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This is how InpharmD™ transforms LITERATURE.

What's Being Asked...

Are there any resources or review articles that provide renal dosing recommendations or strategies for renal dose adj...
regarding high intensity statin for acute ischemic stroke (AIS) 1) should lipitor 80mg daily be used for AIS in pati...
Please summarize current evidence of chlorothalidone for hypertension in CKD since the CLICK trial.
Is stress ulcer prophylaxis really necessary in high dose steroids? At what methylprednisone or prednisone equivalen...
What evidence exists that describes the duration of action of induction agents used for intubation (primarily etomida...

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InpharmD's Answer GPT's Answer

Author:azkaa@inpharmd.com, PharmD, BCPS + InpharmD™ AI LEARN MORE 

Several review articles and primary studies provide guidance on antimicrobial dosing in patients receiving prolonged intermittent renal replacement therapy (PIRRT), consistently emphasizing the need for individualized dosing based on patient-specific factors (e.g., residual renal function, severity of illness, comorbidities), drug pharmacokinetics, and RRT characteristics. These patients exhibit significant pharmacokinetic alterations, including changes in volume of distribution and drug clea...

A 2019 review article presents a comprehensive update on antibiotic dosing for critically ill adult patients receiving various forms of renal replacement therapy (RRT), including intermittent hemodialysis (IHD), prolonged intermittent renal replacement therapy (PIRRT), and continuous renal replacement therapy (CRRT). This review synthesizes data from studies published between January 2008 and May 2019, evaluating antibiotic dosing recommendations and pharmacokinetic/pharmacodynamic (PK/PD) considerations for these patient populations. The authors conducted a literature search using PubMed to identify relevant English-language publications, subsequently synthesizing empirical dosing recommendations for antibiotics commonly used in critically ill patients undergoing different RRT modalities. These recommendations aim to individualize therapy by considering renal function assessment, RRT system properties affecting drug clearance, and drug properties influencing clearance during RRT. T...

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A search of the published medical literature revealed 3 studies investigating the researchable question:

Are there any resources or review articles that provide renal dosing recommendations or strategies for renal dose adjustments for patients receiving PIRRT?

Level of evidence
C - Multiple studies with limitations or conflicting results  

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[1] Hoff BM, Maker JH, Dager WE, Heintz BH. Antibiotic Dosing for Critically Ill Adult Patients Receiving Intermittent Hemodialysis, Prolonged Intermittent Renal Replacement Therapy, and Continuous Renal Replacement Therapy: An Update. Ann Pharmacother. 2020;54(1):43-55. doi:10.1177/1060028019865873
[2] Kanji S, Roger C, Taccone FS, Muller L. Practical considerations for individualizing drug dosing in critically ill adults receiving renal replacement therapy. Pharmacotherapy. 2023;43(11):1194-1205. doi:10.1002/phar.2858
[3] Grewal A, Thabet P, Dubinsky S, et al. Antimicrobial pharmacokinetics and dosing in critically ill adults receiving prolonged intermittent renal replacement therapy: A systematic review. Pharmacotherapy. 2023;43(11):1206-1220. doi:10.1002/phar.2861
[4] Sethi SK, Krishnappa V, Nangethu N, Nemer P, Frazee LA, Raina R. Antibiotic Dosing in Sustained Low-Efficiency Dialysis in Critically Ill Patients. Can J Kidney Health Dis. 2018;5:2054358118792229. Published 2018 Aug 10. doi:10.1177/2054358118792229
[5] Mariano F, Mella A, Biancone L. Focusing on the Basic Principles of Dialysis to Optimize Antibiotic Therapy during Renal Replacement Therapy in Critically Ill Patients. Antibiotics (Basel). 2024;13(9):864. Published 2024 Sep 9. doi:10.3390/antibiotics13090864
[6] Schmidt JJ, Strunk AK, David S, et al. Single- and multiple-dose pharmacokinetics and total removal of colistin in critically ill patients with acute kidney injury undergoing prolonged intermittent renal replacement therapy. J Antimicrob Chemother. 2019;74(4):997-1002. doi:10.1093/jac/dky511
[7] Scoville BA, Mueller BA. Medication dosing in critically ill patients with acute kidney injury treated with renal replacement therapy. Am J Kidney Dis. 2013;61(3):490-500. doi:10.1053/j.ajkd.2012.08.042
[8] Chusiri S, Vamananda J, Rungkitwattanakul D, et al. Levetiracetam dosing in critically ill patients receiving prolonged intermittent renal replacement therapy. J Crit Care. 2026;91:155246. doi:10.1016/j.jcrc.2025.155246
[9] Cheng V, Rawlins M, Chang T, et al. Pharmacokinetics of Benzylpenicillin (Penicillin G) during Prolonged Intermittent Renal Replacement Therapy. Chemotherapy. 2019;64(1):17-21. doi:10.1159/000499375
InpharmD's Answer GPT's Answer

