Ebook Critical care handbook of the massachusetts general hospital (6/E): Part 2

(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.

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 renalfailure (ARF) Prior to this, no consensus was available on the diagnosis or degree ofseverity

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 (≥0.3mg/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 toimprove outcome staging and future clinical research (since RIFLE and AKIN did notcompletely 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 ofmanagement (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 patientsafter cardiopulmonary bypass with significant positive fluid balance resulting inhemodilution)

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 fromthe 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 areassociated with progression to CKD and increasing morality Future insults are much lesswell tolerated in these patient populations (e.g., additive effect of renal injuries overtime)

TABLE

Classification of Acute Kidney Injury

23.1

shading indicates actions that are equally appropriate at all stages whereas graded shading indicatesincreasing priority as intensity increases AKI, acute kidney injury; ICU, intensive-care unit (From

A Prerenal (Kidney Hypoperfusion)

1 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 veryhigh mortality

(diuretics, hypotension, NSAIDs, nephrotoxins)

CHF) resulting in decreased intravascular volume, other pathophysiologicalprocesses are likely involved Mechanisms likely include a combination ofvenous congestion (elevated CVP) and visceral edema resulting in

decreased abdominal perfusion pressure (APP) and elevated neuroendocrine(angiotensin, vasopressin) hormones, resulting in decreased renal perfusion

c Warfarin-related nephropathy (WRN) is a recently described entity where an

elevated INR (>3.0) places patients at risk for hematuria and erythrocyteocclusion in Bowman’s space and renal tubules (erythrocyte casts present onbiopsy) 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 preventsome but not all cases

2 Amphotericin B can cause AKI due to nephrotoxicity and vasoconstriction.

It is also associated with the development of a distal RTA Liposomal andcolloid dispersion may decrease the incidence of severe AKI

3 Vancomycin has been shown to be associated with ATN; however, the

incidence has decreased since the preparation has changed Higherdoses/levels may lead to increased incidence

4 Hydroxylethyl starches (HES) are associated with significant AKI, and

increased mortality, when used in the critically ill patients with sepsis as a

5 Contrast-induced AKI (CIAKI) or contrast-induced nephropathy (CIN):

Contrast is both directly cytotoxic and decreases renal blood flow byvasoconstriction This usually is in combination with

hypovolemia/hypotension

e Proteins (immunoglobulin light chains—multiple myeloma): Notably,

intravenous immunoglobulin (IVIG) therapy has been associated with proximaltubular osmotic nephrosis and possibly arterial vasoconstriction

f Crystals (uric acid, acyclovir, methotrexate)

2 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

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)

7 Serologic testing (primarily for glomerular etiologies): ANA, C3, C4, ANCA, anti-GBM, cryocrit, HCV, HBV, SPEP, serum-free light chains, urine Bence Jonesproteins, PLA2R Ab (membranous nephropathy) (involve nephrology to assist withworkup and to assess need for RRT)

8 Imaging studies

a Renal ultrasound: can assess for hydronephrosis and estimate chronicity of

kidney disease (small kidneys <10 cm suggest dysplasia or chronic disease).Color Doppler flow can evaluate perfusion and assess for thrombosis or renalartery stenosis (RAS)

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 ahistory of chronic hypertension The recent SEPSISPAM trial compared the use

of elevated MAP goals with conventional goals in patients with septic shock andfound that in a predefined cohort of patients with chronic hypertension, there was

a decreased incidence of AKI and a decreased need for renal replacementtherapies (but no mortality benefit) with higher MAPs However, targeting ahigher MAP was also associated with an increased incidence of atrial

fibrillation The primary methods for increasing MAP (fluids vs vasoactivedrugs) 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 ofhypervolemia)

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

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, orrecurrent pulmonary edema)

d Glomerulonephritis: Steroids and immunosuppressive therapies may have a

role Specialty consultation should be requested for the management of thesepatients

3 Postrenal

a Relieve obstruction (e.g., ureteral stent placement, nephrostomy, Foley

manipulation or placement) with close monitoring as complications can occurwith 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 usuallyinitiated when more conservative measures have proven ineffective

A Volume Overload

1 Minimize fluid administration

2 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 IVlasix dose = 30 × Cr, i.e., if Cr: 4, use 120 mg IV lasix) The combination of athiazide diuretic (such as chlorothiazide or metolazone) and a loop diuretic may beused if a loop diuretic alone is ineffective Diuretics have not been shown to have anoutcome benefit in the setting of AKI, but their use may make management of volumestatus 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 <7.15) Sodium bicarbonate infusions may be used for severe metabolic acidemia

ventilation See Chapter 8 for details of symptomatic management of academia The use

of bicarbonate may be considered therapeutic if the primary reason for acidosis is renalbicarbonate wasting

C Electrolyte Abnormalities

1 Hyperkalemia (assess for EKG changes, though this is not a sensitive measure to

predict subsequent arrhythmias—do not delay treatment of marked hyperkalemiabecause ECG changes have not yet appeared)

a Antagonism of the effects of potassium (membrane stabilization)

1 Calcium: Calcium gluconate (or calcium chloride) acts as a physiologic

antagonist of potassium at the cell membrane 10 mL of a 10% calciumgluconate solution should be used initially If calcium chloride is usedinstead, remember that it provides about three times the amount of calciumper volume compared with calcium gluconate

be dose limiting, although initial studies that used high-dose albuterol didnot report significant tachycardia

3 Increasing blood pH: If pH <7.3, an ampule (50 mEq) of NaHCO3 can be

given IV If possible (within limits of lung-protective ventilation) minuteventilation should be increased

c Removal of potassium from the body

1 Renal replacement therapy: See Section VIII.

2 Ion-exchange resins: Kayexalate (sodium polystyrene sulfonate) can

effectively remove potassium from the gut However, it is not effectiveacutely—may require 12 to 24 hours for effect In addition, there are

multiple reports of intestinal necrosis with its use, and it should therefore

be used with caution and should be avoided in the setting of altered bowelfunction New potassium-binding agents will likely be available soon

E Coagulation Abnormalities: usually due to uremic platelet dysfunction Management is

discussed in Chapter 24.

