Show Notes

Diuretic Resistance Reminders:

• What is diuretic resistance?
  • Failure to achieve therapeutically desired congestion relief despite using appropriate or escalating doses of diuretics.
• Consider… Is something else going on?
  • Think about blood flow first
    • Diuretics cannot work if they are not reaching the kidney!

Case 1: Diuretic Resistance from Ascites and Intra-abdominal Hypertension

• Case Summary:
  • 46F with hypertrophic cardiomyopathy with worsening SOB, edema, and abdominal girth and signs of volume overload. Objective otherwise:
    • AKI with Cr 1.0 -> 2.0 mg/dl and poor urine output
      • No response despite high doses of bumetanide and acetazolamide.
    • Urinalysis: mostly hyaline casts [Absence of proteinuria and hematuria]
    • Other Data:
      • Normal blood pressures
      • Tense distended abdomen
      • Warm extremities
      • Normal lactate [Lactic Acidosis from StatPearls, Last Update: July 17, 2023.] “Normal lactate levels are less than two mmol/L, with hyperlactatemia defined as lactate levels between 2 mmol/L and 4 mmol/L. Severe levels of lactate are 4 mmol/L or higher. Other definitions for lactic acidosis include pH less than or equal to 7.35 and lactatemia greater than 2 mmol/L with a partial pressure of carbon dioxide (PaC02) less than or equal to 42 mmHg.”
  • Bladder pressure measured ~30 mmHg so paracentesis was performed.
    • Urine output significantly improved
    • Creatinine normalized back to baseline
    • Bladder pressure dropped to 12 mmHg.
• What is intra-abdominal hypertension (IAH)?
  • Sustained intra-abdominal pressure > 12 mmHg
  • Abdominal compartment syndrome = IAH + end-organ dysfunction (generally when this pressure > 20 mmHg)
  • Under-recognized cause of acute kidney injury
    • IAH causes a significant drop in renal blood flow and GFR.
• When to consider IAH as the cause of diuretic resistance:
  • Patients who have cirrhosis or cardiac ascites and a tense abdomen on exam

Case 2: Diuretic Resistance from Low Cardiac Output

• Case Summary:
  • 48M with ischemic HFrEF (EF 15-20%) admitted for volume overload and “feeling unwell,” started on IV diuretics.
    • Quickly escalated to multiple high-dose agents with poor urine output
    • AKI with Cr 1.0 -> 2.0 mg/dl and rising BUN
    • Other Data:
      • BPs 90s/50s mmHg
      • Warm extremities
      • Elevated bilirubin
      • Lactate 2.5 mmol/L
  • Right heart catheterization obtained:
    • RA 18 mmHg, PA 32/22 mmHg, PCWP 25 mmHg
    • Low cardiac index (CI) 1.7 L/min/m2 by Fick
  • Given concern for cardiogenic shock, he was started on dobutamine
    • Significant improvement in urine output
    • Improvement in creatinine and other perfusion markers
• Memory trick for normal right heart catheterization numbers [Link is to Right Heart Catheterization—Background, Physiological Basics, and Clinical Implications, 2019]: Nickel-dime-quarter-dollar rule. [Link is to a discussion of right heart normal cath pressures]
• pulmonary hypertension]
• Remember: Shock ≠ Hypotension
  • Sometimes known as  “normotensive cardiogenic shock” [Link is to Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association, 2017] in this patient population
    • Related to higher central pressures and lower perfusion pressure (more below)
• When to consider low cardiac output as the cause of diuretic resistance:
  • Patients who have multiple other signs of hypoperfusion
  • Can be tricky and easy to miss
    • Similar abnormalities (like elevated LFTs) can be seen in just congestion alone
    • Must have a high level of suspicion for low output to catch it!

Case 3: Diuretic Resistance from Inadequate Renal Perfusion Pressure

• Case Summary:
  • 44M with WHO group I pulmonary hypertension on treprostenil [Link is to Treprostenil from StatPearls, 2023] who was admitted for volume overload and “feeling unwell,” started on IV diuretics
    • Quickly escalated to multiple high-dose agents with still suboptimal urine output
    • Worsening AKI with Cr 1.2 -> 3.3 mg/dl
    • Other Data:
      • BPs 100s/50s mmHg
      • SpO2 mid-90s on 6L NC
      • Warm extremities
      • Skin flushing
  • Echocardiogram was obtained:
    • Normal LV function, dilated RV with decreased function, significant tricuspid regurgitation
  • Suspicion was for worsening right heart failure:
    • Vasopressin was started to target a mean arterial pressure (MAP) goal closer to 75
    • Urine output increased dramatically
    • Cr improved to near baseline
• What is perfusion pressure?
  • Blood pressure gradient through an organ
    • I.e. Difference in the blood pressure going into the kidney and the blood pressure leaving the kidney
    • Organ Perfusion Pressure = MAP – CVP (approximately)
      • *MAP is the mean arterial pressure
      • *CVP is the central venous pressure obtained on a right heart catheterization or estimated by JVP assessment
• Why does perfusion pressure matter?
  • The kidneys (and other organs) depend on an adequate perfusion pressure to maintain blood flow (and GFR).
    • Through autoregulatory mechanisms in the blood vessels
  • In general: Perfusion pressure above 60 mmHg is enough to maintain adequate GFR.
    • May be a difficult target in some cases of decompensated heart failure
      • Since the CVP can be quite high!
      • Target of 50 mmHg may be enough anecdotally
      • *May require vasopressors or inotropy
• Why was vasopressin used?
  • Preferred by some experts in patients with pulmonary hypertension
    • Theoretically causes less pulmonary vasoconstriction compared to other vasopressors
      • Only studied in animal models
• When to consider inadequate renal perfusion pressure as the cause of diuretic resistance:
  • Patients with borderline MAPs (near 65) and relatively preserved LV function
    • *Caution in patients with poor LV function
      • Vasopressors increase afterload which may be detrimental in these cases
      • Definitely worth a multidisciplinary discussion