Daily Fluid Balance Research Articles

Adherence to standard medication infusion concentrations and its impact on paediatric intensive care patient outcomes

AimTo review compliance with the DERS, and to evaluate the impact on daily fluid balances as a standard outcome in paediatric intensive care. MethodA prospective audit of patients admitted to our tertiary level PICU over a 10day period. The audit tool collated information on patient’s weight, diagnosis, medication infusions, whether standard concentrations were selected, daily fluid balance, target fluid balance, and renal support including use of diuretics. ResultsSeventy-seven (84%) of patients weighed less than 10kg. On average, there were seven medication infusions per patient and 98% of the medication infusions adhered to standard concentrations for medication infusions and DERS. In 2% of medication infusions staff opted not to use the DERS, or selected non-standard concentration, and 2% of patients had no labels on the syringe. 90% of patients had a minimal positive balance of 0.5mL/kg/h, averaged over 24h; 48% of patients received renal support and 16% of patients were 24h post cardiac surgery, where a negative fluid balance was recorded. It is standard practice post cardiac surgery to receive diuretics. Standard concentrations did not have a significant impact on patients’ daily fluid balance. ConclusionsThe use of standard concentrations and short infusions in PICU using DERS is feasible & achievable as demonstrated by high compliance, and does not have a negative impact on patient outcome, especially fluid balance.

Combined aquaretic and diuretic therapy in acute heart failure.

IntroductionAcute heart failure (AHF) is a leading cause of hospitalization and readmission in the US. The present study evaluated maximum diuresis while minimizing electrolyte imbalances, hemodynamic instability, and kidney dysfunction, to achieve a euvolemic state safely in a shorter period of time.Methods and resultsA protocol of combined therapy with furosemide, metolazone, and spironolactone, with or without tolvaptan and acetazolamide, was used in 17 hospitalized patients with AHF. The mean number of days on combination diuretic protocol was 3.8 days. The mean daily fluid balance was 3.0±2.1 L negative. The mean daily urine output (UOP) was 4.1±2.0 L (range 1.8–10.5 L). There were minimal fluctuations in serum electrolyte levels and serum creatinine over the duration of diuretic therapy. There was no statistically significant change in patients’ creatinine from immediately prior to therapy to the last day of therapy, with a mean increase in creatinine of 0.14 mg/dL (95% CI −0.03, +0.30, p=0.10).ConclusionOur strategy of treating AHF by achieving high UOP, while maintaining stable electrolytes and creatinine in a short period to euvolemic state, is safe.

Daily Lowest Hemoglobin and Risk of Organ Dysfunctions in Critically Ill Patients.

To determine the association between hemoglobin levels and the daily risk of individual organ dysfunctions in critically ill patients. Post hoc analysis of prospectively collected data. Vanderbilt University Medical Center and Saint Thomas Hospital Medical and Surgical ICUs. Medical and surgical ICU patients admitted with respiratory failure or shock. Baseline demographic data, and detailed in-ICU and hospital data, including daily lowest hemoglobin, were collected up to hospital day 30. We assessed patients daily for brain dysfunction (delirium, using Confusion Assessment Method for ICU), for renal and respiratory dysfunction (using the ordinal renal and respiratory Sequential Organ Failure Assessment score), and for ICU mortality. Associations between the lowest hemoglobin on a given day and organ dysfunctions the following day were assessed using multivariable regressions, adjusting for age, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity index, Framingham Stroke Risk Profile, ICU day, ICU type, sepsis, and current organ dysfunction status. A sensitivity analysis further adjusted for daily transfusions and fluid balance in a subset of our patients. We enrolled 821 patients with a median (interquartile range) age of 61 (51-71) years, Acute Physiology and Chronic Health Evaluation II score of 25 (19-31), and hemoglobin level of 10.0 (9.0-11.1) g/dL. There was no evidence of an association between lowest daily hemoglobin and brain dysfunction (p = 0.69 for delirium), renal dysfunction (p = 0.30), or ICU mortality (p = 0.95). The lowest hemoglobin on a given day was significantly associated with the respiratory Sequential Organ Failure Assessment score the following day; for each increasing hemoglobin unit, the odds of worsened respiratory Sequential Organ Failure Assessment score the following day were decreased by 36% (OR, 0.64; 95% CI, 0.53-0.77; p < 0.001). The sensitivity analysis including daily transfusions and fluid balance (in a subset of 518 patients) did not qualitatively change any of these associations. In this study in ICU patients, lower hemoglobin was associated with a higher probability of worsening respiratory dysfunction scores the following day. There was no evidence of association between hemoglobin and brain or renal dysfunction, or ICU mortality. The possible differential effects of anemia on organ dysfunctions seen in this hypothesis-generating study will have to be studied in a larger prospective study before any alterations to present restrictive transfusion guidelines can be recommended.

