Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Comparison of Dilute Unfractionated Heparin and Standard Concentrated Unfractionated Heparin Protocols for Anticoagulation of the Extra-corporeal Circuit During Continuous Renal Replacement Therapy in the ICU
Brief Summary: Heparin is commonly used for anticoagulation of the extracorporeal circuit during continuous renal replacement therapy (CRRT) but the optimal mode of delivery has not yet been validated. Our study will compare dilute heparin to a standard concentration of heparin. The investigators hypothesize that heparin delivered in a dilute solution will augment coating of the filter fibers with anticoagulants, decreasing clotting events and increasing filter life. By improving delivery of heparin to the filter and circuit, where clotting events can disrupt dialysis, less heparin would be required for the extra-corporeal circuit and thus less heparin would be delivered back to the patient with blood return from the machine. By exposing the patient to less heparin it is hypothesized that fewer bleeding events would occur, making the dialysis treatment safer. If more of the filter's fibers remain patent and the filter is functional for a longer period of time, the CRRT would also be more effective.


Options:
A: Inclusion Criteria:

* Male or female critically ill patients over the age of 18 years old
* Acute Kidney Injury requiring CRRT defined using the Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE) classification with criterion I or worse.
* Septic shock as defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference.
* Written informed consent obtained from the patient or a patient's legal representative
* Patient patient's legal representative able to agree to patient's enrollment in the study with informed consent.

Exclusion Criteria:

* Pregnancy
* Participation in another research study protocol
* Known heparin induced thrombopenia or contraindication to heparin
* Pre-existing chronic renal failure on chronic dialysis
* Therapeutic anticoagulation with heparin for another reason (e.g. chonic arrhythmia)
* Severe liver failure (15% prothrombin time)
B: Inclusion Criteria:

1. Critically ill patients with clinical indication for CRRT (clinical decision to use continuous RRT due to hemodynamic instability)

   Or

   Severe acute kidney injury (KDIGO 3-classification) despite optimal resuscitation
2. At least one of the following conditions

   * Sepsis or septic shock
   * Use of catecholamines (norepinephrine or epinephrine ≥ 0.1 µg/kg/min or norepinephrine ≥ 0.05 µg/kg/min + dobutamine (any dose) or norepinephrine ≥ 0.05 µg/kg/min + vasopressin (any dose) or epinephrine ≥ 0.05 µg/kg/min + norepinephrine ≥ 0.05 µg/kg/min)
   * Refractory fluid overload: worsening pulmonary edema: PaO2/FiO2 \< 300 mmHg and/or fluid balance \> 10% of body weight)
3. 18-90 years old
4. Intention to provide full intensive care treatment for at least 3 days
5. Written informed consent of the patient or the legal representatives or the authorized representative or the inclusion due to an emergency situation

Exclusion Criteria:

1. Patients with increased bleeding risk (e.g. an active bleeding from ulcers in the gastro-intestinal tract, hypertension with a diastolic blood pressure higher than 105 mm Hg, injuries (intracranial hemorrhage, aneurysm of brain arteries) of or surgical procedures on the central nervous system if a heparinization with a target aPTT 45-60 s is not allowed by the treating neurologist or neurosurgeon, severe retinopathies, bleeding into the vitreum, ophthalmic surgical procedures)) or injuries, active tuberculosis; infective endocarditis)
2. Disease or organ damage related with hemorrhagic diathesis (coagulopathy, thrombocytopenia, severe liver or pancreas disease)
3. Dialysis-dependent chronic kidney insufficiency
4. Need of therapeutic systemic anticoagulation
5. Allergic reaction to one of the anticoagulants or ingredients, Heparin-induced thrombocytopenia
6. AKI caused by permanent occlusion or surgical lesion of the renal artery
7. AKI caused by (glomerulo)nephritis, interstitial nephritis, vasculitis or postrenal obstruction
8. Do-not-resuscitate order
9. Hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura
10. Persistent and severe lactate acidosis in the context of an acute liver failure and/or shock
11. Kidney transplant within the last 12 months
12. Pregnancy and nursing period
13. Abortus imminens
14. No hemofiltration machine free for use at the moment of inclusion
15. Participation in another clinical intervention trial in the last 3 months
16. Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
17. Persons held in an institution by legal or official order
C: Inclusion Criteria:

* patients who have at least one of the hemorrhagic tendencies of following conditions and needs CRRT hemodynamically;

  1. Platelet count \< 100,000
  2. aPTT \> 60 sec
  3. PT-INR \> 2.0
  4. active hemorrhage
  5. surgery within 48 hours
  6. cerebral hemorrhage within 3 months or history of major bleeding
  7. septic shock or DIC.

Exclusion Criteria:

* pregnancy, breast feeding, possibility of pregnancy,
* allergy to nafamostat mesilate,
* other conditions that physician consider unfit for candidate.
D: Inclusion Criteria:

* Age greater than 18 years
* Renal failure, electrolyte disturbance, or volume overload requiring continuous venovenous hemodialysis (CVVHD) as determined by the Nephrology consult service

Exclusion Criteria:

* Age less than 18 years
* Active bleeding
* Coagulopathy as defined by baseline INR \> 1.8, aPTT \> 45 seconds, or platelet count \< 50 thousand/μL
* Active administration of systemic anticoagulation (such as warfarin, therapeutic unfractionated heparin, or therapeutic enoxaparin)
* Contraindication to heparin (allergy, thrombocytopenia with platelet count \< 50, known or suspected heparin induced thrombocytopenia \[HIT\])
* Contraindication to systemic anticoagulation (recent surgical or other invasive procedure, significant bleeding disorder, concern for intracranial bleeding, or other contraindication as determined by treating physician)
* Administration of drotrecogin (Xigris™)
* Anticipated surgical or other invasive procedure that would necessitate withdrawal of anticoagulation within 72 hours
* Expected termination of continuous renal replacement therapy (CRRT) or death in \< 24 hours
* The need for more than 500 cc an hour of IV fluids delivered proximal to the filter for the purpose of performing continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF)

Answer: D