Hepatorenal Syndrome With Acute Kidney Injury: Diagnosis and Medical Management.

OBJECTIVES: To review the current definitions and diagnostic criteria for acute kidney injury (AKI) and type 1 hepatorenal syndrome (HRS) now termed HRS-AKI and discuss the challenges in deciding the most appropriate medication regimens to treat patients with HRS-AKI. DATA SOURCES: PubMed (inception to April 2023) with bibliographies of retrieved articles searched for additional articles; organizational websites for clinical practice guidelines (CPGs). STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials (RCTs) evaluating albumin and vasoconstrictors for HRS-AKI. DATA SYNTHESIS: A major change in the most recent revision of definitions and diagnostic criteria for HRS-AKI is the elimination of the set cutoff serum creatinine values for AKI. This change should be considered when comparing studies of HRS-AKI over time. Albumin has been administered to both vasoconstrictor treatment and placebo groups in all recent RCTs; however, there has never been a large RCT evaluating a no-albumin group. Most prospective trials comparing a midodrine/octreotide combination or norepinephrine to placebo or terlipressin have enrolled less than 100 patients limiting any conclusions regarding clinically important outcomes. Terlipressin with albumin has shown mixed results for complete HRS-AKI reversal with no reductions in crude mortality but adverse effect concerns involving ischemic and pulmonary events. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Type 1 hepatorenal syndrome with acute kidney injury is a potentially life-threatening syndrome with diagnostic and treatment challenges. Albumin plus a vasoconstrictor has become the routine HRS-AKI treatment even though there has not been a large RCT evaluating a no-albumin group. Terlipressin is the vasoconstrictor of choice for HRS-AKI in current CPGs, but it has adverse effect concerns and, until recently, was not available in the United States. CONCLUSIONS: In conjunction with changes in the definitions and diagnostic criteria for HRS-AKI, debate continues regarding the optimal therapy for HRS-AKI, particularly considering recent trials demonstrating ischemic and pulmonary adverse events with terlipressin used in combination with albumin.

Fixed Versus Body-Sized-Based Dosing of Monoclonal Antibodies.

Monoclonal antibody products are an increasing portion of novel drug approvals. The labeling of initial drug approvals frequently involves body-size-based rather than fixed-dose administration regimens for adults without clear rationale for doing so. This presents challenges when prescribing these products for patients with extremes of body habitus who constitute a small portion of enrollment in pre-approval investigations. Fixed-dose regimens allow for standardized preparation with the potential to reduce the risk of calculation errors, drug waste, and make home administration more practical. Fixed-dose rather than body-size-based monoclonal antibody regimens should serve as the initial approach in early phase 1 clinical trials.

Buprenorphine in the Intensive Care Unit: Commentary on the Unanswered Questions.

The removal of the X-waiver in the Mainstreaming Addiction Treatment (MAT) Act of 2023 has substantial implications for buprenorphine prescribing as one of the options to treat opioid use disorder. The purpose of this commentary is to discuss the unanswered questions regarding buprenorphine in the intensive care unit (ICU) including how the passage of the MAT Act will affect ICU providers, which patients should receive buprenorphine, what is the most appropriate route of administration and dose of buprenorphine, what medications interact with buprenorphine, and how can transitions of care be optimized for these patients.

Accuracy of a Chatbot in Answering Questions that Patients Should Ask Before Taking a New Medication.

BACKGROUND: The potential uses of artificial intelligence have extended into the fields of healthcare delivery and education. However, challenges are associated with introducing innovative technologies into healthcare, particularly with respect to information quality. OBJECTIVE: To evaluate the accuracy of answers provided by a chatbot in response to questions that patients should ask before taking a new medication. METHODS: Twelve questions obtained from the Agency for Healthcare Research and Quality were asked to a chatbot for the top 20 drugs. Two reviewers independently evaluated and rated each response on a 6-point scale for accuracy and a 3-point scale for completeness with a score of 2 considered adequate. Accuracy was determined using clinical expertise and a drug information database. After the independent reviews, answers were compared, and discrepancies were assigned a consensus score. RESULTS: Out of 240 responses, 222 (92.5%) were assessed as completely accurate. Of the inaccurate responses, 10 (4.2%) were mostly accurate, 5 (2.1%) more accurate than inaccurate, 2 (0.8%) were equal parts accurate and inaccurate, and 1(0.4%) was more inaccurate than accurate. Of the 240 responses, 194 (80.8%) were comprehensively complete. There were 235 (97.9%) responses that scored 2 or higher. Five responses (2.1%) were considered incomplete. CONCLUSION: Utilizing a chatbot to answer questions commonly asked by patients is mostly accurate but may include inaccurate information or lack valuable information for patients.

