Identifying Potentially Drug-Induced Acute Liver Injury in Children Using a Multinational Healthcare Database Network
Carmen FerrajoloPreciosa M. ColomaKatia VerhammeM SchuemieRosa GiniR HeringsGiampiero MazzagliaGino PicelliCarlo GiaquintoLuciana ScottiPaul AvillachLars T. PedersenF. RossiAlexandra CapuanoJohan van der LeiGianluca TrifiróMiriam Sturkenboom
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Timely recognition of patients at risk or with possible acute kidney injury (AKI) is essential for early intervention to minimize further damage and improve outcome. Initial management of patients with suspected and persistent AKI should include thorough clinical assessment of all patients with AKI to identify reversible factors, including fluid volume status, potential nephrotoxins, and an assessment of the underlying health of the kidney. Based on these assessments, early interventions to provide appropriate and adequate fluid resuscitation while avoiding fluid overload, removal of nephrotoxins, and adjustment of drug doses according to the level of kidney function derangement are important. The judicious use of diuretics for fluid overload and/or in cardiac decompensated patients and introduction of early enteral nutritional support need to be considered to improve outcomes in AKI. Although these basic principles are well recognized, their application in clinical practice in low resource settings is often limited due to lack of education, availability of resources, and lack of trained personnel, which limits access to care. We report the consensus recommendations of the 18th Acute Dialysis Quality Initiative meeting in Hyderabad, India, on strategies to evaluate patients with suspected AKI and initiate measures for prevention and management to improve outcomes, particularly in low resource settings. These recomendations provide a framework for caregivers, who are often primary care physicians, nurses, and other allied healthcare personnel, to manage patients with AKI in resource poor countries. Timely recognition of patients at risk or with possible acute kidney injury (AKI) is essential for early intervention to minimize further damage and improve outcome. Initial management of patients with suspected and persistent AKI should include thorough clinical assessment of all patients with AKI to identify reversible factors, including fluid volume status, potential nephrotoxins, and an assessment of the underlying health of the kidney. Based on these assessments, early interventions to provide appropriate and adequate fluid resuscitation while avoiding fluid overload, removal of nephrotoxins, and adjustment of drug doses according to the level of kidney function derangement are important. The judicious use of diuretics for fluid overload and/or in cardiac decompensated patients and introduction of early enteral nutritional support need to be considered to improve outcomes in AKI. Although these basic principles are well recognized, their application in clinical practice in low resource settings is often limited due to lack of education, availability of resources, and lack of trained personnel, which limits access to care. We report the consensus recommendations of the 18th Acute Dialysis Quality Initiative meeting in Hyderabad, India, on strategies to evaluate patients with suspected AKI and initiate measures for prevention and management to improve outcomes, particularly in low resource settings. These recomendations provide a framework for caregivers, who are often primary care physicians, nurses, and other allied healthcare personnel, to manage patients with AKI in resource poor countries. Acute kidney injury (AKI) is associated with significant morbidity and mortality. Timely recognition of patients at risk for AKI, or with possible AKI, is essential to allow early intervention to minimize further renal injury, and may likely result in better outcomes than treating established AKI.1KDIGO Clinical Practice Guideline for Acute Kidney InjurySection 2: AKI Definition.Kidney Int Suppl. 2012; 2: 19-36Abstract Full Text Full Text PDF Google Scholar Protective measures to avoid worsening should be started immediately, with special attention to ensure adequate hydration, maintain hemodynamic stability and oxygenation, and prevent nephrotoxicity of drugs (Figure 1).2KDIGO Clinical Practice Guideline for Acute Kidney InjurySection 3: Prevention and Treatment of AKI.Kidney Int Suppl. 