(BQ) Part 2 book Critical care handbook of the massachusetts general hospital has contents: Acute kidney injury, burn critical care, adult resuscitation, obstetric critical care, critical care of patients with liver disease, coagulopathy and hypercoagulability,.... and other contents.
I DEFINITION A The RIFLE criteria (Risk, Injury, Failure, Loss, and ESRD) were developed in 2004 to standardize the definition of acute kidney injury (AKI), formerly called acute renal failure (ARF) Prior to this, no consensus was available on the diagnosis or degree of severity 1 Several modifications were introduced by the Acute Kidney Injury Network (AKIN) soon after, though the main addition with AKIN was a more inclusive Stage 1 (≥0.3 mg/dL increase in Cr) 2 In 2012, the Kidney Disease Improving Global Outcomes (KDIGO) organization published clinical practice guidelines to create a unified definition with the goal to improve outcome staging and future clinical research (since RIFLE and AKIN did not completely coincide) 3 Although each of these (see Table 23.1) were created to help standardize clinical outcomes research, they are helpful when assessing severity of injury and level of management (Fig 23.1) 4 Serum creatinine criteria: well validated, but discrepancies exist between various definitions (e.g., misclassification of AKI using AKIN with postsurgical ICU patients after cardiopulmonary bypass with significant positive fluid balance resulting in hemodilution) 5 Urine volume criteria are the same for all three (RIFLE/AKIN/KDIGO) but oftentimes it is less accurate (e.g., morbid obesity) 6 Validation studies are currently underway to establish the utility of these guidelines— particularly with regard to diagnosis and outcome II EPIDEMIOLOGY A The historical lack of a standardized definition results in variable epidemiological data for AKI Information bias and residual confounding (e.g., variability in baseline measures, the use of diagnostic code results), as well as ascertainment bias (AKI vs CKD, which have different pathophysiologic processes and outcome data), results in differences in reported incidence and outcome measurements B Even with the above definitions, studies demonstrate significant differences in the incidence of AKI in the ICU when comparing the same populations C Nonetheless, AKI is common in both hospitalized (5%–20%) and critically ill (30%– 40%) patient populations D Higher level of severity in AKI classification (by any of the above definitions) is associated with adverse outcomes, including increased length of stay, progressive kidney disease, and mortality E AKI is an independent risk factor for cardiovascular complications and mortality; AKI requiring renal-replacement therapy reveals an in-hospital mortality of 50% to 75% Studies have revealed that up to 28% of surviving AKI patients died after discharge from the hospital (i.e., in-hospital mortality likely underestimates the significance of disease) F AKI patients often regain renal function with supportive therapy; however, studies have demonstrated more severe AKI, longer AKI duration, and numerous episodes of AKI are associated with progression to CKD and increasing morality Future insults are much less well tolerated in these patient populations (e.g., additive effect of renal injuries over time) TABLE 23.1 Classification of Acute Kidney Injury FIGURE 23.1 Stage-based management of AKI Shading of boxes indicates priority of action—solid shading indicates actions that are equally appropriate at all stages whereas graded shading indicates increasing priority as intensity increases AKI, acute kidney injury; ICU, intensive-care unit (From Kidney Disease: Improving Global Outcomes [KDIGO] Acute Kidney Injury Work Group KDIGO clinical practice guideline for acute kidney injury Kidney Int Suppl 2012;1(2):1–138.) III ETIOLOGY AND PATHOPHYSIOLOGY AKI is often caused by more than one etiology, but the pathophysiologic processes can be separated into three separate classifications: prerenal, intrinsic (or “renal”), and postrenal injuries This is helpful both to determine the underlying etiology and for management (Table 23.2) A Prerenal (Kidney Hypoperfusion) Decreased intravascular volume a Systemic vasodilation (e.g., sepsis) Sepsis