Author:Naveed Aijaz, PharmD, BCPS + InpharmD™ AI LEARN MORE 

Limited data suggest that high-intensity statin therapy, such as atorvastatin 80 mg daily, may provide secondary cardiovascular protection after acute ischemic stroke (AIS) in patients without markedly elevated low-density lipoprotein cholesterol (LDL-C), but evidence in those with baseline LDL-C below 70 mg/dL is less clear. Guidelines primarily extrapolate from broader atherosclerotic cardiovascular disease management, emphasizing overall cardiovascular risk and potential benefit from LDL-C...

According to the 2021 American Heart Association/American Stroke Association (AHA/ASA) guidelines for patients with stroke and transient ischemic attack, atorvastatin 80 mg daily is recommended for individuals with ischemic stroke who have no known coronary heart disease, no major cardiac sources of embolism, and low-density lipoprotein cholesterol (LDL-C) greater than 100 mg/dL. High-intensity statins are defined as therapies capable of reducing LDL-C by 50% or more, whereas moderate-intensity statins reduce LDL-C by approximately 30% to 49%. However, the guidelines do not specify a lipid threshold for selecting statin intensity in all stroke populations, and recommendations for high-intensity statin therapy are generally extrapolated from broader lipid management guidelines for atherosclerotic cardiovascular disease, which prioritize achieving at least a 50% reduction in LDL-C rather than targeting a specific LDL value. Additionally, current clinical practice guidelines do not cle...

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A search of the published medical literature revealed 4 studies investigating the researchable question:

In patients with acute ischemic stroke (AIS) who have a normal lipid profile or LDL <70 mg/dL, should high-intensity statin therapy (e.g., Lipitor 80 mg daily) still be initiated, and what is the associated risk of intracerebral hemorrhage with high-dose statin use?