2012; 2: 37-68Abstract Full Text Full Text PDF Google Scholar Treatment goals in patients with AKI include: preservation and optimization of renal function; correction and maintenance of electrolyte, acid-base, and mineral homeostasis; minimize secondary organ damage from the consequences of AKI; and manage effects of decreased renal function. The spectrum of AKI includes rapid reversal of AKI, persistent AKI, and acute kidney disease (AKD) as defined previously3Chawla L.S. Bellomo R. Bihorac A. et al.Acute kidney disease and renal recovery: guideline report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup.Clin J Am Soc Nephrol. 2017; 13: 241-257Google Scholar,4Chawla L.S. Bellomo R. Bihorac A. et al.Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Worgroup.Nat Rev Nephrol. 2017; 13: 241-257Crossref PubMed Scopus (0) Google Scholar (Table 1).Table 1DefinitionsFluid bolus: a rapid infusion to correct hypotensive shock. It typically includes the infusion of at least 500 ml over a maximum of 15 minFluid challenge: 100–200 ml over 5–10 min with reassessment to optimize tissue perfusionFluid infusion: continuous delivery of i.v. fluids to maintain homeostasis, replace losses, or prevent organ injury (e.g., prehydration before operation to prevent intraoperative hypotension or for contrast nephropathy)Maintenance: fluid administration for the provision of fluids for patients who cannot meet their needs by oral route. This should be titrated to patient need and context, and should include replacement of ongoing losses. In a patient without ongoing losses, this should probably be no more than 1–2 m/kg per hourDaily fluid balance: daily sum of all intakes and outputsCumulative fluid balance: sum total of fluid accumulation over a set period of timeFluid overload: cumulative fluid balance expressed as a proportion of baseline body weight. A value of 10% is associated with adverse outcomesResponse: Achieving hemodynamic goal and/or improvement of UOP: >0.5 ml/kg per hourPersistent AKI is characterized by the continuance of AKI by creatinine or urine output criteria (defined by KDIGO criteria) beyond 48 hours from onset.Complete reversal of AKI by KDIGO criteria within 48 hours of the onset characterizes rapid reversal of AKIAKD is defined as a condition wherein AKI Stage Ia or greater criteria is present 7 days (or more) after an exposure.aADQI 16 workgroup report.4 AKD that persists beyond 90 days is then considered CKDAKD, acute kidney disease; AKI, acute kidney injury; CKD, chronic kidney disease; KDIGO, Kidney Disease Improving Global Outcomes; UOP, urinary output.a ADQI 16 workgroup report.4Chawla L.S. Bellomo R. Bihorac A. et al.Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Worgroup.Nat Rev Nephrol. 2017; 13: 241-257Crossref PubMed Scopus (0) Google Scholar Open table in a new tab AKD, acute kidney disease; AKI, acute kidney injury; CKD, chronic kidney disease; KDIGO, Kidney Disease Improving Global Outcomes; UOP, urinary output. The spectrum of AKI, its presentation, and the site of development is quite different in poor resource countries compared with the resource rich countries (Table 2). AKI occurs frequently in the community (community-acquired AKI [CAKI]) in rural areas where access to care is limited, and patients may not present to a hospital. In contrast, hospital-acquired AKI (HAKI) is less frequent than that in the developed world,5Mehta R.L. Burdmann E.A. Cerda J. et al.Recognition and management of acute kidney injury in the International Society of Nephrology 0by25 Global Snapshot: a multinational cross-sectional study.Lancet (London, England). 2016; 387: 2017-2025Abstract Full Text Full Text PDF PubMed Google Scholar and is potentially related to poor recognition due to limited resources and lack of knowledge and training. In most countries in the developing world, the number of nephrologists is insufficient; it is primary care physicians, nurses, and allied health personnel who manage AKI patients. They need to be trained to raise awareness, promote prevention, and provide practical management of AKI. Although the Kidney Disease Improving Global Outcomes (KDIGO) guidelines for management of AKI, published in 2012, are available, their application and use for individual patient care in the developing world are often limited secondary to resource limitation, economic disparities, and lack of trained