International Analgesia and Sedation Weaning and Withdrawal Practices in Critically Ill Adults: The Adult Iatrogenic Withdrawal Study in the ICU.

OBJECTIVES: Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population. DESIGN: International, multicenter, observational, point prevalence study. SETTING: Adult ICUs. PATIENTS: All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day. CONCLUSIONS: This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients.

Why Do the Mechanistic Actions of Albumin Not Translate Into Tangible Clinical Benefits?

Albumin has only reduced crude mortality in one randomized controlled trial conducted to date. This raises the question as to why potentially beneficial oncotic and pleiotropic properties of albumin do not consistently translate into clinically important outcomes. Four postulated explanations are provided as to why the theoretical advantages of albumin are not apparent in clinical trials: diminished oncotic action due to leakage of albumin from the intravascular compartment, modification of the pleiotropic properties of albumin both in vitro and in vivo, the ability of other plasma proteins to take over the major functions of albumin, and possible adverse effects.

Recommended Methods of Drug Dosing Adjustment for Patients With Renal Impairment.

Since 2020, there have been changes in Food and Drug Administration guidance and in recommendations by national organizations with a focus on kidney diseases pertaining to the choice of equations used to estimate creatinine clearance and glomerular filtration rate in patients with renal impairment. This includes a recommendation by the National Kidney Foundation to avoid the use of the Cockcroft-Gault equation for drug dosing in patients with renal impairment. This commentary provides an overview of recent recommendations concerning kidney function assessment that have important implications for drug dosing in patients with renal impairment and provides suggestions for implementing these recommendations.

Dilemmas Related to Direct-Acting Oral Anticoagulant Administration in Patients With Extreme Obesity.

OBJECTIVE: The objective of the study was to discuss the controversies surrounding the use and dosing of direct-acting oral anticoagulants (DOACs) in obese patients recognizing the limitations of the existing evidence base that preclude strong recommendations. DATA SOURCES: A literature search of MEDLINE was performed (2020 to end August 2022) subsequent to recent guidelines using the following search terms: direct acting anticoagulants, obesity, rivaroxaban, apixaban, edoxaban, dabigatran, dabigatran etexilate, and clinical practice guidelines. STUDY SELECTION AND DATA ABSTRACTION: English-language studies and those conducted in adults were selected. DATA SYNTHESIS: The available randomized studies evaluating DOACs had relatively small numbers of patients with more extreme forms of obesity (body mass index [BMI] > 40 kg/m2) and none of the larger studies had a specific focus on dosing DOACs in obese patients. Recent guidelines by the International Society on Thrombosis and Haemostasis (ISTH) have specific recommendations for dosing DOACs in obesity. There are pharmacokinetic/pharmacodynamic and observational studies published before and after the ISTH guidelines with a focus on DOAC dosing in obese patients that generally support the recommendations in the guidelines, but most involved small numbers of patients usually with BMIs <45 kg/m2. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review discusses DOAC dosing in obesity with important considerations for clinicians related to DOAC choice and dosing. CONCLUSIONS: Dosing alterations of DOACs do not appear to be necessary when used for either prophylaxis or treatment in patients with BMIs up to approximately 45 to 50 kg/m2, but research is needed for BMIs >50 kg/m2.

Challenges With Using a Weight-Based Approach to Bolus Fluid Dosing in Obese Critically Ill Patients.

At least 30 mL/kg of crystalloid fluid administration within the first 3 hours of resuscitation is suggested by the current Surviving Sepsis Campaign guidelines for management of sepsis and septic shock. This commentary discusses the challenges with using a weight-based approach to bolus fluid dosing during the early phase of resuscitation of adult, obese patients. Based on the available literature, arguments can be made for the use of either ideal or adjusted body weight for weight-based fluid dosing, but there are concerns with fluid overload if using actual body weight to dose patients with more severe forms of obesity.