Level of evidence
C - Multiple studies with limitations or conflicting results  

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[1] Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association [published correction appears in Stroke. 2021 Jul;52(7):e483-e484]. Stroke. 2021;52(7):e364-e467. doi:10.1161/STR.0000000000000375
[2] Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association [published correction appears in Stroke. 2019 Dec;50(12):e440-e441]. Stroke. 2019;50(12):e344-e418. doi:10.1161/STR.0000000000000211
[3] Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2023 Sep 26;148(13):e148] [published correction appears in Circulation. 2023 Dec 5;148(23):e186]. Circulation. 2023;148(9):e9-e119. doi:10.1161/CIR.0000000000001168
[4] Beltrán Romero LM, Vallejo-Vaz AJ, Muñiz Grijalvo O. Cerebrovascular Disease and Statins. Front Cardiovasc Med. 2021;8:778740. Published 2021 Dec 2. doi:10.3389/fcvm.2021.778740
[5] Amarenco P, Bogousslavsky J, Callahan A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549-559. doi:10.1056/NEJMoa061894
[6] Amarenco P, Kim JS, Labreuche J, et al. A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke. N Engl J Med. 2020;382(1):9. doi:10.1056/NEJMoa1910355
[7] Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Circulation. 2019 Jun 18;139(25):e1182-e1186] [published correction appears in Circulation. 2023 Aug 15;148(7):e5]. Circulation. 2019;139(25):e1082-e1143. doi:10.1161/CIR.0000000000000625
[8] Lee M, Cheng CY, Wu YL, Lee JD, Hsu CY, Ovbiagele B. Association Between Intensity of Low-Density Lipoprotein Cholesterol Reduction With Statin-Based Therapies and Secondary Stroke Prevention: A Meta-analysis of Randomized Clinical Trials. JAMA Neurol. 2022;79(4):349-358. doi:10.1001/jamaneurol.2021.5578
[9] Costa FM, Lobo K, Lalor Tavares JL, da Silva Gomes RP, Santos L, Oliveira RCS. Intensive versus non-intensive statin therapy in patients with ischemic stroke: A systematic review and meta-analysis. J Clin Neurosci. 2025;138:111361. doi:10.1016/j.jocn.2025.111361
[10] Yang R, Wu J, Yu H, et al. Is statin therapy after ischaemic stroke associated with increased intracerebral hemorrhage? The association may be dependent on intensity of statin therapy. Int J Stroke. 2023;18(8):948-956. doi:10.1177/17474930231172623
[11] Mowla A, Shah H, Lail NS, Vaughn CB, Shirani P, Sawyer RN. Statins Use and Outcome of Acute Ischemic Stroke Patients after Systemic Thrombolysis. Cerebrovasc Dis. 2020;49(5):503-508. doi:10.1159/000510095
[12] Kim J, Lee HS, Nam CM, Heo JH. Effects of statin intensity and adherence on the long-term prognosis after acute ischemic stroke. Stroke. 2017;48(10):2723-2730. doi:10.1161/STROKEAHA.117.018140
[13] Furie KL, Kelly PJ. Secondary Prevention after Ischemic Stroke. N Engl J Med. 2026;394(8):784-792. doi:10.1056/NEJMcp2415601
[14] Goldstein LB, Toth PP, Dearborn-Tomazos JL, et al. Aggressive ldl-c lowering and the brain: impact on risk for dementia and hemorrhagic stroke: a scientific statement from the american heart association. Arteriosclerosis, Thrombosis, and Vascular Biology. 2023;43(10):e404-e442. doi:10.1161/ATV.0000000000000164
[15] Choi JY, Seo WK, Kang SH, et al. Statins improve survival in patients with cardioembolic stroke. Stroke. 2014;45(6):1849-1852. doi:10.1161/STROKEAHA.114.005518
[16] Ntaios G, Papavasileiou V, Makaritsis K, et al. Statin treatment is associated with improved prognosis in patients with AF-related stroke. Int J Cardiol. 2014;177(1):129-133. doi:10.1016/j.ijcard.2014.09.031
InpharmD's Answer GPT's Answer

Author:Kevin Shin, PharmD, BCPS + InpharmD™ AI LEARN MORE 

Since the CLICK trial was published in 2021, the European Society of Hypertension (ESH) 2023 guidelines now formally recommend chlorthalidone as a potential add-on therapy for treatment-resistant hypertension in CKD patients. However, aside from the CLICK trial, there is a notable lack of follow-up studies with the majority focusing on secondary analyses from CLICK. One randomized controlled trial in older hypertensive patients found chlorthalidone to be similar to hydrochlorothiazide for CKD...

The guidelines from the 2025 American College of Cardiology/American Heart Association for hypertension and 2024 Kidney Disease: Improving Global Outcomes (KDIGO) for management of chronic kidney disease (CKD) notably do not discuss the use of chlorthalidone or thiazide diuretics for treatment of hypertension in CKD patients. However, the 2023 European Society of Hypertension (ESH) guidelines for managing arterial hypertension had included chlorthalidone as a preferred add-on treatment option in patients with CKD stage 4 and 5 (not on dialysis) who failed two previous regimens and present with true resistant hypertension. Supporting reviews also discuss the emergence of chlorthalidone as an option for hypertension in CKD, primarily because of the results from the CLICK trial. However, further follow-up studies appear limited as CLICK remains the primary source when recommending chlorthalidone for treatment. [1-6] A 2023 review assessed chlorthalidone for treatment-resistant hype...

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A search of the published medical literature revealed 3 studies investigating the researchable question:

Please summarize current evidence of chlorothalidone for hypertension in CKD since the CLICK trial.