Forced fluid removal versus usual care in intensive care patients with high-risk acute kidney injury and severe fluid overload (FFAKI): study protocol for a randomised controlled pilot trial

BackgroundIntravenous administration of fluids is an essential part of critical care. While some fluid administration is likely beneficial, there is increasing observational evidence that the development of fluid overload is associated with increased mortality. There are no randomised trials to confirm this association in patients with acute kidney injury. We aim to perform a pilot trial to test the feasibility of forced fluid removal compared to standard care in patients with acute kidney injury and severe fluid overload, the FFAKI trial.MethodsThen FFAKI trial is a pilot, multicentre, randomised clinical trial recruiting adult intensive care patients with acute kidney injury and fluid overload, defined as more than 10% of ideal bodyweight. Patients are randomised with concealed allocation to either standard care or forced fluid removal with a therapeutic target of negative net fluid balance ≥1 mL/kg/h. The safety of fluid removal is continually evaluated according to predefined criteria of hypoperfusion: lactate ≥4 mmol/L, mean arterial pressure <50 mmHg or mottling beyond the edge of the kneecaps. If patients fulfil one of these criteria, fluid removal is suspended until hypoperfusion has resolved. The primary outcome measure is fluid balance at 5 days after randomisation and secondary outcomes include mean daily fluid balance, fluid balance at discharge from the intensive care unit, time to neutral fluid balance, number of serious adverse reactions and number of protocol violations. All patients are followed for 90 days.DiscussionThe FFAKI trial started in October 2015 and, when completed, will provide data to evaluate whether a large trial of forced fluid removal in critically ill patients is feasible. Our primary outcome will show if the experimental intervention leads to a clinically relevant difference in fluid balance, which could prove beneficial in intensive care patients with acute kidney injury.Trial registrationEudraCT, identifier: 2015-001701-13. Registered on 19 September 2015;ClinicalTrials.gov, identifier: NCT02458157. Registered on 21 May 2015;Danish Ethics Committee, identifier: H-15009589H. Registered on 22 September 2015; Danish Health and Medicines Authority, identifier: 2015070013. Registered on 11 August 2015.

Outcomes from a cohort of patients with acute kidney injury subjected to continuous venovenous hemodiafiltration: The role of negative fluid balance.

BackgroundSeveral factors influence the outcomes in acute kidney injury (AKI), especially in intensive care unit (ICU) patients. In this scenario, continuous renal replacement therapies (CRRT) are used to control metabolic derangements and blood volume. Knowing this fact, it may be possible to change the course of the disease and decrease the high mortality rate observed. Thus, we aimed to evaluate the main risk factors for death in AKI patients needing CRRT.ResultsThis was a prospective, observational cohort study of ICU patients (N = 183) with AKI who underwent continuous venovenous hemodiafiltration (CVVHDF) as their initial dialysis modality choice. The patients were predominantly male (62.8%) and their median age was 65 (55–76) years. The most frequent comorbidities were cardiovascular disease (39.3%), hypertension (32.8%), diabetes (24%), and cirrhosis (20.7%). The main cause of AKI was sepsis (52.5%). At beginning of CVVHDF, 152 patients (83%) were using vasopressors. The median SAPS 3 and SOFA score at ICU admission was 61 (50–74) and 10 (7–12), respectively. The dialysis dose delivered was 33.2 (28.9–38.7) ml/kg/h. The median time between ICU admission and CVVHDF initiation was 2 (1–4) days. The median cumulative fluid balance during the CVVHDF period was -1838 (-5735 +2993) ml. The mortality rate up to90 days was 58%. The independent mortality risk factors in propensity score model were: chronic obstructive pulmonary disease (OR = 3.44[1.14–10.4; p = 0.028]), hematologic malignancy (OR = 5.14[1.66–15.95; p = 0.005]), oliguria (OR = 2.36[1.15–4.9; p = 0.02]), positive daily fluid balance during CVVHDF (OR = 4.55[2.75–13.1; p<0.001]), and total SOFA score on first dialysis day (OR = 1.27[1.12–1.45; p<0.001]).ConclusionsDialysis-related factors may influence the outcomes. In our cohort, positive daily fluid balance during CRRT was associated with lower survival. Multicenter, randomized studies are needed to assess fluid balance as a primary outcome to define the best strategy in this patient population.

The relation between positive fluid balance and the prognosis in severe sepsis patients with acute kidney injury

