No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Fluid Stewardship of Maintenance Intravenous Fluids
Abstract
Despite the frequent use of maintenance intravenous fluids (mIVF) in critically ill patients, limited guidance is available. Notably, fluid overload secondary to mIVF mismanagement is associated with significant adverse patient outcomes. The Four Rights (right drug, right dose, right duration, right patient) construct of fluid stewardship has been proposed for the safe evaluation and use of fluids. The purpose of this evidence-based review is to offer practical insights for the clinician regarding mIVF selection, dosing, and duration in line with the Four Rights of Fluid Stewardship.
... It can be defined as a series of coordinated interventions introduced to select the optimal fluid, dose, and duration of therapy that may result in the best clinical outcome, prevent adverse events, and reduce cost. Selecting the right patient, right drug, right dose, and right duration can be used as a conceptual framework for IV fluid stewardship [10]. The questions in this survey were used to assess the prescription pattern and knowledge of IV fluids in this framework. ...
... Periodic monitoring of fluid balance and electrolytes can help in the estimation of fluid overload and is an integral component of fluid stewardship [9,10,34]. Higher cumulative fluid balance and fluid overload are directly linked to AKI risk and intra-abdominal hypertension, which strongly correspond to increased morbidity and mortality in ICU [20,35,36]. Daily body weight measurement correlates with a cumulative fluid balance of critically ill patients [37]. ...
Purpose
In the absence of recent international recommendations supported by scientific societies like Anesthesiology or Intensive Care Medicine, healthcare professionals (HCP) knowledge on IV fluid is expected to vary. We undertook a cross-sectional survey, aiming to assess prescription patterns and test the knowledge of HCP for IV fluid use in the operating room (OR) and intensive care unit (ICU).
Methods
An online international cross-sectional survey was conducted between October 20, 2019, and November 27, 2021. The survey included multiple-choice questions on demographics, practice patterns and knowledge of IV fluids, and a hemodynamically unstable patient assessment.
Results
1045 HCP, from 97 countries responded to the survey. Nearly three-quarters reported the non-existence of internal hospital or ICU-based guidelines on IV fluids. The respondents' mean score on the knowledge assessment questions was 46.4 ± 14.4. The cumulative mean scores were significantly higher among those supervising trainees (p = 0.02), specialists (p < 0.001) and those working in high-income (p < 0.001) countries. Overall performance of respondents on the knowledge testing for IV fluid was unsatisfactory with only 6.5% respondents performed above average.
Conclusion
There is a wide difference in the knowledge and prescription of IV fluids among the HCP surveyed. These findings reflect the urgent need for education on IV fluids.
... Se puede concluir que los LEV deben ser considerados un medicamento más y, como tal, se deben tener claras las 4D de la administración de todo medicamento para su prescripción: droga (tipo de solución a utilizar), dosis (volumen a administrar), duración (por cuánto tiempo) y desescalamiento (medidas tendientes a remover el exceso de lo administrado) [57][58][59]. Además de las 4D, al momento de utilizar LEV, se sugiere hacernos estas cuatro preguntas: ¿cuándo iniciar la administración?, ¿cuándo suspenderla?, ¿cuándo iniciar la remoción del exceso de líquidos? y ¿cuándo parar dicha remoción? ...
Contexto: la lesión renal aguda (LRA) es una condición frecuentemente encontrada por el nefrólogo, tanto en unidades de cuidado crítico como en salas de hospitalización. Objetivo: profundizar en los principales determinantes fisiopatológicos del estado de volumen y la aplicación clínica de estos en la cabecera del paciente crítico. Metodología: este artículo explica la fisiología de la administración de los LEV, discute críticamente los patrones de prescripción actuales y examina los dispositivos y las pruebas más frecuentemente utilizadas para la monitorización hemodinámica y predecir la respuesta a la administración de volumen. Resultados: la primera causa para descartar siempre es la hipovolemia y el manejo inicial de esta se realiza usualmente a través de la administración temprana de líquidos endovenosos (LEV), incluso antes de la evaluación por el nefrólogo. Es importante que este especialista comprenda que la administración adicional de líquidos no es inocua y puede llevar a la sobrecarga de volumen. Por lo tanto, la administración de LEV solo debería realizarse posterior a una maniobra de respuesta a volumen positiva. Conclusiones: se propone un algoritmo para guiar la administración de volumen en pacientes con LRA.
... Optimizing fluid management (or fluid stewardship) has been previously defined by the ROSE model of Resuscitation, Optimization, Stabilization, and dE-resuscitation 35 . After an initial 24-48 h period characterized by overt volume resuscitation (e.g., a crystalloid bolus) and IV medication initiation (e.g., antibiotics), and the associated fluid administration, the care priority shifts from volume administration to volume removal. ...
Fluid overload, while common in the ICU and associated with serious sequelae, is hard to predict and may be influenced by ICU medication use. Machine learning (ML) approaches may offer advantages over traditional regression techniques to predict it. We compared the ability of traditional regression techniques and different ML-based modeling approaches to identify clinically meaningful fluid overload predictors. This was a retrospective, observational cohort study of adult patients admitted to an ICU ≥ 72 h between 10/1/2015 and 10/31/2020 with available fluid balance data. Models to predict fluid overload (a positive fluid balance ≥ 10% of the admission body weight) in the 48–72 h after ICU admission were created. Potential patient and medication fluid overload predictor variables (n = 28) were collected at either baseline or 24 h after ICU admission. The optimal traditional logistic regression model was created using backward selection. Supervised, classification-based ML models were trained and optimized, including a meta-modeling approach. Area under the receiver operating characteristic (AUROC), positive predictive value (PPV), and negative predictive value (NPV) were compared between the traditional and ML fluid prediction models. A total of 49 of the 391 (12.5%) patients developed fluid overload. Among the ML models, the XGBoost model had the highest performance (AUROC 0.78, PPV 0.27, NPV 0.94) for fluid overload prediction. The XGBoost model performed similarly to the final traditional logistic regression model (AUROC 0.70; PPV 0.20, NPV 0.94). Feature importance analysis revealed severity of illness scores and medication-related data were the most important predictors of fluid overload. In the context of our study, ML and traditional models appear to perform similarly to predict fluid overload in the ICU. Baseline severity of illness and ICU medication regimen complexity are important predictors of fluid overload.
... Other approaches include the administration of intravenous crystalloids and potentially nephroprotective antioxidant agents. Intravenous crystalloids can mitigate the haemodynamic effects of AmB by increasing intravascular volume and decreasing tubuloglomerular feedback [30,31]. N-Acetyl cysteine (NAC), an antioxidant, administered orally at 600 mg twice daily has demonstrated potential for reducing nephrotoxicity in a small doubleblinded placebo-controlled clinical trial [32]. ...
Purpose of review
Drug associated kidney injury (D-AKI) occurs in 19–26% of hospitalized patients and ranks as the third to fifth leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Given the high use of antimicrobials in the ICU and the emergence of new resistant organisms, the implementation of preventive measures to reduce the incidence of D-AKI has become increasingly important.
Recent findings
Artificial intelligence is showcasing its capabilities in early recognition of at-risk patients for acquiring AKI. Furthermore, novel synthetic medications and formulations have demonstrated reduced nephrotoxicity compared to their traditional counterparts in animal models and/or limited clinical evaluations, offering promise in the prevention of D-AKI. Nephroprotective antioxidant agents have had limited translation from animal studies to clinical practice. The control of modifiable risk factors remains pivotal in avoiding D-AKI.
Summary
The use of both old and new antimicrobials is increasingly important in combating the rise of resistant organisms. Advances in technology, such as artificial intelligence, and alternative formulations of traditional antimicrobials offer promise in reducing the incidence of D-AKI, while antioxidant medications may aid in minimizing nephrotoxicity. However, maintaining haemodynamic stability using isotonic fluids, drug monitoring, and reducing nephrotoxic burden combined with vigilant antimicrobial stewardship remain the core preventive measures for mitigating D-AKI while optimizing effective antimicrobial therapy.
... Fluid overload is a common though often unintentional consequence of caring for critically ill adults in the initial phase of their ICU stay. Despite the clinical need for volume resuscitation or intravenous (IV) medications that can lead to fluid overload, it is associated with increased rates of ICU complications, including acute kidney injury, use of invasive positive pressure ventilation, and prolonged ICU stay [20][21][22][23]. As such, fluid management is a clinically complex challenge. ...
Objective: The challenge of irregular temporal data, which is particularly prominent for medication use in the critically ill, limits the performance of predictive models. The purpose of this evaluation was to pilot test integrating synthetic data within an existing dataset of complex medication data to improve machine learning model prediction of fluid overload.
Materials and Methods: This retrospective cohort study evaluated patients admitted to an ICU ≥ 72 hours. Four machine learning algorithms to predict fluid overload after 48-72 hours of ICU admission were developed using the original dataset. Then, two distinct synthetic data generation methodologies (synthetic minority over-sampling technique (SMOTE) and conditional tabular generative adversarial network (CTGAN)) were used to create synthetic data. Finally, a stacking ensemble technique designed to train a meta-learner was established. Models underwent training in three scenarios of varying qualities and quantities of datasets.