Critical Care Pharmacist Attitudes and Perceptions of Neuromuscular Blocker Infusions in ARDS.

BACKGROUND: Current critical care pharmacist (CCP) practices and perceptions related to neuromuscular infusion (NMBI) use for acute respiratory distress syndrome (ARDS) maybe different with the COVID-19 pandemic and the publication of 2020 NMBI practice guidelines. OBJECTIVE: To evaluate CCP practices and perceptions regarding NMBI use for patients with moderate-severe ARDS. METHODS: We developed, tested, and electronically administered a questionnaire (7 parent-, 42 sub-questions) to 409 American College of Clinical Pharmacy (ACCP) Critical Care Practice and Research Network members in 12 geographically diverse states. The questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2<150) whose causes of dyssynchrony were addressed. Two reminders were sent at 10-day intervals. RESULTS: Respondents [131/409 (32%)] primarily worked in a medical intensive care unit (ICU) 102 (78%). Compared to COVID-negative(-) ARDS patients, COVID positive(+) ARDS patients were twice as likely to receive a NMBI (34 ± 18 vs.16 ± 17%; P < 0.01). Respondents somewhat/strongly agreed a NMBI should be reserved until after trials of deep sedation (112, 86%) or proning (92, 81%) and that NMBI reduced barotrauma (88, 67%), dyssynchrony (87, 66%), and plateau pressure (79, 60%). Few respondents somewhat/strongly agreed that a NMBI should be initiated at ARDS onset (23, 18%) or that NMBI reduced 90-day mortality (12, 10%). Only 2/14 potential NMBI risks [paralysis awareness (101, 82%) and prolonged muscle weakness (84, 68%)] were frequently reported to be of high/very high concern. Multiple NMBI titration targets were assessed as very/extremely important including arterial pH (109, 88%), dyssynchrony (107, 86%), and PaO2: FiO2 ratio (82, 66%). Train-of-four (55, 44%) and BIS monitoring (36, 29%) were deemed less important. Preferred NMBI discontinuation criteria included absence of dysschrony (84, 69%) and use ≥48 hour (72, 59%). CONCLUSIONS AND RELEVANCE: Current critical care pharmacists believe NMBI for ARDS patients are best reserved until after trials of deep sedation or proning; unique considerations exist in COVID+ patients. Our results should be considered when ICU NMBI protocols are being developed and bedside decisions regarding NMBI use in ARDS are being formulated.

Usefulness of the Biomarker TIMP-2•IGFBP7 for Acute Kidney Injury Assessment in Critically Ill Patients: A Narrative Review.

OBJECTIVES: To review the clinical usefulness of the biomarker TIMP-2•IGFBP7 in adult, general medical-surgical intensive care unit (ICU) settings. DATA SOURCES: PubMed (1946 to mid-February 2021) and EMBASE (1947 to mid-February 2021) with bibliographies of retrieved articles reviewed for additional articles. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating use of the urinary TIMP-2•IGFBP7 assay in adult patients in ICU settings. DATA SYNTHESIS: Studies published after investigations leading to TIMP-2•IGFBP7 assay approval confirm the appropriateness of considerations discussed in product labeling, such as use of the test within 12 hours of assessment, use of a dichotomous 0.3 (ng/mL)2/1000 cutoff, and use only in combination with other assessments of acute kidney injury (AKI). However, as a biomarker routinely used for early identification of patients at risk for AKI in mixed ICU populations, the additional resources required for TIMP-2•IGFBP monitoring are difficult to justify because of limited data demonstrating usefulness in preventing or ameliorating AKI and its attendant complications. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Biomarkers are potentially useful not only for assessment and diagnosis of AKI, but also for practitioners involved in the management of nephrotoxic medications and medications needing adjustment for decreased kidney function. CONCLUSIONS: Although there is evidence to suggest that the urinary TIMP-2•IGFBP7 biomarker is helpful in predicting AKI progression in general medical-surgical ICU patients when used within 12 hours of patient assessment in combination with routine testing, including serum creatinine and urine output, there is little evidence that its use leads to improvements in clinically important patient outcomes.

