysis, and mortality at 1 month postcontrast including primary cause, as well as complications of prophylaxis. Results were stratified by contrast procedure type and corrected for potential confounders. RESULTS Of all 55,474 elective procedures with intravascular contrast administration, 362 patients met the inclusion criteria: 281 (78%) received standard 0.9% NaCl prophylaxis and 81 (22%) received no prophylaxis. Prophylaxis versus no prophylaxis adjusted odds ratios were nonsignificant and less than 1 for postcontrast renal outcomes (postcontrast acute kidney injury, eGFR decline, dialysis), indicating a trend toward a protective effect of prophylaxis. For mortality, adjusted odds ratios were nonsignificant and greater than 1, indicating a trend toward higher mortality risk after prophylaxis. Of the primary causes of death analyzed in prophylaxis patients, 24% (5/21) were related to prophylaxis. Among 281 prophylaxis patients, 18 (6.4%) complications of prophylaxis occurred: 15 heart failures and 3 arrhythmias. CONCLUSIONS Based on this study, no standard recommendation with regard to giving or withholding prophylaxis can be given. Prophylactic fluids may confer some protection against postcontrast renal adverse events but may also contribute toward increased risk of short-term death. In this setting, benefits and risks of prophylaxis must be carefully weighed and cardiac parameters assessed for each individual patient.
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Fluid Balance Is Associated with Clinical Outcomes and Extravascular Lung Water in Children with Acute Asthma Exacerbation.
Kantor, DB, Hirshberg, EL, McDonald, MC, Griffin, J, Buccigrosso, T, Stenquist, N, Smallwood, CD, Nelson, KA, Zurakowski, D, Phipatanakul, W, et al
American journal of respiratory and critical care medicine. 2018;(9):1128-1135
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Abstract
RATIONALE The effects of fluid administration during acute asthma exacerbation are likely unique in this patient population: highly negative inspiratory intrapleural pressure resulting from increased airway resistance may interact with excess fluid administration to favor the accumulation of extravascular lung water, leading to worse clinical outcomes. OBJECTIVES Investigate how fluid balance influences clinical outcomes in children hospitalized for asthma exacerbation. METHODS We analyzed the association between fluid overload and clinical outcomes in a retrospective cohort of children admitted to an urban children's hospital with acute asthma exacerbation. These findings were validated in two cohorts: a matched retrospective and a prospective observational cohort. Finally, ultrasound imaging was used to identify extravascular lung water and investigate the physiological basis for the inferential findings. MEASUREMENTS AND MAIN RESULTS In the retrospective cohort, peak fluid overload [(fluid input - output)/weight] is associated with longer hospital length of stay, longer treatment duration, and increased risk of supplemental oxygen use (P values < 0.001). Similar results were obtained in the validation cohorts. There was a strong interaction between fluid balance and intrapleural pressure: the combination of positive fluid balance and highly negative inspiratory intrapleural pressures is associated with signs of increased extravascular lung water (P < 0.001), longer length of stay (P = 0.01), longer treatment duration (P = 0.03), and increased risk of supplemental oxygen use (P = 0.02). CONCLUSIONS Excess volume administration leading to fluid overload in children with acute asthma exacerbation is associated with increased extravascular lung water and worse clinical outcomes.
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Impact of intra-operative fluid and noradrenaline administration on early postoperative renal function after cystectomy and urinary diversion: A retrospective observational cohort study.
