Handbook of Clinical Anesthesia

Chapter 56

Critical Care Medicine

In North America, anesthesiologists were integral to the development of critical care medicine as a specialty (Treggiari MA, Deem S: Critical care medicine. In Clinical Anesthesia. Edited by Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Philadelphia: Lippincott Williams & Wilkins, 2009, pp 1444–1472). However, in contrast to other countries, in the United States, anesthesiologists have played an ever-diminishing role in the specialty, and today they make up a minority of the intensivist workforce. The driving forces behind intensive care unit (ICU) development included advances in surgical techniques, polio epidemics that resulted in widespread respiratory failure, and later the recognition of the acute respiratory distress syndrome (ARDS). In the late 1960s, a group including Dr. Safar and another anesthesiologist, Ake Grenvik, were instrumental in inaugurating the Society of Critical Care Medicine (SCCM). Anesthesiologists working through SCCM were instrumental in developing the board certification process for critical care medicine, and in 1986, the first Critical Care Medicine Certification examination was administered by the American Board of Anesthesiology.

  1. Anesthesiology and Critical Care Medicine: The Future

Forces that will shape the evolution of the specialty of critical care medicine and the contribution that anesthesiologists will make to this evolution include quality of care issues and the contribution of intensivists to improved ICU outcomes, business and economic factors, and the aging population and increasing demand for critical care services. Mortality and other intermediate end points such as ICU length of stay can be reduced when “high-intensity” physician staffing models that mandate management or co-management by intensivists are used.


Table 56-1 Evaluating Evidence for Medical Therapies

Levels of Evidence Large, randomized trials with clear-cut results; low risk of false-positive (α) or false-negative (β) errors
Small, randomized trials with uncertain results; moderate to high risk of false-positive (α) or false-negative (β) errors
Non-randomized, contemporaneous controls
Non-randomized, historical controls, and expert opinion
Case series, uncontrolled studies, and expert opinion
Grades of Recommendation Based on Expert Consensus*
Supported by two or more level I studies
Supported by only one level I study
Supported by level II studies
Supported by level III studies
Supported by level IV or V studies

  1. Critical Care Medicine: A System and Evidence-Based Approach (Table 56-1)
  2. Process of Care in the Intensive Care Unit
  3. Implementation of evidence-based practices in the ICU could save up to 200,000 lives per year in the United States.
  4. The Leapfrog Groupis a coalition of more than 150 purchasers and providers of health care benefits with the stated goal of improving healthcare, particularly by reducing deaths caused by medical errors. To accomplish this aim, the Group formulated the Leapfrog Initiative, which includes a series of “safety standards” that health care providers (largely hospitals) should strive for if they are to provide care for Leapfrog.

III. Neurologic and Neurosurgical Critical Care

  1. Neuromonitoringdevices used in the ICU setting may help in assessing pathophysiologic processes and adjusting therapy.
  2. Transcranial Doppler (TCD) ultrasonographymeasures mean, peak systolic, and end-diastolic flow velocities and indirectly estimates cerebral blood


flow. In patients with subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI), TCD can be used as a tool to identify vasospasm. In patients with TBI, flow velocities are depressed, and impaired autoregulation and vascular reactivity are common. In these patients, monitoring of TCD and jugular venous oxygen saturation (SjO2) may be used to define the optimum cerebral perfusion pressure (CPP) level.

  1. Brain tissue oxygenation(PbrO2) measurements are performed by introducing a small, oxygen-sensitive catheter into the brain tissue (normal PbrO2 values, 25–30 mm Hg). An increase in intracranial pressure (ICP) and a decrease in CPP or arterial oxygenation along with hyperventilation may result in decreased PbrO2. CPP above 60 mm Hg has been identified as the most important factor determining sufficient brain tissue oxygenation.
  2. Microdialysisuses a probe as an interface to the brain to continuously monitor the chemistry of a small focal volume of the cerebral extracellular space. (This allows measurement of chemical substances such as lactate, pyruvate, glucose, glutamate, glycerol, metabolites of several biochemical pathways, and electrolytes and thus provides insight into the bioenergetic status of the brain.) Increased lactate, decreased glucose, and an elevated lactate/glucose ratio indicate accelerated anaerobic glycolysis. This metabolic pattern commonly occurs with cerebral ischemia or hypoxia, and increased glycolysis in this setting is associated with a poor outcome.
  3. Diagnosis and Clinical Management of the Most Common Types of Neurologic Failure
  4. Traumatic brain injuryis the leading cause of death from blunt trauma, and in patients between the age of 5 and 45 years, TBI represents the leading cause of death (Table 56-2). Examination of the pupils can predict neurologic outcome.
  5. Resuscitation.The goal of resuscitation in traumatic and other types of brain injury is to prevent continuing cerebral insult after a primary injury has occurred. A primary insult is often associated with intracranial hypertension and systemic hypotension, leading to decreased


cerebral perfusion and brain ischemia. Concomitant hypoxemia aggravates brain hypoxia, especially in the presence of hyperthermia, which increases the brain's metabolic demand. The combined effect of these factors leads to secondary brain injury characterized by excitotoxicity, oxidative stress, and inflammation. The resulting cerebral ischemia may be the single most important secondary event affecting outcome after a cerebral insult.