personnel. Management of AKI in these settings needs to consider these limitations. To address these issues, the steering committee of the 18th Acute Dialysis Quality Initiative (ADQI) conference dedicated a work group with the task of identifying elements that might affect the evaluation and management of AKI based on the availability of resources. Using a modified Delphi process, this group reached consensus regarding strategies to manage AKI risk in low resource settings. In this article, we provide consensus recommendations that address the following 4 questions:Q1.What should be the initial management of patients with suspected AKI and/or persistent AKI?Q2.How should patients with suspected AKI and/or persistent AKI be monitored for drug selection and dosages?Q3.Should diuretics be used in patients with suspected AKI and/or persistent AKI? Or are diuretics useful in patients with suspected AKI and/or persistent AKI?Q4.What are the nutritional requirements in patients with suspected AKI and/or persistent AKI?Table 2Typical characteristics of acute kidney injury (AKI) in high- and low-income countriesCharacteristicsAKI in high-income coutriesAKI in low-income and middle-income countriesPattern of occurrenceOccurs predominantly in intensive care unitsOccurs in health centers and hospitals in rural areas and large hospitals and intensive care units in large citiesDisease patternsAssociated with multiple organ failureOften caused by a single disease; multiple organ failure less commonAssociationsAssociated with sepsis and complex surgery (major trauma, cardiovascular surgery)Frequently associated with specific disease (e.g., diarrhea) and specific infection (e.g., malaria)MortalityHigh mortalitySame or lower mortality than in high-income countriesPopulations affectedA disease of older adult populationsA disease of young, otherwise healthy peoplePrevalenceCould be increasingly prevalentCould be increasingly prevalentSufficiency of reportingAccurately reportedSeverely under-reportedPreventable statusDifficult to preventPreventableExpenseVery expensive to treatVery inexpensive to treat at early stages, too costly for most Open table in a new tab This consensus meeting followed the established ADQI process, as previously described.6Kellum J.A. Bellomo R. Ronco C. Acute Dialysis Quality Initiative (ADQI): methodology.Int J Artif Organs. 2008; 31: 90-93Crossref PubMed Scopus (0) Google Scholar The broad objective of ADQI is to provide expert-based statements and interpretation of current knowledge for use by clinicians according to professional judgment, as well as identify evidence care gaps to establish research priorities. The 18th ADQI Consensus Conference focused on "Management of AKI in the Developing World," convening a diverse panel for a 2-1/2 day meeting in Hyderabad, India from September 27 to 30, 2016. The consensus-building process was informed by preconference, conference, and postconference activities. Before the conference, the work group searched PubMed for English language articles on prevention and management for AKI. This search included the following terms: acute kidney injury in developing world, acute kidney failure, systematic review/meta-analysis in acute kidney injury, prevention, treatment, fluid resuscitation in AKI/critically ill patients, diuretics in AKI, nutritional support in acute kidney injury, and drug selection and/or dosing in AKI. A preconference series of emails that involved work group members was used to identify the current state of knowledge and enable the formulation of key questions. A formal systematic review was not conducted. At the in-person meeting, the work group developed consensus statements through a series of alternating breakout and plenary sessions. In each breakout session, the work group refined the key questions, identified the supporting evidence, and generated consensus statements. Work group members presented the results for feedback to all ADQI participants during the plenary sessions, and then revised the drafts based upon the plenary comments until a final version was accepted. We developed recommendations and consensus of expert opinion with evidence, when possible, to distill the current literature. To address important unanswered questions, we articulated a research agenda. Following the conference, this summary report was generated, revised, and approved by all members of the work group. 