Furrer, MA, Schneider, MP, Löffel, LM, Burkhard, FC, Wuethrich, PY
European journal of anaesthesiology. 2018;(9):641-649
Abstract
BACKGROUND The use of noradrenaline to enable a restrictive approach to intra-operative fluid therapy to avoid salt and water overload has gained increasing acceptance. However, concerns have been raised about the impact of this approach on renal function. OBJECTIVES To identify risk factors for acute kidney injury (AKI) in patients undergoing cystectomy with urinary diversion and determine whether administration of noradrenaline and intra-operative hydration regimens affect early postoperative renal function. DESIGN Retrospective observational cohort study. SETTING University hospital, from 2007 to 2016. PATIENTS A total of 769 consecutive patients scheduled for cystectomy and urinary diversion. Those with incomplete data and having pre-operative haemodialysis were excluded. MAIN OUTCOME MEASURES AKI was defined as a serum creatinine increase of more than 50% over 72 postoperative hours. Multiple logistic regression analysis was performed to model the association between risk factors and AKI. RESULTS Postoperative AKI was diagnosed in 86/769 patients (11.1%). Independent predictors for AKI were the amount of crystalloid administered (odds ratio (OR) 0.79 [95% confidence interval (CI), 0.68 to 0.91], P = 0.002), antihypertensive medication (OR 2.07 [95% CI, 1.25 to 3.43], P = 0.005), pre-operative haemoglobin value (OR 1.02 [95% CI, 1.01 to 1.03], P = 0.010), duration of surgery (OR 1.01 [95% CI, 1.00 to 1.01], P = 0.002), age (OR 1.32 [95% CI, 1.44 to 1.79], P = 0.002) but not the administration of noradrenaline (OR 1.09 [95% CI, 0.94 to 1.21], P = 0.097). Postoperative AKI was associated with longer hospital stay (18 [15 to 22] vs. 16 [15 to 19] days; P = 0.035) and a higher 90-day major postoperative complication rate (41.9 vs. 27.5%; P = 0.002). CONCLUSION Noradrenaline administration did not increase the risk for AKI. A too restrictive approach to administration of crystalloids was associated with an increased risk for AKI, particularly in older patients, those receiving antihypertensive medication, and those whose surgery was prolonged. As AKI was associated with longer hospital stay and increased postoperative morbidity, these observations should be taken into account to improve outcome when addressing peri-operative fluid management. TRIAL REGISTRATION Not applicable.
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What fluids are given during air ambulance treatment of patients with trauma in the UK, and what might this mean for the future? Results from the RESCUER observational cohort study.
Naumann, DN, Hancox, JM, Raitt, J, Smith, IM, Crombie, N, Doughty, H, Perkins, GD, Midwinter, MJ, ,
BMJ open. 2018;(1):e019627
Abstract
OBJECTIVES We investigated how often intravenous fluids have been delivered during physician-led prehospital treatment of patients with hypotensive trauma in the UK and which fluids were given. These data were used to estimate the potential national requirement for prehospital blood products (PHBP) if evidence from ongoing trials were to report clinical superiority. SETTING The Regional Exploration of Standard Care during Evacuation Resuscitation (RESCUER) retrospective observational study was a collaboration between 11 UK air ambulance services. Each was invited to provide up to 5 years of data and total number of taskings during the same period. PARTICIPANTS Patients with hypotensive trauma (systolic blood pressure <90 mm Hg or absent radial pulse) attended by a doctor. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome was the number of patients with hypotensive trauma given prehospital fluids. Secondary outcomes were types and volumes of fluids. These data were combined with published data to estimate potential national eligibility for PHBP. RESULTS Of 29 037 taskings, 729 (2.5%) were for patients with hypotensive trauma attended by a physician. Half were aged 21-50 years; 73.4% were male. A total of 537 out of 729 (73.7%) were given fluids. Five hundred and ten patients were given a single type of fluid; 27 received >1 type. The most common fluid was 0.9% saline, given to 486/537 (90.5%) of patients who received fluids, at a median volume of 750 (IQR 300-1500) mL. Three per cent of patients received PHBP. Estimated projections for patients eligible for PHBP at these 11 services and in the whole UK were 313 and 794 patients per year, respectively. CONCLUSIONS One in 40 air ambulance taskings were manned by physicians to retrievepatients with hypotensive trauma. The most common fluid delivered was 0.9% saline. If evidence justifies universal provision of PHBP, approximately 800 patients/year would be eligible in the UK, based on our data combined with others published. Prospective investigations are required to confirm or adjust these estimations.