Objective To investigate the relation between positive fluid balance and the prognosis in severe sepsis patients with acute kidney injury (AKI). Methods A retrospective analysis of clinical data of 90 patients in our department was carried out. According to the final outcome, patients were divided into survival group (n=26) and non-survival group (n=64), in which the relation between patients’positive fluid balance and the prognosis was evaluated. Results (1)There was no statistically significant difference in the age and severity between survival group and non-survival group of patients with severe sepsis and consequent AKI, but the patients in non-survival group had greater volume overload. Compared with the survival group, higher mean fluid balance [(1 112.12±546.85) mLvs.(644.69±474.93)mL, P=0.00], and less urine output [(1 224.07±708.79)mL vs.(2 032.36±723.53)mL, P=0.00) in non-survival group.(2)There was no significant difference in mortality between early and late continuous renal replacement therapy (CRRT) during ICU care. However, the average daily fluid load in late CRRT patients was significantly greater than that in early CRRT patients [(1178.81±397.03)mLvs.(287.22±433.53)mL, P=0.00]and the lung oxygenation index in late CRRT patients was significantly worse than that in early CRRT patients [(211.22±42.56)vs.(169.46±57.40), P=0.04](3)The relevant variables to 28-day mortality in AKI patients with severe sepsis included CRRT treatment, oxygenation index and the average daily fluid balance>500 mL.Among them, fluid balance>500mL was an independent risk factor for AKI patients with severe sepsis. Their prognosis was worse if they had greater positive fluid balance. CRRT was the protective factor which could affect the prognosis of patients with severe sepsis complicated by AKI. Conclusions Patients with severe sepsis complicated by AKI has a high mortality. Persistent fluid overload can lead to increased mortality in patients with severe sepsis complicated by AKI. Early CRRT can reduce fluid retention in patients with renal failure and improve oxygenation index. Key words: Acute kidney injury; Severe sepsis; Positive fluid balance

Fluid overload is an independent risk factor for acute kidney injury in critically Ill patients: results of a cohort study

BackgroundAcute Kidney injury (AKI) is common and increases mortality in the intensive care unit (ICU). We carried out this study to explore whether fluid overload is an independent risk factor for AKI.MethodsSingle-center prospective, observational study. Consecutively admitted, ICU patients were followed for development of AKI. Intravenous fluid volumes, daily fluid balances were measured, hourly urine volumes, daily creatinine levels were recorded.ResultsThree hundred thirty nine patients were included; AKI developed in 141 (41.6%) patients; RISK in 27 (8%) patients; INJURY in 25 (7%); FAILURE in 89 (26%) by the RIFLE criteria. Fluid balance was significantly higher in patients with AKI; 1755 ± 2189 v/s 924 ± 1846 ml, p < 0.001 on ICU day 1. On multivariate regression analysis, a net fluid balance in first 24 h of ICU admission, OR 1.02 (95% CI 1.01,1.03 p = 0.003), percentage of fluid accumulation adjusted for body weight OR1.009 (95% CI 1.001,1.017, p = 0.02), fluid balance in first 24 h of ICU admission with serum creatinine adjusted for fluid balance, OR 1.024 (95% CI 1.012,1,035, p = 0.005), Age, OR 1.02 95% CI 1.01,1.03, p < 0.001, CHF, OR 3.1 (95% CI 1.16,8.32, p = 0.023), vasopressor requirement on ICU day one, OR 1.9 (95% CI 1.13,3.19, p = 0.014) and Colistin OR 2.3 (95% CI 1.3, 4.02, p < 0.001) were significant predictors of AKI. There was no significant association between fluid type; Chloride-liberal, Chloride-restrictive, and AKI.ConclusionsFluid overload is an independent risk factor for AKI.

Cumulative changes in weight but not fluid volume balances reflect fluid accumulation in ICU patients.

The cumulative fluid balance of critically ill patients seems to be an outcome-relevant variable. However, there are no validated data for their reliability calculated for longer (> 5 days) periods of time. All ICU patients ≥ 18 years, with an ICU stay ≥ 5 days and a body weight ≤ 195 kg were evaluated from 1 January 2013 to 31 December 2013. Daily standardized weighing was performed using bed-integrated scales simultaneously with the daily 24-h fluid balance. Simultaneously, a fluid balance without and with insensible perspiration (10 ml/kg/day) was calculated for each 24 h. Primary endpoint: difference between cumulative fluid balance and body weight changes at the day of transfer to the normal ward or the day of death in the ICU, respectively, in each patient. All data are presented as medians with interquartile ranges (IQR) with 25 and 75 percentiles (IQR/25/75) unless otherwise noted. One hundred and six critically ill patients were evaluated; 82 survivors and 24 nonsurvivors. Cumulative 24-h fluid balances rose continuously while body weight decreased over time. Correction of cumulative fluid balances for insensible perspiration (10 ml/kg/day) also did not match with body weight changes. Only survivors had a significant loss in body weight -1.8 (27.5/-6.1/1.0) kg. Assuming that changes in body weight reflect changes in whole body water content cumulative daily fluid volume balances without or with correction for insensible water loss are not useful for estimating cumulative fluid balance of ICU patients. Survivors but not nonsurvivors had a significant loss of weight over time.

Acute kidney injury adjusted to volume status in critically ill patients: recognition of delayed diagnosis, restaging, and associated outcomes.