1.1.Every patient with suspected and/or persistent AKI should be assessed for volume status.1.2.The volume status should be assessed by history, physical examination, laboratory testing, and imaging, depending on clinical severity and the setting. Every patient with suspected AKI, confirmed AKI, and/or persistent AKI should be assessed for volume status as a part of hemodynamic optimization. Volume depletion is one of the major risk factors for AKI. In contrast, some suspected, confirmed, and/or persistent AKI can present with volume overload and worsening renal function, such as congestive heart failure, or cardiorenal syndrome. Fluid overload was defined as the difference between cumulative fluid intake and cumulative fluid output, divided by initial body weight.7Bouchard J. Soroko S.B. Chertow G.M. et al.Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury.Kidney Int. 2009; 76: 422-427Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar There is no specific study that used these parameters to show the benefit for AKI outcomes. A combination of history taking, including medications, physical examination, laboratory testing, and hemodynamic parameters (both static and dynamic) should be performed to obtain the best information for fluid assessment. Clinical variables used for fluid assessment include baseline body weight, history of recent fluid loss, cumulative fluid balance, vital signs, urine output, capillary refill, and skin turgor, whereas laboratory variables should include blood lactate, lactate clearance, mixed venous oxygen saturation, and urinary indexes (fractional excretion of sodium, lithium, urea). Several trials have shown the limitation of static hemodynamic parameters such as central venous pressure and pulmonary capillary wedge pressure in guiding fluid responsiveness.8Osman D. Ridel C. Ray P. et al.Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge.Crit Care Med. 2007; 35: 64-68Crossref PubMed Scopus (380) Google Scholar Dynamic hemodynamic variables (stroke volume or pulse pressure variation, change in vena cava diameter, and passive leg raising test) have been used as part of clinical decision-making during fluid assessment and have shown superior results over static hemodynamic variables.9Feissel M. Teboul J.L. Merlani P. et al.Plethysmographic dynamic indices predict fluid responsiveness in septic ventilated patients.Intensive Care Med. 2007; 33: 993-999Crossref PubMed Scopus (104) Google Scholar, 10Gruenewald M. Meybohm P. Koerner S. et al.Dynamic and volumetric variables of fluid responsiveness fail during immediate postresuscitation period.Crit Care Med. 2011; 39: 1953-1959Crossref PubMed Scopus (0) Google Scholar However, no study has shown superiority of a particular method in determining clinical outcomes. Therefore, it is advised to combine these variables to make a decision on fluid administration. Clinical reassessment is the key concept of fluid administration. It is becoming apparent that the concept "one size fits all" cannot be applied to fluid therapy in patients with suspected, confirmed, and/or persistent AKI. The amount of fluid should be based on requirements of the individual. Careful fluid assessment can be performed many ways, depending on sites of care and stage of disease. We have proposed the minimum parameters for fluid assessment in Figures 2a (community setting) and Figure 2b (hospital setting). 1.3.We recommend use of crystalloid over colloid for initial fluid resuscitation as initial treatment for suspected, confirmed, and/or persistent AKI. Many trials have been conducted to compare fluid types for fluid resuscitation using survival as the primary outcome and using AKI outcome as the secondary outcome. No study has used AKI as a primary outcome. Crystalloid Versus Colloid. Colloids have been widely used for fluid therapy in the critical care setting during the past few years.11Finfer S. Vincent J.L. Critical care–an all-encompassing specialty.N Engl J Med. 2013; 369: 669-670Crossref PubMed Scopus (8) Google Scholar The amount of colloids used for fluid resuscitation were expected to be less than the amount of crystalloid by approximately 3 times.12Starling E.H. On the absorption of fluids from the connective tissue spaces.J Physiol. 