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This lecture was conducted during the Nephrology Unit Grand Ground by Medical Student rotated under Nephrology Division under the supervision and administration of Prof. Jamal Al Wakeel, Head of Nephrology Unit, Department of Medicine and Dr. Abdulkareem Al Suwaida, Chairman of the Department of Medicine. Nephrology Division is not responsible for the content of the presentation for it is intended for learning and /or education purpose only. Critical Care Issues in Nephrology Presented by: Waleed Alharbi Medical Student June 2008 Lessons I have learned during my Nephrology Rotation Training 1. Knowledge 2. Behavior 3. Excellent Brain Workout! 4. Meet superb & sincere persons like Dr.Iqbal Knowledge… • Renal, acid-base & electrolyte complications are common in ICU. • Only selected topics… • Dialysis issues in ICU… • I wish if I had more consultation exposure… Acute Renal failure • ARF in ICU is alarming why?! • Mortality 78% in those who require dialysis • 1/3 will require chronic dialysis • ARF development in ICU is marked by poor prognosis & ↑ long-term complications Protecting the Kidney… How to prevent ARF in ICU? • NSAIDs + ACEIs + ARBs • Alter intrarenal hemodynamics • Common causes of acute renal dysfunction in patients who have associated volume depletion How to prevent ARF in ICU? • Crush injuries • Associated with severe rhabdomyolysis & myoglobinuric renal failure • To reduce risk of ARF development: • Aggressive volume repletion with solution that includes HCO3 for urinary alkalinzation why?! • To ↓ myoglobin precipitation in tubules • Mannitol to ↓ myoglobin precipitation + provides free radical scavenging How to prevent ARF in ICU? • • Amphotericin B High risk are: 1. 2. 3. 4. 5. >60mg/day In ICU On cyclosporin Baseline renal insufficiency Diuretic use • Pretreatment with NS which suppresses the vasoconstrictive effect of the tubuloglomerular feedback mechanism • Lipid formulations 30-50% risk reduction • Infusion over 24hrs rather than 4 hrs 60% less How to prevent ARF in ICU? • Aminoglycosides • 10-15% cause ARF • Most important intervention is MONITORING of levels • Single dosing daily has 13-26% risk reduction Prevention of ARF in the ICU • Prevention of contrast nephropathy • Predisposing factors: 1. 2. 3. DM Baseline renal dysfunction Presence of volume depletion • Patients with renal impairement exposure to dye results in ARF in up to 30% of cases • Measures: 1. 2. 3. NAC NaHCO3 + Hydration Low-osmolality contrast ARF – Making the Dx • Clinical • Biochemical • RIFLE Criteria… Crit Care Journal 2004 presented by Prof.Al-Wakeel Clinical Approach to the Patient Work-Up of ARF Diagnostic Approach to ARF • Review of Medications Diagnostic Approach to ARF • Rule out Obstruction • Urinanalysis & microscopy • RBC casts – Dysmorphic RBCs = GN – Vasculitis • WBC casts – Sterile pyuria = Interstitial nephritis • Muddy brown – pigmented casts = ATN • Hyaline casts = PRA • Eosinophiluria?!! • Limited specifity it can be seen in: • • • • GN atheroembolic renal disease Pyelonephritis Prostatis • Need special staining Most Interesting Topic in Dx of ARF is differentiating between PRA & ATN • Assessing volume status?! • Best is the use of urinary indices Differentiating between PRA & ATN • FENa = [U/P]Na : [U/P]Cr x 100 • If nonoliguric?! There will be greater overlap • If on diuretics?! FEUrea* *Cavernouis et al. FE urea in ARF.Kidney International Journal.Vol 16; 2223-2229: 2002 Specific Therapeutic interventions in ARF • Diuretics • Dopamine Diuretics • Loop diuretics alone or in combination with thiazides are often used in an attempt to convert oliguric ARF into non-oliguric ARF • Does it make the recovery of renal function faster? • Does it improve mortality? Diuretics • Diuretics should continue to be used in an attempt to ↑ UOP in oliguric pts ONLY after careful correction of volume status • Trial should be short in duration (good idea of response can be obtained in 4 to 6 hrs) • Must not cause delay in the institution of RRT Renal-Dose Dopamine • ↑ Renal blood flow • Short-lived diuretic activity • Does it improve mortality? • Does it improve time to recovery of renal function? • Need of Dialysis? • Several studies have analyzed the use of renal dose DA in the prevention & treatment of multiple clinical conditions related to ARF Renal-Dose Dopamine • Randomized double-blind trial* • 328 pts who had early RF in the setting of SIRS • DA had no effect on the: • severity of RF (Cr 245 DA vs. 249 placebo) • Need for dialysis (22% DA vs. 25% placebo) • In-hospital mortality (43% DA vs. 40% placebo) * Bellomo et al. Low-dose dopamine in pts with early renal dysfunction. ANZICS