PaJR Case Reports: Hypoalbuminemia ProJR

Sunday, January 21, 2024

Thesis protocol: Outcomes of patients with HYPOALBUMINEMIA, their associated comorbidities AND their OUTCOMES

Title: Outcomes of patients with HYPOALBUMINEMIA, their associated comorbidities AND their OUTCOMES

Introduction: Hypoalbuminemia is a medical sign in which the level of albumin in the blood is low. This can be due to decreased production in the liver, increased loss in the gastrointestinal tract or kidneys, increased use in the body, or abnormal distribution between body compartments. Patients often present with hypoalbuminemia as a result of another disease process such as malnutrition as a result of severe anorexia nervosa, sepsis, cirrhosis in the liver, nephrotic syndrome in the kidneys, or protein losing enteropathy in the gastro intestinal tract. (ref)

Problem statement:

"Three theoretical constructs drive current collective medical cognition around the relationship between hypoalbuminemia and comorbidities and outcomes.

First, albumin might serve as a nutritional marker, such that hypoalbuminemia represents poor nutritional status in patients who go on to experience poor outcomes.

Second, albumin has its own pharmacologic characteristics as an antioxidant or transporter, and therefore, the lack of albumin might result in a deficiency of those functions, resulting in poor patient outcomes.

Or third, albumin is known to be a negative acute phase protein, and as such hypoalbuminemia might represent an increased inflammatory status of the patient, potentially leading to poor outcomes

A thorough review of the literature reveals the fallacy of these arguments and fails to show a direct cause and effect between low albumin levels per se and adverse outcomes. Interventions designed solely to correct preoperative hypoalbuminemia, in particular intravenous albumin infusion, do little to change the patient's course of hospitalization." (Entirely quoted from ref 1)

Also there are very few studies available that have evaluated the diagnostic and therapeutic event factors which influence the comorbidities in patients with hypoalbuminemia (ref number 1) and our study aims to bridge this gap.

Ref 1 : https://journals.sagepub.com/doi/abs/10.1177/000313481708301123?journalCode=asua

Aim: To learn about factors influencing the clinical Profile and Comorbidities in the Development of Hypoalbuminemia and It's outcomes and correlating team learning outcomes with patient improvement outcomes

Objectives:

1) To collect and document hypoalbuminemia patient illness event data reflecting their morbidities and comorbidities in their individual historical timeline.

2)To match collected individual particular patient event data with past generalizable data around hypoalbuminemia

3)To evaluate each thematic category of hypoalbuminemia patient event data into diagnostically labeled morbidities as well as comorbidities and establish a relation between their intervention outcomes over time

4) To synthesise new learning outcomes over what is currently available and documented globally for patients with hypoalbuminemia and establish the relationship, if any, between the newly synthesized learning outcomes from each hypoalbuminemia patient participant and their or their subsequent hypoalbuminemia patient's healing outcomes.

MATERIALS AND METHODS:

STUDY DESIGN:

Qualitative, Prospective and Observational study that evaluates each thematic category of patient illness event data into diagnostically labeled morbidities as well as comorbidities and establishes a relation between their intervention outcomes over time

METHODOLOGY:

1) Patients having low serum albumin are selected from CASUALTY, OPD, IPD in ... Institute of Medical Sciences

2) Consent is taken for study participation as well as deidentified data sharing from the patient and their advocates/relatives after explaining the potential harms and benefits along with need for further follow up.

Sample informed Consent forms:

1) For deidentified case reporting

https://medicinedepartment.blogspot.com/2020/05/informed-patient-consent-and.html?m=1

2) Patient information sheet:

English:

https://drive.google.com/file/d/12LLDgFBVfnTxDdNv5K715uSyLYPUEgrY/view?usp=drivesdk

Telugu:

https://drive.google.com/file/d/13Df9wCu9zhjECpPxcHEULSAphv6-tDHl/view?usp=drivesdk

Template of this "patient information sheet" is borrowed from👇

https://www.ncbi.nlm.nih.gov/books/NBK261334/

And modified according to the thesis topic.