is the most common cause of AKI in the ICU (approximately 50% can be attributed) and is associated with a very high mortality b Hypovolemia (e.g., hemorrhage, GI losses, burns) c Hypotension, decreased cardiac output (CHF, arrhythmias) d Small vessel (renal) vasoconstriction 1 Nonsteroidal anti-inflammatory drugs (NSAIDs): Prostaglandins have important vasodilatory effects on the afferent arteriolar vessels Cyclooxygenase inhibitors inhibit the production of prostaglandins, resulting in decreased renal blood flow ACEi/ARBs: Angiotensin-II is a potent efferent arteriolar vasoconstrictor, and the inhibition of its production (ACE inhibitors) or the blockage of angiotensin receptors (ARBs) results in decreased glomerular perfusion pressure This is of particular concern when the patient has other risk factors (chronic kidney disease, renal artery stenosis, older age) or exposures (diuretics, hypotension, NSAIDs, nephrotoxins) 3 Contrast: IV contrast is both cytotoxic to renal tubular cells and causes intrarenal vasoconstriction Hypercalcemia: directly causes vasoconstriction 5 Calcineurin inhibitors (CNIs): Both cyclosporine and tacrolimus, which lead to afferent and efferent arteriolar vasoconstriction, are used as immunosuppressants for patients after renal transplant Hepatorenal syndrome (HRS): Splanchnic and systemic vasodilation causes increased neuroendocrine (angiotensin, vasopressin) tone, resulting in renal vasoconstriction Prognosis is very poor Intra-abdominal hypertension (IAH; IAP ≥12 mmHg) and abdominal compartment syndrome (ACS; IAP ≥20 mmHg with new organ failure): The pathophysiology is likely a combination of (initially) intrarenal venous congestion/hypertension (normally a low-pressure system), followed by decreased cardiac output and elevated catecholamines, neurohormones, and cytokines (inflammation) Similar to cerebral perfusion pressure (CPP), abdominal perfusion pressure (APP) is a helpful marker of renal perfusion, where APP = MAP – IAP (typical target APP ≥60 mmHg) Cardiorenal syndrome: In addition to decreased cardiac output (acute CHF) resulting in decreased intravascular volume, other pathophysiological processes are likely involved Mechanisms likely include a combination of venous congestion (elevated CVP) and visceral edema resulting in decreased abdominal perfusion pressure (APP) and elevated neuroendocrine (angiotensin, vasopressin) hormones, resulting in decreased renal perfusion TABLE 23.2 Etiologies of Acute Kidney Injury in the Intensive Care Unit Prerenal Intrinsic Renal Postrenal (Obstructive) Intravascular volume depletion • GI fluid loss (e.g., vomiting, diarrhea, EC fistula) • Renal fluid loss (e.g., diuretics) • Burns • Blood loss • Redistribution of fluid (e.g., “thirdspacing,” pancreatitis, cirrhosis) Decreased renal perfusion pressure • Shock (e.g., sepsis) • Vasodilatory drugs • Preglomerular (afferent) arteriolar vasoconstriction • Postglomerular (efferent) arteriolar vasodilation Acute tubular necrosis • Ischemic • Toxin-induced • Drugs • IV contrast • Rhabdomyolysis • Massive hemolysis • Tumor lysis syndrome Upper urinary tract obstruction • Nephrolithiasis • Hematoma • Aortic aneurysm • Neoplasm Acute interstitial nephritis • Drug-induced • Infection-related • Systemic diseases (e.g., SLE) • Malignancy Lower urinary tract obstruction • Urethral stricture • Hematoma • Benign prostatic hypertrophy • Neurogenic bladder • Malpositioned urethral catheter • Neoplasm Decreased cardiac output • Congestive heart failure Acute glomerulonephritis • Postinfectious • Systemic vasculitis • Myocardial ischemia • TTP/HUS • Rapidly progressive GN Vascular • Atheroembolic disease • Renal artery or vein thrombosis • Renal artery dissection • Malignant hypertension Hepatorenal syndrome Increased intra-abdominal pressure GI, gastrointestinal; EC, enterocutaneous; IV, intravenous; SLE, systemic lupus erythematosus; TTP, thrombotic thrombocytopenic purpura; HUS, hemolytic uremic syndrome; GN, glomerulonephritis Adapted with permission from Barozzi L, Valentino M et al Renal ultrasonography in critically ill patients Crit Care Med 2007;35(5 suppl):S198–S205 and Acute renal failure In: Glassock RJ, ed Nephrology self-assessment program (NephSAP), Vol