Table 56-2 Predictors of Poor Outcome After Traumatic Brain Injury

Age >55 years
Poor pupillary reactivity (bilateral dilated and unreactive associated with poor neurologic outcome and death as high as 90%)
Postresuscitation Glasgow Coma Scale score (most widely used measure of injury severity; may be unmeasurable initially; injury is severe when score is ≤8)
Unfavorable intracranial diagnosis based on radiologic features (CT scan, degree of diffuse injury, and midline shift)
Hyperglycemia (>200 mg/dL)

  1. Prevention of secondary injuryis the main goal of resuscitative efforts. Traumatized areas of the brain manifest impaired autoregulation, with increased dependency of flow on perfusion pressure and disruption of the blood–brain barrier. The goals of neuroresuscitation are oriented at restoration of cerebral blood flow by maintenance of adequate CPP, reduction of ICP, evacuation of space-occupying lesions, and initiation of therapies for cerebral protection and avoidance of hypoxia (Table 56-3).
  2. Drug-Induced Sedation.A common practice is to provide sedation with propofol or benzodiazepines in patients after TBI. These agents have favorable effects on cerebral oxygen balance. Despite the induction of systemic hypotension, propofol decreases cerebral metabolism, resulting


in a coupled decline in cerebral blood flow with consequent decrease in ICP. Barbiturates should be considered if ICP is not controlled by moderate doses of propofol. Although neuromuscular blockade may result in a decrease in ICP, the routine use of neuromuscular blockade is discouraged because its use has been associated with longer ICU course, a higher incidence of pneumonia, and a trend toward more frequent sepsis without any improvement in outcome.

Table 56-3 Intensive Care Unit Management of Patients with Severe Traumatic Brain Injury (Assuming Initial Surgical Management)

Head elevation 30 to 45 degrees*
CPP >70 mm Hg
Euvolemia, vasopressors as needed
ICP <20 mm Hg
   Mannitol, hypertonic saline
   CSF drainage
SaO2 ≥95%; PaCO2 35–40 mm Hg
Temperature ≤37°C
Glucose <180 mg/dL
Sedation and analgesia
Early enteral nutrition
Seizure, stress ulcer, and DVT prophylaxis
Refractory intracranial hypertension
   Optimized hyperventilation with SjO2 monitoring, PbrO2 monitoring, or both
   Barbiturate coma
   Mild therapeutic hypothermia (33°–35°C)
   Decompressive craniectomy

*Unless contraindicated by spine injury or hemodynamic instability.
CPP = cerebral perfusion pressure; DVT = deep vein thrombosis; ICP = intracranial pressure.

  1. Hyperventilationeffectively reduces ICP by reducing CBF, but in small randomized trials, prophylactic hyperventilation has not proven to be beneficial in patients with TBI. Prolonged or prophylactic hyperventilation should be avoided after severe TBI. Hyperventilation may be necessary for brief periods to reduce intracranial hypertension refractory to sedation, osmotic therapy, and cerebrospinal fluid drainage, and


should be guided by SjO2, PbrO2, or both (a decrease in either of these values suggests a harmful effect of hyperventilation).

  1. Hypothermia.There is insufficient evidence to provide recommendations for the use of moderate hypothermia in patients with TBI.
  2. Corticosteroidsto reduce posttraumatic inflammatory injury should not be administered as therapy for acute TBI.
  3. Anticonvulsants may be used to prevent early posttraumatic seizures within 7 days after head trauma. (Evidence does not indicate that prevention of early seizures improves outcome after TBI.)
  4. Albumin as fluid replacement therapy in patients with TBI may increase mortality when compared with saline.
  5. Subarachnoid hemorrhageis most commonly caused by the rupture of an intracranial aneurysm with only one third of the patients with SAH being functional survivors. The leading causes of death and disability are the direct effects of the initial bleed—cerebral vasospasm and rebleeding. At the time of aneurysm rupture, a critical reduction in CBF takes place because of an increase in ICP toward arterial diastolic values. The persistence of a no-flow pattern is associated with acute vasospasm. In survivors of the initial bleed, emphasis has been placed on early aneurysm securing with either surgery or interventional neuroradiology (coiling). Early aneurysm occlusion substantially reduces the risk of this rebleeding.
  6. Cerebral vasospasmafter SAH is correlated with the amount and location of subarachnoid blood. A reduction in cerebral blood flow is ultimately responsible for the appearance of delayed ischemic neurologic deficits (DINDS). Oral nimodipine (60 mg every 4 hours for 21 days) as prophylaxis for cerebral vasospasm is recognized as an effective treatment in improving neurologic outcome (reduction of cerebral infarction and poor outcome) and mortality from cerebral vasospasm in patients with SAH. The benefits of nimodipine have been attributed to a cytoprotective effect related to the reduced availability of


intracellular calcium and improved microvascular collateral flow.