Results: Training machine learning algorithms on the combined synthetic and original dataset overall increased the performance of the predictive models compared to training on the original dataset. The highest performing model was the meta-model trained on the combined dataset with 0.83 AUROC while it managed to significantly enhance the sensitivity across different training scenarios.
Discussion: The integration of synthetically generated data is the first time such methods have been applied to ICU medication data and offers a promising solution to enhance the performance of machine learning models for fluid overload, which may be translated to other ICU outcomes. A meta-learner was able to make a trade-off between different performance metrics and improve the ability to identify the minority class.
... [14][15][16][17][18] Administration of resuscitation fluids, maintenance IV fluids, and "hidden fluids," or fluids contained in flushes and diluents for IV drugs all contribute to fluid overload. [29][30][31] In patients with HF, excess fluid balance combined with cardiac dysfunction may have detrimental interrelated consequences. 32 Notably, positive fluid balance may serve as an "intervenable" patient Clinical Medicine Insights: Cardiology event during an ICU stay that pharmacists can target and prevent, as diuretics represent a readily available strategy. ...
Introduction
De-resuscitation practices in septic patients with heart failure (HF) are not well characterized. This study aimed to determine if diuretic initiation within 48 hours of intensive care unit (ICU) admission was associated with a positive fluid balance and patient outcomes.
Methods
This single-center, retrospective cohort study included adult patients with an established diagnosis of HF admitted to the ICU with sepsis or septic shock. The primary outcome was the incidence of positive fluid balance in patients receiving early (<48 hours) versus late (>48 hours) initiation of diuresis. Secondary outcomes included hospital mortality, ventilator-free days, and hospital and ICU length of stay. Continuous variables were assessed using independent t-test or Mann-Whitney U, while categorical variables were evaluated using the Pearson Chi-squared test.
Results
A total of 101 patients were included. Positive fluid balance was significantly reduced at 72 hours (−139 mL vs 4370 mL, P < .001). The duration of mechanical ventilation (4 vs 5 days, P = .129), ventilator-free days (22 vs 18.5 days, P = .129), and in-hospital mortality (28 (38%) vs 12 (43%), P = .821) were similar between groups. In a subgroup analysis excluding patients not receiving renal replacement therap (RRT) (n = 76), early diuretics was associated with lower incidence of mechanical ventilation (41 [73.2%] vs 20 (100%), P = .01) and reduced duration of mechanical ventilation (4 vs 8 days, P = .018).
Conclusions
Diuretic use within 48 hours of ICU admission in septic patients with HF resulted in less incidence of positive fluid balance. Early diuresis in this unique patient population warrants further investigation.
... Maintenance and resuscitation fluids can be targeted through conservative dosing strategies, and all sources of hidden fluids should be considered when assessing fluid balance. 1,15 Focusing on the reduction of volumes associated with IV medications, many methods many be considered. The most effective approach is to discontinue these medications when clinically appropriate. ...
Introduction: Fluid stewardship targets optimal fluid management to improve patient outcomes. Intravenous (IV) medications, flushes, and blood products, collectively referred to as hidden fluids, contribute to fluid intake in the intensive care unit (ICU). The impact of specific IV medications on fluid intake is unknown. Objective: Characterize IV medication classes based on contribution to ICU fluid intake by frequency of administration and total volume infused to identify targets for fluid stewardship. Methods: This multi-center, retrospective nested cohort study included patients admitted to a medical or surgical ICU between January 2017 and December 2018. The primary outcome was to identify the volume contribution of specific IV medication classes administered over the first 3 ICU days. Secondary outcomes were the administration frequency of these medications and their proportion of total daily volume intake over the first 3 ICU days. Results: The study included 210 patients. The largest mean administration volumes over the course of the first 3 ICU days were attributed to antibacterials (968 ± 846 mL), vitamins/minerals/electrolytes (416 ± 935 mL), pain/agitation/delirium agents (310 ± 512 mL), and vasoactive agents (282 ± 744 mL). The highest frequencies over the course of the first 3 ICU days were attributed to antibacterials (n = 180; 86%), pain/agitation/delirium agents (n = 143; 68%), vitamins/minerals/electrolytes (n = 123; 59%), and vasoactive agents (n = 96; 46%). IV medications contributed 2601 ± 2573 mL of fluid volume per patient over the first 3 ICU days, accounting for 42% ± 29% of overall volume. Conclusion: IV medications contribute over 40% of total fluid intake within the first 3 days of ICU admission, with antibacterials as top contributors by administration volume and frequency. Future research implementing fluid stewardship to ICU fluid sources, such as concentrating IV medications, switching IV medications to oral formulations, de-escalation of antibacterials, and reduction of maintenance fluids, should be performed to minimize hidden fluids from IV medications.
Purpose of review
This review aims to provide a perspective on fluid resuscitation strategies and emerging trends in deresuscitation, with a particular emphasis on fluid stewardship, monitoring, and personalized fluid management.
Recent findings
Recent studies underscore a paradigm shift in resuscitation strategies. Notably, aggressive plasma volume expansion has been linked to higher morbidity and mortality, favoring conservative fluid resuscitation. Dynamic parameters, such as pulse pressure variation (PPV) and stroke volume variation (SVV) outperform static markers like central venous pressure (CVP) in predicting preload responsiveness. Advances in hemodynamic monitoring and automated closed-loop fluid administration demonstrate efficacy in optimizing resuscitation. Fluid stewardship, supported by machine learning, is reshaping deresuscitation practices, and promoting negative fluid balance to reduce complications. Moreover, next-generation closed-loop systems and fluid management personalization as part of precision medicine are emerging as future directions.
Summary
Advances in fluid resuscitation challenge traditional practices, with evidence favoring personalized and goal-directed strategies. Technological innovations in hemodynamic monitoring, automated fluid control, and machine learning are driving precision fluid management. Fluid stewardship and deresuscitation aim to mitigate fluid accumulation syndrome and improve patient outcomes.
Background
Fluid overload (FO) in the intensive care unit (ICU) is common, serious, and may be preventable. Intravenous medications (including administered volume) are a primary cause for FO but are challenging to evaluate as a FO predictor given the high frequency and time‐dependency of their use and other factors affecting FO. We sought to employ unsupervised machine learning methods to uncover medication administration patterns correlating with FO.
Methods
This retrospective cohort study included 927 adults admitted to an ICU for ≥72 h. FO was defined as a positive fluid balance ≥7% of admission body weight. After reviewing medication administration record data in 3‐h periods, medication exposure was categorized into clusters using principal component analysis (PCA) and Restricted Boltzmann Machine (RBM). Medication regimens of patients with and without FO were compared within clusters to assess their temporal association with FO.
Results
FO occurred in 127 (13.7%) of 927 included patients. Patients received a median (interquartile range) of 31(13–65) discrete intravenous medication administrations over the 72‐h period. Across all 47,803 intravenous medication administrations, 10 unique medication clusters, containing 121 to 130 medications per cluster, were identified. The mean number of Cluster 7 medications administered was significantly greater in the FO cohort compared with patients without FO (25.6 vs.10.9, p < 0.0001). A total of 51 (40.2%) of 127 unique Cluster 7 medications were administered in more than five different 3‐h periods during the 72‐h study window. The most common Cluster 7 medications included continuous infusions, antibiotics, and sedatives/analgesics. Addition of Cluster 7 medications to an FO prediction model including the Acute Physiologic and Chronic Health Evaluation (APACHE) II score and receipt of diuretics improved model predictiveness from an Area Under the Receiver Operation Characteristic (AUROC) curve of 0.719 to 0.741 ( p = 0.027).
Conclusions
Using machine learning approaches, a unique medication cluster was strongly associated with FO. Incorporation of this cluster improved the ability to predict FO compared to traditional prediction models. Integration of this approach into real‐time clinical applications may improve early detection of FO to facilitate timely intervention.
Purpose
The medication regimen complexity intensive care unit (MRC-ICU) score has previously been associated with pharmacist workload and fluid overload. The purpose of this study was to determine the relationship of MRC-ICU score with pharmacist-driven fluid stewardship recommendations as a means of establishing its role in risk stratifying critically ill patients for pharmacist intervention.
Methods
Adult patients admitted to the medical ICU and followed by the academic pharmacy team were included in this retrospective, single-center cohort study. Patient and pharmacist data were collected via electronic medical record and surveillance tool, respectively. MRC-ICU and sequential organ failure assessment (SOFA) scores were captured at ICU admission. The primary outcome was correlation between MRC-ICU score and number of pharmacist-driven fluid stewardship recommendations. Secondary outcomes included the relationships between MRC-ICU score, accepted recommendations, and patient outcomes (fluid overload and length of stay [LOS]). Descriptive statistics were calculated for each variable. Spearman’s rank-order correlation was used.
Results
Of 168 patients, 22 (13%) experienced fluid overload. Median MRC-ICU and SOFA scores were 13 and 7, respectively, and were higher for patients experiencing fluid overload than for those without fluid overload. MRC-ICU had a weakly positive correlation with the number of pharmacist-driven fluid stewardship recommendations (ρ = 0.200; P = 0.010), fluid overload (ρ = 0.167; P = 0.030), and ICU LOS (ρ = 0.354; P < 0.001). These relationships remained true when looking at only the fluid stewardship recommendations that were accepted by the team.