Critically ill patients receive a significant amount of fluids leading to a positive fluid balance; this dilutes serum creatinine resulting in an overestimated glomerular filtration rate. The goal of our study is to identify undiagnosed or underestimated acute kidney injury (AKI) in the intensive care unit (ICU). It will also identify the morbidity and mortality associated with an underestimated AKI. We reviewed records of patients admitted to our institution (Staten Island University Hospital) between 2012 and 2013 for more than 2 days. Patients with end stage renal disease were excluded. AKI was defined using the Acute Kidney Injury Network criteria. The following formula was used to identify and restage patients with AKI: adjusted creatinine = serum creatinine × [(hospital admission weight (kg) 0.6 + Σ (daily cumulative fluid balance (L))/hospital admission weight × 0.6]. The primary outcome identified newly diagnosed AKI and those who were restaged. The secondary outcome identified associated morbidities. Seven-hundred and thirty-three out of 1,982 ICU records reviewed, were used. Two-hundred and fifty-seven (mean age 69.8±14.9) had AKI, out of which 15.9% were restaged using the equation. Comparison of mean by Student’s t-test showed no difference between patients who were restaged. Similarly, chi-square revealed no differences between both arms, except mean admission weight (lower in patients who were restaged), fluid balance on days 1, 2, and 3 (higher in the restaged arm), and the presence of congestive heart failure (more prevalent in the restaged arm). Of note, the mean cost of stay was US$150,562.82 vs $197,174.63 for same stage vs restaged, respectively, however, without statistical significance (P=0.74). Applying the adjustment equation showed a modest (15.9%) increase in the AKI staging slightly impacting outcomes (mortality, length, and cost of stay) without statistical significance.

Excessive Postoperative Fluid Administration in Infants with Gastroschisis

Careful fluid management is a cornerstone of neonatology because the cardiovascular, respiratory, and gastrointestinal systems in the newborn are sensitive to overhydration. Fluid management in gastroschisis is complicated by insensible fluid loss and postoperative third-space fluid shifts. Study of perioperative fluid management in gastroschisis is limited and has not undergone careful scrutiny. We reviewed perioperative fluid administration and urine output in all infants with gastroschisis over a 5-year period. Data included whether the patient underwent primary closure or staged repair, weight, and events during hospitalization (length of hospitalization and duration of gastric decompression, parenteral nutrition, and ventilator support). Paired t test gave statistical comparisons with significance at P < 0.05. From 2010 to 2014, 24 patients underwent abdominal closure, 17 had primary and 7 had staged closures. Fluid administration exceeded 100 mL/kg/d after primary closure, and was significantly higher (>150 mL/kg/d; P < 0.05) after staged closure on postoperative days 0 to 5. Postoperative urinary output exceeded 75 mL/kg/d for all patients, with higher volumes reaching 100 mL/kg/d after staged closure on postoperative days 4 to 6 (P < 0.05). Two patients died of sepsis. All survivors were discharged with intestinal continuity and gaining weight on oral feeding. Patients with gastroschisis received large volumes of fluid after operation despite similarly high urine output and positive daily fluid balances. The amounts of fluid administered after both primary and staged closure may be excessive and potentially deleterious.

The Dose Response Multicentre Investigation on Fluid Assessment (DoReMIFA) in critically ill patients.

BackgroundThe previously published “Dose Response Multicentre International Collaborative Initiative (DoReMi)” study concluded that the high mortality of critically ill patients with acute kidney injury (AKI) was unlikely to be related to an inadequate dose of renal replacement therapy (RRT) and other factors were contributing. This follow-up study aimed to investigate the impact of daily fluid balance and fluid accumulation on mortality of critically ill patients without AKI (N-AKI), with AKI (AKI) and with AKI on RRT (AKI-RRT) receiving an adequate dose of RRT.MethodsWe prospectively enrolled all consecutive patients admitted to 21 intensive care units (ICUs) from nine countries and collected baseline characteristics, comorbidities, severity of illness, presence of sepsis, daily physiologic parameters and fluid intake-output, AKI stage, need for RRT and survival status. Daily fluid balance was computed and fluid overload (FO) was defined as percentage of admission body weight (BW). Maximum fluid overload (MFO) was the peak value of FO.ResultsWe analysed 1734 patients. A total of 991 (57 %) had N-AKI, 560 (32 %) had AKI but did not have RRT and 183 (11 %) had AKI-RRT. ICU mortality was 22.3 % in AKI patients and 5.6 % in those without AKI (p < 0.0001). Progressive fluid accumulation was seen in all three groups. Maximum fluid accumulation occurred on day 2 in N-AKI patients (2.8 % of BW), on day 3 in AKI patients not receiving RRT (4.3 % of BW) and on day 5 in AKI-RRT patients (7.9 % of BW). The main findings were: (1) the odds ratio (OR) for hospital mortality increased by 1.075 (95 % confidence interval 1.055–1.095) with every 1 % increase of MFO. When adjusting for severity of illness and AKI status, the OR changed to 1.044. This phenomenon was a continuum and independent of thresholds as previously reported. (2) Multivariate analysis confirmed that the speed of fluid accumulation was independently associated with ICU mortality. (3) Fluid accumulation increased significantly in the 3-day period prior to the diagnosis of AKI and peaked 3 days later.ConclusionsIn critically ill patients, the severity and speed of fluid accumulation are independent risk factors for ICU mortality. Fluid balance abnormality precedes and follows the diagnosis of AKI.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1355-9) contains supplementary material, which is available to authorized users.