F Anemia: multifactorial etiology common In the absence of active bleeding or ongoing

coronary ischemia, it is recommended that hemoglobin values as low as 7 g/dL not be

G Infectious complications are a major cause of death in patients with AKI Both uremia

and renal replacement therapy (particularly continuous RRT) blunt the ability of patients

to mount an effective response to infections, and typical signs (such as fever) may bemasked

H Uremic pericarditis occurs for unknown reasons and can lead to cardiac tamponade It is

an indication for RRT

I Decreased Drug Elimination: Assess medications for renal clearance and adjust doses

accordingly It should be kept in mind that in evolving AKI, the calculated creatinineclearance may be inaccurate and typically an overestimate

J Nutritional support is an important component of the management of critically ill

patients with AKI—see Chapter 11 for details.

VIII RENAL REPLACEMENT THERAPY (RRT): Can be classified into intermittent or

continuous methods Prototypical examples are intermittent hemodialysis (IHD) or continuousvenovenous hemofilteration (CVVH), although other modalities are occasionally used IHD isused for hemodynamically stable patients whereas CVVH may be more appropriate for

patients who are hemodynamically unstable, have intracranial hypertension, or are

encephalopathic secondary to cirrhosis The choice between intermittent versus continuousRRT is often based on institutional experience and culture Although continuous RRT

intuitively seems to be preferable when dealing with hemodynamically unstable, critically illpatients, the data do not support a robust benefit for continuous RRT over intermittent modes.Although several single-center trials revealed possible benefit of high-intensity CVVH,

multicenter RCTs have revealed no such results In some countries, CVVH is initiated andmanaged by critical care physicians, while in the United States it is much more common fornephrologists to be responsible for managing patients on CVVH In either case, close

communication between the ICU and nephrology teams is essential for optimum management

A Indications: The classic indications for RRT initiation are listed below Early initiation

of RRT in critically ill patients has been recommended by some authorities—however,the data do not show improved outcomes for early CVVH compared with conventionaluse

membrane from a higher concentration (in patient’s blood) to a lower concentration (in the dialysis fluid)

B: Hemofiltration (which is the mechanism used in CVVH) achieves solute clearance by convection

across a semipermeable membrane from a higher hydrostatic pressure (in a patient’s blood) to a lowerhydrostatic pressure (in the hemofiltrate) (Modified from Forni LG, Hilton PJ Continuous hemofiltration

4 Complications: Hypotension (much less common than with IHD), infection, citrate

toxicity (in the setting of poor hepatic function), complications associated withanticoagulation (may be required with HCO3)

D Access for RRT: In the acute setting, double-lumen temporary hemodialysis catheters

(14 Fr) are commonly used The catheters are typically inserted percutaneously using theSeldinger technique and ultrasound guidance The right internal jugular vein is the mostfrequent site of cannulation, often preferred for optimal catheter function However, alarge, randomized study comparing internal jugular with femoral site insertions found thatthe rate of catheter colonization and bloodstream infection was equivalent between the

jugular and femoral sites in nonobese, bed-bound, critically ill patients The subclavian

site is often avoided due to concerns for subclavian vein stenosis, which can limit futuresuccess of arteriovenous fistulas and grafts.

United States Their in-hospital mortality is more than 50% The most common reasons for ICU admission are variceal hemorrhage, sepsis, and encephalopathy.

A Pathophysiology Chronic hepatic fibrosis leads to distortion of the hepatic vasculature,

increased vascular resistance, and elevated portal venous pressures Impaired hepatic

function, coupled with elevated portal venous pressures, lead to end-stage liver disease

and the systemic effects of cirrhosis: encephalopathy, hyperdynamic circulation, renal dysfunction, ascites, and variceal hemorrhage.

B MELD (Model for End-Stage Liver Disease) is a prognostic scoring system initially

developed to predict survival in cirrhotic patients undergoing elective TIPS (transjugularintrahepatic portosystemic shunt) placement It has been validated as a predictor forsurvival in patients with liver disease and is the basis for ranking patients on the liver

transplantation wait list MELD = 9.57*In[Cr] + 3.78*In[total bilirubin] + 11.2*

In[INR] + 6.43 The Child-Turcotte-Pugh (CTP) score was originally developed to predict surgical risk in cirrhotic patients It is based on the concentrations of total bilirubin and serum albumin as well as the INR, degree of ascites, and degree of hepatic encephalopathy The subjective components of the score limit its predictive capacity General ICU prognostic scores such as the SOFA (Sequential Organ Failure Assessment) and APACHE (Acute Physiology and Chronic Health Evaluation) scores have been

shown to have greater discriminatory power for predicting mortality in cirrhotic patientswho are admitted to the ICU

C Variceal Hemorrhage Endotracheal intubation for airway protection, volume

resuscitation, and the administration of blood component therapy should be carried out

as needed on the basis of the patient’s condition and laboratory values Standard therapy

for acute variceal hemorrhage consists of the administration of a splanchnic vasoconstrictor and prophylactic antibiotic along with endoscopic intervention.

effects including cardiac and peripheral ischemia It can only be usedcontinuously at the highest effective dose for 24 hours It should be accompanied

by nitroglycerin administration to minimize the potential harmful effects ofvasopressin

4 TIPS (transjugular intrahepatic portosystemic shunt) is indicated for patients who

have uncontrollable or recurrent variceal hemorrhage despite pharmacologic andendoscopic therapy

D Spontaneous Bacterial Peritonitis (SBP) is an infection of the ascites in the absence of

a primary intra-abdominal focus SBP accounts for 10% to 30% of bacterial infections inhospitalized cirrhotic patients The in-hospital mortality for the first episode ranges from10% to 50%

1 Diagnosis As signs and symptoms may be absent, diagnostic paracentesis should

be performed for cirrhotic patients with ascites admitted to the hospital Thediagnosis is made on the basis of the presence of >250 polymorphonuclear cells(PMN)/mm3 in ascites, in the absence of an intra-abdominal source of infection