Balanced Salt Solutions for Critically Ill Patients: Nonplused and Back to Basics.

OBJECTIVES: The purpose of this article is to summarize the results of major randomized controlled trials (RCTs) comparing clinical outcomes of critically ill patients treated with normal saline (NS) or balanced salt solutions (BSSs), address discordant results of these studies, and provide direction for future investigations. DATA SOURCES: PubMed (2011 to January 2022) with bibliographies of retrieved articles searched for additional articles. STUDY SELECTION AND DATA EXTRACTION: RCTs comparing NS and BSSs in critically ill adult patients. DATA SYNTHESIS: Recently published large RCTs comparing NS with BSSs in heterogeneous populations of intensive care unit patients did not find significant differences in mortality, despite positive findings in some end points in prior RCTs. However, there were a number of methodologic issues common to the RCTs including: varying study designs and end points, clinician discretion for the majority or all treatments other than the primary intervention fluid, heterogeneous patients with varying levels of acuity, and lack of power to investigate potential subgroup differences. In addition, there were problematic issues related to blinding and use of nonstudy fluids. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Intravenous fluids are a mainstay of supportive care for critically ill patients. Similar to the so-called crystalloid-colloid debate, there has been a long-standing debate among critical care clinicians and researchers concerning the preferred crystalloid solution, NS versus one of the available BSSs. CONCLUSIONS: Despite the recent publication of large multicenter RCTs, the preferred resuscitation fluid, NS or a BSS, for critically ill patients is still open for debate, although the available investigations do provide some direction for clinicians and for future investigations.

Drug dosing in hospitalized obese patients with COVID-19.

Obesity is highly prevalent in hospitalized patients admitted with COVID-19. Evidence based guidelines are available for COVID-19-related therapies but dosing information specific to patients with obesity is lacking. Failure to account for the pharmacokinetic alterations that exist in this population can lead to underdosing, and treatment failure, or overdosing, resulting in an adverse effect. The objective of this manuscript is to provide clinicians with guidance for making dosing decisions for medications used in the treatment of patients with COVID-19. A detailed literature search was conducted for medications listed in evidence-based guidelines from the National Institutes of Health with an emphasis on pharmacokinetics, dosing and obesity. Retrieved manuscripts were evaluated and the following prioritization strategy was used to form the decision framework for recommendations: clinical outcome data > pharmacokinetic studies > adverse effects > physicochemical properties. Most randomized controlled studies included a substantial number of patients who were obese but few had large numbers of patients more extreme forms of obesity. Pharmacokinetic data have described alterations with volume of distribution and clearance but this variability does not appear to warrant dosing modifications. Future studies should provide more information on size descriptors and stratification of data according to obesity and body habitus.

Influence of Timing and Catecholamine Requirements on Vasopressin Responsiveness in Critically ill Patients with Septic Shock.

Introduction: Despite its widespread use, there is a paucity of data to guide the optimal use of arginine vasopressin (AVP) in critically ill patients with septic shock. Methods: This multicenter retrospective cohort study conducted in critically ill adults sought to evaluate the role of catecholamine requirements and timing on responsiveness to AVP. Responsiveness was defined as both a decrease in ≥ 50% of catecholamine requirements and no decrease in mean arterial pressure (MAP) at 4 hours post-AVP initiation. Primary outcomes of interest included the proportion of patients who started AVP within 4 hours after starting catecholamine therapy, as well as baseline norepinephrine (NE) equivalents (< 15, 15-39, or ≥ 40 mcg/min). Multivariate analyses and logistic regression were performed to identify other factors associated with AVP responsiveness. Results: There were 300 patients included in this study, with 74 patients being responders and 226 being non-responders. There was no significant difference in the number of patients who received AVP within 4 hours from catecholamine initiation between responders and non-responders (35% vs. 42%, P = 0.29). There were more patients in the non-responder group requiring ≥ 40 mcg/min of NE equivalents at AVP initiation (30% vs. 16%, P = 0.023). Stress dose steroid use was less common in responders (35% vs. 52%, P = 0.011), which was consistent with logistic regression analysis (OR 0.56, 95% 0.32-0.98, P = 0.044). Clinical outcomes between responders and non-responders were similar, apart from ICU (5.4% vs. 19.5%) and hospital (5.4% vs. 20.4%) mortality being lower in responders (P = 0.0032 and P = 0.0002, respectively). Conclusion: Shorter times to AVP initiation was not associated with responsiveness at 4 hours post-catecholamine initiation, although non-responders tended to require higher doses of NE equivalents at time of AVP initiation. Concomitant corticosteroids were associated with a lower likelihood of AVP responsiveness.