  1. Hypervolemic, hypertensive, and hemodilution (“triple-H”) therapyis one of the mainstays of treatment for cerebral ischemia associated with SAH-induced vasospasm despite the lack of evidence for its effectiveness. The rationale for hypertension derives from the concept that a loss of cerebral autoregulation associated with vasospasm results in pressure-dependent blood flow. Hemodilution is a consequence of hypervolemic therapy and is thought to optimize the rheologic properties of the blood and thereby improve microcirculatory flow. Common complications of treatment are pulmonary edema and myocardial ischemia.
  2. Interventional neuroradiologywith the use of balloon angioplasty (within 6 to 12 hours) can reverse or improve vasospasm-induced neurologic deficits.
  3. Hyponatremiausually develops several days after the hemorrhage and is attributed to a syndrome of inappropriate antidiuretic hormone (SIADH) and an excess of free water.
  4. Acute Ischemic Stroke.More than half of strokes can be attributed to a thrombotic mechanism. Transient ischemic attacks may precede stroke and thus should be considered a warning sign.
  5. Thrombolysis.Rapid clot lysis and restoration of circulation using alteplase (rt-PA) should be provided within 3 hours of stroke onset. Patients receiving systemic rt-PA should not receive aspirin, heparin, warfarin, clonidine, or other antithrombotic or antiplatelet aggregating drugs within 24 hours of treatment. Because hyperglycemia is associated with poor outcome in ischemic stroke, tight glucose control is recommended. (The mortality benefit at 90 days has not been demonstrated.)
  6. Anoxic brain injurymost commonly occurs as a result of cardiac arrest. The pathophysiology of anoxic brain injury is multifactorial and includes excitatory neurotransmitter release, accumulation of intracellular calcium, and oxygen free radical generation. A strong experimental literature supports a


role for mild therapeutic hypothermia in anoxic brain injury (temperature. 32°–34°C). Hypothermia is recommended in neonatal hypoxic encephalopathy.

  1. Cardiovascular and Hemodynamic Aspects of Critical Care
  2. Principles of Monitoring and Resuscitation.Shock states are associated with impairment of adequate oxygen delivery, resulting in decreased tissue perfusion and tissue hypoxia. (Global hemodynamic monitoring may not reflect regional perfusion or the peripheral tissue energy status.) Invasive monitoring in shock states provides insight into the circulatory status, organ perfusion, tissue microcirculation, and cellular metabolic status of the critically ill patient.
  3. Functional Hemodynamic Monitoring
  4. Pulmonary Artery Catheter (PAC).The information provided by the PAC may assist in the differentiation of cardiogenic and noncardiogenic circulatory and respiratory failure and may help guide fluid, inotropic, and vasopressor therapy.
  5. Despite the theoretical benefits of pulmonary artery catheterization, little data support a positive effect of PACs on mortality or other substantive outcome variables. A trial conducted in patients assigned to receive PAC-guided or central venous catheter–guided therapy did not find any survival or organ function differences between the two groups, and there was an equal number of catheter-related complications (dysrhythmias).
  6. Studies do not support the routine use of the PAC for the management of acute lung injury (ALI) or septic shock.
  7. Arterial Pressure Waveform Analysis.The variation in systolic blood pressure and pulse pressure during positive pressure ventilation is highly predictive of the response to intravascular fluid administration in both normal subjects and critically ill patients. Cardiac output derived using pulse contour analysis correlates well with thermodilution cardiac output in a variety of conditions and has the advantage of providing continuous measurement without necessitating the


placement of a PAC. The use of pulse contour analysis may potentially obviate the need for pulmonary artery catheterization to measure cardiac output, particularly if combined with the measurement of ScvO2 as an indicator of the balance between oxygen delivery and consumption.

  1. Echocardiography.Transthoracic and transesophageal echocardiography (TEE) provide accurate noninvasive diagnostic information with regard to right and left ventricular function, valve function, pericardium anatomy, traumatic vascular injury, and pulmonary embolism (direct and indirect signs). TEE can also be used to assess volume status or preload via measurement of left ventricular end-diastolic volume or area.
  2. Definition and Types of Circulatory Failure.The common denominator of shock is circulatory instability characterized by severe hypotension and inadequate tissue perfusion. Shock states are classified according to the primary cause of circulatory failure. Distributive or vasodilatory shock results from a reduction in systemic vascular resistance (SVR) often associated with an increased cardiac output. On the other hand, cardiogenic (left or right cardiac failure) and hypovolemic shock are low cardiac output states that are usually characterized by increased peripheral resistance. The most common forms of shock encountered in the ICU are cardiogenic, septic, and hypovolemic shock.
  3. Cardiogenic Shock.The initiating event in cardiogenic shock is a primary pump failure (myocardial infarction, cardiomyopathy, arrhythmias, mechanical complications [mitral regurgitation, ventricular septal defect], tamponade). The onset of pump failure is associated with a compensatory reflex vasoconstriction in systemic vessels that causes an increase in left ventricular workload and myocardial oxygen demand and a redistribution of blood volume toward the heart and the lungs. Consequently, therapy should minimize myocardial oxygen demand and increase oxygen delivery to the ischemic area; this goal is complicated by the fact that many resuscitative approaches to correct hypotension (preload augmentation, inotropes, and vasopressors) increase myocardial oxygen


consumption. In patients without hypotension, pharmacologic vasodilatation using nitrates or sodium nitroprusside may reduce myocardial oxygen consumption and improve ventricular ejection by reducing left ventricular afterload and possibly produce a shift of blood from the lungs to the periphery by reducing venous tone. When pharmacologic interventions are not sufficient to restore hemodynamic stability, the use of mechanical support with the insertion of intra-aortic balloon pump counterpulsation and ventricular assist devices can help unload the ventricles. In patients with myocardial infarction, coronary reperfusion can be achieved with thrombolysis or, preferably, primary percutaneous coronary intervention.