Conclusion
MRC-ICU displayed a weakly positive correlation with pharmacist workload, suggesting its potential use in identifying patients likely to benefit from pharmacist intervention.
Purpose
We describe the implementation of a fluid conservation strategy in a 2-hospital community health system and its effects on utilization of 1,000-mL bags of 0.9% sodium chloride and lactated Ringer’s solution.
Summary
Disruptions to medical supply chains are unpredictable and can cause significant impacts on patient care. A fluid conservation strategy including guidance statements and mandatory order modifications in a 2-hospital community health system was associated with decreases in the use of 1,000-mL bags of 0.9% sodium chloride and lactated Ringer’s solutions of 52% and 39%, respectively, compared with the utilization rates over the prior year.
Conclusion
Institutions facing shortages should consider multidisciplinary strategies with trackable metrics when faced with supply chain disruptions.
Despite significant advancements in oncology, conventional chemotherapy remains the primary treatment for diverse malignancies. Acute kidney injury (AKI) stands out as one of the most prevalent and severe adverse effects associated with these cytotoxic agents. While platinum compounds are well-known for their nephrotoxic potential, other drugs including antimetabolites, alkylating agents, and antitumor antibiotics are also associated. The onset of AKI poses substantial risks, including heightened morbidity and mortality rates, prolonged hospital stays, treatment interruptions, and the need for renal replacement therapy, all of which impede optimal patient care. Various proactive measures, such as aggressive hydration and diuresis, have been identified as potential strategies to mitigate AKI; however, preventing its occurrence during chemotherapy remains challenging. Additionally, several factors, including intravascular volume depletion, sepsis, exposure to other nephrotoxic agents, tumor lysis syndrome, and direct damage from cancer’s pathophysiology, frequently contribute to or exacerbate kidney injury. This article aims to comprehensively review the epidemiology, mechanisms of injury, diagnosis, treatment options, and prevention strategies for AKI induced by conventional chemotherapy.
INTRODUCTION: Intravenous (IV) medications are a fundamental cause of fluid overload (FO) in the intensive care unit (ICU); however, the association between IV medication use (including volume), administration timing, and FO occurrence remains unclear.
METHODS: This retrospective cohort study included consecutive adults admitted to an ICU ≥72 hours with available fluid balance data. FO was defined as a positive fluid balance ≥7% of admission body weight within 72 hours of ICU admission. After reviewing medication administration record (MAR) data in three-hour periods, IV medication exposure was categorized into clusters using principal component analysis (PCA) and Restricted Boltzmann Machine (RBM). Medication regimens of patients with and without FO were compared within clusters to assess for temporal clusters associated with FO using the Wilcoxon rank sum test. Exploratory analyses of the medication cluster most associated with FO for medications frequently appearing and used in the first 24 hours was conducted.
RESULTS: FO occurred in 127/927 (13.7%) of the patients enrolled. Patients received a median (IQR) of 31 (13-65) discrete IV medication administrations over the 72-hour period. Across all 47,803 IV medication administrations, ten unique IV medication clusters were identified with 121-130 medications in each cluster. Among the ten clusters, cluster 7 had the greatest association with FO; the mean number of cluster 7 medications received was significantly greater in patients in the FO cohort compared to patients who did not experience FO (25.6 vs.10.9. p<0.0001). 51 of the 127 medications in cluster 7 (40.2%) appeared in > 5 separate 3-hour periods during the 72-hour study window. The most common cluster 7 medications included continuous infusions, antibiotics, and sedatives/analgesics. Addition of cluster 7 medications to a prediction model with APACHE II score and receipt of diuretics improved the ability for the model to predict fluid overload (AUROC 5.65, p =0.0004).
CONCLUSIONS: Using ML approaches, a unique IV medication cluster was strongly associated with FO. Incorporation of this cluster improved the ability to predict development of fluid overload in ICU patients compared with traditional prediction models. This method may be further developed into real-time clinical applications to improve early detection of adverse outcomes.
Purpose:
Maintenance and hidden/creep fluids are a major source of fluid and sodium intake in intensive care unit (ICU) patients. Recent research indicates that low versus high sodium content maintenance fluids could decrease fluid and sodium burden. We conducted a systematic review (SR) with meta-analysis to summarize the impact of maintenance fluid choice on total daily sodium in ICU patients.
Materials and methods:
Systematic literature search in Pubmed, Embase, the Cochrane Library and the.
Clinical trials registry:
Only controlled clinical trials were included.
Exclusion criteria:
trials on resuscitation fluids, performed in the emergency department only and in pediatric patients. Primary objective was the reduction in mean total sodium intake with low versus high sodium content maintenance/creep fluids.
Results:
Five studies (1105 patients) were included. Heterogeneity was high.Risk of bias was moderate. Mean daily sodium reduction was 117 mmol (95%Confidence Interval [CI] -174; -59; p < 0.001) with low versus high sodium content maintenance/creep fluids. Incidence of hyperchloremia was lower (OR 0.26; 95%CI 0.1; 0.64) with low sodium. There were no differences in the incidences of hyper-/hyponatremia and fluid balances.
Conclusion:
Using low sodium content maintenance/creep fluids substantially reduces daily sodium burden in adult ICU patients. Significant knowledge/research gaps exist regarding relevance and safety.
Trial registration:
PROSPERO 2022 CRD42022300577 (February 2022).
Purpose
Intravenous fluids are the most commonly prescribed medication in the intensive care unit (ICU) and can have a negative impact on patient outcomes if not utilized properly. Fluid stewardship aims to heighten awareness and improve practice in fluid therapy. This report describes a practical construct for implementation of fluid stewardship services and characterizes the pharmacist’s role in fluid stewardship practice.
Summary
Fluid stewardship services were integrated into an adult medical ICU at a large community hospital. Data characterizing these services over a 2-year span are reported and categorized based on the 4 rights (right patient, right drug, right route, right dose) and the ROSE (rescue, optimization, stabilization, evacuation) model of fluid administration. The review encompassed 305 patients totaling 905 patient days for whom 2,597 pharmacist recommendations were made, 19% of which were related to fluid stewardship. This corresponded to an average of 1.52 fluid stewardship recommendations per patient. Within the construct of the 4 rights, 39% of recommendations were related to the right patient, 33% were related to the right route, 17% were related to the right drug, and 11% were related to the right dose. By the ROSE model, 1% of recommendations were related to the rescue phase, 3% were related to optimization, 79% were related to stabilization, and 17% were related to evacuation.
Conclusion
Implementation of fluid stewardship pharmacy services in a community hospital medical ICU is feasible. Integration of this practice contributed to 19% of pharmacy recommendations. The most common recommendations involved evaluation of the patient for the appropriateness of fluid therapy during the stabilization phase. The impact of fluid stewardship on patient outcomes needs to be explored.
Background:
Recent reports have demonstrated that among patients with subarachnoid hemorrhage (SAH) treated with hypertonic NaCl, resultant hyperchloremia has been associated with the development of acute kidney injury (AKI). We report a trial comparing the effect of two hypertonic solutions with different chloride contents on the resultant serum chloride concentrations in SAH patients, with a primary outcome aimed at limiting chloride elevation.
Methods:
A low ChloridE hyperTonic solution for brain Edema (ACETatE) trial is a single-center, double-blinded, double-dummy, randomized pilot trial comparing bolus infusions of 23.4% NaCl and 16.4% NaCl/Na-acetate for the treatment of cerebral edema in patients with SAH. Randomization occurred when patients developed hyperchloremia (serum Cl- ≥ 109 mmol/L) and required hyperosmolar treatment.
Results:
We enrolled 59 patients, of which 32 developed hyperchloremia and required hyperosmolar treatment. 15 patients were randomized to the 23.4% NaCl group, and 17 patients were randomized to the 16.4% NaCl/Na-acetate group. Although serum chloride levels increased similarly in both groups, the NaCl/Acetate group showed a significantly lower Cl- load at the end of the study period (978mEq vs. 2,464mEq, p < 0.01). Secondary outcome analysis revealed a reduced rate of AKI in the Na-acetate group (53.3% in the NaCl group vs. 11.8% in the Na-acetate group, p = 0.01). Both solutions had similar effects on ICP reduction, but NaCl/Acetate treatment had a more prominent effect on immediate post-infusion Na+ concentrations (increase of 2.2 ± 2.8 vs. 1.4 ± 2.6, (p < 0.01)). Proximal tubule renal biomarkers differed in concentration between the two groups.
Conclusions:
Our pilot trial showed the feasibility and safety of replacing 23.4% NaCl infusions with 16.4% NaCl/Na-acetate infusions to treat cerebral edema in patients with SAH. The degree of hyperchloremia was similar in the two groups. 16.4% NaCl/Na-acetate infusions led to lower Cl- load and AKI rates than 23.4% NaCl infusions. Further multi-center studies are needed to corroborate these results.
Trial registration:
clinicaltrials.gov # NCT03204955, registered on 6/28/2017.
Background:
Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety.
Methods:
The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy.
Results:
The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy.
Conclusion:
The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.
Background:
Dexmedetomidine has been reported to improve organ dysfunction in critically ill patients. In a recent randomized controlled trial (Dexmedetomidine for Sepsis in Intensive Care Unit (ICU) Randomized Evolution [DESIRE]), we demonstrated that dexmedetomidine was associated with reduced mortality risk among patients with severe sepsis. We performed this exploratory sub-analysis to examine the mechanism underlying improved survival in patients sedated with dexmedetomidine.