Philadelphia: Lippincott Williams & Wilkins, 2003:42–43 e Large-vessel etiologies 1 Renal artery stenosis (RAS): This usually is in combination with other etiologies (e.g., ACE inhibitors, hypotension) Aortic or renal artery dissection (or compression) 3 Thrombosis or embolism of the renal vessels B Intrinsic Renal Injury Acute tubular necrosis (ATN) a Ischemia (prerenal azotemia naturally progresses into ATN): This is the most significant cause of ATN in the intensive care unit b Pigments (hemoglobin, myoglobin): Of note, rhabdomyolysis should be considered with CPK (creatinine phosphokinase) levels >5,000 units/L This frequently results in hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and acidosis Injury is secondary to direct tubular toxicity from cast formation, in addition to intrarenal vasoconstriction and hypovolemia (muscle inflammation and third spacing) It is important to remember that CPK levels are a marker for muscle injury, and direct injury is caused by myoglobin c Warfarin-related nephropathy (WRN) is a recently described entity where an elevated INR (>3.0) places patients at risk for hematuria and erythrocyte occlusion in Bowman’s space and renal tubules (erythrocyte casts present on biopsy) Further investigation is underway d Drugs 1 Aminoglycosides, particularly at high doses, are toxic to proximal tubular cells Once-daily dosing and vigilant dosing of medications can prevent some but not all cases Amphotericin B can cause AKI due to nephrotoxicity and vasoconstriction It is also associated with the development of a distal RTA Liposomal and colloid dispersion may decrease the incidence of severe AKI Vancomycin has been shown to be associated with ATN; however, the incidence has decreased since the preparation has changed Higher doses/levels may lead to increased incidence Hydroxylethyl starches (HES) are associated with significant AKI, and increased mortality, when used in the critically ill patients with sepsis as a volume expander Osmotic nephrosis is seen in the proximal tubules Contrast-induced AKI (CIAKI) or contrast-induced nephropathy (CIN): Contrast is both directly cytotoxic and decreases renal blood flow by vasoconstriction This usually is in combination with hypovolemia/hypotension e Proteins (immunoglobulin light chains—multiple myeloma): Notably, intravenous immunoglobulin (IVIG) therapy has been associated with proximal tubular osmotic nephrosis and possibly arterial vasoconstriction f Crystals (uric acid, acyclovir, methotrexate) Acute interstitial nephritis (AIN) a Allergic (drug-induced): The most common drugs include β-lactam antibiotics and sulfonamides Others include NSAIDs, PPIs, fluoroquinolones, vancomycin, and phenytoin b Infection: Bacterial and viral infections can lead to AIN by direct (pyelonephritis) and indirect (legionella) renal involvement c Infiltrative/autoimmune: Sarcoidosis, lupus, lymphoma/leukemia, and other systemic diseases can lead to interstitial inflammation 3 Glomerulonephritis a Intraglomerular inflammation with various timelines of progression and acuity of disease: Progression can be acute or rapidly progressive and severe requiring early diagnosis Pulmonary hemorrhage is a rare but feared complication (can be seen with ANCA or anti-GBM disease) Typically classified on the basis of pathology, that is, pauci-immune (ANCA vasculitis), anti-GBM, and immune complex (postinfectious, IgA, lupus nephritis, membranoproliferative, cryoglobulinemia, etc.) 4 Small vessel disease a Thrombosis: various pathophysiological processes including hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), preeclampsia, antiphospholipid antibody syndrome (APLAS), polyarthritis nodosa (PAN), scleroderma, and disseminated intravascular coagulopathy (DIC) b Cholesterol embolism C Postrenal (Obstruction and Hydronephrosis) Bilateral ureteral obstruction a Malignancy (including lymphadenopathy), aneurysmal compression, nephrolithiasis, or retroperitoneal fibrosis or hematoma Bladder/urethral pathology a Prostate enlargement (from benign prostatic hyperplasia or malignancy), Foley catheter or urethral obstruction, anticholinergic medications, and neurogenic bladder can all contribute to urinary obstruction and postrenal kidney dysfunction IV