  1. Septic shockis a form of distributive shock associated with the activation of the systemic inflammatory response, and it is usually characterized by a high cardiac output, low SVR, hypotension, and regional blood flow redistribution, resulting in tissue hypoperfusion. In patients with systemic infections, the physiologic response may be staged on a continuum from a systemic inflammatory response syndrome (SIRS) to sepsis, severe sepsis, and septic shock (Table 56-4). Multiple organ dysfunction syndrome (MODS) refers to the presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention. MODS accounts for most deaths in the ICU.
  2. Clinical Management of Shock or Circulatory Failure Based on Hemodynamic Parameters.The mainstay of treatment of hemodynamic instability is correction of hypotension and restoration of regional blood flow with intravascular volume expansion and vasopressors, inotropes, or both. Adequacy of regional perfusion is usually assessed by evaluating indices of organ function, including myocardial ischemia, renal dysfunction (urine output and renal function tests), arterial lactate levels as an indicator of anaerobic metabolism, central nervous system dysfunction as indicated by abnormal sensorium, and hepatic parenchymal injury by liver function tests. Additional end points of treatment consist of mean arterial pressure and DO2 or some surrogate of the latter (SvO2 or ScvO2).


Table 56-4 Definitions of Sepsis and Organ Failure

Clinical Evidence of Infection
Infection: Microbial phenomenon characterized by an inflammatory response to the presence of microorganisms or the invasion of normally sterile tissue by those organisms.
Bacteremia: Presence of viable bacteria in the blood.
Systemic Inflammatory Response Syndrome (SIRS): Systemic inflammatory response to a variety of severe clinical insults. The response is manifested by two or more of the following conditions:
   Core temperature <36°C or >38°C
   Tachycardia >90 bpm
   Tachypnea >20 breaths/min while breathing spontaneously or PaCO2 <32 mm Hg
   White blood count >12,000 cells/mm3, <4000 cells/mm3, or >10% immature forms
Sepsis: The systemic response to infection. This systemic response is manifested by three or more of the conditions described above (SIRS) and presented clinical or microbiologic evidence of infection.
Severe Sepsis: Sepsis associated with organ dysfunction, hypoperfusion, or hypotension.
Hypoperfusion and perfusion abnormalities may include, but are not limited to, lactic acidosis, oliguria, or an acute alteration in mental status.
Septic Shock: Sepsis with hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities that may include, but are not limited to, lactic acidosis, oliguria, or an acute alteration in mental status. Patients taking inotropic or vasopressor agents may not be hypotensive at the time that perfusion abnormalities are measured.
Sepsis-Induced Hypotension: A systolic blood pressure of <90 mm Hg or a reduction of >40 mm Hg from baseline in the absence of other causes of hypotension.
Multiple Organ Dysfunction Syndrome: Presence of several altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.

  1. Management of Hypotension with Fluid Replacement Therapy.Intravascular volume expansion is the first line of therapy in all forms of shock. Clinical indicators of the response to a fluid challenge (bolus fluid therapy of 250–1000 mL of crystalloids over 5–15 minutes) are heart rate, blood


pressure, and urine output as well as invasively acquired measures, including CVP, PaOP, systolic and pulse pressure variation, and cardiac output.

  1. Management of Shock with Vasopressors or Inotropes.If patients remain persistently hypotensive despite volume expansion and markers of adequate preload, the use of vasopressors is indicated.
  2. Norepinephrine(NE) increases systemic arterial pressure, with variable effects on cardiac output and heart rate. A concern that NE may compromise renal perfusion has led to some hesitancy to use this drug; however, the majority of available evidence suggests that NE improves renal function in volume-resuscitated, hypotensive patients with septic shock. NE is the drug of first choice in the management of septic shock.
  3. Dopamineincreases mean arterial pressure by increasing cardiac index and less so SVR. Comparing low dose-dopamine with placebo in critically ill patients shows no differences in renal function tests or survival, and the use of low-dose dopamine is therefore not recommended. In addition, dopamine may have detrimental effects on the splanchnic circulation and gastric mucosal perfusion.
  4. Dobutaminedemonstrates potent inotropic and chronotropic effects and mild peripheral vasodilatation, with the ultimate effect of increasing oxygen delivery and consumption. Dobutamine is the drug of choice in patients with circulatory failure primarily caused by cardiac pump failure (cardiogenic shock). However, dobutamine should not be used as first-line single therapy when hypotension is present.
  5. Epinephrineincreases cardiac index by increasing contractility and heart rate, and it also increases SVR. In patients with septic shock, epinephrine may reduce splanchnic perfusion despite an increase in global hemodynamic and oxygen transport. In addition, epinephrine therapy consistently increases plasma lactate levels in septic shock. Epinephrine treatment brings no additional benefit to other catecholamine therapy in the management of patients with septic shock.