trial. Lancet2000;356:2139-43. Renal-Dose Dopamine • Meta-analysis till 2000* • 17 randomized trials • 854 pts • Had similar findings *Kellum et al. Use of dopamine in ARF: a meta-analysis. Crit Care Med 2001;29:1526-31. Renal dose Dopamine • Renal-dose dopamine can be used as diuretic agent in ARF if synergistic diuretic schemes are needed • But there is no support for its use in the Rx of ARF • Better to be avoided becoz of unpredictable levels of plasma clearance between pts Selected Issues in Electrolyte disorders • New causes & novel approaches to hyponatremia • Hypernatremia: Important balance in the quality of ICU care • K-Mg interactions in critical care • Important aspects of hypophosphatemia to the nephrologist New Causes & Novel approaches to Hyponatremia • Classic approach… • SIADH is the most common cause of hyponatremia in hospitalized pts • SIADH: • 1. 2. 3. 4. Clinical euvolemia ↑Na urine >20 ↑urinary osmolality >100 ↓Na Clinical exam has poor sensitivity & specifity in the setting of hyponatremia when compared with the urine Na conc.* * Chung et al. Clinical assessment of extracellular fluid volume in hyponatremia. Am J Med 1987; 83:905-8. SIADH • Caused by multiple mechanisms in critically ill pts: 1. 2. 3. 4. 5. 6. Malignancy – lung, brain Primary brain disorders-hemorrhages Lungs disorders- acute infections, respiratory failure Postop pain & nausea Hypotonic postop fluid replacement Drugs a) b) c) d) Vasopressin analogs – desmopressin, oxytocin Enhance vasopressin release – opiates, TCA, carbamazepine Potentiate renal vasopressin activity – cyclo, NSAIDs Unkown mechanism – Haloperidol, SSRI Treatment Hyponatremia • Untreated severe hyponatremia is marked by a risk of: • Respiratory compromise • Anoxic encephalopathy • Frequent monitoring of serum Na is essential to prevent overshoot Hypernatremia: Important Balance in the quality of ICU care • 6% in pts in the ICU • Development of ↑Na during ICU stay associated with greater mortality 32% than the presence of ↑Na on admission 20%* • Development of ↑Na in critically ill pts results from combination of lack of access to water & excessive loss of hypotonic fluids *Palvesky et al. Hypernatremia in hospitalized pts. Ann Intern Med 1996; 124:197-203. Hypernatremia Hypernatremia • Evaluation of ↑Na is straightforward • It is always associated with net state of water defeciency regardless of extracellular volume status • Aquapenia or Hypoaquemia!! • Management is focused on the correction of possible underlying mechansims & replacement of water losses • We have to understand that replacement of previous & ongoing losses is necessary to correct serum osmolality *Polderman et al. Hypernatremia in the ICU: an indicator of quality of care? Crit Care Med 1999; 27:1105-8. Value of the AG in the ICU Value of AG in the ICU • Two valuable factors are often overlooked in the assessment of the AG in the ICU 1. Need to acount for the degree of hypoalbuminemia → false underestimation of the AG • 2. Figge formula: Adjusted AG = observed AG + [0.25 x (4 – albumin) Use of the measured not corrected serum Na when calculating the AG in the setting of hyperglycemia → overestimate the AG when using corrected Na K-Mg Interactions in critical care • K & Mg defeciency are often coexistent in critically ill pts why?! • Causes of ↓K are also causes of ↓Mg • Diarrhea • Diuretics • Post-ATN diuresis • any state of aldesterone excess K-Mg Interactions in critical care • ↓Mg is cause of ↓K in its own how?! • Current evidence suggests that Mg leads to ↓ATP activity → ↑ activity of ATP-inhibitable luminal K channels* • Only aggressive replacement of Mg will allow successful K repletion * Agus ZS. Hypomagnesemia. J Am Soc Nephrol 1999; 10:1616-22. Important aspects of Hypophosphatemia to the nephrologist • Can be caused by multiple mechanisms in the ICU: 1. Transcellular shifts 2. ↓ Intestinal absorption 3. 4. Respiratory alkalosis Dextrose therapy Insulin Refeeding Sepsis Vit D defeciency Antacids Prolonged decreased intake ↑ renal losses Osmotic diuresis Glycosuria Chronic alcoholism hyperparathyroidism Hypophsphatemia • Severe hypophosphatemia promotes significant morbidity in pts in the ICU • Even moderate degrees of phosphate depletion leads to impaired diaphragmatic contractility & impair weaning from MV* • Associated with impaired myocardial contractility# *Aubier et al. Effect of hypophosphatemia on diaphragmatic contractility in pts with acute respiratory failure. NEJM 1985; 313:420-4 #Vered et al. LV function in pts with chronic hypophosphatemia. Am Heart J 1984; 107:796-8. “The practice of medicine is an art, not a trade; a calling, not a business; a calling in which your heart will be exercised equally with your head.” William Osler