CONSENT FORMS

https://docs.google.com/presentation/d/1dWNeHi6nSgfqbrFV3jmP6R15gasZrGHD/edit?usp=drivesdk&ouid=109331939192934520503&rtpof=true&sd=true

More here: https://vamsikrishna1996.blogspot.com/2020/10/thesis.html?m=1

3) Methodology of data collection and analysis illustrated through a Sample case report form to demonstrate thesis objectives:

Please see this sample case report form/proforma (collected and suitably archived albeit semi structured case data):

Thesis participant is a 50M Hypoalbuminemia, Viral thrombocytopenia comorbidities Diabetes 10 yrs CAD CCF

https://chat.whatsapp.com/J73wQ60iSov7c30Xhi7hRV

Demonstration of thematic analysis and objectively structured clinical evaluation(OSCE) data extraction process from the above single case report proforma in line with the objectives below:

1) To collect and document hypoalbuminemia patient illness event data reflecting their morbidities and comorbidities in their individual historical timeline.

Morbidities:

Fever 3 days

Body pain 3 days

Shortness of breath 1 day

Subsequently:

Hypotension

Severe thrombocytopenia

Impression: Viral fever with thrombocytopenia, hypoalbuminemia

Comorbidities:

Trunkal obesity

Diabetes 10 years

Hypertension 1 year

CAD

CCF

Renal failure AKI on CKD

Albuminuria

Hypoalbuminemia

Diagnostic and therapeutic Outcome interventions:

Diagnostic:

Fever pattern monitoring

Platelet monitoring

Vitals and Respiratory parameters monitoring

Urine output monitoring

Therapeutic:

For thrombocytopenia: platelets

For hypotension : iv vasopressors

Hypoxia: adjusted fio2

Diabetes: Insulin short acting

CCF: iv loop diuretics

AKI: conservative

2)To match collected individual particular patient event data with past generalizable data around cardiac arrhythmias and associated comorbidities and their outcomes

The above patient data was matched to past available data around similar clinical scenarios with similar hypoalbuminemia and comorbidities and following learning themes emerged that needed to be pursued further:

Diagnostic uncertainties:

Hypoalbuminemia in this 50M with Diabetes, CAD, CCF, AKI, CKD, albuminuria and a recent fever with thrombocytopenia can be due to:

Diabetic nephropathy glomerular injury or even a recent onset non diabetic kidney disease due to acute glomerular injury

Negative acute phase reactant

Liver failure

Unlikely malnutrition or malabsorption

Therapeutic uncertainties:

Role of platelet therapy

Role of albumin therapy

Absence of afterload reducing agents for his left heart failure management

Role of indiscriminate antibiotics in absence of definite microbiological drivers

Role of CAD prophylactic agents and their stopping in indirectly precipitating the current outcomes of arrhythmias

The patient timeline that is usually displayed daywise in a single fever chart along with soap notes is currently missing from the above sample case report proforma and hence this third objective is not met at this point of time

From the above diagnostic and therapeutic uncertainty themes extracted from the single sample case report form and on review of literature of existing knowledge around these, it's clear that more research using similar clinically complex patient data is needed to synthesize information over what is currently available. In this given individual patient the hypoalbuminemia appears to appears to have multiple influences, namely: a

Diabetic nephropathy glomerular injury or even a recent onset non diabetic kidney disease due to acute glomerular injury or as a negative acute phase reactant due to the recent viral fever or due to liver failure again due to the acute febrile inflammatory illness and his outcomes needs to be gathered meticulously over time using currently available "medical cognition" tools.

EFFECT OF IV ALBUMIN INFUSION FOR PATIENTS WITH CHRONIC HYPOALBUMINEMIA DUE TO LIVER FAILURE.

[20/06, 10:43] PaJR Gastro Hepatologist: Is there a possibility that she might benefit from biweekly albumin infusions?