2 Pathogenesis SBP is caused by the pathologic translocation of intestinal bacteria

due to increased intestinal permeability, impaired immunity, and intestinal bacterialovergrowth in cirrhotic patients Patients may also develop SBP following

gastrointestinal hemorrhage or endoscopic procedures In the majority of cases,enteric gram-negative bacteria are isolated from the ascites Less frequently gram-

positive cocci or anaerobes may be isolated Polymicrobial SBP is rare and the

presence of multiple bacteria in ascites may indicate bowel perforation

3 Management Empiric antibiotic therapy should be initiated immediately following

the establishment of the diagnosis Treatment consists of Cefotaxime 2 g every 8 hours Alternatively, patients with SBP can be treated with Ofloxacin 400 mg twice per day in the absence of (a) prior exposure to quinolones, (b) shock, (c) grade II or

more severe hepatic encephalopathy, and (d) serum creatinine >3 mg/dL

Vancomycin should be added if MRSA is suspected Antibiotic therapy should be

continued for 5 days If PMN count doesn't decrease by 25% within 48 hours ofinitiating therapy, the antibiotic should be changed Patients with a history of SBP or

with esophageal hemorrhage should be treated prophylactically with Norfloxacin Adjuvant therapy with albumin (1.5 g/kg on day 1 and 1 g/kg on day 3) may prevent

worsening of renal function and improve survival in patients with cirrhosis and SBP

E Hepatic Encephalopathy develops in up to 50% of patients with cirrhosis and is

associated with increased mortality Up to 80% of episodes are precipitated by infection

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) Serum ammonialevels are elevated but do not correlate with the severity of the disease Intracranialhypertension (ICH) is rare in patients with hepatic encephalopathy secondary tochronic liver disease unlike in the setting of ALF

c Rifaximin 400 mg po tid is added if there is no improvement after 48 hours.

d Neomycin has been associated with ototoxicity and nephrotoxicity It is used in

patients who are unresponsive to lactulose and intolerant of rifaximin Oralvancomycin and oral metronidazole have also been used

F Ascites is the most common complication of cirrhosis leading to hospitalization The

presence of ascites is suspected on the basis of history and physical exam and confirmed

by abdominal ultrasound (US) and paracentesis Physical exam findings include bulging abdomen and dullness to percussion along the flanks Approximately 1,500 mL of fluid

must be present before flank dullness is detected

1 Differential diagnosis The most common etiology of ascites is cirrhosis and portal

hypertension Other potential causes include heart failure, cancer, nephroticsyndrome, and pancreatitis

2 Diagnostic paracentesis should be performed on all patients presenting with ascites.

The fluid should be analyzed for cell count, differential, total protein, and albumin

I Hepatopulmonary Syndrome (HPS) can be found in 10% to 30% of patients with

cirrhosis It is due to pulmonary vasodilation and arteriovenous shunting, giving rise tohypoxia

1 Signs and symptoms may include shortness of breath, cyanosis, clubbing, platypnea,

and orthodeoxia

2 Diagnosis is based on the presence of liver disease, an A-a gradient ≥15 mmHg

(≥20 mmHg if age is >64), and the demonstration of intrapulmonary shunting by

3 Management In the absence of OLTx, the 5-year survival is 23% Most patients

with PaO2 <60 mmHg die within 6 months There is no effective medical therapy forHPS Intra-arterial coil embolization of pulmonary arteriovenous fistulae has beenshown to improve hypoxia OLTx is the only effective treatment for HPS

J Portopulmonary Hypertension (PoPH) is found in approximately 6% of candidates for

liver transplantation It is defined as mean pulmonary artery pressure (mPAP) >25 mmHg in the setting of a pulmonary artery occlusion pressure (PAOP) <15 mmHg and pulmonary vascular resistance (PVR) >240 dyn·s·cm –5 in a patient with portal

hypertension

Liver transplantation in a patient with PoPH and an mPAP >35 mmHg is associated

with significant mortality Screening for PoPH is conducted with TTE In patients with anestimated right ventricular systolic pressure (RVSP) >40 to 50 mmHg, right heart

catheterization (RHC) is conducted to confirm the diagnosis of PoPH Patients withPoPH are treated with pulmonary vasodilators to reduce the mPAP below 35 mmHg

Therapeutic options include sildenafil (phosphodiesterase inhibitor), bosentan (endothelin receptor antagonist), and epoprostenol (intravenous prostacyclin) Nitric oxide may be used in intubated patients Patients with mPAP <35 mmHg on pulmonary

vasodilator therapy are candidates for liver transplantation as long as right ventricularfunction is preserved and PVR is <400 dyn·s·cm-5

II ACUTE LIVER FAILURE (ALF) has an incidence of less than 10 cases per million

persons per year It most commonly occurs in previously healthy adults and presents with hepatic dysfunction, coagulopathy, and encephalopathy It is associated with a mortality of up

g/day Physical examination should focus on the determination of the degree of encephalopathy as well as the presence of stigmata of chronic liver disease Laboratory analysis should include chemistries, complete blood count, coagulation profiles, and

arterial blood gas analysis Serum glucose should be monitored as patients may develophypoglycemia Viral serologies as well as screens for acetaminophen and other toxins

D Management The condition of a patient with ALF can deteriorate rapidly It is essential

to consult a liver transplantation service as soon as possible to determine theappropriateness of listing the patient for transplantation For most etiologies of ALF,management is supportive (Table 24.2)

II encephalopathy should be treated with oral or rectal lactulose (30–45 mL

administered 3–4 times per day to produce 2–3 soft stools daily) Patients withGrade III or IV encephalopathy should be intubated for airway protection

of ALF The pathogenesis is not completely understood but involves elevations in theserum ammonia concentration Intracranial pressure (ICP) monitoring is

controversial due to coagulopathy and the risk of intracranial hemorrhage as well asquestionable mortality benefit In the presence of an ICP monitor, ICP should bemaintained below 20 mmHg Cerebral perfusion pressure (CPP) should bemaintained above 50 to 60 mmHg A number of interventions can be used to reduceICP

acetaminophen toxicity, hepatitis A, or shock liver is associated with a >50% transplant-transplant-free survival

F Liver Transplantation Orthotopic liver transplantation (OLTx) may be an option for

therapy in ALF Early consultation with the liver transplant (LT) surgical team should be

carried out to determine the suitability of the patient The King’s College Hospital Criteria were developed to identify patients with ALF who would benefit from OLTx.