Methods:
The DESIRE trial compared a sedation strategy with and without dexmedetomidine among 201 mechanically ventilated adult patients with sepsis across eight ICUs in Japan. In the present study, we included 104 patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of ≥ 23 (54 in the dexmedetomidine [DEX] group and 50 in the non-dexmedetomidine [non-DEX] group). Initially, we compared the changes in the sequential organ failure assessment (SOFA) scores from the baseline within 6 days after randomization between groups. Subsequently, we evaluated the variables comprising the organ component of the SOFA score that showed relevant improvement in the initial comparison.
Results:
The mean patient age was 71.0 ± 14.1 years. There was no difference in the median APACHE II score between the two groups (29 [interquartile range (IQR), 25-31] vs. 30 [IQR, 25-33]; p = 0.35). The median SOFA score at the baseline was lower in the DEX group (9 [IQR, 7-11] vs. 11 [IQR, 9-13]; p = 0.01). While the renal SOFA subscore at the baseline was similar for both groups, it significantly decreased in the DEX group on day 4 (p = 0.02). During the first 6 days, the urinary output was not significantly different (p = 0.09), but serum creatinine levels were significantly lower (p = 0.04) in the DEX group. The 28-day and in-hospital mortality rates were significantly lower in the DEX group (22% vs. 42%; p = 0.03, 28% vs. 52%; p = 0.01, respectively).
Conclusion:
A sedation strategy with dexmedetomidine is associated with improved renal function and decrease mortality rates among patients with severe sepsis.
Trial registration:
This trial was registered on ClinicalTrials.gov (NCT01760967) on January 1, 2013.
Intravenous fluids (IVFs) are the most common drugs administered in the intensive care unit. Despite the ubiquitous use, IVFs are not benign and carry significant risks associated with under- or overadministration. Hypovolemia is associated with decreased organ perfusion, ischemia, and multi-organ failure. Hypervolemia and volume overload are associated with organ dysfunction, delayed liberation from mechanical ventilation, and increased mortality. Despite appropriate provision of IVF, adverse drug effects such as electrolyte abnormalities and acid–base disturbances may occur. The management of volume status in critically ill patients is both dynamic and tenuous, a process that requires frequent monitoring and high clinical acumen. Because patient-specific considerations for fluid therapy evolve across the continuum of critical illness, a standard approach to the assessment of fluid needs and prescription of IVF therapy is necessary. We propose the principle of “fluid stewardship,” guided by 4 rights of medication safety: right patient, right drug, right route, and right dose. The successful implementation of fluid stewardship will aid pharmacists in making decisions regarding IVF therapy to optimize hemodynamic management and improve patient outcomes. Additionally, we highlight several areas of focus for future research, guided by the 4 rights construct of fluid stewardship.
The introductions of more efficient antiviral drugs are common cause drug-induced acute kidney injury (AKI). The true prevalence of antiviral drugs induced nephrotoxicity is hardly determined. It causes AKI by many mechanisms including acute tubular necrosis (ATN), allergic interstitial nephritis (AIN), and crystal nephropathy. ATN has been described with a few kinds of antiviral drugs such as cidofovir, adefovir and tenofovir with unique effects on transporter defects, apoptosis, and mitochondrial injury. AIN from atazanavir is rapid onset of AKI and usually non-oliguric but dialytic therapy are needed because of severity. Additionally, crystal nephropathy from acyclovir, indinavir, and foscarnet can cause AKI due to intratubular obstruction. In this article, the mechanisms of antiviral drug-induced AKI were reviewed and strategies for preventing AKI were mentioned.
Background
Obesity is a major medical issue nationally with rates continually increasing. In obese patients, minimal data exists with acyclovir for appropriate dosing to decrease the risk of nephrotoxicity. The purpose of this study was to determine the prevalence of and risk-factors associated with acyclovir-induced nephrotoxicity.
Methods
A retrospective case-control of patients who received intravenous acyclovir for >48 hours at the University of Mississippi Medical Center over a 4-year period were evaluated to elucidate the prevalence of acyclovir-induced nephrotoxicity. Additionally, risk factors for the development of nephrotoxicity, including the effect of obesity and dosing strategy, were assessed.
Results
One hundred fifteen patients were included in the study. A total of 24 (21%) patients developed nephrotoxicity after acyclovir exposure and were in the Risk (9.6%), Injury (4.3%), and Failure (7%) categories defined by the RIFLE criteria. Neither acyclovir dosage, fluid status, nor baseline characteristics, other than obesity, varied between those that developed nephrotoxicity versus those that did not. Independent predictors of nephrotoxicity were obesity (OR 3.2; 95% confidence interval [CI] 1.19-8.67) and receipt of vancomycin (OR 4.73; 95% CI 1.57-14.25). No differences in vancomycin dosing or concentrations were observed between the patients that developed nephrotoxicity and those who did not.
Conclusions
In this study, nephrotoxicity occurred in 21% of patients receiving acyclovir. Concomitant vancomycin receipt and obesity led to higher rates of toxicity. Efforts should be made to target obese patients on acyclovir plus vancomycin and discontinue therapy in patients not warranting antiviral coverage to minimize chances of toxicity.
Objective
Quantify the efficacy of strategies to prevent contrast-induced acute kidney injury (CI-AKI) in high-risk patients undergoing coronary angiography (CAG) with or without percutaneous coronary intervention (PCI).
Background
CI-AKI remains a common problem. The renoprotective efficacy of existing pharmacological agents remains uncertain in high-risk populations.
Methods
Systematic review and meta-analysis of randomised controlled trials (RCTs) to compare different strategies versus hydration in patients with chronic kidney disease (CKD) undergoing CAG±PCI. Primary outcome was incident CI-AKI. Fixed-effects meta-analyses estimated ORs, 95% CIs and heterogeneity.
Results
Forty-eight RCTs were included. Seven pharmacological strategies were evaluated by multiple RCTs and 10 by one RCT each. These had varying risk of bias; >25% of trials were at high risk of performance bias. Five strategies significantly reduced the odds of CI-AKI: N-acetylcysteine (NAC) (27 trials, 5694 participants; OR=0.77, 95% CI 0.65 to 0.91, p=0.002, I ² =36%), ascorbic acid (four trials, 759 participants; OR=0.59, 95% CI 0.39 to 0.89, p=0.01, I ² =0%), statin (two trials, 3234 participants; OR=0.59, 95% CI 0.39 to 0.89, p=0.75, I ² =0%), trimetazidine (two trials, 214 participants; OR=0.27, 95% CI 0.10 to 0.71, p=0.01, I ² =0%) and nicorandil (two trials, 389 participants; OR=0.47, 95% CI 0.23 to 0.94, p=0.03, I ² =52%). Theophylline had a similar, but non-significant, effect. A subgroup analysis found that the benefit of NAC was highest in patients requiring a high-contrast dose.
Conclusions
Several drugs are renoprotective in patients with CKD undergoing CAG±PCI. The evidence is strongest for NAC. We recommend that NAC should be used when a high dose of contrast is anticipated.
Trial registration number
PROSPERO registration CRD42014014704.
Open Science Framework link: https://osf.io/vxg7d/?view_only=62bad0404b18405abd39ff2ead2575a8
Intravenous (IV) acyclovir is commonly administered medication for viral infection but is well known for its nephrotoxicity. However, there was no study for incidence, risk factors, and clinical outcomes of acute kidney injury (AKI) associated with IV acyclovir administration. We retrospectively reviewed the medical records of 287 patients who were medicated IV acyclovir from January 2008 to May 2013 in Gyeongsang National University Hospital. All had documented medical histories and underwent medical review. Demographic data, risk factors, concomitant drugs, laboratory findings and outcome were gathered from the medical records and analyzed. AKI occurred in 51 patients (17.8%). As per RIFLE classification, renal injury was graded as either at risk of renal dysfunction (62.7%), renal injury (15.6%), and renal failure (21.6%). There was no significant difference in age, sex, total dose, drug duration, and presence of hydration between AKI and non-AKI group. However, systolic pressure, underlying diabetes, concomitant vancomycin and non-steroidal anti-inflammatory drugs (NSAIDs) use was positively correlated with AKI occurrence (p = .04, p < .001, 0.01, and 0.04, respectively). Two patients underwent hemodialysis and these patients died. Higher mortality was observed in AKI patients (p < .001). Multivariate analysis also presented that presence of diabetes, concomitant NSAIDs, and vancomycin use was independent risk factor of acyclovir associated with AKI (p = .001, OR 3.611 (CI: 1.708–7.633), p = .050, OR 2.630 (CI: 1.000–6.917), and p = .009, OR 4.349 (CI: 1.452–13.022), respectively). AKI is relatively common in patients administrating acyclovir injection. Physicians should attempt to prevent, detect, and manage acyclovir associated AKI in patients prescribing acyclovir due to possible association of poor prognosis.
In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal-directed fluid removal. In addition, we expand on the concept of the "four D's" of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are "When to start intravenous fluids?", "When to stop intravenous fluids?", "When to start de-resuscitation or active fluid removal?" and finally "When to stop de-resuscitation?" In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship.