  1. Vasopressinis a potent vasoconstrictor when administered in low doses to patients in shock, particularly those with distributive shock caused by sepsis or hepatic failure or with circulatory failure after cardiopulmonary bypass. Vasopressin may also be useful in resuscitation from cardiac arrest, particularly if it is caused by asystole. Vasopressin may be added to norepinephrine with the expectation that the effect on blood pressure will be similar to that produced by norepinephrine. Epinephrine should be the first choice alternative agent in patients with septic shock who are poorly responsive to norepinephrine or dopamine.
  2. Additional Treatment Considerations for Critically Ill Patients with Septic Shock
  3. Activated Protein C.Clinical or subclinical manifestations of disseminated intravascular coagulation and consumption coagulopathy (increase in D-dimers, decreased protein C, thrombocytopenia, and increased prothrombin time) are present in essentially all patients with septic shock. The activation of protein C is thought to be an important mechanism for modulating sepsis-induced consumption coagulopathy. Activated protein C works as an antithrombotic agent by inactivating factors Va and VIIIa. The rationale for replacing activated protein C relates to its anticoagulant and profibrinolytic properties, which interrupt the consumption coagulopathy and are particularly effective at preventing microvascular thrombosis.
  4. Corticosteroidsare of no benefit for the treatment of septic shock, but low doses (hydrocortisone 200–300 mg/day) can reduce the dependency on vasopressors.
  5. Treatment of Infection.Identifying the source of the infection and early initiation of appropriate antibiotic therapy are critical priorities in addition to hemodynamic support. Empiric antibiotic therapy should be started as soon as possible after appropriate culture collection.
  6. Acute Respiratory Failure

Acute Respiratory Failure is a generic term that encompasses the need for mechanical ventilation or airway intubation, independent of cause.


  1. Principles of Mechanical Ventilation.Mechanical ventilation in the ICU is provided through the application of positive pressure to the airway; a preset tidal volume and rate are commonly provided, and any breathing that the patient does above this set minute ventilation is either supported (assist-control [AC]) or not (intermittent mandatory ventilation [IMV]). There is little evidence to suggest that the mode of mechanical ventilation contributes significantly to any major outcome measure. Mechanical ventilation using tidal volumes of 10 to 15 mL/kg may be injurious in certain settings.
  2. Air-trappingand auto PEEP (positive end-expiratory pressure) lead to significant morbidity and mortality in patients with obstructive lung disease. The ventilatory strategy in these patients should focus on prolongation of expiratory time by limiting minute ventilation by using low tidal volumes (≤6–8 mL/kg) and a low rate (8–12 breaths/min) and by reducing the inspiratory time of the respiratory cycle. To accomplish these goals, deep sedation is often required, and rarely neuromuscular blockade must be used. Separation from mechanical ventilation is expedited when respiratory therapy–driven protocols are used that focus on daily assessment of the ability to breath without assistance, assuming improvement of the inciting process, adequate oxygenation, and hemodynamic stability (grade A recommendation). After the patient can breathe comfortably for 30 to 120 minutes without support, the trachea can be extubated, assuming that there are no other precluding factors such as airway abnormalities or coma.
  3. Acute Lung Injury and Acute Respiratory Distress Syndromeare characterized by acute hypoxemic respiratory failure and diffuse alveolar damage with resulting increased lung permeability. Diffuse alveolar edema and mortality in patients with ARDS and ALI appear to be similar.
  4. The treatment of ALI and ARDS is largely supportive and includes aggressive treatment of inciting events, avoidance of complications, and mechanical ventilation. It is critical that tidal volumes (≤6 mL/kg) and static ventilatory pressures (≤30 cm H2O) are


minimized to avoid further injury to the remaining relatively uninjured lung.

  1. Because ARDS is marked by high intrapulmonary shunt, hypoxemia is relatively unresponsive to oxygen therapy. Thus, strategies to recruit the collapsed lung are necessary. This is most commonly achieved by using PEEP. Long-term outcome benefits of inhaled nitric oxide have not been demonstrated, although inhaled nitric oxide may still be useful as “rescue” therapy in selected patients with severe refractory hypoxemia.
  2. It is intuitive that administration of excessive fluids be avoided.
  3. Corticosteroids administered early in the course of ARDS are of no benefit but may be beneficial during the fibroproliferative phase.
  4. Acute Renal Failure (ARF)

Acute Renal Failure is reported to occur in as many as 1.5% to 24% of critically ill patients. Mortality associated with ARF requiring dialysis has remained approximately 60% for nearly five decades. In the ICU, ARF occurs from prerenal causes and tubular injury (acute tubular necrosis) in the vast majority of cases. Urine sodium concentration and fractional excretion of sodium can help identify prerenal azotemia (Table 56-5).

  1. Treatment.In incipient and established ARF, supportive care is the rule, with the focus on maintenance of euvolemia, avoidance of renal toxins, adjustment of medication doses, and monitoring of electrolytes and acid–base status. Pharmacologic approaches to the prevention and treatment of ARF, including low-dose dopamine, have been uniformly disappointing.
  2. Diuretics should be administered with caution in early ARF and in response to defined physiologic problems (hypervolemia, hyperkalemia.)
  3. Prophylactic administration of N-acetyl cysteine and sodium bicarbonate to patients with pre-existing renal disease appears to be beneficial in preventing contrast-induced nephropathy.
  4. The weight of evidence supports an increased intensity of dialysis using either daily standard hemodialysis, CRRT, or extended daily hemodialysis (“slow dialysis”).