A retrospective review of fluid balance control in CRRT

IntroductionAn effect of severe acute kidney injury (AKI) is the development of oliguria and subsequent retention of fluid. Recent studies have reported an association between fluid overload and increased mortality in critically ill patients. Achieving fluid balance control through haemofiltration is an important part of dialysis dose delivery in continuous renal replacement therapy (CRRT). Aims(1) Compare the prescribed dose with the delivered dose of dialysis and haemofiltration for CRRT. (2) Identify how interruptions and delays in treatment delivery impact on fluid balance management. MethodA retrospective cohort study was undertaken of daily fluid balance and fluid removal for patients who required CRRT. Each observation chart and prescription order for every treatment day was reviewed. Each patient was exposed to the same treatment mode, predilutional continuous veno-venous haemodiafiltration (CVVHDf). A comparison was made of fluid balance control delivered to the patient over 24h against the dose of fluid removal prescribed. ResultsThe observation charts of 46 consecutive patients were reviewed for total of 288 treatment days. Median number of days patients received CRRT was 5 (range 1–31). Median circuit life was 16h (range 0–66). Fluid removal targets did not occur in 75 (26%) treatment days. Median daily fluid removal shortfall was 300mL (range 25–3800mL). Mean number of daily treatment interruptions 1.25, SD±0.49. The most frequent cause of treatment downtime was circuit clotting (45%). Mean length of treatment down time was 3.71, SD±4.36h excluding delays attributed to assessment of renal function. ConclusionIn over a quarter of treatment days prescribed fluid removal was not achieved. Frequency of interruptions and delays in resumption of treatment compromised fluid balance control. Daily targets for fluid removal which are not achieved contribute to fluid overload and may compromise the outcome of patients who require CRRT.

Incidence and prognosis of intra-abdominal hypertension and abdominal compartment syndrome in severely burned patients: Pilot study and review of the literature.

Burn patients are at high risk for secondary intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) due to capillary leak and large volume fluid resuscitation. Our objective was to examine the incidence the incidence of IAH and ACS and their relation to outcome in mechanically ventilated (MV) burn patients. This observational study included all MV burn patients admitted between April 2007 and December 2009. Various physiological parameters, intra-abdominal pressure (IAP) measurements and severity scoring indices were recorded on admission and/or each day in ICU. Transpulmonary thermodilution parameters were also obtained in 23 patients. The mean and maximum IAP during admission was calculated. The primary endpoint was ICU (burn unit) mortality. Fifty-six patients were included. The average Simplified Acute Physiology Score (SAPS II) and Sequential Organ Failure Assessment (SOFA) scores were 43.4 (± 15.1) and 6.4 (± 3.4), respectively. The average total body surface area (TBSA) affected by burns was 24.9% (± 24.9), with 33 patients suffering inhalational injuries. Forty-four (78.6%) patients developed IAH and 16 (28.6%) suffered ACS. Patients with ACS had higher TBSAs burned (35.8 ± 30 vs. 20.6 ± 21.4%, P = 0.04) and higher cumulative fluid balances after 48 hours (13.6 ± 16L vs. 7.6 ± 4.1 L, P = 0.03). The TBSA burned correlated well with the mean IAP (R = 0.34, P = 0.01). Mortality was notably high (26.8%) and significantly higher in patients with IAH (34.1%, P = 0.014) and ACS (62.5%, P < 0.0001). Most patients received more fluids than calculated by the Parkland Consensus Formula while, interestingly, non-survivors received less. However, when patients with pure inhalation injury were excluded there were no differences. Non-surgical interventions (n = 24) were successful in removing body fluids and were related to a significant decrease in IAP, central venous pressure (CVP) and an improvement in oxygenation and urine output. Non-resolution of IAH was associated with a significantly worse outcome (P < 0.0001). Based on our preliminary results we conclude that IAH and ACS have a relatively high incidence in MV burn patients compared to other groups of critically ill patients. The percentage of TBSA burned correlates with the mean IAP. The combination of high CLI, positive (daily and cumulative) fluid balance, high IAP, high EVLWI and low APP suggest a poor outcome. Non-surgical interventions appear to improve end-organ function. Non-resolution of IAH is related to a worse outcome.

Fluid Overload Is Associated With Higher Mortality and Morbidity in Pediatric Patients Undergoing Cardiac Surgery.