[20/06, 17:01]cm: Apparently yes. Looks like chronic multi organ failure due to metabolic syn

[20/06, 17:01]cm: Are there RCTs to suggest their effectiveness?

[20/06, 18:07] PaJR Gastro Hepatologist: It's still open for debate, good quality but contradictory evidence from ANSWER and MACHT trials

[20/06, 18:08] PaJR Gastro Hepatologist: The ANSWER trial (Caraceni 2018) may be extrapolated to our scenario

[20/06, 18:09] PaJR Gastro Hepatologist: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30840-7/abstract

[20/06, 18:10] PaJR Gastro Hepatologist: https://journals.lww.com/hep/fulltext/2025/01000/controversies_regarding_albumin_therapy_in.26.aspx

[20/06, 18:11] PaJR Gastro Hepatologist: This is a high quality narrative review authored by domain experts, published very recently in Hepatology (the AASLD journal).

[20/06, 19:11]cm: Open label

[20/06, 19:13] PaJR Gastro Hepatologist: Yes but that's the best available evidence till now.

[20/06, 19:17] PaJR Gastro Hepatologist: https://www.jhep-reports.eu/article/S2589-5559(24)00225-8/fulltext

[20/06, 19:18] PaJR Gastro Hepatologist: This came from the same group last year. This is a real world evidence study and not RCT

[20/06, 19:19] PaJR Gastro Hepatologist: https://efclif.com/projects/preciosa-effects-of-long-term-administration-of-human-albumin-in-subjects-with-decompensated-cirrhosis-and-ascites/

[20/06, 19:21] PaJR Gastro Hepatologist: This is an ongoing phase 3 study from Paolo Angeli's group which may shed some more light. Again this is open label. I guess albumin trials are more likely to be open label.

[20/06, 19:30]cm: Going by the pharmacokinetics and pharmacodynamics of human albumin is it real world feasible for it to have sustained benefit? What is the duration of stay for the infused albumin as opposed to the expected half life of 21 days? We followed up a few patients of hypoalbuminemia here with their daily serum albumin once their albumin infusion was started and found it rising for two days and then again falling after that. @⁨ PG 2023⁩ can you share that case report where you had been instrumental in the data collection?

Continuing to take biweekly iv albumin appears to be a very expensive affair?

[20/06, 19:46] PG 2023: Yes sir, in that patient the transfused albumin didn't last more than 2 days and it cost around 7000₹+ for each albumin pint.

[20/06, 19:49] PG 2023: These seem to be the only details available from that day sir😬

[20/06, 19:50] PG 2023: There was another patient with similar condition where transfusing albumin didn't last long enough.

[20/06, 20:51] PaJR Gastro Hepatologist: The albumin in cirrhotics is not only quantitatively low, it is also qualitatively dysfunctional.

[20/06, 20:55] cm: Yes our contention is about the apparently low quantitative values achieved after infusion. Previously we didn't even believe that serum albumin rise post albumin infusions were even correlate-able but after these patients we feel it needs to be observed in a larger number

[20/06, 20:57] PaJR Gastro Hepatologist: Yes sir, the expenses are an issue, specially in India and there is still no guideline to recommend routine albumin administration in decompensated cirrhotics

[20/06, 20:58] PaJR Gastro Hepatologist: https://www.jhep-reports.eu/article/S2589-5559(23)00116-7/fulltext

[20/06, 20:59] PaJR Gastro Hepatologist: This was the closest to a consensus statement on albumin in Hepatology published a couple of years back. Can we get LLM to summarise the key pointers?

[20/06, 22:04] LLM: Based on the comprehensive review of the 2023 international position statement and related evidence, here are the key clinical recommendations and insights regarding albumin use in cirrhosis:

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### 🔑 *1. Strong Recommendations for Short-Term Albumin Infusion*

- *Hepatorenal syndrome (HRS):* Albumin + vasoconstrictors (e.g., terlipressin) is critical for improving renal function and survival.