EVALUATION A History should focus on baseline kidney function, risk factors (see Sections V.A and V.B), including medications, comorbidities, and recent procedures or events B Physical examination to include vital signs and volume status (intravascular volume), bedside focused ultrasonography (e.g., inferior vena cava diameter), and signs/symptoms of vascular disease C Renal Function Evaluation BUN (nonspecific; increased with gastrointestinal bleeding, steroids, high-protein tube feeds, hypermetabolism—especially with proteins) Serum creatinine (Cr; affected by muscle mass, amputation, drugs, and volume status) 24-hour creatinine clearance (can also check if more rapid results are desired) Urine output (not sensitive) Biomarkers of AKI (NGAL, KIM-1, cystatin C, etc.) might provide future early AKI diagnosis; however, prospective trials are necessary before these are clinically applicable 6 Urine evaluation (Table 23.3) a Urinalysis and sediment 1 Prerenal: bland urinalysis and (transparent) hyaline casts 2 Intrinsic etiologies demonstrate: a Granular (muddy brown) casts (ATN secondary to ischemia or nephrotoxic injuries) can also be seen in the setting of glomerular disease b Pigmented casts (ATN secondary to hemoglobin or myoglobin or with hyperbilirubinemia) c RBC casts (glomerulonephritis) d WBC casts (pyelonephritis, AIN, or glomerulonephritis) e Urine eosinophils (AIN, cholesterol emboli, though not very sensitive or specific) 3 Postrenal: bland urinalysis RBCs with nephrolithiasis TABLE 23.3 The Berlin Definition of ARDS b Indices (electrolytes, osmolalities) 1 Prerenal injuries preserve renal salt and water balance mechanisms (initially), revealing FeNa 500 Intrinsic (e.g., ATN) renal injury disrupts such mechanisms resulting in FeNa >2% and FeUr >50% Note that diuretic use will prevent FeNa from maintaining utility [FENa = (UNa / PNa) / (UCr / PCr)]; [FEUrea = (UUr / PUr) / (UCr / PCr)] Note: FeNa may not be accurate in the setting of sepsis, CHF, cirrhosis, or pigment-induced injury 7 Serologic testing (primarily for glomerular etiologies): ANA, C3, C4, ANCA, antiGBM, cryocrit, HCV, HBV, SPEP, serum-free light chains, urine Bence Jones proteins, PLA2R Ab (membranous nephropathy) (involve nephrology to assist with workup and to assess need for RRT) Imaging studies a Renal ultrasound: can assess for hydronephrosis and estimate chronicity of kidney disease (small kidneys 30 Chronic kidney disease Diabetes mellitus Sepsis/septic shock (very high risk) Liver disease Congestive heart failure Lymphoma/leukemia Low baseline creatinine (less muscle mass—suggested to be a surrogate marker of overall health and age) B Exposures Nephrotoxic medications (see drugs listed in Section III) ACEi, ARBs NSAIDs Chronic HTN + shock (see SEPSISPAM study in Section VI) 5 Prolonged arterial cross-clamp (aorta, renal artery) Cardiopulmonary bypass Emergent surgery Blood product transfusion IV contrast (CIN)—risk from contrast exposure may be dose dependent Patients with hypovolemia are more susceptible to CIN VI MANAGEMENT OF AKI (Fig 23.1) A The management of AKI Stage I focuses primarily on (1) assessing and treating the etiology (see evaluation and risk factors), (2) removing and avoiding insults (see exposures above), (3) optimizing hemodynamics, and (4) managing complications If AKI Stage 2 to 3 develops, (5) check for renal dosing of medications and (6) assess for renal replacement therapy B Assessing and Treating Specific Etiologies Prerenal a Optimize hemodynamics and establish appropriate monitoring—including invasive monitors when appropriate b Fluid resuscitation: In general, crystalloid-based resuscitation with balanced salt solutions is preferred initially In patients with septic shock and hypoalbuminemia, albumin supplementation may have an improved effect on mortality (the ALBIOS trial) Increasing evidence suggests that large volumes of chloride-containing fluids (such as normal saline) may be associated with worse renal outcomes, and perhaps even worse mortality While these data need confirmation, it seems prudent to avoid the exclusive use of normal saline in most patients Patients with traumatic brain injuries and other CNS lesions that need hyperosmolar therapy are an exception and