They are based on the etiology of ALF as well as clinical characteristics of the patient.They have been found to have a sensitivity and specificity of 69% and 82% to 92%,respectively A number of studies have shown positive predictive values of 70% to

100% and negative predictive values of 25% to 94% OLTx is contraindicated in

patients with hemodynamic instability requiring vasopressors, known malignancy outside

of the liver, and advanced age

III POSTOPERATIVE MANAGEMENT OF THE LT PATIENT

involved in the patient’s care As there can be significant variation between transplantprograms in terms of types of donors utilized and the severity of illness within thewaitlist candidate population, there are often center-specific practices for postoperativemanagement of an LT recipient Thus, overall, it is of paramount importance that there be

an open line of communication at all times, with a primary point of contact establishedbetween the critical care team and the transplant service in advance in order to expeditedecision making and care of this patient population

B Survival Rates Current estimates of the 1-year unadjusted survival rate for an LT

recipient are nearly 90%

C Donor Factors Consideration must be given to donor factors that influence graft function

in the immediate postoperative period Given the disparity in organ supply and demand,there has been increased application of expanded criteria donors (ECD) Indeed, the use

of certain ECD liver grafts may result in slower initial graft function and/or portend ahigher risk of primary nonfunction or vascular/biliary complications Although thedefinition of these more marginal grafts may vary based on institution, they are generallythought to encompass donors of advanced age (>60 years old), higher degree of steatosis(>30% macrosteatosis), donation after cardiac death (vs donation after brain death), andsplit LTs Additional donor factors to consider as they relate to immediate graft functionare donor instability prior to procurement, cold ischemia time, and warm ischemia time

D Intraoperative Factors Sign-out from the anesthesia and surgical team should include

occurrence of hypotension, vasopressor use, degree of acidosis, urine output,intraoperative bile production, and technical concerns that may affect outcome

E Systems-based Considerations for Postoperative Management The majority of LT

patients are admitted to the Intensive Care Unit (ICU) in the initial postoperative periodfor a typical 24-to-48-hour stay

2 Analgesics As the majority of analgesics are metabolized and excreted by

the liver or the kidney, poor liver graft function or concomitant renal failuremay impact clearance of these medications

recovers quickly following implantation of the liver, encephalopathy can linger

in the postoperative period necessitating standard precautions for patients withalterations in mental status With any change in mental status, in addition toroutine workup, attention should be paid to reevaluation of graft function as well

as electrolyte and glucose levels, which may be directly affected by hepaticfunction Antipsychotics should be avoided if possible as they are oftenhepatotoxic; however, if needed, low-dose haldol or quetiapine may be used

2 Cardiovascular

a Preoperative baseline Preoperative cardiovascular testing is uniformly used

for the waitlisted population, but may vary in type depending on institutionalpreference Cardiovascular testing should be reviewed in all patients in whom itwas performed Special consideration should be given to those with knowncoronary artery disease, a history of nonalcoholic steatohepatitis and diabetes,valvular stenosis or insufficiency, and known portopulmonary hypertension (seeI.J above)

b Perioperative hypotension may result postoperatively given the risk for

bleeding, as well as the fact that vasodilatory and hyperdynamic state of liverfailure often takes times to resolve post-LT Unremitting acidosis or vasopressorrequirement should warrant further investigation

c Venous pressures Increased venous pressures may lead to hepatic congestion

and graft dysfunction due to outflow obstruction Invasive monitoring can helpdistinguish cardiac from vasodilatory hypotension and guide appropriate use ofinotropic agents, vasopressors, and fluid administration (see II.E.5.a below)

d Perioperative hypertension may be seen in the post-LT patient with adequate

graft function who may have inadequate analgesia

e Atrial fibrillation Post-LT atrial fibrillation may result due to significant

perioperative fluid shifts and electrolyte fluxes If possible, it should be managedwithout the use of amiodarone due to this medications potential for

hepatotoxicity

3 Respiratory

a Weaning and extubation Early weaning and extubation from the ventilator is

recommended in post-LT patients in order to decrease risk of infection,deconditioning, and prolonged recovery Care should be taken for those patientswith hepatopulmonary syndrome (HPS), as the hypoxemic state can persist in thepostoperative period (see I.I above and II.E.3.c below)

b Ventilator management In optimizing ventilator settings, given theoretical risks

of decreased venous return and hepatic outflow, positive end-expiratory pressure(PEEP) should be limited up to 15 cm of H2O, which has been shown to notimpair overall hemodynamics in the post-LT patient

c HPS The postoperative management of the patient with HPS is difficult, as the

timing of resolution of hypoxemia is variable and can take up to 12 months toreturn to baseline A lowered expectation of a resting O2 saturation is needed inthe postoperative period Extubation of the HPS patient postoperatively should

be undertaken after careful assessment of the patient The clinical

d Hypoxemia Other etiologies for post-LT hypoxemia include the presence of

ascites, atelectasis, and pleural effusion, causing restrictive lung disease Allpatients should be optimized with adequate analgesia, rigorous chest

physiotherapy, and incentive spirometry Thoracentesis may be considered for ahydrothorax-limiting extubation, but should be approached with caution given thecoagulopathy and thrombocytopenia in the immediate postoperative period.Placement of an indwelling chest tube is avoided given the infectious risk