Table 56-5 Urinalysis, Urine Chemistries, and Osmolality in Acute Renal Failure



Acute Tubular Necrosis

Acute Interstitial Nephritis





Broad, brownish granular casts

WBCs, eosinophils, cellular casts

RBCs, RBC casts



None or low

None or low

Minimal but may be increased with NSAIDs

Increased, >100 mg/dL


Urine Na+ (mEq/L)*

<20 <40 (days)





Urine osmolality (mOsm/kg)






FENa+ (%)†





<1 (acute) >1 (days)

*The sensitivity and specificity of urine sodium of less than 20 in differentiating prerenal azotemia from acute tubular necrosis are 90% and 82%, respectively.
†FENa+: Fractional excretion of sodium is the urine to plasma (U/P) of sodium divided by U/P of creatinine 3100. The sensitivity and specificity of fractional excretion of sodium of less than 1% in differentiating prerenal azotemia from acute tubular necrosis are 96% and 95%, respectively.
NSAID = nonsteroidal anti-inflammatory drug; RBC = red blood cell; WBC = white blood cell.


VII. Endocrine Aspects of Critical Care Medicine

  1. Glucose Management in Critical Illness.Hyperglycemia is associated with increased risk of postoperative infection (wound and otherwise) and poor outcome in patients with stroke or TBI.
  2. Strict glycemic control in critically ill patients has been advocated based on evidence from a single randomized trial in surgical patients in the ICU. A subsequent study by the same investigators in medical patients found no benefit of intensive insulin therapy on mortality.
  3. The enthusiasm for intensive insulin therapy with tight glycemic control in the ICU has diminished.
  4. Adrenal Function in Critical Illness.The stress response to injury includes an increase in serum cortisol levels in most critically ill patients. Adrenal insufficiency may also occur in critically ill patients, reflecting inhibition of adrenal stimulation or corticosteroid synthesis by drugs or cytokines and direct injury to or infection of the pituitary or adrenal glands. Until free cortisol assays are more widely available, the diagnosis of adrenal insufficiency in critical illness must be based on clinical suspicion and total cortisol levels. Adrenal insufficiency should be considered in all critically ill patients with pressor-dependent shock.
  5. Thyroid Function in Critical Illness.Depression of triiodothyronine (T3) occurs within hours of injury or illness and can persist for weeks. Low thyroid hormone levels, particularly for T3, correlate with the severity of illness and are associated with an increased risk of death. Hypothyroidism (elevation of thyroid-stimulating hormone in the presence of a low thyroxine level) may be present in critically ill patients, particularly in the geriatric population, and should be considered in the face of refractory shock; adrenal insufficiency; unexplained coma; and prolonged, unexplained respiratory failure.
  6. Somatotropic Function in Critical Illness.Growth hormone levels are low in patients with prolonged critical illness.


VIII. Anemia and Transfusion Therapy in Critical Illness

The vast majority of patients admitted to the ICU are anemic at some point in their hospital stay, and more than one third of them will receive transfused blood. The cause of anemia in critical illness is multifactorial and is related to blood loss from the primary injury or illness, iatrogenic blood loss caused by daily blood sampling, and nutritional deficiencies (e.g., folate). It is assumed that critically ill patients have less efficient compensatory mechanisms and reduced physiologic reserve and thereby require a higher hemoglobin concentration than unstressed individuals. Data collected from ICUs at multiple centers in the United States suggest that the transfusion trigger is nearer 8.6 g/dL than the previously recommended 7 g/dL. Hemoglobin is an important determinant of oxygen delivery (DO2), and transfusion is an integral component of goal-directed therapeutic strategies that aim to optimize DO2 in early shock states.

  1. Nutrition in Critically Ill Patients

Poor nutritional status is associated with increased mortality and morbidity rate among critically ill patients; adequate nutritional support should be considered a standard of care. Enteral nutrition is preferred over parenteral nutrition whenever possible because of its lower cost and less frequent complications.

  1. Complicationsassociated with enteral feedings include aspiration of gastric feeding, diarrhea, and fluid and electrolyte imbalance. To prevent aspiration with gastric feeding, the head of the patient's bed should be raised 30 to 45 degrees during feeding; jejunal access can be considered in patients with recurrent tube feeding aspiration. To prevent or reduce diarrhea, all potential causes should be considered and corrected.
  2. Sedation of Critically Ill Patients

Critically ill patients are often deeply sedated because of the potential benefits afforded by a reduction in the sympathoadrenal response to injury. Additionally, complications associated with undersedation include ventilator


dyssynchrony, patient injury, agitation, anxiety, stress disorders, and possibly unplanned extubation.

  1. Recent studies have tempered the enthusiasm for deep sedation in the ICU. (Daily interruption of continuous sedative and analgesic drug infusions has been shown to be effective in reducing the length of mechanical ventilation and length of ICU stay.)
  2. The depth of sedation may also play a role in long-term outcomes after discharge from the ICU. (The extent of ICU recall, including delusional memories, is a function of the extent of sedation.)
  3. It is important to titrate medications according to established therapeutic goals and re-evaluate the sedation requirements frequently (Ramsay sedation scale, Richmond agitation sedation scale).
  4. Confusion and agitationare common in ICU patients and may have unfavorable consequences on patient outcome. Agitation should be distinguished from delirium, which is relatively common in ICU patients and equally associated with increased length of stay, morbidity, and mortality. The distinguishing characteristics of delirium include acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness.
  5. Nonpharmacologic and pharmacologicmeans can be used to provide comfort and safety to ICU patients. The former include communication, frequent reorientation, maintenance of a day–night cycle, noise reduction, and ensuring ventilation synchrony. Pharmacologic agents include hypnotics–anxiolytics, opioids, and antipsychotics.
  6. The most commonly used hypnoticsare propofol, midazolam, and lorazepam. Continuous infusion of propofol is associated with a shorter length of mechanical ventilation and ICU stay compared with lorazepam administration.
  7. Dexmedetomidinehas been effectively used as a single agent or in combination with other drugs in postsurgical and medical ICU patients.
  8. Opioids.Morphine and fentanyl are the most commonly used opioids to provide analgesia in the ICU. Morphine should be avoided in patients with renal failure because of active metabolites that accumulate in the presence of impaired renal elimination.