Fluid overload after pediatric cardiac surgery is common and has been shown to increase both mortality and morbidity. This study explores the risk factors of early postoperative fluid overload and its relationship with adverse outcomes. Secondary analysis of the prospectively collected data of children undergoing open-heart surgery between 2004 and 2008. Tertiary national cardiac center. One thousand five hundred twenty consecutive pediatric patients (<18 years old) were included in the analyses. None. In the first 72 hours of the postoperative period, the daily fluid balance was calculated as milliliter per kilogram and the daily fluid overload was calculated as fluid balance (L)/weight (kg) × 100. The primary endpoint was in-hospital mortality; the secondary outcomes were low cardiac output syndrome and prolonged mechanical ventilation. One thousand three hundred and sixty-seven patients (89.9%) had a cumulative fluid overload below 5%; 120 patients (7.8%), between 5% and 10%; and 33 patients (2.1%), above 10%. After multivariable analysis, higher fluid overload on the day of the surgery was independently associated with mortality (adjusted odds ratio, 1.14; 95% CI, 1.008-1.303; p = 0.041) and low cardiac output syndrome (adjusted odds ratio, 1.21; 95% CI, 1.12-1.30; p = 0.001). Higher maximum serum creatinine levels (adjusted odds ratio, 1.01; 95% CI, 1.003-1.021; p = 0.009), maximum vasoactive-inotropic scores (adjusted odds ratio, 1.01; 95% CI, 1.005-1.029; p = 0.042), and higher blood loss on the day of the surgery (adjusted odds ratio, 1.01; 95% CI, 1.004-1.025; p = 0.015) were associated with a higher risk of fluid overload that was greater than 5%. Fluid overload in the early postoperative period was associated with higher mortality and morbidity. Risk factors for fluid overload include underlying kidney dysfunction, hemodynamic instability, and higher blood loss on the day of the surgery.

Pulmonary Congestion (White Lungs) on VA ECMO

&#x0D; &#x0D; &#x0D; &#x0D; Background&#x0D; Veno-arterial extracorporeal membrane oxygenation therapy (VA ECMO) is used for short-term circulatory support in the setting of cardiogenic shock or cardiac arrest. While VA-ECMO improves hemodynamics and gas exchange, it may result in left ventricular distention and pulmonary congestion.&#x0D; &#x0D; &#x0D; &#x0D; Methods&#x0D; The records of all patients supported with VA ECMO for at least three consecutive days at our institution from 2012-2014 were retrospectively analyzed. All chest radiographs taken during VA ECMO support were graded on a scale of 1 to 4. A score of 1 was used when no pulmonary congestion was present. A score of 2 was used for congestion occupying less than half of both lungs. A score of 3 was used for diffuse congestion occupying over half of both lung fields. A score of 4 was used when complete opacification of both lungs was present. Grades 3 and 4 were considered “white lungs”. The presence of white lungs was examined as a categorical variable. The grade of congestion was examined as a continuous variable. Ordinal logistic regression was used for the analysis.&#x0D; &#x0D; &#x0D; &#x0D; Results&#x0D; The sample size analyzed included 46 events of VA ECMO support in 44 individual patients. In 34 (73.9%) patients the lungs became opacified and reached a score of 3 or 4 (the white lungs group), while in 12 (%) patients there were no white lungs. Overall, the percentage of patients that survived to weaning off VA ECMO was 60.9%. The percentage of patients that survived to hospital discharge was 37.0%. In patients who did not have white lungs the percentages of survival to weaning off VA ECMO and survival to hospital discharge were 91.7% and 66.7%, respectively. In those with white lungs, the percentages of survival to weaning off VA ECMO and survival to hospital discharge were 50.0% and 26.5%, respectively (p=0.019 for discharged alive). The duration of VA ECMO support, ECMO flow, daily fluid balance, sum net fluid balance for the length of stay, and use of hemodialysis predicted a higher degree of pulmonary congestion.&#x0D; &#x0D; &#x0D; &#x0D; Conclusion&#x0D; Severe pulmonary congestion, or white lungs, is common in patients on VA ECMO and is associated with very poor prognosis. Longer duration of support, greater positive fluid balance, higher ECMO flow, and use of hemodialysis are linked to development of white lungs.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Prognostic value of extravascular lung water and its potential role in guiding fluid therapy in septic shock after initial resuscitation

