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SEPSIS DAN EGDTReassess after 48-72 hours to narrow the spectrum of antibiotic therapy Duration of therapy should typically be 7-10 days and guided by clinical response Some experts prefer combination therapy for Pseudomonas infections or neutropenic patientsStop antimicrobials promptly if clinical syndrome is determined to be noninfectious3.Antibiotic TherapyGrade EGrade EGrade EGrade E7This particular recommendation was one of two which the consensus panel did not reach consensus. The solution was achieved with the inclusion of sub recommendations that expressed some difference in expert opinion. P. 860For neutropenic patients, broad-spectrum therapy usually must be continued for the duration of the neutropenia. p. 861Clinicians should be cognizant that blood cultures will be negative in the majority of cases of sepsis or septic shock. Thus, the decision to continue, narrow, or stop antimicrobial therapy must be made on the basis of clinician judgment and other culture results. p. 861Central Venous Pressure 8-12 mm Hg (12-15 in ventilator pts)Mean arterial pressure > 65 mm HgUrine output > 0.5 mL/kg/hrScvO2 or SvO2 70%; if not achieved with fluid resuscitation during first 6 hours: - Transfuse PRBC to hematocrit > 30% and/or - Administer dobutamine (max 20 mcg/kg/min) to goalResuscitation should begin as soon as severe sepsis or sepsis induced tissue hypoperfusion is recognizedElevated Serum lactate identifies tissue hypoperfusion in patients at risk who are not hypotensiveGoals of therapy within first 6 hours are

1.Initial Resuscitation-

3Establishing vascular access and initiating aggressive fluid resuscitation is the first priority when managing patients with severe sepsis or septic shock. p. 860Resuscitation should begin as soon as severe sepsis or sepsis-induced tissue hypoperfusion [hypotension or lactic acidosis] is recognized and should not be delayed pending ICU admission.Elevated serum lactate concentration identifies tissue hypoperfusion in patients at risk who are not hypotensive.Lactate measurement lacks precision as a measure of tissue metabolic status.Central venous and mixed venous oxygen saturation are equivalent.In mechanically ventilated patients a higher target central venous pressure 12-15 mm Hg is recommended to account for the increased intrathoracic pressure.Decrease in pulse is a useful marker of improving intravascular filling. The consensus panel judged central venous (superior vena cava) and mixed venous oxygenation to be equivalent.Rationale for this recommendation is based on Manny Rivers protocol published in NEJM. This protocol was associated with an improvement in survival.

NOTE: The references listed in the right hand corner of the slide relate to recommendations on the slide. When the slides are viewed in the show mode, clicking on the reference will automatically take you to an abstract of the specific study (this is only if your computer is connected to the internet and has access to Pubmed.)

Protocol for Early Goal-Directed TherapySupplement O2 Endotracheal intubationsMechanical ventilationCentral venous and arterial catheterizationSedation, Paralysis (if intubated), or bothCVP MAPScvO2CrystalloidColloid< 8 mmHgVasoactive agents< 65 mmHg> 90 mmHg8 12 mmHg65 90 mmHg 70%Goal achieved

Transfusion of RC until Ht 30% 70%< 70%Inotropic agentsHospital admissionYesNo< 70%Before the initiation of antimicrobial therapy, at least two blood cultures should be obtainedAt least one drawn percutaneously At least one drawn through each vascular access device if inserted longer than 48 hoursOther cultures such as urine, cerebrospinal fluid, wounds, respiratory secretions or other body fluids should be obtained as the clinical situation dictatesOther diagnostic studies such as imaging and sampling should be performed promptly to determine the source and causative organism of the infection may be limited by patient stabilityGrade DGrade E

2.DiagnosisGrade D5Do not need to draw a blood culture through vascular access devices that were recently inserted (2hrs) then the PAD might be the source of infection.Volume of blood may also be important

Start intravenous antibiotic therapy within the first hour of recognition of severe sepsis after obtaining appropriate cultures Empirical choice of antimicrobials should include one or more drugs with activity against likely pathogens, both bacterial or fungalPenetrate presumed source of infectionGuided by susceptibility patterns in the community and hospitalContinue broad spectrum therapy until the causative organism and its susceptibilities are defined3.Antibiotic TherapyGrade E

Grade D6May require additional vascular access portsAn empirical antimicrobial regimen should have coverage for all likely pathogens since there is little margin for error in critically ill patients.Failure to initiate appropriate therapy promptly has adverse consequences on outcomes.Once the organism and its susceptibilities have been defined narrowing the spectrum of antibiotics reduces the risk of resistance, superinfections and costs.Due to renal and hepatic dysfunction in severe sepsis patients and due to the altered volume of distribution, it is recommended to involve the ICU pharmacist to ensure serum concentrations are attained that maximize efficacy and minimize toxicity.Establishing vascular access and initiating aggressive fluid resuscitation is the first priority when managing patients with severe sepsis or septic shock. (p. 860) However, prompt infusion of antimicrobial agents is also a logical strategy and may require additional access ports.