PurposeResearch on intravenous fluid therapy and its side effects, volume, sodium, and chloride overload, has focused almost exclusively on the resuscitation setting. We aimed to quantify all fluid sources in the ICU and assess fluid creep, the hidden and unintentional volume administered as a vehicle for medication or electrolytes. Methods
We precisely recorded the volume, sodium, and chloride burdens imposed by every fluid source administered to 14,654 patients during the cumulative 103,098 days they resided in our 45-bed tertiary ICU and simulated the impact of important strategic fluid choices on patients’ chloride burdens. In septic patients, we assessed the impact of the different fluid sources on cumulative fluid balance, an established marker of morbidity. ResultsMaintenance and replacement fluids accounted for 24.7% of the mean daily total fluid volume, thereby far exceeding resuscitation fluids (6.5%) and were the most important sources of sodium and chloride. Fluid creep represented a striking 32.6% of the mean daily total fluid volume [median 645 mL (IQR 308–1039 mL)]. Chloride levels can be more effectively reduced by adopting a hypotonic maintenance strategy [a daily difference in chloride burden of 30.8 mmol (95% CI 30.5–31.1)] than a balanced resuscitation strategy [daily difference 3.0 mmol (95% CI 2.9–3.1)]. In septic patients, non-resuscitation fluids had a larger absolute impact on cumulative fluid balance than did resuscitation fluids. Conclusions
Inadvertent daily volume, sodium, and chloride loading should be avoided when prescribing maintenance fluids in view of the vast amounts of fluid creep. This is especially important when adopting an isotonic maintenance strategy.
Background:
The risk of fluid overload and mortality is increased in patients with severe acute kidney injury. Charting of daily fluid balance is a key component of fluid assessment but not without problems affecting accuracy. The introduction of electronic bed scales has made routine patient-weighing easier and focused attention on monitoring fluid-related weight changes.
Objectives:
This paper investigated the frequency of compliance in weighing patients daily using electronic bed scales and evaluated the relationship between calculated fluid balance and body weight changes in patients receiving continuous renal replacement therapy (CRRT).
Methods:
A prospective cohort interventional observation study was conducted in a tertiary ICU between June 2015 and February 2016. All patients who required CRRT, >18 years with an admission >24 hours were enrolled. Each patient was able to be weighed daily using electronic bed scales. At the same time daily fluid balances were calculated using paper-based charting. Trends in compliance of recording body weight changes with daily charting of fluid balances was observed until patient no longer required CRRT. Daily differences were compared using Pearson correlation and Bland-Altman analysis.
Results:
A total of 61 patients were recruited. Four hundred and three days of CRRT was recorded with 286 days (71%) accompanied by a measured body weight. One hundred and eighty-one paired comparisons between body weight change and corresponding fluid balance was obtained from 39 patients (64%). Correlation between changes in body weight with fluid balance was weak (r=0.34, p<.0001). On Bland-Altman analysis mean bias was 0.18kg (95% CI -ve8.9 to +ve8.6kg).
Conclusion:
Change in body weight offers an alternative to charting inputs and outputs in monitoring fluid balance. A physical representation of fluid status is provided rather than a calculated value. Lack of compliance in weighing of patients on two consecutive days was shown to reduce utility as a routine monitoring practice. The relationship between fluid balance and changes in body weight was not strong.
Implications for practice:
Glucarpidase is a rarely used medication that is less effective when given after more than 60 hours of exposure to high-dose methotrexate, so predicting early which patients will need it is imperative. There are no currently available consensus guidelines for the use of this medication. The indication on the label does not give specific methotrexate concentrations above which it should be used. An international group of experts was convened to develop a consensus guideline that was specific and evidence-based to identify the population of patients who would benefit from glucarpidase.
Background. Daily and globally, millions of adult hospitalized patients are exposed to maintenance i.v. fluid solutions supported by limited scientific evidence. In particular, it remains unclear whether fluid tonicity contributes to the recently established detrimental effects of fluid, sodium, and chloride overload.
Methods. This crossover study consisted of two 48 h study periods, during which 12 fasting healthy adults were treated with a frequently prescribed solution (NaCl 0.9% in glucose 5% supplemented by 40 mmol litre⁻¹ of potassium chloride) and a premixed hypotonic fluid (NaCl 0.32% in glucose 5% containing 26 mmol litre⁻¹ of potassium) at a daily rate of 25 ml kg⁻¹ of body weight. The primary end point was cumulative urine volume; fluid balance was thus calculated. We also explored the physiological mechanisms behind our findings and assessed electrolyte concentrations.
Results. After 48 h, 595 ml (95% CI: 454–735) less urine was voided with isotonic fluids than hypotonic fluids (P<0.001), or 803 ml (95% CI: 692–915) after excluding an outlier with ‘exaggerated natriuresis of hypertension’. The isotonic treatment was characterized by a significant decrease in aldosterone (P<0.001). Sodium concentrations were higher in the isotonic arm (P<0.001), but all measurements remained within the normal range. Potassium concentrations did not differ between the two solutions (P=0.45). Chloride concentrations were higher with the isotonic treatment (P<0.001), even causing hyperchloraemia.
Conclusions. Even at maintenance rate, isotonic solutions caused lower urine output, characterized by decreased aldosterone concentrations indicating (unintentional) volume expansion, than hypotonic solutions and were associated with hyperchloraemia. Despite their lower sodium and potassium content, hypotonic fluids were not associated with hyponatraemia or hypokalaemia.
Clinical trial registration. ClinicalTrials.gov (NCT02822898) and EudraCT (2016-001846-24).
Objective
To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”. DesignA consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods
The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. ResultsThe Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Conclusions
Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.
Despite near ubiquity, information regarding fluids consumption at a health care systems level, and patient exposure at an individual level, is surprisingly limited in the medical literature. The epidemiology of the foundational medical intervention of intravenous fluid administration is incredibly complex, with millions of patients being exposed internationally every year. Fluid is being given for different reasons, to different targets, following different triggers, by different specialties in different countries, and any observations that can be made are thought to have limited external validity to other jurisdictions and patient groups. The independent effects of fluid administration and fluid accumulation are very hard to separate from other markers of illness severity and aspects of the process of care. Fluid accumulation can result in organ injury, even when the fluid is being given to purportedly ameliorate or prevent such injury, and if it were independently associated with mortality then would be an easily accessible and modifiable risk factor for subsequent morbidity or death. Despite their ubiquity, it is clear that we have limited understanding of the effects of the intravenous fluids we use daily in the most vulnerable of patient groups. The research agenda in this field is large and urgent.
Practice guidelines (PGs) are recommendations for diagnosis and treatment of diseases and injuries, and are designed to define optimal evaluation and management. The first PGs for burn care addressed the issues encountered in developed countries, lacking consideration for circumstances in resource-limited settings (RLS). Thus, the mission of the 2014–2016 committee established by the International Society for Burn Injury (ISBI) was to create PGs for burn care to improve the care of burn patients in both RLS and resource-abundant settings. An important component of this effort is to communicate a consensus opinion on recommendations for burn care for different aspects of burn management. An additional goal is to reduce costs by outlining effective and efficient recommendations for management of medical problems specific to burn care. These recommendations are supported by the best research evidence, as well as by expert opinion. Although our vision was the creation of clinical guidelines that could be applicable in RLS, the ISBI PGs for Burn Care have been written to address the needs of burn specialists everywhere in the world.
Background
Fluid overload is frequently found in acute kidney injury patients in critical care units. Recent studies have shown the relationship of fluid overload with adverse outcomes; hence, manage and optimization of fluid balance becomes a central component of the management of critically ill patients.
Discussion
In critically ill patients, in order to restore cardiac output, systemic blood pressure and renal perfusion an adequate fluid resuscitation is essential. Achieving an appropriate level of volume management requires knowledge of the underlying pathophysiology, evaluation of volume status, and selection of appropriate solution for volume repletion, and maintenance and modulation of the tissue perfusion. Numerous recent studies have established a correlation between fluid overload and mortality in critically ill patients. Fluid overload recognition and assessment requires an accurate documentation of intakes and outputs; yet, there is a wide difference in how it is evaluated, reviewed and utilized. Accurate volume status evaluation is essential for appropriate therapy since errors of volume evaluation can result in either in lack of essential treatment or unnecessary fluid administration, and both scenarios are associated with increased mortality. There are several methods to evaluate fluid status; however, most of the tests currently used are fairly inaccurate. Diuretics, especially loop diuretics, remain a valid therapeutic alternative. Fluid overload refractory to medical therapy requires the application of extracorporeal therapies.
In critically ill patients, fluid overload is related to increased mortality and also lead to several complications like pulmonary edema, cardiac failure, delayed wound healing, tissue breakdown, and impaired bowel function. Therefore, the evaluation of volume status is crucial in the early management of critically ill patients. Diuretics are frequently used as an initial therapy; however, due to their limited effectiveness the use of continuous renal replacement techniques are often required for fluid overload treatment. Successful fluid overload treatment depends on precise assessment of individual volume status, understanding the principles of fluid management with ultrafiltration, and clear treatment goals.