Antibiotic prophylaxis for traumatic facial fractures.

WHAT IS KNOWN AND OBJECTIVE: The purpose of this paper is to discuss the limitations of the evidence supporting the SIS recommendations for antibiotic prescribing in patients with traumatic facial fractures and to provide suggestions for clinical decision-making and further research in this area given the wide variation in prescribing practices. COMMENT: The Surgical Infection Society (SIS) recently published guidelines on antibiotic use in patients with traumatic facial fractures. The guidelines recommend against the use of prophylactic antibiotics for all adult patients with mandibular or non-mandibular facial fractures undergoing non-operative or operative procedures. Despite the available evidence, surveys conducted in the United States and the United Kingdom prior to the publication of the SIS guidelines demonstrate substantial preoperative, intraoperative and postoperative prophylactic prescribing of antibiotics for patients with facial fractures undergoing surgery. WHAT IS NEW AND CONCLUSION: With the exception of strong recommendations based on moderate-quality evidence to avoid prolonged postoperative antibiotic prophylaxis, the weak recommendations in the guidelines are a function of low-quality evidence. A logical choice for a narrow-spectrum antibiotic is cefazolin administered within 1 h of surgery and no longer than 24 h after surgery, since it is the gold standard of comparison based on clinical practice guidelines concerning antibiotic prophylaxis.

Dosing Medications for Coagulopathy Reversal in Patients with Extreme Obesity.

BACKGROUND: The reversal of anticoagulant or antiplatelet medications is a priority in the management of patients with severe injury with the goal of minimizing further bleeding without thrombotic complications. There are few studies, however, evaluating the dosing of reversal agents in the setting of trauma specific to patients with extreme obesity. Nevertheless, clinicians must still make decisions, balancing concerns of ongoing bleeding with excessive thrombosis. OBJECTIVES: We describe the literature pertaining to dosing of medications used for the reversal of both drug-induced and trauma-related coagulopathy with the intent of providing a framework for clinicians to make dosing decisions in this challenging population. DISCUSSION: Obesity is known to impact both the volume of distribution and the clearance of medications, but these changes are not usually linear with size nor are they uniform across drugs. Current strategies for dosing reversal agents in obesity include a capped dose (e.g., prothrombin complex concentrates), fixed dosages (e.g., andexanet alfa, idarucizumab, and tranexamic acid), and weight-based dosing (e.g., desmopressin). Extreme obesity, however, was not highly prevalent in the studies that have validated these dosing strategies. In fact, many of the clinical studies fail to report the average weight of the patients included. CONCLUSION: Future studies should make efforts to increase reporting of patients with obesity included in clinical trials along with results stratified by weight class. In the meantime, doses listed in product labels should be used. Desmopressin should be dosed using either ideal body weight or a dose-capping strategy.

Serum Albumin Levels: Who Needs Them?

OBJECTIVES: The purpose of this critical narrative review is to discuss common indications for ordering serum albumin levels in adult critically ill patients, evaluate the literature supporting these indications, and provide recommendations for the appropriate ordering of serum albumin levels. DATA SOURCES: PubMed (1966 to August 2020), Cochrane Library, and current clinical practice guidelines were used, and bibliographies of retrieved articles were searched for additional articles. STUDY SELECTION AND DATA EXTRACTION: Current clinical practice guidelines were the preferred source of recommendations regarding serum albumin levels for guiding albumin administration and for nutritional monitoring. When current comprehensive reviews were available, they served as a baseline information with supplementation by subsequent studies. DATA SYNTHESIS: Serum albumin is a general marker of severity of illness, and hypoalbuminemia is associated with poor patient outcome, but albumin is an acute phase protein, so levels vacillate in critically ill patients in conjunction with illness fluctuations. The most common reasons for ordering serum albumin levels in intensive care unit (ICU) settings are to guide albumin administration, to estimate free phenytoin or calcium levels, for nutritional monitoring, and for severity-of-illness assessment. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Because hypoalbuminemia is common in the ICU setting, inappropriate ordering of serum albumin levels may lead to unnecessary albumin administration or excessive macronutrient administration in nutritional regimens, leading to possible adverse effects and added costs. CONCLUSIONS: With the exception of the need to order serum albumin levels as a component of selected severity-of-illness scoring systems, there is little evidence or justification for routinely ordering levels in critically ill patients.