Level of evidence
C - Multiple studies with limitations or conflicting results  

READ MORE→

[1] Writing Committee Members*, Jones DW, Ferdinand KC, et al. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Hypertension. 2025;82(10):e212-e316. doi:10.1161/HYP.0000000000000249
[2] Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-S314. doi:10.1016/j.kint.2023.10.018
[3] Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023;41(12):1874-2071. doi:10.1097/HJH.0000000000003480
[4] Minutolo R, De Nicola L, Mallamaci F, Zoccali C. Thiazide diuretics are back in CKD: the case of chlorthalidone. Clin Kidney J. 2022;16(1):41-51. Published 2022 Sep 7. doi:10.1093/ckj/sfac198
[5] Georgianos PI, Agarwal R. Hypertension in chronic kidney disease-treatment standard 2023. Nephrol Dial Transplant. 2023;38(12):2694-2703. doi:10.1093/ndt/gfad118
[6] Georgianos PI, Kourtidou C, Tsinari A, Vaios V, Leivaditis K, Liakopoulos V. Pharmacotherapy of treatment-resistant hypertension in patients with chronic kidney disease. Expert Opin Pharmacother. 2025;26(8):919-922. doi:10.1080/14656566.2025.2503854
[7] Agarwal R. Should we CLICK on chlorthalidone for treatment-resistant hypertension in chronic kidney disease?. Clin Kidney J. 2022;16(5):793-796. Published 2022 Dec 20. doi:10.1093/ckj/sfac272
[8] Agarwal R, Sinha AD, Tu W. Chlorthalidone for Resistant Hypertension in Advanced Chronic Kidney Disease. Circulation. 2022;146(9):718-720. doi:10.1161/CIRCULATIONAHA.122.060167
InpharmD's Answer GPT's Answer

Author:Muna Said, PharmD, BCPS + InpharmD™ AI LEARN MORE 

Guidelines regarding management of stress ulcer prophylaxis typically recommend prophylaxis in inpatients who are at high risk of bleeding or stress ulceration, including those who receive high-dose corticosteroid therapy, defined as exposure exceeding 250 mg/day of hydrocortisone or equivalent or 1,000 mg of prednisone or equivalent. Though literature delineating a specific risk incidence with high-dose corticosteroid use is scarce and dated, greater corticosteroid exposure is associated wit...

A 2024 guideline developed by the Society of Critical Care Medicine and the American Society of Health-System Pharmacists provides detailed recommendations for the prevention of stress-related upper gastrointestinal bleeding (UGIB) in critically ill adults. The guideline identifies several factors that increase the risk of clinically important stress-related UGIB, including coagulopathy, shock, and chronic liver disease, and recommends pharmacologic stress ulcer prophylaxis (SUP) with a proton pump inhibitor or histamine-2 receptor antagonist in critically ill patients with these risk factors. Additional recommendations address the role of enteral nutrition, preferred pharmacologic agents, route of administration, dosing considerations, and discontinuation of prophylaxis once risk factors resolve. Notably, corticosteroid therapy is not identified as a risk factor for stress-related UGIB in this guideline, and no recommendations are provided regarding the use of SUP based on corticos...

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A search of the published medical literature revealed 0 studies investigating the researchable question:

Is stress ulcer prophylaxis necessary in patients receiving high-dose corticosteroids, and if so, what dose (prednisone or methylprednisolone equivalent) or duration of therapy warrants prophylaxis?

Level of evidence
C - Multiple studies with limitations or conflicting results  

READ MORE→

[1] MacLaren R, Dionne J, Granholm, A, et al. Society of Critical Care Medicine and American Society of Health-System Pharmacists guideline for the prevention of stress-related gastrointestinal bleeding in critically ill adults. Crit Care Med. 2024 Aug;52(8):e421-e430.
[2] Ringerson RL, Smith N. Stress Ulcer Prophylaxis Evidence Based Medicine Guideline. Updated February 22, 2023. Accessed March 31, 2026. https://www.surgicalcriticalcare.net/Guidelines/Stress%20Ulcer%20Prophylaxis%202023.pdf
[3] EAST Practice Management Guidelines Committee. PRACTICE MANAGEMENT GUIDELINES FOR STRESS ULCER PROPHYLAXIS. Updated 2008. Accessed March 31, 2026. https://www.east.org/Content/documents/practicemanagementguidelines/stress-ulcer-prophylaxis%20.pdf
[4] ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm. 1999;56(4):347-379. doi:10.1093/ajhp/56.4.347
[5] Guslandi M. Steroid ulcers: Any news?. World J Gastrointest Pharmacol Ther. 2013;4(3):39-40. doi:10.4292/wjgpt.v4.i3.39
[6] Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open. 2014;4(5):e004587. Published 2014 May 15. doi:10.1136/bmjopen-2013-004587
[7] Butler E, Møller MH, Cook O, et al. The effect of systemic corticosteroids on the incidence of gastrointestinal bleeding in critically ill adults: a systematic review with meta-analysis. Intensive Care Med. 2019;45(11):1540-1549. doi:10.1007/s00134-019-05754-3
InpharmD's Answer GPT's Answer