Maintenance fluids in critically ill brain-injured patients are part of routine critical care. Both the amounts of fluid volumes infused and the type and tonicity of maintenance fluids are relevant in understanding the impact of fluids on the pathophysiology of secondary brain injuries in these patients. In this narrative review, current evidence on routine fluid management of critically ill brain-injured patients and use of haemodynamic monitoring is summarized. Pertinent guidelines and consensus statements on fluid management for brain-injured patients are highlighted. In general, existing guidelines indicate that fluid management in these neurocritical care patients should be targeted at euvolemia using isotonic fluids. A critical appraisal is made of the available literature regarding the appropriate amount of fluids, haemodynamic monitoring and which types of fluids should be administered or avoided and a practical approach to fluid management is elaborated. Although hypovolemia is bound to contribute to secondary brain injury, some more recent data have emerged indicating the potential risks of fluid overload. However, it is acknowledged that many factors govern the relationship between fluid management and cerebral blood flow and oxygenation and more research seems warranted to optimise fluid management and improve outcomes.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-016-1309-2) contains supplementary material, which is available to authorized users.
There is increasing evidence that fluid overload and acute kidney injury (AKI) are associated but the exact cause-effect relationship remains unclear. Wang and colleagues analysed patients admitted to 30 intensive care units in China and found that fluid accumulation was independently associated with an increased risk of AKI and mortality. This commentary focuses on the close pathophysiological link between AKI and fluid overload and discusses the implications for clinical practice. It outlines some of the challenges, including the difficulty in diagnosing fluid overload reliably with current methods, and stresses the importance of personalised fluid therapy with physiological end-points to avoid the deleterious effects of fluid overload.
Fluid input/output charts in hospital inpatients are a valuable source of information for doctors reviewing intravenous fluid prescription, but are notorious for being incomplete and inaccurate. Lack of awareness of the importance of fluid balance amongst nursing staff and an excess of unnecessary monitoring are two factors contributing to the problem. We conducted a quality improvement project on the respiratory ward in a large district general hospital aiming to specifically address these two factors. Pre-intervention audit showed that only 53% of input/output monitoring was clinically indicated, with an average chart completion of 50%. Using e-Learning and verbal presentation to raise awareness around fluid balance, we implemented a new system whereby daily medical review of charts lead to rationalisation of monitoring. Post-intervention audit showed a 93% reduction in unnecessary monitoring, with corresponding increases in completion (40%) and accuracy (48%) of remaining charts. In conclusion, education has enabled a culture change on the ward that has drastically increased the quality of fluid balance monitoring.
This review considers the physiological principles that guide the appropriate selection of intravenous fluids in acutely ill patients, as well as the recent literature evaluating the safety of various intravenous fluids.
Tumor lysis syndrome is an oncometabolic emergency resulting from rapid cell death. Tumor lysis syndrome can occur as a consequence of tumor targeted therapy or spontaneously. Clinicians should stratify every hospitalized cancer patient and especially those receiving chemotherapy for the risk of tumor lysis syndrome. Several aspects of prevention include adequate hydration, use of uric acid lowering therapies, use of phosphate binders and minimization of potassium intake. Patients at high risk for the development of tumor lysis syndrome should be monitored in the intensive care unit. Established tumor lysis syndrome should be treated in the intensive care unit by aggressive hydration, possible use of loop diuretics, possible use of phosphate binders, use of uric acid lowering agents and dialysis in refractory cases.
Randomized trials of prehospital cooling after cardiac arrest have shown that neither prehospital cooling nor targeted temperature management differentially affected short-term survival or neurological function. In this follow-up study, we assess the association of prehospital hypothermia with neurological function at least 3 months after cardiac arrest and survival 1 year after cardiac arrest.
There were 508 individuals who were discharged alive from hospitals in King County, Washington; 373 (73%) were interviewed by telephone 123±43 days after the initial event. Overall, 59% of the treatment group and 58% of the control group had Cerebral Performance Category (CPC) 1 or 2 (P=0.70), and 50% of the treatment group and 49% of the control group had slight disability or better by the Modified Rankin Scale (MRS; (P=0.35). One-year survival was 87% in the treatment group and 84% in the control group (P=0.42). Of those with CPC 1 at hospital discharge, 68% had CPC 1 or 2 at follow-up, and 59% had MRS of slight disability or better. Of 41 patients with CPC 3 or 4 at discharge, only 12% had CPC 2 at follow-up, and just 5% had MRS of slight disability or better. One-year survival was 92% for CPC 1 at discharge, but only 40% for CPC 4.
In addition to excellent survival, patients who had good neurological function at discharge continued to have good function at least 3 months after the event.
URL: Clinicaltrials.gov. Unique identifier: NCT00391469.
© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
C ontrast-associated decrease administration in kidney of iodinated function acute that contrast kidney occurs material. within injury days In is the characterized after 1950s, the intravascular initial cases by a were reported in patients with preexisting kidney disease who were undergoing intravenous pyelography with contrast agents that were associated with a high incidence of acute kidney injury and other adverse effects.¹⁻⁴ Over time, an evolution in the design of contrast agents, improved recognition of risk factors, and implementation of preventive care resulted in lower rates of acute kidney injury after the administration of contrast material⁵⁻⁷ (Fig. 1). More recent studies have suggested that the risk of acute kidney injury due to contrast material is overestimated.⁹⁻¹³ Such studies are important, considering that angiographic procedures may be underused in patients with chronic kidney disease who present with conditions such as acute coronary syndromes, presumably because of concern about precipitating acute kidney injury.¹⁴ This review summarizes the pathophysiology of contrast-associated acute kidney injury, the diagnostic criteria, and risk stratification; discusses current controversies regarding the incidence of this condition; and highlights studies that have provided the evidence that forms the basis for preventive care.
Contrast-induced nephropathy has been the common cause of hospital-acquired acute kidney injury in the elderly patients. This study aimed to analyze the risk factors for contrast-induced nephropathy in over-aged patients undergoing coronary angiography or percutaneous coronary intervention. A total of 470 over-aged patients (≥80 years old) were judged as the contrast-induced nephropathy group ( n = 46) and non-contrast-induced nephropathy group ( n = 424) according to the postoperative 48-h serum creatinine levels. The patients’ clinical information such as hypertension grade, number and degree of coronary artery stenosis, and death rate was compared. The risk factors for contrast-induced nephropathy were also analyzed. The hypertension grade in the contrast-induced nephropathy group was significantly higher than that in the non-contrast-induced nephropathy group ( P = 0.004). The degree of coronary artery stenosis was significantly more in the contrast-induced nephropathy group compared with the non-contrast-induced nephropathy group ( P = 0.003). The death rate of the contrast-induced nephropathy group (15.8%) was significantly higher than that of the non-contrast-induced nephropathy group (0.6%; P = 0.000). The percentage of patients with abnormal urine microalbumin was significantly bigger in the contrast-induced nephropathy group (62.5%) when comparing to the non-contrast-induced nephropathy group (23.6%; P = 0.00). Besides, there was also significant difference in the emergency/selective operation between the contrast-induced nephropathy group and non-contrast-induced nephropathy group ( P = 0.001). Further, hypertension grade ( P = 0.019), emergency/selective operation ( P = 0.025), degree of coronary artery stenosis ( P = 0.038), eGFR ( P = 0.034), and urine microalbumin ( P = 0.005) were the risk factors for contrast-induced nephropathy. Hypertension grade, emergency/selective operation, degree of coronary artery stenosis, eGFR, and urine microalbumin were the risk factors for contrast-induced nephropathy in over-aged patients receiving coronary angiography and percutaneous coronary intervention, providing guidance for the clinical prevention of contrast-induced nephropathy.
Impact statement
In this work, we evaluated the risk factors for contrast-induced nephropathy (CIN) in over-aged patients receiving coronary angiography (CAG) and percutaneous coronary intervention (PCI). We found that hypertension grade, emergency/selective operation, degree of coronary artery stenosis, eGFR, and urine microalbumin were the risk factors for CIN in over-aged patients receiving CAG and PCI. This study provides guidance for the clinical prevention of CIN in over-aged patients undergoing coronary intervention, highlighting that a perioperative comprehensive management strategy is needed to improve the prognosis.
Background:
Acute acidaemia is frequently observed during critical illness. Sodium bicarbonate infusion for the treatment of severe metabolic acidaemia is a possible treatment option but remains controversial, as no studies to date have examined its effect on clinical outcomes. Therefore, we aimed to evaluate whether sodium bicarbonate infusion would improve these outcomes in critically ill patients.
Methods:
We did a multicentre, open-label, randomised controlled, phase 3 trial. Local investigators screened eligible patients from 26 intensive care units (ICUs) in France. We included adult patients (aged ≥18 years) who were admitted within 48 h to the ICU with severe acidaemia (pH ≤7·20, PaCO2 ≤45 mm Hg, and sodium bicarbonate concentration ≤20 mmol/L) and with a total Sequential Organ Failure Assessment score of 4 or more or an arterial lactate concentration of 2 mmol/L or more. We randomly assigned patients (1:1), by stratified randomisation with minimisation via a restricted web platform, to receive either no sodium bicarbonate (control group) or 4·2% of intravenous sodium bicarbonate infusion (bicarbonate group) to maintain the arterial pH above 7·30. Our protocol recommended that the volume of each infusion should be within the range of 125-250 mL in 30 min, with a maximum of 1000 mL within 24 h after inclusion. Randomisation criteria were stratified among three prespecified strata: age, sepsis status, and the Acute Kidney Injury Network (AKIN) score. The primary outcome was a composite of death from any cause by day 28 and the presence of at least one organ failure at day 7. All analyses were done on data from the intention-to-treat population, which included all patients who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02476253.