PurposesTo explore whether extravascular lung water (EVLW) provides a valuable prognostic tool guiding fluid therapy in septic shock patients after initial resuscitation. Materials and MethodsWe performed a retrospective study of septic shock patients who achieved adequate initial fluid resuscitation with extended hemodynamic monitoring, analyzing the prognostic value of EVLW and whether fluid therapy for 24 (T24) or 24-48 hours (T24-48) after initial resuscitation with a recommended value of EVLW yielded a 28-day mortality advantage. ResultsOne hundred five patients with septic shock were included in this study, 60 (57.1%) of whom died after 28 days. For 48 hours after initial resuscitation, the daily fluid balance (DFB; T24: 2494 ± 1091 vs 1965 ± 964 mL [P = .011] and T24-48: 2127 ± 783 vs 1588 ± 665 mL [P < .001]) and daily maximum values of the EVLW index (EVLWImax; T24: 13.9 ± 3.7 vs 11.5 ± 3.2 mL/kg [P < .001] and T24-48: 14.4 ± 5.3 vs 12.0 ± 4.4 mL/kg [P < .001]) were significantly higher in nonsurvivors than in survivors. In multivariate regression analysis, the DFB (T24: odds ratio [OR] 1.001 [P = .016] and T24-48: OR 1.001 [P = .008]), EVLWImax (T24: OR 2.158 [P = .002] and T24-48: OR 3.277 [P = .001]), blood lactate (T24: OR 1.368 [P = .021] and T24-48: OR 4.112 [P < .001]), and central venous blood oxygen saturation (T24: OR 0.893 [P = .013] and T24-48: OR 0.780 [P = .004]) were all independently associated with the 28-day mortality. A receiver operating characteristic analysis revealed that area under the curve values of 0.82 (95% confidence interval, 0.74-0.91; P < .001) and 0.90 (95% confidence interval, 0.83-0.96; P < .001) for EVLWImax ≥ 12.5 mL/kg (T24 and T24-48) predicted a 28-day mortality with sensitivities of 88% (80%-96%) and 95% (90%-100%) and specificities of 60% (46%-74%) and 76% (63%-89%).The EVLWImax was correlated with DFB with Spearman ρ values of 0.497 (T24: P < .001) and 0.650 (T24-48: P < .001). Cox survival and regression analyses demonstrated that EVLWImax ≥ 12.5 mL/kg (T24 and T24-48) was associated with higher risk and increased mortality, with adjusted ORs of 4.77 (P < .001) and 10.86 (P < .001). ConclusionsA higher EVLW in septic shock patients after initial resuscitation was associated with a more positive fluid balance and increased mortality, which is an independent predictor of the 28-day mortality in septic shock patients after initial resuscitation.

Incomparable Subsequent Effects between Study and Control Fluids Might Cause Questionable Results in Randomized Controlled Trials

Dr. Wiedermann commented on our systematic review and meta-regression for the sources of heterogeneity in trials reporting HES 130/0.4 or 0.42 associated excess mortality in septic patients[1] that the pooled analysis of mortality, which showed neither benefit nor harm, might be influenced by trials of low-quality. Statistically, we agree with this conclusion if two of the recruited trials judged as the intermediate risk of bias are precluded. Sensitivity tests in a meta-analysis are important. But an issue need for further discussing is that whether the results from a sensitivity analysis should be considered as the confirmatory or just exploratory. The fundamental thought of meta-analysis is to synthesis all the evidence current available. The article search strategy and the study inclusion/exclusion criteria had both been prespecified without any knowledge of the pooled analysis of mortality. The overall results should be taken as primary analysis because all the studies were fulfilled the prespecified principle. Over-interpretation of any subgroup analysis may have raised potential risk even if only focus on the trials with low risk of bias, the reasons were followed below. (1) Quality of the reporting of a study does not equal to the quality of the study itself. A well conduct study may have a very low-quality on reporting.[2] In addition, the process for risk of bias assessment is a sort of subjective even two independent reviewers assessing separately. It is hard to demonstrate any solid result from sensitivity analysis unless the consensus on the risk of bias assessment focus on study conducting could be achieved. (2) The multiplicity issue is not very common mentioned in the meta-analysis. However, the false-positive rate does significantly increased accompany with the raised number of tests. Currently, the meta-analysis includes 11 trials in total.[1] If we assume 6 of them are a low risk of bias, but the question is they are not easy to identify. Theoretically, there will be 462 possible combinations (randomly choose 6 trials from 11) under this scenario. The corresponding type I error rate (at least to observe one false-positive subgroup result) would be almost 100% (=1-0.95^462). By this reason, it should use a more restricted significant level for each subgroup result. Further, the test for subgroup difference between trials with low versus high risk of bias is a kind of interaction test. It also has to face the multiplicity issue. More importantly, the uncertainty of chosen the threshold for the significant level for interaction test is still controversial. Thus, the significant results of subgroup should be interpreted with cautions.[3] There are many reasons for the heterogeneity of mortality as primary outcome under the same intervention in randomized controlled trials (RCTs).[4] Most importantly, bias associated with execution factors such as intervention or its subsequent effects may cause questionable results in RCTs.[5] The efficiency of fluid therapy as a subsequent effect was found incomparable between HES and control group in some of the recruited RCTs in this meta-regression. Interestedly, all of 3 out of 11 RCTs, which were calculated with more positive fluid balance in HES group (a colloid with more efficiency on plasma volume expansion than crystalloids in general) than in control group, similarly reported a high risk of HES on excess mortality in septic patients and with significance in Perner's trial.[6] Our analysis further suggested daily delta fluid balance being likely associated with mortality in septic patients receiving HES 130/130/0.4* (P = 0.079). Whereas, we failed to determine a dose-effect relationship of HES 130/0.4 or 0.42 with mortality (P = 0.298). These results indicated that fluid balance was an important factor confounding the results of these RCTs. This was the main finding of this meta-regression. In conclusion, information from bedside (such as incomparable subsequent effects in fluid therapy) should be considered with priority over statistics in interpreting the results of available RCTs in evaluating the impact of any clinical intervention on mortality in critically ill patients.