  1. Neuromuscular blockademay be occasionally indicated in ICU patients with severe TBI or respiratory failure, but routine use is discouraged because of concerns that this practice may predispose patients to critical illness, polyneuropathy, and myopathy and because of an increased risk of nosocomial pneumonia in patients receiving these agents.
  2. Complications in the Intensive Care Unit: Detection, Prevention, and Therapy
  3. Nosocomial infectionsare a major source of morbidity and mortality in critically ill patients. At some level, nosocomial infections are unavoidable and occur because of the nature of intensive care: patients are critically ill with altered host defenses; they require invasive devices (endotracheal tubes, intravascular catheters) for support, monitoring, and therapy that provide portals of entry for infectious organisms; and they receive therapies that increase the risk of infection (glucocorticoids, parenteral nutrition). On the other hand, many nosocomial infections are preventable with relatively simple interventions.
  4. Sinusitisis common in critically ill patients with indwelling oral and nasal tubes. Prevention of sinusitis should focus on efforts to improve sinus drainage, including semi-recumbent positioning and avoidance of nasal tubes. Bacterial sinusitis should be considered in patients with unexplained fever and leukocytosis in the ICU.
  5. Ventilator-Associated Pneumonia (VAP).Endotracheal intubation and mechanical ventilation increase the risk of VAP. Interventions that can reduce the incidence of VAP include strict hand washing before and after patient contact and semi-recumbent positioning of the patient (head height at 30 degrees or greater from horizontal) (level II evidence). These practices should be rigorously applied in all ICUs (granted that semi-recumbent positioning is not possible in all patients).
  6. Gastric and oropharyngeal colonization with resistant organisms appears to be a risk factor for the development of VAP. Oral decontamination with chlorhexidine (not non-absorbable


antimicrobial agents) appears to reduce VAP rates without leading to excess antibiotic resistance.

  1. Acid-suppression therapies as prophylaxis against gastrointestinal (GI) bleeding have been associated with an increased risk of VAP because they allow bacterial overgrowth in the stomach. (Sucralfate should be considered as an alternative agent to acid-suppressive regimens despite its potentially reduced effectiveness.)
  2. An important approach to reduce the overall mortality from VAP involves refinement of the diagnostic process and limitation of antibiotic therapy to avoid the development of antibiotic resistance. Antibiotics can than be narrowed in spectrum or discontinued depending on the results from quantitative cultures after 48 to 72 hours.
  3. Intravascular catheter-associated bacteremiais strictly defined as clinical suspicion of catheter-related infection plus positive culture of blood drawn from the catheter or of a segment of catheter and matching positive blood culture drawn from another site.
  4. Catheter infection is more likely when placement occurs under emergency conditions and is reduced by the use of strict aseptic technique with full barrier precautions. Catheter-related infection and bacteremia increase with the duration of catheterization, particularly for durations of greater than 2 days. However, routine catheter replacement at 3 or 7 days does not reduce the incidence of infection and results in increased mechanical complications. Thus, routine guidewire change of catheters is not recommended.
  5. Based on incidence of infection at the insertion site, the subclavian route should be used when possible if the duration of catheterization is predicted to be longer than 2 days.
  6. Catheter-related venous thrombosis occurs commonly and is associated with an increased risk of infection. Routine flushing of catheter ports with heparin reduces the incidence of both thrombosis and infection.


  1. When catheter-related bacteremia is confirmed, the offending catheter should be removed and appropriate antibiotics continued for a minimum of 7 days.
  2. Urinary tract infection (UTI)is the second most common source of infection in the ICU. Its incidence increases with the duration of bladder catheterization.
  3. Invasive fungal infectionsin non-neutropenic patients is caused by Candida species in the vast majority of cases. These infections are increasingly common in the ICU population, accounting for 5% to 10% of all bloodstream infections in the ICU. A high level of suspicion for invasive Candida infection in critically ill patients is necessary, and “pre-emptive” therapy should be considered in patients with a high likelihood of invasive Candida infection while awaiting blood culture results.

An ophthalmologic examination is warranted in patients with documented or suspected bloodstream infection because patients with endophthalmitis may require longer courses of therapy. Intravascular catheters that are potential sources of bloodstream infection should be removed. Organisms sensitive to the azole derivative fluconazole cause the majority of invasive Candida infections in the ICU, and fluconazole is the first-line treatment given its reasonable efficacy and limited toxicity.

  1. Stress Ulceration and Gastrointestinal Hemorrhage.Gastric mucosal breakdown with resulting gastritis and ulceration (“stress ulceration”) can lead to GI bleeding in ICU patients. The major risk factors for stress-related GI bleeding are mechanical ventilation and coagulopathy; secondary risk factors among mechanically ventilated patients include renal failure, thermal injury, and possibly head injury. Enteral nutrition may protect against significant GI bleeding.
  2. Prevention.Agents used to prevent stress ulceration and GI bleeding include methods to suppress acid production (H2 blockers and proton pump inhibitors) and cytoprotective agents (sucralfate). The agent of choice—and whether any prophylaxis is beneficial or indicated—is somewhat controversial. It appears that stress ulcer prophylaxis is more widely used than necessary.