Evaluate patients for focus of infection amenable to source control measures Drainage of an abscess or local focus of infectionDebridement of infected necrotic tissueRemoval of a potentially infected deviceDefinitive control of a source of ongoing microbial contaminationSource control methods must weigh benefits and risks of the specific intervention 4.Source ControlGrade EGrade E8Clinical judgmentEngage other specialists in other disciplines such as radiology, surgery, pulmonary medicine and gastroenterology in caring for sepsis patients.Example: Percutaneous rather than surgical drainage of an abscessOnce a focus of infection has been identified, source control should be implemented as soon as possible following initial resuscitation Especially important for patients with necrotizing soft tissue infection or intestinal ischemiaIf intravascular access devices are suspected to be the source of infection, remove them promptly after establishing other vascular access It may be reasonable to leave access devices in place when patients develop sepsis of unknown source, until the source of infection is determinedSource Control (cont)Grade EGrade E9Source control intervention should only take place following adequate initial resuscitation and when a focus of infection is amenable to source control measures.Case series and expert opinion support rapid correction of a source of microbial contamination to maximize survival of septic patients. See the example above at the end of the slideClinicians should consider removal and replacement of vascular access devices to be a priority, even if the device is tunneled or surgically implanted.Intravascular access devices are thought to be the source of the majority of nosocomial bloodstream infections.

Source Control: Examples of Potential SitesDrainageIntra-abdominal abscess - Septic arthritisThoracic empyema - Pyelonephritis, cholangitisDebridementNecrotizing fasciitis - MediastinitisInfected pancreatic necrosis - Intestinal infarctionDevice RemovalInfected vascular catheter Urinary catheter Colonized endotracheal tubeDefinitive ControlSigmoid resection for diverticulitis Amputation for clostridial myonecrosisCholecystectomy for gangrenous cholecystitis Fluid resuscitation may consist of natural or artificial colloids or crystalloidsNo evidenced-based support for one type of fluid over anotherCrystalloids have a much larger volume of distribution compared to colloidsCrystalloid resuscitation requires more fluid to achieve the same endpoints as colloidCrystalloids result in more edema5a.Fluid Therapy: Choice of FluidGrade C11No evidence-based support for one type of crystalloid over anotherNo studies that are specific to sepsis populationNote: since development of these guidelines the preliminary results of the SAFE (Fluid resuscitation with Albumin vs. Saline) study results have been reported at the Society of Critical Care Medicine National Scientific Meeting held in Feb. 2004. This randomized controlled trial of over 7,000 patients demonstrated that in the subset of severe sepsis patients there was a mortality benefit with albumin over saline (RR .087; CI 0.74-1.02). This data set was locked in late 2003; therefore, final manuscript publication is pending.

Fluid challenge in patients with suspected hypovolemia may be given500 - 1000 mL of crystalloids over 30 mins300 - 500 mL of colloids over 30 minsRepeat based on response and toleranceInput is typically greater than output due to venodilation and capillary leakMost patients require continuing aggressive fluid resuscitation during the first 24 hours of management5a.Fluid Therapy: Fluid ChallengeGrade E12Fluid Challenge describes the initial volume expansion period in which the patients response is closely monitored. Fluid Challenge must be clearly separated from an increase in maintenance fluid administrationResponse may be measured by increase in blood pressure and urine outputTolerance may be measured by evidence of intravascular volume overloadInput/output ratio is of no utility to judge fluid resuscitation during this time periodInitiate vasopressor therapy if appropriate fluid challenge fails to restore adequate blood pressure and organ perfusionVasopressor therapy should also be used transiently in the face of life-threatening hypotension, even when fluid challenge is in progress Either norepinephrine or dopamine are first line agents to correct hypotension in septic shockNorepinephrine is more potent than dopamine and may be more effective at reversing hypotension in septic shock patients Dopamine may be particularly useful in patients with compromised systolic function but causes more tachycardia and may be more arrhythmogenic 6.VasopressorsGrade EGrade D13Perfusion becomes dependent on pressure below a certain mean arterial pressure because autoregulation in various vascular beds can be lost. Supplement goal such as blood pressure with the assessment of global perfusion such as blood lactate concentrationsDopamine increases mean arterial pressure and cardiac output due to an increase in stroke volume and heart rateNorepinephrine increases mean arterial pressure due to vasoconstrictive effectsNorepinephrine causes little change in heart rate and less increase in stroke volume compared to dopamineDopamine causes more tachycardia and may be more arrhythmogenic