1896; 19: 312-326Crossref PubMed Scopus (276) Google Scholar, 13Varadhan K.K. Lobo D.N. A meta-analysis of randomised controlled trials of intravenous fluid therapy in major elective open abdominal surgery: getting the balance right.Proc Nutr Soc. 2010; 69: 488-498Crossref PubMed Scopus (0) Google Scholar Since the publication of 2 large randomized controlled trial (RCTs), 6S and the CHEST trials 4 years ago, use of hydroxyethyl starch (HES) has been restricted by regulatory authorities with a warning for the potential of worsening kidney function.14Perner A. Haase N. Guttormsen A.B. et al.Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.N Engl J Med. 2012; 367: 124-134Crossref PubMed Scopus (836) Google Scholar, 15Myburgh J.A. Finfer S. Bellomo R. et al.Hydroxyethyl starch or saline for fluid resuscitation in intensive care.N Engl J Med. 2012; 367: 1901-1911Crossref PubMed Scopus (721) Google Scholar The 6S trial studied fluid optimization in patients with severe sepsis and/or septic shock. The third-generation HES (6% HES 130/0.4) increased the mortality or dialysis dependent rate higher than Ringer's acetate (51% vs. 43%; P = 0.03). Moreover, the HES group had a higher incidence rate of renal replacement therapy (RRT) than the Ringer's acetate group (22% vs. 16%; P = 0.04). The CHEST trial studied fluid optimization in patients in the intensive care unit (ICU). There was no difference in the mortality rate between the HES and saline groups, but the HES group had a higher incidence rate of RRT than the saline group (7% vs. 5.8%; P = 0.04). In theory, human albumin is the main protein for maintaining plasma colloid oncotic pressure. It also works as a carrier for several endogenous and exogenous compounds with antioxidant and anti-inflammatory properties. Moreover, albumin can act as a buffer molecule for controlling acid-base homeostasis.16Quinlan G.J. Martin G.S. Evans T.W. Albumin: biochemical properties and therapeutic potential.Hepatology. 2005; 41: 1211-1219Crossref PubMed Scopus (343) Google Scholar, 17Weil M.H. Henning R.J. Puri V.K. Colloid oncotic pressure: clinical significance.Crit Care Med. 1979; 7: 113-116Crossref PubMed Google Scholar, 18Sudlow G. Birkett D.J. Wade D.N. The characterization of two specific drug binding sites on human serum albumin.Mol Pharmacol. 1975; 11: 824-832PubMed Google Scholar, 19King T.P. On the sulfhydryl group of human plasma albumin.J Biol Chem. 1961; 236: PC5PubMed Google Scholar, 20Quinlan G.J. Margarson M.P. Mumby S. et al.Administration of albumin to patients with sepsis syndrome: a possible beneficial role in plasma thiol repletion.Clin Sci (Lond). 1998; 95: 459-465Crossref PubMed Scopus (0) Google Scholar The result from large RCTs, the SAFE study in the ICU setting and the latest ALBIOS study in the setting of severe sepsis and/or septic shock, did not show the benefit of human albumin over crystalloids. In addition, there was no difference in renal outcomes between human albumin and crystalloid in both studies.21Finfer S. Bellomo R. Boyce N. et al.A comparison of albumin and saline for fluid resuscitation in the intensive care unit.N Engl J Med. 2004; 350: 2247-2256Crossref PubMed Google Scholar, 22Caironi P. Tognoni G. Masson S. et al.Albumin replacement in patients with severe sepsis or septic shock.N Engl J Med. 2014; 370: 1412-1421Crossref PubMed Scopus (256) Google Scholar However, albumin is safe for the kidney when used in the high-risk setting. With the high cost and no obvious advantage over crystalloids, human albumin should not be used as the firstline therapy. In tropical infections, Wills et al. conducted a double-blind RCT of 3 fluids (Ringer's lactate, 6% dextran 70, or 6% HES) for initial resuscitation in Vietnamese children with dengue shock syndrome. The primary outcome was rescue colloid at any time after administration of the study fluid. There was no difference of requirement of rescue colloid among children with moderate shock.23Wills B.A. Nguyen M.D. Ha T.L. et al.Comparison of three fluid solutions for resuscitation in dengue shock syndrome.N Engl J Med. 2005; 353: 877-889Crossref PubMed Scopus (0) Google Scholar Balanced Crystalloid Solution Versus Nonbalanced Crystalloid Solution. There were several studies that addressed the adverse effect of nonbalanced crystalloid solution (isotonic saline) on the kidney.24Hadimioglu N. Saadawy I. Saglam T. et al.The effect of different crystalloid solutions on acid-base balance and early kidney function after kidney transplantation.Anesth Analg. 