Thus, although stress ulcer prophylaxis, predominantly with ranitidine, is commonly used in critically ill patients, the utility of this intervention is unclear.

  1. Venous thromboembolism(VTE) occurs frequently in critically ill patients, with incidences of deep venous thrombosis (DVT) of 10% to 30% and of pulmonary embolism (PE) of 1.5% to 5%. In addition to classic lower extremity DVT, upper extremity DVT occurs with increased frequency in the ICU population. This is directly associated with the use of central venous catheters in the subclavian and internal jugular sites. Upper extremity DVT can result in pulmonary embolism in up to two thirds of cases, with occasional fatalities.
  2. Prophylaxis.The risks of VTE prophylaxis, including heparin-induced thrombocytopenia and bleeding, must be weighed when considering prophylaxis in the ICU population. Nonetheless, it is generally agreed that high-risk patients without contraindications should receive prophylaxis with low-molecular-weight heparin (LMWH) and that patients with low to moderate risk should receive low-dose unfractionated heparin (UFH) (Table 56-6). To reduce central venous catheter–associated thrombosis and infection, catheter tips should be positioned in the superior vena cava, and catheters should be flushed with a dilute heparin solution. Heparin bonding of catheters may also reduce local thrombosis.
  3. Diagnosis.Despite the high incidence of DVT, routine screening studies for DVT do not appear to improve clinical outcomes in the ICU. VTE should be considered in critically ill patients in the face of relatively nonspecific findings, such as unexplained tachycardia, tachypnea, fever, asymmetric extremity edema, and gas exchange abnormalities (including high dead space ventilation). Compression Doppler ultrasonography is the most commonly used test for diagnosis of DVT. Ventilation-perfusion scanning and pulmonary angiography may have utility in specific circumstances, including in the presence of renal insufficiency (concerns about contrast-induced nephrotoxicity) or equivocal results on computed tomography scan. Pulmonary angiography may be


the test of choice when the likelihood of PE is high and anticoagulation is contraindicated, necessitating immediate placement of a vena cava filter.

Table 56-6 Risk Factors for Venous Thromboembolism

Strong Risk Factors
Fracture (hip or leg)
Hip or knee replacement
Major trauma
Spinal cord injury
Moderate Risk Factors
Arthroscopic knee surgery
Central venous lines
Congestive heart or respiratory failure
Hormone replacement therapy
Oral contraceptive therapy
Paralytic stroke
Pregnancy or postpartum period
Previous venous thromboembolism
Weak Risk Factors
Bed rest >3 days
Immobility caused by sitting (prolonged car or air travel)
Increasing age
Laparoscopic surgery (cholecystectomy)
Pregnancy or antepartum period
Varicose veins

  1. Treatment.The mainstay of treatment for VTE is heparin, which should be started before the results of confirmatory studies if clinical suspicion is high. LMWH may be superior to UFH in efficacy with comparable rates of bleeding. The advantage of UFH in the ICU population is its titratability and rapid reversibility, which may be desirable in patients at high risk for bleeding. For patients who have contraindications to anticoagulation or who have recurrent PE despite anticoagulation, vena cava filters can be placed in the SVC or IVC, depending on DVT location.
  2. Acquired Neuromuscular Disorders in Critical Illness.Neuromuscular abnormalities developing as a


consequence of critical illness can be found in the majority of patients hospitalized in the ICU for 1 week or more. These disorders range from isolated nerve entrapment with focal pain or weakness to disuse muscle atrophy with mild weakness to severe myopathy or neuropathy with associated severe, prolonged weakness. It is likely that there is considerable overlap between the neuropathic and myopathic syndromes in terms of risk factors, presentation, and prognosis.

  1. Prospective studies suggest that neuromuscular abnormalities are present in 42% to 72% of patients in the ICU for 7 days or more and in 68% to 100% of patients with sepsis or the systemic inflammatory response syndrome. The ultimate role of corticosteroids and neuromuscular blocking agents in the pathogenesis of this problem is undefined.
  2. ICU-acquired neuromuscular abnormalities may result in severe weakness with flaccid quadriplegia that last for weeks or months. (This prolongs the duration of mechanical ventilation and is a significant contributor to mortality.)
  3. Preventionof acquired neuromuscular disorders in the ICU centers on avoidance or minimization of contributory risk factors, including high-dose steroids, prolonged administration of neuromuscular blockade, and hyperglycemia.
  4. Diagnosisof ICU-acquired neuromuscular abnormalities should be entertained in all critically ill patients with unexplained weakness; electrodiagnostic studies can help confirm the diagnosis and rule out other potentially treatable causes of weakness such as Guillain-Barré syndrome.
  5. Treatment.No treatment for ICU-acquired neuromuscular abnormalities has been identified; avoidance of potentially contributing agents and aggressive physical therapy are warranted.

Editors: Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K.; Cahalan, Michael K.; Stock, M. Christine

Title: Handbook of Clinical Anesthesia, 6th Edition

Copyright ©2009 Lippincott Williams & Wilkins

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