4 Gastrointestinal

a Liver function tests There is a typical rise in transaminase levels due to

hepatocellular ischemia/reperfusion injury often peaking within 24 hours

Persistent rise, however, may indicate ongoing ischemia Laboratoryabnormalities should be communicated with the surgeon as they may promptfurther investigation with Doppler US Alkaline phosphatase and bilirubin risemay indicate biliary obstruction

b Synthetic function laboratory tests Platelet count, prothrombin international

normalized ratio (INR), fibrinogen level, and activate partial thromboplastintimes (aPTT) are markers of coagulation, and abnormalities may reflectinsufficient liver synthetic function Please see below for additional hematologicconsiderations (see II.E.7 below)

be beneficial in those patients with rising lactate levels secondary to decreasedconsumption of lactate due to decreased liver gluconeogenesis in the

transplanted graft Thus, generally, 5% dextrose with 0.45% normal saline isused unless the recipient has a serum sodium of <130 mEq/L at which point 5%dextrose with 0.9% normal saline may be more appropriate If volume expansion

is needed, colloid solutions, or if indicated, packed red blood cells should beconsidered

b Pretransplant renal dysfunction Present in up to 25% of recipients If renal

replacement therapy is needed in the immediate postoperative period, CVVH isthe preferred route Reinstitution of standard hemodialysis posttransplant shouldnot be attempted until the patient has been stabilized Transplant nephrology isoften consulted to aid in the management of dialysis, as well as any electrolyteabnormalities related to renal dysfunction As fresh LT patients will not

metabolize citrate in the setting of liver dysfunction, dialysis replacement fluidshould be bicarbonate based in most cases Even in patients without renaldysfunction prior to LT, some degree of acute kidney injury (AKI) can be

concomitant oliguria or anuria, assessment of intravascular status by CVPmeasurement will allow avoidance of over- or underresuscitation

c Electrolytes Abnormalities should be appropriately addressed promptly.

1 Hyponatremia—Sodium should be corrected carefully keeping in

consideration that the post-LT patient should be kept euvolemic ormarginally hypovolemic in the early postoperative period

2 Hypocalcemia—Calcium should be optimized as it is an important element

in the coagulation cascade, which may already be challenged in the earlypost-LT period

3 Hypophosphatemia Phosphate is important in cellular energy metabolism,

and deficiency can have respiratory, cardiac, neurologic, and endocrinesystem consequences

4 Hypomagnesemia Cirrhotic patients often have decreased magnesium,

which is often further depleted through operative blood loss as well ascertain immunosuppressants (i.e., tacrolimus)

6 Endocrine

a Glucose levels Hyperglycemia may be present due to postsurgical stress and

use of steroid therapy for immunosuppression This should be managed usingICU protocols and may require insulin drips with minimization of dextrose-containing fluids If hypoglycemia is noted, graft US with Doppler should beperformed as this may be indicative of graft dysfunction

7 Hematologic

a Monitoring In the early post-LT period (first 24–48 hours), patients should

receive serial complete blood count tests and coagulation labs to assess forbleeding and hepatic synthetic function Any significant changes should promptnotification of the transplant team, and triggers for transfusion should be clarifiedfor each patient

1 General Considerations

a A gradual decline of the INR should be expected with a functioning liver

and should not require further fresh frozen plasma (FFP), thus a risingINR should prompt concern for early graft dysfunction and considerationfor repeat Doppler US and notification of the transplant team

b More aggressive correction of an INR with FFP should be undertaken in

the setting of continued drops in the hematocrit

c Cirrhotic patients can often demonstrate a significant degree of

thrombocytopenia due to splenomegaly and sequestration, which is onlyexacerbated by the immunosuppressive and antiviral/-biotic medicationsadministered Consideration for administration of platelets should begiven for platelet counts <50 for the first 12 hours postoperatively andshould be continued beyond 12 hours only if clinical signs of bleedingexist The latter must be balanced with the understanding that a numericalincrease in peripheral platelet counts with continued platelet transfusions

a Bacterial prophylaxis Standard perioperative antibacterial prophylaxis is

utilized, with consideration for organism-specific antibiotics of longer duration

if the recipient has an infectious history or if the donor carries an infectioushistory

b Viral prophylaxis Herpes simplex virus (HSV) reactivation is the most common

opportunistic viral infection in the immediate posttransplant period (first month)and can be reduced by prophylactic antiviral administration Additional

considerations include mismatch of cytomegalovirus (CMV)-seronegativerecipients with grafts from CMV-seropositive donors as these patients benefitfrom antiviral therapy In patients for lower risk of CMV, antiviral administrationcan be pursued, or alternatively, monitoring by CMV polymerase change reactioncan be done and therapy instituted if the virus is detected

c Fungal prophylaxis Pneumocystis jirovecii infection can be prevented by

routine use of prophylactic trimethoprim-sulfamethoxazole post-LT Additionalwidespread use of antifungal prophylaxis is not standard practice; however,special consideration should be given to patients requiring retransplantation,reoperation, renal replacement therapy pre- or posttransplant, and thosereceiving transplant for fulminant hepatic failure

9 Nutrition Enteral nutrition is preferred to the parenteral route as it is associated with

a lower incidence of wound infections and complications and should be started assoon as possible postoperatively Early enteric feeding aids in nourishing enterocytesand thus decreasing bacterial translocation in addition to stimulating enterohepaticcirculation Validated data on the use of probiotics in this patient population islacking Special consideration for nasal gastric or nasal jejunal tube feeds should begiven for those patients with prolonged intubation or with encephalopathy and at riskfor aspiration

10 Immunosupression Immunosupressive medications will be managed by the

transplant team, and typical regimens include triple therapy with a calcineurininhibitor such as tacrolimus or cyclosporine, an antiproliferative agent such asmycophenolate mofetil, and a steroid such as prednisone