Low dose dopamine should not be used for renal protection in severe sepsisAn arterial catheter should be placed as soon as practical in all patients requiring vasopressorsArterial catheters provide more accurate and reproducible measurement of arterial pressure in shock states when compared to using a cuff

Vasopressin may be considered in refractory shock patients that are refractory to fluid resuscitation and high dose vasopressorsInfusion rate of 0.01-0.04 units/min in adultsMay decrease stroke volume

Vasopressors (cont)Grade BGrade EGrade E14Arterial catheter placement in an emergency department is typically not possible or practical.Vasopressin is a direct vasoconstrictor without inotropic or chronotropic effects and may result in decreased cardiac output and hepatosplanchnic flow. Most published reports exclude patients from treatment with vasopressin if the cardiac index is < 2 or 2.5.Low doses of vasopressin may be effective in raising blood pressure in patients refractory to other vasopressors, although no outcome data are available.

In patients with low cardiac output despite adequate fluid resuscitation, dobutamine may be used to increase cardiac output Should be combined with vasopressor therapy in the presence of hypotension It is not recommended to increase cardiac index to target an arbitrarily predefined elevated level Patients with severe sepsis failed to benefit from increasing oxygen delivery to supranormal levels by use of dobutamineInotropic TherapyGrade EGrade A15Dobutamine is the first-choice inotrope for patients with measured or suspected low cardiac output in the presence of adequate left ventricular filling pressure (or clinical assessment of adequate fluid resuscitation) and adequate mean arterial pressure.The goal of resuscitation should be to achieve adequate levels of oxygen delivery or avoid flow dependent tissue hypoxia.Two large prospective clinical trials that included critically ill ICU patients who had severe sepsis failed to demonstrate benefit from increasing oxygen delivery to supranormal levels by use of dobutamine. P. 863

Intravenous corticosteroids are recommended in patients with septic shock who require vasopressor therapy to maintain blood pressureAdminister intravenous hydrocortisone 200-300 mg/day for 7 days in three or four divided doses or by continuous infusionShown to reduce mortality rate in patients with relative adrenal insufficiency7.SteroidsGrade C16Adrenal insufficiency is defined as post-adrencorticotropic hormone [ACTH] cortisol increase < 9 mcg/dL within 30-60 mins post ACTH administrationThis was one of two recommendations that did not achieve total consensus. The solution was achieved with the inclusion of sub recommendations that expressed some difference in expert opinion. P. 860.May use 250 mcg ACTH stimulation test to identify responders and discontinue therapy in these patientsResponders can be defined as >9 mcg/dL increase in cortisol 30-60 minutes post ACTH administrationClinicians should not wait for ACTH stimulation test results to administer corticosteroidsAfter the resolution of septic shock, may decrease dosage of steroidsConsider tapering the dose of corticosteroids at the end of therapyMay add fludrocortisone to the hydrocortisone regimenSteroidsGrade E17Adrenal insufficiency is defined as post-adrencorticotropic hormone [ACTH] cortisol increase < 9 mcg/dL within 30-60 mins post ACTH administrationThese sub recommendations were developed because the panel could not reach complete consensus on the specific recommendation for use of low dose replacement steroid therapy for adrenal insufficiency.One study added 50 mcg of fludrocortisone orally. Since hydrocortisone has intrinsic mineralocorticoid activity, there is controversy as to whether fludrocortisone should be added. P. 863Doses of hydrocortisone >300 mg daily should NOT be used in septic shock or severe sepsis for the purpose of treating shock In the absence of shock, corticosteroids should not be used for treatment of sepsisSteroidsGrade AGrade E18No contraindications to continuing maintenance steroids if the patients endocrine history warrantsHigh dose corticosteroid therapy was found ineffective or harmful for treatment of severe sepsis or septic shock (based on results of two RCT studies and two meta-analyses).May maintain higher steroid doses for other medical condition other than septic shock