Caring for the COVID Patient: A Clinical Pharmacist's Perspective.

Physicians and nurses have received many accolades in commercial and scientific media for their heroic efforts in caring for patients with COVID-19. These accolades are appropriate and deserved. However, there are a number of clinical pharmacists involved in the daily care of patients who are caring and competent practitioners, and also deserve our thanks and praise. The purpose of this article is to provide the impactful comments of a front-line, critical care pharmacist dedicated to providing the best possible care for patients with COVID-19 in a medical intensive care unit.

Creatinine Assessment in Non-Steady-State Conditions: A Critical Review.

OBJECTIVES: To discuss methods for the assessment of creatinine clearance (Clcr) when serum creatinine (SCr) is not at steady state in order to estimate kidney function and apply the estimate to kidney function staging for clinical assessment or drug dosing. DATA SOURCES: A PubMed search was conducted from 1976 to mid-January 2021 with other articles identified through review of bibliographies of retrieved articles and citations in Scopus. STUDY SELECTION AND DATA EXTRACTION: Articles assessing Clcr under non-steady-state conditions and studies evaluating predictive equations were selected. DATA SYNTHESIS: When SCr is systematically changing (ie, trending up or down), kinetic methods to estimate Clcr are appropriate. Estimates from kinetic methods should be individual based and not indexed to body surface area, and careful monitoring is required to confirm predictions as the situation evolves. Standard methods intended for steady-state conditions should not be used to estimate Clcr in patients with unstable SCr. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Creatinine continues to be a monitoring parameter of choice and is an important variable in all the commonly used equations for estimating Clcr and most important for estimating glomerular filtration rate. However, standard methods of estimating Clcr for medication dosing are not accurate under non-steady-state conditions. CONCLUSION: The methods for kinetic clearance estimation and standards methods for clearance estimation, such as the Cockcroft-Gault equation, are mutually exclusive. There are no benefits of using the kinetic method in patients with stable SCr concentrations, and standard equations are not appropriate with unstable SCr concentrations.

Assessment of Kidney Function in Patients With Extreme Obesity: A Narrative Review.

OBJECTIVES: To discuss the evidence and caveats associated with estimated and measured creatinine clearance (eClCr and mClCr) and glomerular filtration rate (eGFR and mGFR) assessments of kidney function in patients with more extreme forms of obesity. DATA SOURCES: PubMed (1976 to mid-May 2020) was used, with bibliographies of retrieved articles searched for additional articles. STUDY SELECTION AND DATA EXTRACTION: Articles using gold standard mGFR to evaluate eClCr, mClCr, and eGFR assessments of kidney function in patients with more extreme forms of obesity were included. DATA SYNTHESIS: The overestimation of GFR by mClCr is well established, but mClCr is an alternative to mGFR assessments for determining medication dosing in patients with extremes of body size or muscle mass, or in patients receiving narrow therapeutic index medications when eGFR is likely to be inaccurate. The vast majority of studies comparing eGFR assessments with gold standard indicators of kidney function were attempts to validate eGFR equations for diagnosing and staging chronic kidney disease (CKD). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: For dosing medications in patients with stable kidney function and extreme obesity, a deindexed 4-variable Modification of Diet in Renal Disease or CKD Epidemiology Collaboration equation is an alternative to Cockcroft-Gault. Consistent use of the same equation by provider and between providers within any given setting is of paramount importance. CONCLUSIONS: In patients with extreme obesity and stable kidney function, eClCr or eGFR using deindexed values provides estimates of function for dosing adjustments of medications with elimination by the kidneys, but more research is needed with respect to the best size descriptor to use with estimating equations.