11 Tube/Lines/Drains

a Surgical intra-abdominal drains Decisions on management of surgical drains

are made by the surgical team and are dependent on the volume and type of fluiddraining Any significant change in drainage (such as increasing bilious drainage

or bloody drainage) should be immediately communicated to the surgical team.Patients with long-standing portal hypertension and ascites prior to transplantwill often have high serous output from the surgical drains until the portalhypertension begins to resolve

b Nasogastric tube (NGT) The standard LT patient should have NGT removal

once they are alert, awake, and able to take their medications orally Patientswith roux-en-y creation for biliary drainage will often have an NGT in thepostoperative period

c Foley catheter Although stable patients can have their foley removed on

postoperative day 2 in order to decrease the risk of catheter-associated urinarytract infection, complex or debilitated patients or those with renal dysfunctionmay require bladder drainage for longer periods of time

d Endotracheal tube (ETT) and invasive vascular lines ETT and invasive

vascular lines should be removed as soon as clinically indicated in order todecrease risk of ventilator-associated pneumonia (see II.F.4.b) and central line–associated blood stream infection

12 Prophylaxis

a Thromboprophylaxis Definitive data on the use of routine prophylactic

chemoprophylaxis for deep venous thrombosis or pulmonary embolism iscurrently lacking; however, mechanical thromboprophylaxis is often employed.Post-LT patients are often thought to be in a hypocoagulable state since

coagulation may take time to normalize as it takes the new liver time to makesufficient coagulation factors and for thrombocytopenia to resolve

2 Vascular complications

a Hepatic artery thrombosis (HAT) or stenosis HAT occurs in approximately

3% of post-LT patients and is the most common technical complication EarlyHAT (within 1 week of LT) may clinically result in rapid onset hepatic failure,sepsis, fever, altered mental status, and coagulopathy with laboratory studiessuggestive of transaminitis Delayed diagnosis can result in peritonitis due tobiliary necrosis as the bile duct receives its blood supply from the hepatic artery

b Portal vein thrombosis (PVT) or stenosis PVT occurs in 1% to 3% of post-LT

patients and may clinically result in ascites, sepsis secondary to bacterialtranslocation due to intestinal congestion, gastrointestinal bleeding, and rapidonset hepatic failure with laboratory studies suggestive of transaminitis Graft

US with Doppler is preferable to CTA or MRA, which have decreasedsensitivity If portal vein stenosis is of concern, percutaneous transhepaticportography may be used to measure pressures across the area of concern(generally considered to be significant if the gradient is >5 mmHg) Treatment ofearly PVT in the early post-LT period may necessitate operative exploration andvascular reconstruction Often, portal vein stenosis can initially be managed withangioplasty and stenting

c Hepatic vein and inferior vena cava (IVC) anastomosis complications These

complications are relatively uncommon, resulting from kinking, thrombosis, orstenosis and often clinically present with dependent edema and/or ascites due toimpeded hepatic outflow Similar to other vascular complications, diagnosticstudies include graft US with Doppler Depending on the degree of outflowobstruction, hepatic outflow anastomosis complications can often be managedthrough interventional methods including angioplasty and/or stenting

abdominal drains, and possibly antibiotics

drainage, biliary stents, possible reconstructive surgery, use of intra- 2 Biliary stricture Biliary stricture clinically may present with jaundice,

pruritus, or as cholangitis with laboratory studies suggestive of increased

to checking drain bilirubin levels, graft US with Doppler should beperformed to assess for concomitant HAT or stenosis ERCP can be bothdiagnostic and therapeutic Treatment is similar to that of biliary leak

Surgical conversion from a biliary duct-to-duct anastomosis to roux-en-ydrainage can also be considered

4 Infectious complications These are the most common cause of postoperative

morbidity and mortality and include bacteremia, fungemia, pneumonia, wound

infection, urinary infection, and Clostridium difficile colitis given the

immunosuppressed state of the transplant recipient Prevention (see InfectiousDisease section [II.E.8] above regarding antibiotic prophylaxis) as well as sourcecontrol/treatment form the main principles in management and can be complimentedwith reductions in immunosuppression when indicated

a Line- and tube-related infections Catheter-associated urinary tract infections,

central line–associated blood stream infection, and ventilator-associatedpneumonias can be minimized by removal of invasive lines and tubes asexpeditiously as possible

b Pneumonia Early onset hospital-acquired pneumonia within 7 days of LT occurs

in approximately 15% of patients and is associated with prolonged ventilation(>48 hours) Early diagnostic bronchoscopy is favored over empiric treatmentwhenever possible

c Clostridium difficile colitis Clostridium difficile colitis occurs in

approximately 19% of liver recipients, compared with 1% of patients withouttransplants, and is likely due to empiric antibiotic use, immunosuppression, andincreased nosocomial exposure These patients should be managed with closeattention given to consequences on allograft function induced by diarrhea andassociated hypovolemia and hypotension, as well as electrolyte abnormalities

5 Renal Complications

a Definition AKI can be stratified on the basis of the Risk, Injury, Failure, Loss,

and End-Stage Kidney Disease (RIFLE) criteria or Acute Kidney Injury Network(AKIN) staging system, both of which use creatinine and urine output as criteria

1 In the post-LT patient, AKI has been associated with reduced patient and

graft survival in the perioperative and long-term periods

2 Baseline creatinine levels in patients with cirrhosis can lead to

overestimation of renal function due to lower creatinine production ratessecondary to malnutrition and decreased muscle mass in these patients

b Etiology and risk factors Post-LT AKI is often multifactorial and includes

intraoperative factors such as hypotension, bleeding, vena cava clamping,increased transfusion requirement, and ischemia/reperfusion injury

c Management Hemodynamic optimization and initiation of renal support may be

necessary in the management of post-LT AKI Consideration for modification ofimmunosuppression regimen to decrease calcineurin inhibitors as well as

decreasing potentially nephrotoxic prophylactic medications should also beperformed in patients with post-LT AKI