2008; 107: 264-269Crossref PubMed Scopus (0) Google Scholar, 25Hasman H. Cinar O. Uzun A. et al.A randomized clinical trial comparing the effect of rapidly infused crystalloids on acid-base status in dehydrated patients in the emergency department.Int J Med Sci. 2012; 9: 59-64Crossref PubMed Google Scholar, 26Khajavi M.R. Etezadi F. Moharari R.S. et al.Effects of normal saline vs. lactated ringer's during renal transplantation.Ren Fail. 2008; 30: 535-539Crossref PubMed Scopus (0) Google Scholar Isotonic saline contains 154 mmol/L chloride, and administration of a large volume can result in hyperchloremic metabolic acidosis. This condition can lead to renal vasoconstriction, decrease in renal artery flow velocity and in renal blood flow, afferent arteriolar vasoconstriction, and a decreased glomerular filtration rate (GFR).27Wilcox C.S. Regulation of renal blood flow by plasma chloride.J Clin Invest. 1983; 71: 726-735Crossref PubMed Google Scholar Current evidence from 3 large observational studies also suggested that the high chloride content of isotonic saline might cause harm, especially to the kidney. The first study, by Shaw et al.,28Shaw A.D. Bagshaw S.M. Goldstein S.L. et al.Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte.Ann Surg. 2012; 255: 821-829Crossref PubMed Scopus (259) Google Scholar in 30,994 adult patients who underwent major abdominal surgery, showed that patients who received isotonic saline had significantly greater blood transfusion requirements, more infectious complications, and more renal support requirements than those who received balanced crystalloids. However, there was no difference in the mortality rate between the 2 groups.28Shaw A.D. Bagshaw S.M. Goldstein S.L. et al.Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte.Ann Surg. 2012; 255: 821-829Crossref PubMed Scopus (259) Google Scholar The second study, by Yunos et al.,29Yunos N.M. Bellomo R. Hegarty C. et al.Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.JAMA. 2012; 308: 1566-1572Crossref PubMed Scopus (416) Google Scholar was an open-label prospective sequential study that compared traditional chloride-rich solutions (isotonic sodium chloride, 4% succinylated gelatin solution, or 4% albumin solution) and chloride-restricted fluids (Hartmann's solution, Plasma-Lyte 148, or chloride-poor 20% albumin). After adjusting for confounding variables, the chloride-restricted group had decreased incidence of AKI (odds ratio [OR]: 0.52; P = 0.001) and reduced use of RRT (OR: 0.52; P = 0.004). Again, there were no differences in hospital mortality and hospital or ICU length of stay.29Yunos N.M. Bellomo R. Hegarty C. et al.Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.JAMA. 2012; 308: 1566-1572Crossref PubMed Scopus (416) Google Scholar A third study by McCluskey et al.30McCluskey S.A. Karkouti K. Wijeysundera D. et al.Hyperchloremia after noncardiac surgery is independently associated with increased morbidity and mortality: a propensity-matched cohort study.Anesth Analg. 2013; 117: 412-421Crossref PubMed Scopus (0) Google Scholar on postoperative patients showed that the incidence of acute postoperative hyperchloremia was 22%. Patients with hyperchloremia were found to be at increased risk of 30-day postoperative mortality (3.0% vs 1.9%; OR: = 1.58), had a longer hospital length of stay, and were more likely to have postoperative renal dysfunction. These large observational studies suggest that it might be time to consider the use of balanced crystalloid solution as the fluid of choice, especially with metabolic acidosis. However, the SPLIT trial, the largest RCT that aimed to compare the effect of balanced crystalloid and nonbalanced crystalloid on kidney injury, did not show a difference of AKI incidence within 90 days between Plasma-Lyte 148 solution and isotonic saline (9.6% vs. 0.2%; P = 0.77). Moreover, there was no difference in the RRT incidence rate and hospital mortality rate between the 2 groups. The incidence of AKI in this study was quite low, and the adverse effects of isotonic saline on AKI outcome might not have been evident.31Young P. Bailey M. Beasley R. et al.Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial.JAMA. 2015; 314: 1701-1710Crossref PubMed Scopus (115) Google Scholar Therefore, based on this study, it would be too early to conclude that there is no harmful effect of isotonic saline on kidney function. With the limited resource setting in developing countries and considering the number one cause of out-of-hospital AKI (volume depletion), the work group concluded that isotonic saline could still be the crystalloid of choice for fluid resuscitation. We need more large RCTs to study the beneficial effect of balanced crystalloid solution on kidney function, especially in the high-risk setting of kidney injury. 1.4a.The amount of fluid to be given should be individualized based on the initial assessment of volume status and clinical background and/or associated comorbidities.1.4b.Oral fluid administration should be considered in the community setting.1.4c.Fluid overload should be avoided. Since the publication of the Early Goal-Directed Therapy (EGDT) study by River et al.32Rivers E. Nguyen B. Havstad S. et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med. 2001; 345: 1368-1377Crossref PubMed Scopus (6074) Google Scholar 15 years ago, the concept of a protocolized strategy that consisted of fluids, vasopressors, and blood transfusion that targeted hemodynamic parameters has been widely adopted.33Dellinger R.P. Levy M.M. Carlet J.M. et al.Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008.Crit Care Med. 2008; 36: 296-327Crossref PubMed Scopus (3360) Google Scholar The average fluid administration during the first 72 hours in this single center study was 13 L. However, during the past few years, there were many studies that showed the adverse effects of fluid overload on patient outcome.7Bouchard J. Soroko S.B. Chertow G.M. et al.Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury.Kidney Int. 2009; 76: 422-427Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar Supporting the concept of restricted fluid therapy by 3 large RCTs, the PROCESS,34Pro C.I. Yealy D.M. Kellum J.A. et al.A randomized trial of protocol-based care for early septic shock.N Engl J Med. 2014; 370: 1683-1693Crossref PubMed Scopus (0) Google Scholar ARISE,35Peake S.L. et al.ARISE Investigators; ANZICS Clinical Trials GroupGoal-directed resuscitation for patients with early septic shock.N Engl J Med. 2014; 371: 1496-1506Crossref PubMed Scopus (559) Google Scholar and PROMISE36Mouncey P.R. Osborn T.M. Power G.S. et al.Trial of early, goal-directed resuscitation for septic shock.N Engl J Med. 2015; 372: 1301-1311Crossref PubMed Scopus (379) Google Scholar studies, which compared the mortality between protocolized care and the usual care in patients with sepsis, showed that only 3 to 4 L of fluid intake was adequate in the first 72 hours. All of these 3 major RCTs also revealed that protocolized therapy and the usual care provided comparable outcomes. This emphasized the concept that the amount of fluid to be given should be individualized based on the initial assessment of volume status and clinical background and/or associated comorbidities. In patients with tropical infections that cause AKI, som
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Patient safety, which includes adverse event reporting and routine collection of outcome measures, has become an increasingly important aspect of inpatient care worldwide. In the United States, the National Quality Forum leads the effort in developing such measures for use in payment and public reporting programs. However, choosing and prioritizing events to serve as patient safety indicators is difficult in a dynamically changing and complex healthcare environment. In this perspective, we propose that hospital-acquired acute kidney injury (HA-AKI), for example, contrast-induced and postoperative AKI, should be added to existing, more traditional measures, such as surgical site infections and patient falls. The article highlights the significance of HA-AKI as a common complication resulting from a multitude of diagnostic and therapeutic procedures, how it lends itself well to measuring patient safety, and how reporting of this complication can contribute to further improvement of patient safety and overall quality of care.
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In Brief The authors provide a deeper perspective on the concept of "failure to rescue" in pediatric liver transplantation. They emphasize the importance of "field strength." That is, the expertise and training of the institutional team beyond the primary transplant clinicians in establishing liver transplantation. This topic is critical as transplantation spreads across the developing international landscape.