Findings:
Between May 5, 2015, and May 7, 2017, we enrolled 389 patients into the intention-to-treat analysis in the overall population (194 in the control group and 195 in the bicarbonate group). The primary outcome occurred in 138 (71%) of 194 patients in the control group and 128 (66%) of 195 in the bicarbonate group (absolute difference estimate -5·5%, 95% CI -15·2 to 4·2; p=0·24). The Kaplan-Meier method estimate of the probability of survival at day 28 between the control group and bicarbonate group was not significant (46% [95% CI 40-54] vs 55% [49-63]; p=0·09. In the prespecified AKIN stratum of patients with a score of 2 or 3, the Kaplan-Meier method estimate of survival by day 28 between the control group and bicarbonate group was significant (63% [95% CI 52-72] vs 46% [35-55]; p=0·0283). Metabolic alkalosis, hypernatraemia, and hypocalcaemia were observed more frequently in the bicarbonate group than in the control group, with no life-threatening complications reported.
Interpretation:
In patients with severe metabolic acidaemia, sodium bicarbonate had no effect on the primary composite outcome. However, sodium bicarbonate decreased the primary composite outcome and day 28 mortality in the a-priori defined stratum of patients with acute kidney injury.
Funding:
French Ministry of Health and the Société Française d'Anesthésie Réanimation.
There are very few clinical studies that highlight a definitive and comprehensive guideline for the management of enterocutaneous fistulas. Most accepted guidelines are found in textbooks and are taken from expert advice and case reports. The goal of this review is to highlight advancements relevant to the management of enterocutaneous fistulas from the recent two to three years. Although strong evidence-based guidelines are lacking, the consensus is that a multidisciplinary team working with a clear treatment plan targeting multiple aspects of management can maximize patient outcomes.
Background
Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy.
Methods
Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point.
Results
The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury.
Conclusions
Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466.)
Burns are common injuries that vary in severity from small superficial scalds to massive full-thickness flame burns with high morbidity and mortality. The purpose of this article is to review common burn presentations, the pathophysiology of these injuries and to give an overview of multidisciplinary burns management from the emergency department through to the specialist burns centre.
Following high-dose methotrexate (HD-MTX) treatment, delayed MTX elimination is an important problem because it necessitates increased leucovorin rescue and additional hospitalization for hydration and urinary alkalinization. Our purpose was to identify factors associated with high-risk MTX plasma concentrations (defined by plasma concentration > or = 1.0 mumol/L at 42 hours from the start of MTX) and with toxicity.
Variables associated with MTX concentrations and toxicity were assessed in 134 children treated with one to five courses of HD-MTX (900 to 3,700 mg/m2 intravenously [i.v.] over 24 hours for a total of 481 courses) for acute lymphoblastic leukemia (ALL).
High-risk MTX concentrations, toxicity (usually mild mucositis), and delay in resuming continuation chemotherapy occurred in 106 (22%), 123 (26%), and 66 (14%) of 481 courses, respectively. Using a mixed effects model for repeated measures, high-risk MTX concentrations were significantly associated with a higher MTX area-under-the-concentration-time curve (AUC), low urine pH, emesis, low MTX clearance, low urine output relative to intake, use of antiemetics during the MTX infusion, and concurrent intrathecal therapy (all p values < .01). Clinical toxicities and delay in resumption of continuation chemotherapy due to myelosuppression were more common in those with high 42-hour MTX concentrations, despite increased leucovorin rescue for all patients with high-risk MTX concentrations. However, with individualized rescue, no patient developed life-threatening toxicity. A more aggressive hydration and alkalinization regimen for subsequent courses reduced the frequency of high-risk MTX concentrations to 7% of courses (13 of 183) (P = .0001), and the frequency of toxicity decreased to 11% of courses (P = .0074).
This study identified several clinical variables that influence MTX disposition that, when modified, can reduce the frequency of high-risk MTX concentrations and toxicity.
Contrast-induced nephropathy (CIN) has been considered to be a cause of renal failure for over 50 years, but careful review of past and recent studies reveals the risks of CIN to be overestimated. Older studies frequently cited the use of high-osmolality contrast media, which have since been replaced by low-osmolality contrast media, which have lower risks for nephropathy. In addition, literature regarding CIN typically describes the incidence following cardiac angiography, whereas the risk of CIN from intravenous injection is much lower. Most of the early published literature also lacked appropriate control groups to compare to those that received iodinated contrast, and thus attributed rises in creatinine to intravenous contrast without considering normal creatinine fluctuations (frequent in patients with kidney disease) and other acute pathologic states such as hypotension or nephrotoxic drug administration. The aim of this paper is to review the literature detailing CIN risk, discuss why CIN risk is often overestimated and how withholding contrast can lead to misdiagnosis and delay in appropriate patient management.
Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are the most serious and life-threatening hyperglycemic emergencies in diabetes. DKA is more common in young people with type 1 diabetes and HHS in adult and elderly patients with type 2 diabetes. Features of the 2 disorders with ketoacidosis and hyperosmolality may coexist. Both are characterized by insulinopenia and severe hyperglycemia. Early diagnosis and management are paramount. Treatment is aggressive rehydration, insulin therapy, electrolyte replacement, and treatment of underlying precipitating events. This article reviews the epidemiology, pathogenesis, diagnosis, and management of hyperglycemic emergencies.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Implications for practice:
High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m(2), is used for a range of cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI), attributable to crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. When AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase allow renal recovery without the need for dialysis. This article, based on a review of the current associated literature, provides comprehensive recommendations for prevention of toxicity and, when necessary, detailed treatment guidance to mitigate AKI and subsequent toxicity.
Introduction:
Sepsis and septic shock continue to be syndromes that carry a high mortality rate worldwide. Early aggressive fluid and vasopressor support have resulted in significant improvement in patient outcomes. The prognostic clinical significance of a positive fluid balance in septic intensive care unit (ICU) patients remains undetermined.
Methods:
We collected data from 297 septic patients hospitalized in our general and medical ICUs at Soroka Medical Center between January 2005 and June 2011 and divided the 4 study groups into the following 4 fluid balances: group 1, patients with fluid balance at discharge from ICU (FBD) less than 10 L; group 2, patients with an FBD of 10 to 20 L; group 3, patients with an FBD of 20 to 30 L; and group 4, patients with FBD in excess of 30 L.
Results:
The ICU and in-hospital mortality rate was also significantly higher in groups 2 to 4 as compared with group 1 (P < .001 for both ICU and in-hospital mortality). The positive cumulative FBD was found to be an independent predictor of ICU mortality (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06; P < .001; Table 3) and in-hospital mortality (OR, 1.06; 95% CI, 1.03-1.08; P < .001; Table 5) and also to constitute a risk factor for new organ system dysfunction at hospital discharge (OR, 1.01; 95% CI, 1.01-1.013; P < .001; Table 6) in critically ill patients with severe sepsis/septic shock.
Conclusions:
Although it is a monocentric retrospective study, we suggest that positive cumulative fluid balance is one of the major factors that can predict the clinical outcome of critically ill patients during their ICU stay and after their discharge from the ICU.
Management of enterocutaneous fistula represents one of the most protracted and difficult problems in colorectal surgery with substantial morbidity and mortality rates. This article summarizes the current classification systems and successful management protocols, provides an in-depth review of fluid resuscitation, sepsis control, nutrition management, medication management of output quantity, wound care, nonoperative intervention measures, operative timeline, and considerations, and discusses special considerations such as inflammatory bowel disease and enteroatmospheric fistula.
Hypernatremia is defined as a serum sodium level above 145 mmol/L. It is a frequently encountered electrolyte disturbance in the hospital setting, with an unappreciated high mortality. Understanding hypernatremia requires a comprehension of body fluid compartments, as well as concepts of the preservation of normal body water balance. The human body maintains a normal osmolality between 280 and 295 mOsm/kg via Arginine Vasopressin (AVP), thirst, and the renal response to AVP; dysfunction of all three of these factors can cause hypernatremia. We review new developments in the pathophysiology of hypernatremia, in addition to the differential diagnosis and management of this important electrolyte disorder.
Sepsis is a common and life-threatening inflammatory response to severe infection treated with antibiotics and fluid resuscitation. Despite the central role of intravenous fluid in sepsis management, fundamental questions regarding which fluid and in what amount remain unanswered. Recent advances in understanding the physiologic response to fluid administration, and large clinical studies examining resuscitation strategies, fluid balance after resuscitation, colloid versus crystalloid solutions, and high- versus low-chloride crystalloids, inform the current approach to sepsis fluid management and suggest areas for future research.
Introduction:
In addition to the fluid intake in the form of intravenous maintenance or boluses in intensive care unit (ICU) patients, there are sources of fluids that may remain unrecognized but contribute significantly to the overall fluid balance. We hypothesized that fluids not ordered as boluses or maintenance infusions-"hidden obligatory fluids"-may contribute more than a liter to the fluid intake of a patient during any random 24 hours of critical care admission.