6 Early immunological complications

rejection, is a rare complication that usually occurs within minutes to hours of

LT In this case, rejection is secondary to preformed recipient antibodies that arepresent at the time of LT depositing in the newly transplanted graft, resulting inactivation of the complement and coagulation cascade causing subsequent graftthrombosis and necrosis This is typically secondary to ABO incompatibility andattempts of plasma exchange, intravenous gamma globulin, B-cell depletiontherapy, and splenectomy can be performed, however, if acute hepatic failureensues, emergent retransplantation may be necessary

b Acute cellular rejection (ACR) ACR typically occurs within 6 weeks of LT

and is secondary to cytotoxic and helper T-cell activation The clinicalmanifestation of ACR is usually nonspecific, but laboratory studies typicallymanifests with increasing alanine aminotransferase (ALT) followed byelevations in AST and bilirubin After other etiologies of laboratoryabnormalities are ruled out, diagnosis is typically made through biopsy

Management typically involves optimization of immunosuppressive therapy formild ACR, steroid pulse therapy for moderate ACR, and adjunctive therapyutilizing T-cell depletion therapy for severe ACR

7 Bleeding Post-LT bleeding may be secondary to insufficient surgical hemostasis or

more commonly due to coagulopathy and thrombocytopenia

a Coagulopathy may occur secondary to dilution associated with massive

transfusion, inadequate replacement of components, hypothermia,hyperfibrinolysis, or inadequate hepatic synthetic function

Coagulopathy in the critically ill covers a range of abnormal states of coagulation It is defined as theblood’s inability to clot normally.

I COAGULOPATHIES AND HEMOSTATIC ABNORMALITIES IN THE CRITICALLY

ILL

A Disseminated Intravascular Coagulation (DIC) is defined by the International Society

on Thrombosis and Hemostasis as an “acquired syndrome characterized by theintravascular activation of coagulation with loss of localization arising from differentcauses.” There are many potential causes of DIC (Table 25.1)

1 Pathophysiology of DIC is based on the following main mechanisms (Fig 25.1).

First, bacterial exo- and endotoxins (LPS) as well as inflammatory cytokines inducetissue factor-expression on circulation monocytes and endothelial cells This results

in a loss of localization of thrombin generation to the site of endothelial injury Tissuefactor-expression on monocytes is further enhanced by the surfaces of extracorporealassist devices such as dialysis, ECMO, and ventricular assist devices (VADs)

However, tissue factor-expression on monocytes cannot be detected by standardplasmatic coagulation testing but by whole-blood viscoelastic testing

(ROTEM/TEG) Second, the early phase of DIC is characterized byhypercoagulability (increased clot firmness due to acute phase reaction with highfibrinogen levels and high clot firmness in viscoelastic testing), consumption ofphysiologic coagulation inhibitors (antithrombin and protein C), platelet dysfunction,and inhibition of fibrinolysis (up-regulation of plasmin activator inhibitor-1 [PAI-1]).This results in thrombosis of the microcirculation and multiple organ failure Finally,when coagulation factors and fibrinolytic inhibitors are consumed, hypocoagulationand secondary fibrinolysis can result in severe bleeding Early detection of

blood impedance aggregometry on admission at the ICU are associated with worseoutcomes

Trauma Vascular abnormalities

Burns (extensive) Peritoneovenous shunt Extracorporeal circulation (e.g., ECMO) Intra-aortic balloon pump

infection, and sepsis, finally resulting in microthrombosis, multiple organ failure, and microvascularbleeding

2 Clinical features of DIC include hemorrhage from operative or traumatic wounds,

oozing from venipuncture sites, petechiae, and ecchymosis Micro and macrovascular thrombosis can lead to organ failure

5 Treatment of DIC is aimed at correcting the underlying cause, blood product

transfusion when indicated, and pharmacologic treatment (Table 25.2) Bloodproducts should be transfused to correct for active bleeding or in preparation for life-saving procedures Fibrinogen levels should then be corrected to 150 to 200 mg/dL.Platelet transfusion should be considered in patients who are actively bleeding andwho have a platelet count of <50,000/mm3 However, platelet transfusion should beconsidered carefully since it may aggravate multiple organ failure and result insecondary bacterial infections In nonbleeding patients, the threshold for platelettransfusion should be 10,000–20,000/mm3 Other blood components such as FFP andPRBC should be transfused only in patients with active bleeding or at high risk ofbleeding

a Pharmacologic treatment depends on the type of DIC and includes

anticoagulation or antifibrinolytics The balance of coagulation and fibrinolysiscan be further characterized with point-of-care testing (ROTEM/TEG andwhole-blood impedance aggregometry) to guide treatment, but hematologicconsult should be considered in complicated cases of DIC

B Liver Disease affects coagulation as the majority of factors, except factor VIII and von

Willebrand’s factor (vWF), are produced in the liver In chronic liver disease,coagulation factors (I, II, V, VII, IX, X, and plasminogen) and inhibitors (antithrombin,protein C and S, α2-antiplasmin, as well as the vWF-cleaving enzyme ADAMTS13)synthesized by the liver are decreased while the vascular endothelium-derived factorVIII, vWF, tPA, and PAI-1 are elevated (Fig 25.3) Clinically, this results in a rebalancedhemostasis, though standard plasmatic coagulation tests such as PT and PTT may beelevated In fact, thrombin generation assays containing thrombomodulin and viscoelastictests (thromboelastography and thromboelastometry) demonstrate that patients with long-standing liver disease tend to be hypercoagulable They should be considered for

thromboprophylaxis unless contraindicated Similarly, in acute liver failure, overtbleeding is less common than would be expected due to a “rebalanced” coagulationdysfunction Thrombocytopenia frequently occurs as the result of splenic sequestrationbut may be compensated by high vWF levels