- *Large-volume paracentesis (LVP):* Administer 6–8 g albumin per liter of ascites removed to prevent post-paracentesis circulatory dysfunction (PPCD) and renal injury.

- *Spontaneous bacterial peritonitis (SBP):* Use 1.5 g/kg on day 1 and 1 g/kg on day 3 alongside antibiotics to reduce HRS risk and mortality by 50%.

---

### ⚠ *2. Conditional or Context-Dependent Use*

- *Long-term administration* may be considered in decompensated cirrhosis with recurrent ascites (e.g., 40 g albumin biweekly), but only where "budget and logistical issues can be resolved" (based on mixed trial data: ANSWER trial benefits vs. ATTIRE trial null effects).

- *Non-SBP infections (e.g., pneumonia, UTI):* Routine albumin is *not recommended* due to lack of mortality benefit and increased pulmonary edema risk (Fernandez 2020 RCT) .

- *Hepatic encephalopathy (HE) or hyponatremia:* Evidence remains insufficient for routine use.

---

### ⚗ *3. Mechanisms of Action Beyond Volume Expansion*

Albumin's benefits derive from both:

- *Oncotic effects:* Plasma volume expansion counteracts arterial underfilling.

- *Non-oncotic properties:*

- Antioxidant and immunomodulatory effects (binds endotoxins, reduces inflammation).

- Endothelial stabilization and toxin scavenging (e.g., bilirubin, cytokines).

In decompensated cirrhosis, endogenous albumin is dysfunctional, making exogenous infusion critical for restoring homeostasis.

---

### 🚩 *4. Safety Considerations*

- *Pulmonary edema* is the most significant adverse effect, especially in patients with borderline cardiac function or when co-administered with terlipressin.

- *Fluid status assessment* (e.g., point-of-care ultrasound for lung B-lines, inferior vena cava collapsibility) is essential before infusion to avoid volume overload .

- *Avoid in hemodynamically stable patients* without specific indications (e.g., hypoalbuminemia alone is not an indication) .

---

### ❓ *5. Unresolved Controversies & Research Gaps* - *Dosing and duration:* Optimal regimens for HRS and long-term use remain undefined (e.g., weight-based vs. fixed dosing).

- *Patient selection:* Biomarkers to identify albumin responders are lacking.

- *Timing in AKI:* Recent studies challenge guidelines restricting albumin to 24 hours, with responses observed between 24–48 hours .

- *Hepatic encephalopathy/hyponatremia:* Efficacy not yet validated in robust trials.

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### 📊 *Key Practice Implications*

| *Scenario* | *Recommendation* | *Evidence Certainty* |

|----------------------------|-------------------------------------------------|------------------------|

| HRS | Albumin + vasoconstrictors | High ✅ |

| LVP (≥5L ascites) | 6–8 g/L albumin | High ✅ |

| SBP | 1.5 g/kg Day 1 + 1 g/kg Day 3 | High ✅ |

| Non-SBP infections | Not recommended | Moderate 🚫 |

| Long-term ascites | Conditional (40 g biweekly) | Low ⚠ |

---

### 💡 *Conclusion*

The 2023 position statement consolidates albumin as a cornerstone therapy for HRS, LVP, and SBP but urges caution in non-evidence-based settings. Future studies should refine dosing, expand indications for hepatic encephalopathy/hyponatremia, and validate biomarkers for personalized use. Integrating fluid status assessment via ultrasound may mitigate safety risks.

> ✨ *Key Takeaway:* Albumin is a *disease-modifying agent* in cirrhosis complications but requires precision in patient selection, dosing, and monitoring to avoid harm.

[20-06-2025 20:44] PPM 8: Yes sir, in that patient the transfused albumin didn't last more than 2 days and it cost around 7000₹+ for each albumin pint.

[20-06-2025 19:49] PPM 8: These seem to be the only details available from that day sir😬

[20-06-2025 19.50] PPM 8: There was another patient with similar condition where transfusing albumin didn't last long enough.