Methods:
Patients admitted to the Harlem Hospital ICU for at least 24 hours were included in this study (N = 98). Medical records and nursing charts were reviewed to determine the sources and volumes of various fluids for the study patients.
Results:
The mean hidden obligatory volume for an ICU patient was calculated to be 978 mL (standard deviation [SD]: 904, median: 645) and 1571 mL (SD: 1023, median: 1505), with enteral feeds compared to the discretionary volume of 2821 mL (SD: 2367, median: 2595); this obligatory fluid volume was affected by a patient's need for pressor support and renal replacement therapy.
Conclusion:
Hidden obligatory fluids constitute a major source of the fluid intake among patients in a critical care unit. Up to 1.5 L should be taken into account during daily decision making to effectively regulate their volumes.
Objective:
To determine whether restrictive fluid resuscitation results in increased rates of acute kidney injury (AKI) or infectious complications.
Background:
Studies demonstrate that patients often receive volumes in excess of those predicted by the Parkland equation, with potentially detrimental sequelae. However, the consequences of under-resuscitation are not well-studied.
Methods:
Data were collected from a multicenter prospective cohort study. Adults with greater than 20% total burned surface area injury were divided into 3 groups on the basis of the pattern of resuscitation in the first 24 hours: volumes less than (restrictive), equal to, or greater than (excessive) standard resuscitation (4 to 6 cc/kg/% total burned surface area). Multivariable regression analysis was employed to determine the effect of fluid group on AKI, burn wound infections (BWIs), and pneumonia.
Results:
Among 330 patients, 33% received restrictive volumes, 39% received standard resuscitation volumes, and 28% received excessive volumes. The standard and excessive groups had higher mean baseline APACHE scores (24.2 vs 16, P < 0.05 and 22.3 vs 16, P < 0.05) than the restrictive group, but were similar in other characteristics. After adjustment for confounders, restrictive resuscitation was associated with greater probability of AKI [odds ratio (OR) 3.25, 95% confidence interval (95% CI) 1.18-8.94]. No difference in the probability of BWI or pneumonia among groups was found (BWI: restrictive vs standard OR 0.74, 95% CI 0.39-1.40, excessive vs standard OR 1.40, 95% CI 0.75-2.60, pneumonia: restrictive vs standard, OR 0.52, 95% CI 0.26-1.05; excessive vs standard, OR 1.12, 95% CI 0.58-2.14).
Conclusions:
Restrictive resuscitation is associated with increased AKI, without changes in infectious complications.
In this double-blind crossover study, the effects of bolus infusions of 0.9% saline (NaCl) and Hartmann's solution on serum albumin, haematocrit and serum and urinary biochemistry were compared in healthy subjects. Nine young adult male volunteers received 2-litre intravenous infusions of 0.9% saline and Hartmann's solution on separate occasions, in random order, each over 1h. Body weight, haematocrit and serum biochemistry were measured pre-infusion and at 1h intervals for 6h. Biochemical analysis was performed on pooled post-infusion urine. Blood and plasma volume expansion, estimated by dilutional effects on haematocrit and serum albumin, were greater and more sustained after saline than after Hartmann's solution ( P 105mmol/l), which was sustained for >6h, while serum chloride concentrations remained normal after Hartmann's ( P <0.001 for difference between infusions). Serum bicarbonate concentration was significantly lower after saline than after Hartmann's ( P = 0.008). Thus excretion of both water and sodium is slower after a 2-litre intravenous bolus of 0.9% saline than after Hartmann's solution, due possibly to the more physiological [Na+]/[Cl-] ratio in Hartmann's solution (1.18:1) than in saline (1:1) and to the hyperchloraemia caused by saline.
Purpose
Hyperhydration and urinary alkalinization is implemented with all high-dose (HD)-methotrexate infusions to promote excretion and prevent precipitation of methotrexate in the renal tubules. Our institution utilized enteral alkalinizing agents (sodium bicarbonate tablets and sodium citrate/citric acid solution) to alkalinize the urine of patients receiving HD-methotrexate during a parenteral sodium bicarbonate and sodium acetate shortage. The purpose of this study is to establish the safety and efficacy of the enteral route for urine alkalinization.
Methods
A single-center, retrospective, cohort study was conducted comparing cycles of HD-methotrexate using enteral alkalinizing agents to parenteral sodium bicarbonate. The primary objective was to compare the time, in hours, from administration of first inpatient administered dose of alkalinizing agent to time of achieving goal urine pH. Secondary objectives evaluated total dose of sodium bicarbonate required to achieve goal urine pH, time from start of urine alkalinizing agent until time of achieving methotrexate level safe for discharge, and toxicities associated with methotrexate and the alkalinizing agents.
Results
A total of 118 patients were included in this study, equally divided into two cohorts based on parenteral versus enteral routes of administration. No statistical difference was determined between the two cohorts regarding time to goal urine pH (6.5 h versus 7.9 h, P = 0.051) or regarding time to methotrexate level deemed safe for discharge (63.5 h versus 62.5 h, p = 0.835). There were no significant differences in methotrexate-induced toxicities.
Conclusion
Our study found enteral routes of urine alkalinization to be a viable alternative to the traditional parenteral sodium bicarbonate, especially during parenteral sodium bicarbonate and acetate shortages.
For more than a decade, mild induced hypothermia (32°C–34°C) has been standard of care for patients remaining comatose after resuscitation from out-of-hospital cardiac arrest with an initial shockable rhythm, and this has been extrapolated to survivors of cardiac arrest with initially nonshockable rhythms and to patients with in-hospital cardiac arrest. Two randomized trials published in 2002 reported a survival and neurological benefit with mild induced hypothermia. One recent randomized trial reported similar outcomes in patients treated with targeted temperature management at either 33°C or 36°C. In response to these new data, the International Liaison Committee on Resuscitation Advanced Life Support Task Force performed a systematic review to evaluate 3 key questions: (1) Should mild induced hypothermia (or some form of targeted temperature management) be used in comatose post–cardiac arrest patients? (2) If used, what is the ideal timing of the intervention? (3) If used, what is the ideal duration of the intervention? The task force used Grading of Recommendations Assessment, Development and Evaluation methodology to assess and summarize the evidence and to provide a consensus on science statement and treatment recommendations. The task force recommends targeted temperature management for adults with out-of-hospital cardiac arrest with an initial shockable rhythm at a constant temperature between 32°C and 36°C for at least 24 hours. Similar suggestions are made for out-of-hospital cardiac arrest with a nonshockable rhythm and in-hospital cardiac arrest. The task force recommends against prehospital cooling with rapid infusion of large volumes of cold intravenous fluid. Additional and specific recommendations are provided in the document.
Rationale:
Survivors of septic shock have impaired functional status. Volume overload is associated with poor outcomes in patients with septic shock, but the impact of volume overload on functional outcome and discharge destination of survivors is unknown.
Objectives:
This study describes patterns of fluid management both during and after septic shock, and examines factors associated with volume overload on intensive care unit (ICU) discharge. We then examine associations between volume overload on ICU discharge and mobility limitation and discharge to a healthcare facility in septic shock survivors, with the hypothesis that volume overload is associated with increased odds of these outcomes.
Methods:
We retrospectively reviewed the medical records of 247 patients admitted with septic shock to an academic county hospital from June 2009 to April 2012, who survived to ICU discharge. We defined volume overload as a fluid balance expected to increase the subject's admission weight by 10%. Statistical methods included unadjusted analyses and multivariable logistic regression.
Measurements and main results:
Eighty-six percent of patients had a positive fluid balance and 35% had volume overload on ICU discharge. Factors associated with volume overload in unadjusted analyses included more severe illness, cirrhosis, blood transfusion during shock, and higher volumes of fluid administration both during and after shock. Blood transfusion during shock was independently associated with increased odds of volume overload (odds ratio [OR] 2.65, 95% confidence interval [CI] 1.33-5.27, p=0.01) after adjusting for pre-existing conditions and severity of illness. Only 42% of patients received at least one dose of diuretic during their hospitalization. Volume overload on ICU discharge was independently associated with inability to ambulate on hospital discharge (OR 2.29, 95% CI 1.24-4.25, p=0.01) and, in patients admitted from home, discharge to a healthcare facility (OR 2.34, 95% CI 1.1-4.98, p=0.03).
Conclusions:
Volume overload is independently associated with impaired mobility and discharge to a healthcare facility in survivors of septic shock. Prevention and treatment of volume overload in patients with septic shock warrants further investigation.
Sodium bicarbonate is a well-known antidote for tricyclic antidepressant (TCA) poisoning. It has been used for over half a century to treat toxin-induced sodium channel blockade as evidenced by QRS widening on the electrocardiogram (ECG). The purpose of this review is to describe the literature regarding electrophysiological mechanisms and clinical use of this antidote after poisoning by tricyclic antidepressants and other agents. This article will also address the literature supporting an increased serum sodium concentration, alkalemia, or the combination of both as the responsible mechanism(s) for sodium bicarbonate's antidotal properties. While sodium bicarbonate has been used as a treatment for cardiac sodium channel blockade for multiple other agents including citalopram, cocaine, flecainide, diphenhydramine, propoxyphene, and lamotrigine, it has uncertain efficacy with bupropion, propranolol, and taxine-containing plants.