1 Prophylactic transfusion of FFP and platelets should be avoided, and hemostatic

interventions should only be performed in case of clinically relevant bleeding There

is usually response to vitamin K supplementation Antifibrinolytic drugs orcoagulation factor concentrates such as fibrinogen, prothrombin complex concentrate(PCC), or activated recombinant factor VII (rFVIIa) may be appropriate in certainpatients However, the potential benefit of improving hemostasis at the expense ofincreasing the thrombotic risk should be carefully evaluated in individual patients.Here, viscoelastic testing (ROTEM/TEG) seem to be helpful to guide therapy inbleeding patients Notably, procoagulant agents such as rFVIIa have been shown toimprove laboratory values such as PT, without improving control of bleeding duringliver transplant or upper GI hemorrhage

be given intravenously, though with the risk of anaphylaxis Oral vitamin K in thecritically ill patient depends on ability to have enteric medication and adequateabsorption Furthermore, the activity of vitamin K-dependent coagulation factor is low inpatients under oral anticoagulation with coumarins depicted by an increased INR

antagonists (VKAs), for example, in intracerebral hemorrhage or GI bleeding, the effectcan be reversed rapidly by the administration of four-factor PCCs Four-factor PCC is

to reverse the effect of new oral anticoagulants (NOACs: dabigatran, rivaroxaban,apivaban, and edoxaban) is still under debate

D Uremia Abnormal platelet function in uremia may contribute to significant bleeding in

the trauma or perioperative settings The primary therapy is hemodialysis and should bestrongly considered prior to invasive procedures in the event of uremia-related

coagulopathy IV desmopressin as a slow infusion increases multimers of factor VIII:vWf Cryoprecipitate and treatment of anemia with transfusion of PRBC in the acutesetting can be considered, as well Therapy with less immediate response time includesconjugated estrogens (over the course of 4–7 days) and erythropoietin (over the course ofweeks to months)

E Trauma-Induced Coagulopathy (TIC) or Acute Coagulopathy of Trauma Shock

(ACoTS) is accepted to be a discrete clinical entity different from DIC (Fig 25.4) In

contrast to DIC hypoperfusion-induced activation of protein C with subsequent cleavage

of activated factors V and VIII and down-regulation of PAI-1 result in endogenousanticoagulation and primary hyperfibrinolysis Furthermore, shedding of the endothelialglycocalyx leads to liberation of heparinoids, which intensifies endogenous

anticoagulation In addition, TIC is modulated by hemodilution, hypothermia, andacidosis TIC is functionally characterized by a reduction in clot strength With athreshold of clot amplitude at 5 minutes of ≤35 mm, rotational thromboelastometry canidentify acute traumatic coagulopathy at 5 minutes and predict the need for massivetransfusion Therefore, early administration of tranexamic acid and fibrinogenreplacement is crucial in treatment of TIC Fibrinogen levels should be corrected to atleast 150 to 200 mg/dL Concepts to treat TIC vary widely between the United States andEurope, using a fixed transfusion ratio of packed red blood cells, FFP, and platelets onthe one hand and an individualized goal-directed bleeding management using coagulationfactor concentrates (fibrinogen and four-factor PCC) guided by viscoelastic testing

(ROTEM/TEG) on the other hand RCTs are missing to show which approach is superior

in severe trauma In traumatic brain injury (TBI), the risk of bleeding as well asthrombosis is high A neurointensivist should be involved in the care of a critically illpatient with significant head trauma

F Postoperative Bleeding, for example, after cardiac surgery or liver transplant, usually is

multifactorial Here, hyperfibrinolysis, fibrinogen deficiency, fibrin polymerizationdisorders, thrombocytopenia, thrombocytopathy, and impaired thrombin generation canplay a major role Standard plasmatic coagulation tests are limited due to their long turn-around time and their inability for predicting bleeding and guiding hemostatic therapy inthe perioperative setting Here, ROTEM/TEG as well as point-of-care platelet functionanalysis have been shown to be superior in reducing transfusion requirements,

transfusion-associated adverse events, thromboembolic events, and improving patients’outcomes The use of perioperative bleeding management algorithms guided by

ROTEM/TEG are highly recommended here (Fig 25.5) Their clinical and costeffectiveness has been proven in several studies and health technology assessments

FIGURE 25.4 Pathophysiology of TIC and corresponding triggers of thromboelastometry and whole-blood impedance aggregometry; A10, amplitude of clot firmness 10 minutes after CT; AUC, area underthe curve; CT, coagulation time; EX, extrinsic thromboelastometry (EXTEM); FIB, fibrin

thromboelastometry (FIBTEM); HEP, heparinase modified thromboelastometry (HEPTEM); IN, intrinsicthromboelastometry (INTEM); INR, International normalized ratio; ML, maximum lysis

G Clotting

1 Hypercoagulability abnormalities include congenital conditions such as factor V

Leiden (activated protein C resistance), prothrombin mutation, protein C and Sdeficiencies, antithrombin deficiency, antiphospholipid antibodies (lupusanticoagulant [LA]), and hyperhomocysteinemia Evaluation includes thoroughhistory and labs, supported by genetic testing for the patient and family members.However, in the setting of acute illness and elevation of acute-phase reactants, thesetests may not be specific Expert hematologic consultation is recommended in

critically ill patients

a Medications such as oral contraceptives and smoking or obesity and diabetes

should be taken into consideration when critically ill patients withhypercoagulability are evaluated Pregnancy, trauma, and surgery predispose andcontribute to the multifactorial process of hypercoagulability

b Treatment is individually tailored Compression stockings, sequential

compression devices, and prophylactic and therapeutic anticoagulation aredetermined on the basis of history and clinical setting

2 Heparin-induced thrombocytopenia (HIT) is classified as nonimmune mediated

(HIT type 1) or immune mediated (HIT type 2) HIT type 1 is a benign fall in plateletcount, usually within 5 days of initiating heparin The platelet count usually does notfall below 100,000 mm3 and heparin does not have to be discontinued or avoided inthe future

a HIT type 2 is immune mediated IgG antibodies are formed against heparin-platelet factor 4 (PF-4) complexes This results in platelet activation andaggregation, leading to pathologic platelet aggregation, thrombocytopenia, andvascular thrombosis HIT antibodies binding to endothelial cell surfaces mayresult in tissue factor expression and a prothrombotic state

b Up to half of cardiac surgery patients and 15% of orthopedic surgery patients

develop HIT type 2 by immunologic assays (ELISA) However, only 1% to 3%

of these patients develop clinically significant HIT type 2 This can besignificantly reduced by use of low-molecular-weight heparin (LMWH) and