will need normal saline-based resuscitation c Managing blood pressure: Clinicians often raise the mean arterial pressure (MAP) target from the conventional 65 to 75–80 mmHg in patients who have a history of chronic hypertension The recent SEPSISPAM trial compared the use of elevated MAP goals with conventional goals in patients with septic shock and found that in a predefined cohort of patients with chronic hypertension, there was a decreased incidence of AKI and a decreased need for renal replacement therapies (but no mortality benefit) with higher MAPs However, targeting a higher MAP was also associated with an increased incidence of atrial fibrillation The primary methods for increasing MAP (fluids vs vasoactive drugs) probably effect outcomes and needs to be further investigated d Diuretics, mannitol, and renal-dose dopamine have not demonstrated any outcome benefits (but diuretics may be used to manage volume in the setting of hypervolemia) e Hepato-renal syndrome: possible role for midodrine and octreotide as temporizing measures Liver transplantation is the definitive therapy f Intra-abdominal hypertension/abdominal compartment syndrome: Medical therapy includes deep anesthesia, neuromuscular blockade, paracentesis, nasogastric and rectal decompression, minimizing/correction of positive fluid balance (including ultrafiltration/hemodialysis), vasopressors (for APP >60 mmHg) but surgical decompressive laparotomy may be required g Cardio renal syndrome: Focus should be on (1) optimizing cardiac output/perfusion and (2) decreasing venous congestion (judicious diuresis) h Renal artery stenosis: angiography and stent placement in selected circumstances (bilateral RAS with progressive AKI/CKD, refractory HTN, or recurrent pulmonary edema) Intrinsic renal injury a Acute tubular necrosis: Remove and avoid possible inciting agent(s) b Acute interstitial nephropathy: Consider steroids if no improvement with removal of the offending agent c Contrast induced nephropathy 1 Prevention a Minimize number of contrast exposures Use iso-osmolar and nonionic contrast b Hydration: Hydration with isotonic crystalloids is likely as efficacious as the use of bicarbonate drips c N-acetylcysteine (NAC): Some studies suggest the addition of NAC (600 or 1,200 mg PO twice daily for 2 days) plus hydration was superior to hydration alone for the prevention of CIN, while others have not shown a benefit Given the low-risk profile of NAC, its use may be considered for CIN prophylaxis d Glomerulonephritis: Steroids and immunosuppressive therapies may have a role Specialty consultation should be requested for the management of these patients 3 Postrenal a Relieve obstruction (e.g., ureteral stent placement, nephrostomy, Foley manipulation or placement) with close monitoring as complications can occur with rapid decompression (hemorrhagic cystitis) and hypotonic diuresis VII MANAGING COMPLICATIONS OF AKI: Renal replacement therapy (RRT) may be required for the management of the complications of AKI (see Section VIII) RRT is usually initiated when more conservative measures have proven ineffective A Volume Overload Minimize fluid administration Diurese (when possible or responsive) Favor intravenous over oral loop diuretics Use high-dose loop diuretics in the setting of oliguric AKI (general rule: starting IV lasix dose = 30 × Cr, i.e., if Cr: 4, use 120 mg IV lasix) The combination of a thiazide diuretic (such as chlorothiazide or metolazone) and a loop diuretic may be used if a loop diuretic alone is ineffective Diuretics have not been shown to have an outcome benefit in the setting of AKI, but their use may make management of volume status easier B Metabolic Acidosis: Kidney injury can cause a mixed gap and nongap metabolic acidosis (see Chapter 8) Acidemia is generally not treated symptomatically unless it is severe (pH 25 0 polymorphonuclear cells (PMN)/mm3 in ascites, in the absence of an intra-abdominal source of infection 2 Pathogenesis... The pathophysiology is thought to be due to the impairment of the hepatic clearance of cerebral toxins by the cirrhotic liver 1 Diagnosis is made on the basis of the patient''s symptoms and signs The severity of symptoms determines the grade of encephalopathy (see Table 24 .1)