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The purpose of this study was to examine the implications of a disease management intervention in treating patients with infectious diseases, in terms of both drug and medical resources and the costs associated with those resources. A managed care organization introduced a treatment guideline that was designed to influence the pattern of antibiotic prescribing by providers. The primary intervention was the promotion of treatment guidelines through mailings and face-to-face interventions by two disease management specialists. A relational database was created to assess changes in healthcare resource consumption, antibiotic use, and their respective costs. All patients being treated for the eight most common ambulatory infectious diseases were included. One year of data before and after promoting the treatment guideline was compared to assess the changes in medical and antibiotic resources and costs. The study demonstrated that there were important changes in antibiotic prescribing toward those antibiotics on the treatment guideline. However, the net effect was an increase in antibiotic and medical costs on a per member per month basis after the treatment guidelines were implemented. Analysis of antibiotic prices indicated that if antibiotic costs would have remained constant, the shifts in antibiotic patterns would have resulted in a reduction in total antibiotic costs. This study demonstrates that promotion of an infectious disease treatment guideline is effective in altering prescribing behavior. However, changes in drug prices or use of certain expensive products can overwhelm cost savings from other products.
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Health information technology advancements have resulted in recent increased sophistication of the electronic health record, whereby patient demographic, physiological, and laboratory data can be extracted real-time and integrated into clinical decision support (CDS).The implementation of health information technology advancements into CDS in the renal realm has been focused mainly on assessment of kidney function to guide medication dosing in the setting of reduced function or to reactively detect acute kidney injury (AKI) heralded by an abrupt increase in serum creatinine. More recent work has combined risk stratification algorithms to guide proactive diagnostic or therapeutic intervention to prevent AKI or reduce its severity.Early, real-time identification and notification to healthcare providers of patients at risk for, or with, acute or chronic kidney disease can drive simple interventions to reduce harm. Similarly, screening patients at risk for AKI with these platforms to alert research personnel will lead to improve study subject recruitment. However, sole reliance on electronic health record generated alerts without active healthcare team integration and assessment represents a major barrier to the realization of the potential of CDS to improve healthcare quality and outcomes.
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Purpose of review Long-term survival is now the rule rather than the exception for infants and children who undergo liver transplantation for end-stage liver disease, metabolic liver conditions and a variety of other indications. Pediatricians and primary care providers play vital roles in the care and management of this patient population. The purpose of this review is to highlight key aspects important to the care of the pediatric liver transplant recipient. Recent findings Significant advances in immunosuppressive therapies and surgical techniques have contributed to improved graft and patient survival rates, shifting the focus beyond immediate survival to strategies to minimize comorbidities related to long-term immunosuppression during growing years, attend to patient and parent-reported outcomes and enhance quality of life. A multidisciplinary approach allows for monitoring and surveillance of both routine (growth, nutritional rehabilitation, cognitive development, mental and psychosocial health, contraception and daily activities) and transplant-related (adverse effects of immunosuppression, susceptible infections, extra-hepatic systems, transition from childhood to adolescence to adulthood) themes. Summary Effective communication between the primary care physician and the transplant team is imperative for optimizing best outcomes. The primary care provider should be aware of the multifacet nature of posttransplant management, which includes medication regimens, common complications and infections.
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Acute kidney injury (AKI) is a common complication that occurs in critically ill patients and it is associated with a worse outcome. Since therapy options are limited, prevention and early detection are the essential cornerstones to improve patient outcomes. Therefore, using health information technology (HIT) to detect AKI early might be useful for clinicians. Patient data can be extracted real-time from electronic health records. Programmed electronic alert systems (e-alerts) can increase clinicians' awareness for AKI. Integrated into clinical decision support systems, implementation of HIT might improve clinical processes and patient outcomes. Several studies show the application of e-alerts in AKI detection and the implementation in processes of care. Monitoring nephrotoxic medication is one successful approach of implementing e-alerts in prevention of AKI. Information technology in AKI is in an early phase of development and further multicenter prospective studies are required to draw optimally on the maximum potential of this concept.
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