Influence of Daily Fluid Balance prior to Continuous Renal Replacement Therapy on Outcomes in Critically Ill Patients.

Positive fluid balance is a risk factor for mortality in critically ill patients, especially those requiring continuous renal replacement therapy (CRRT). However, the association between daily fluid balance and various organ impairments remains unclear. This study investigated the impacts of daily fluid balance prior to CRRT on organ dysfunction, as well as mortality in critically ill patients. We identified daily fluid balance between intensive care unit (ICU) admission and CRRT initiation. According to daily fluid balance, the time to CRRT initiation and the rate of organ failure based on the sequential organ failure assessment (SOFA) score were assessed. We recruited 100 patients who experienced CRRT for acute kidney injury. CRRT was initiated within 2 [0, 4] days. The time to CRRT initiation was shortened in proportion to daily fluid balance, even after the adjustment for the renal SOFA score at ICU admission (HR 1.14, P = 0.007). Based on the SOFA score, positive daily fluid balance was associated with respiratory, cardiovascular, nervous, and coagulation failure, independent of each initial SOFA score at ICU admission (HR 1.36, 1.26, 1.24 and 2.26, all P < 0.05). Ultimately, we found that positive fluid balance was related with an increase in the rate of 28-day mortality (HR 1.14, P = 0.012). Positive daily fluid balance may accelerate the requirement for CRRT, moreover, it can be associated with an increased risk of multiple organ failure in critically ill patients.

Fluid balance and mortality in critically ill patients with acute kidney injury: a multicenter prospective epidemiological study.

IntroductionEarly and aggressive volume resuscitation is fundamental in the treatment of hemodynamic instability in critically ill patients and improves patient survival. However, one important consequence of fluid administration is the risk of developing fluid overload (FO), which is associated with increased mortality in patients with acute kidney injury (AKI). We evaluated the impact of fluid balance on mortality in intensive care unit (ICU) patients with AKI.MethodsThe data were extracted from the Beijing Acute Kidney Injury Trial. This trial was a prospective, observational, multicenter study conducted in 30 ICUs among 28 tertiary hospitals in Beijing, China, from 1 March to 31 August 2012. In total, 3107 patients were admitted consecutively, and 2526 patients were included in this study. The data from the first 3 sequential days were analyzed. The AKI severity was classified according to the Kidney Disease: Improving Global Outcomes guidelines. The daily fluid balance was recorded, and the cumulative fluid balance was registered at 24, 48, and 72 h. A multivariate analysis was performed with Cox regression to determine the impact of fluid balance on mortality in patients with AKI.ResultsAmong the 2526 patients included, 1172 developed AKI during the first 3 days. The mortality was 25.7 % in the AKI group and 10.1 % in the non-AKI group (P < 0.001). The daily fluid balance was higher, and the cumulative fluid balance was significantly greater, in the AKI group than in the non-AKI group. FO was an independent risk factor for the incidence of AKI (odds ratio 4.508, 95 % confidence interval 2.900 to 7.008, P < 0.001) and increased the severity of AKI. Non-surviving patients with AKI had higher cumulative fluid balance during the first 3 days (2.77 [0.86–5.01] L versus 0.93 [−0.80 to 2.93] L, P < 0.001) than survivors did. Multivariate analysis revealed that the cumulative fluid balance during the first 3 days was an independent risk factor for 28-day mortality.ConclusionsIn this multicenter ICU study, the fluid balance was greater in patients with AKI than in patients without AKI. FO was an independent risk factor for the incidence of AKI and increased the severity of AKI. A higher cumulative fluid balance was an important factor associated with 28-day mortality following AKI.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1085-4) contains supplementary material, which is available to authorized users.

A positive fluid balance is an independent prognostic factor in patients with sepsis.

IntroductionIntravenous fluid administration is an essential component of sepsis management, but a positive fluid balance has been associated with worse prognosis. We analyzed whether a positive fluid balance and its persistence over time was an independent prognostic factor in septic patients.MethodsWe prospectively studied fluid intake and output for 7 days in 173 consecutive adult patients treated for sepsis in our Department of Intensive Care.ResultsOf the 173 patients, 59 died (34 %). Mean daily fluid intake was higher in non-survivors than in survivors (59 ± 24 ml/kg vs. 48 ± 23 ml/kg, p = 0.03), but output volumes were similar. As a result, the daily fluid balance was more than twice as large in the non-survivors as in the survivors (29 ± 22 vs. 13 ± 19 ml/kg, p <0.001). Persistence of a positive fluid balance over time was associated with increased mortality. Using a multivariable time-dependent Cox model, a positive fluid balance was independently associated with higher mortality (adjusted hazard ratio 1.014 [1.007–1.022] per ml/kg increase, p <0.001).ConclusionsPersistence of a positive daily fluid balance over time was quite strongly associated with a higher mortality rate in septic patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0970-1) contains supplementary material, which is available to authorized users.