Author:Tai Huynh, PharmD, BCPS + InpharmD™ AI LEARN MORE 

Evidence describing the duration of action of induction agents based on body weight and total dose appears limited. For midazolam, pharmacokinetic studies demonstrate that obesity prolongs the half-life, suggesting a risk of accumulation with large or repeated doses. A case report of etomidate overdose (250 mg over 43 minutes) resulted in unconsciousness lasting approximately 5–6 hours, while a case series of ketamine overdoses in children (5 to 100 times the intended dose) produced prolonged...

A comprehensive review on pharmacotherapy optimization for rapid sequence intubation (RSI) in the emergency department highlights important considerations regarding weight-based dosing (see Table 1). RSI medications in obese patients are often underdosed, particularly etomidate and succinylcholine, although the clinical consequences of this underdosing remain unclear. Given the critical importance of achieving full induction and paralysis during RSI, underdosing may carry greater risk than overdosing. In emergent settings, total body weight (TBW) can be used for dosing when calculating ideal or adjusted body weight is not feasible, with suggested maximum doses considered to avoid excessive exposure. However, for induction agents that predispose to hypotension, dosing based on adjusted body weight may be appropriate. Additionally, clinicians should anticipate a potentially prolonged duration of paralysis when large doses of neuromuscular blocking agents are required in obese patients...

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A search of the published medical literature revealed 2 studies investigating the researchable question:

What evidence exists that describes the duration of action of induction agents used for intubation (primarily etomidate, ketamine, propofol, midazolam) based on patient's body weight and total dose administered. Please include all references found, including any case reports describing duration of sedative effect.

Level of evidence
C - Multiple studies with limitations or conflicting results  

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[1] Engstrom K, Brown CS, Mattson AE, Lyons N, Rech MA. Pharmacotherapy optimization for rapid sequence intubation in the emergency department. Am J Emerg Med. 2023;70:19-29. doi:10.1016/j.ajem.2023.05.004
[2] Erstad BL, Barletta JF. Drug dosing in the critically ill obese patient-a focus on sedation, analgesia, and delirium. Crit Care. 2020;24(1):315. doi:10.1186/s13054-020-03040-z
[3] Greenblatt DJ, Abernethy DR, Locniskar A, Harmatz JS, Limjuco RA, Shader RI (1984) Effect of age, gender and obesity on midazolam kinetics. Anesthesiology 61:27–35.
[4] Brill MJ, van Rongen A, Houwink AP, et al. Midazolam pharmacokinetics in morbidly obese patients following semi-simultaneous oral and intravenous administration: a comparison with healthy volunteers. Clin Pharmacokinet. 2014;53(10):931-941. doi:10.1007/s40262-014-0166-x
[5] Valk BI, Struys MMRF. Etomidate and its Analogs: A Review of Pharmacokinetics and Pharmacodynamics. Clin Pharmacokinet. 2021;60(10):1253-1269. doi:10.1007/s40262-021-01038-6
[6] Chalmers P. Etomidate-overdose by continuous infusion. Anaesthesia. 1983;38(5):506. doi:10.1111/j.1365-2044.1983.tb14045.x
[7] Green SM, Clark R, Hostetler MA, Cohen M, Carlson D, Rothrock SG. Inadvertent ketamine overdose in children: clinical manifestations and outcome. Ann Emerg Med. 1999;34(4 Pt 1):492-497. doi:10.1016/s0196-0644(99)80051-1
[8] Bailie GR, Cockshott ID, Douglas EJ, Bowles BJ. Pharmacokinetics of propofol during and after long-term continuous infusion for maintenance of sedation in ICU patients. Br J Anaesth. 1992;68(5):486-491. doi:10.1093/bja/68.5.486

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