Recombinant human Activated Protein C [Drotrecogin alfa (activated)] is recommended in patients at a high risk of death APACHE II score 25, orSepsis-induced multiple organ failure, orSeptic shock, orSepsis induced acute respiratory distress syndromeTreatment with drotrecogin alfa (activated) should begin as soon as possible once a patient has been identified as being at high risk of deathPatients should have no absolute or relative contraindication related to bleeding risk that outweighs the potential benefit of rhAPC7. Recombinant human Activated Protein CGrade B19The inflammatory response in severe sepsis is integrally linked to procoagulant activity and endothelial activation. p. 863.The inflammatory response in sepsis is procoagulant in the early stages. P. 863rhAPC [drotrecogin alfa (activated)] has been shown, in a large, multiple center, randomized, controlled trial to improve survival in patients with sepsis-induced organ dysfunction. p. 863.At present, risk assessment is best determined by bedside clinical evaluation and judgment. Given the uncertainty of risk assessment and the potential for rapid deterioration of patients with severe sepsis and septic shock, once a patient has been identified as at high risk of death, treatment should begin as soon as possible. p. 863Contraindications to use of rhAPCrhAPC (drotrecogin alfa [activated]) increases the risk of bleeding. rhAPC is contraindicated in patients with the following clinical situations in which bleeding could be associated with a high risk of death or significant morbidity:Active internal bleedingRecent (within 3 months) hemorrhagic strokeRecent (within 2 months) intracranial or intraspinal surgery, or severe head traumaTrauma with increased risk of life-threatening bleedingPresence of an epidural catheterIntracranial neoplasm or mass lesion or evidence of cerebral herniationSee labeling instructions for relative contraindications (i.e. warnings)The committee recommends that platelet count be maintained at 30,000 during infusion of rhAPC20From appendix B of SSC Guidelines, p. 872.

Relative Contraindications are the listed as warnings in the drotrecogin alfa (activated) US package insert. These warnings are:

For patients with severe sepsis who have one or more of the following conditions, the increased risk of bleeding should be carefully considered when deciding whether to use drotrecogin alfa (activated) therapy: -Concurrent therapeutic heparin-Platelet count 30,000 x 106/L, even if the platelet count is increased after transfusions-Prothrombin time-INR 3.0-Recent (within 6 weeks) gastrointestinal bleeding-Recent administration (within 3 days) of thrombolytic therapy-Recent administration (within 7 days) of oral anticoagulants or glycoprotein IIb/IIIa inhibitors -Recent administration (within 7 days) of aspirin >650 mg/d or other platelet inhibitors -Recent (within 3 months) ischemic stroke -Intracranial arteriovenous malformation or aneurysm -Known bleeding diathesis -Chronic severe hepatic disease -Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location

An additional absolute contraindication to rhAPC therapy is: Drotrecogin alfa (activated) is contraindicated in patients with known hypersensitivity to drotrecogin alfa (activated) or any component of this product

Red blood transfusion should occur only when hemoglobin decreases to < 7 g/dL Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances such as significant coronary artery disease, acute hemorrhage or lactic acidosisTarget hemoglobin of 7 9 g/dLErythropoietin is not recommended for specific treatment of anemia associated with severe sepsis Unless septic patients have other accepted reasons for administration of erythropoietin Routine use of fresh frozen plasma to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures is not recommended8.Blood Product AdministrationGrade BGrade BGrade E21The Transfusion Requirements in Critical Care trial suggested that a hemoglobin of 7-9 g/dL is adequate for most critically ill patients. A transfusion threshold of 7 g/dL was not associated with increased mortality. P. 863Red Blood Transfusion in septic patients increases oxygen delivery but does not usually increase oxygen consumptionThis transfusion threshold contrasts with the target of a hematocrit of 30% in patients with low central venous oxygen saturation during the first 6 hrs. of resuscitation of septic shock. (Rivers, NEJM, 2001, vol. 345.An example of other accepted reasons for administration of erythropoietin in severe sepsis patients is renal failure induced compromise of red blood cell production.

It is not recommended to use antithrombin for the treatment of severe sepsis or septic shockHigh dose antithrombin in a phase III trial did not demonstrate a beneficial effect on 28-day mortality and was associated with increased risk of bleeding when administered with heparinPlatelets should be administered when platelet counts are < 5000/mm3 regardless of apparent bleeding Platelet transfusion may be considered when counts are 5000 - 30,000/mm3 and there is a significant risk of bleedingPlatelet counts 50,000/ mm3 are typically required for surgery or invasive proceduresBlood Product Administration (cont)Grade BGrade E22Phase III clinical trial of high dose antithrombin did not demonstrate any beneficial effect on 28 day all cause mortality in adults with severe sepsis or septic shock.Recommendations for platelet transfusions are based on experience with patients undergoing chemotherapy.Recommendations for platelet transfusions take into account the etiology of thrombocytopenia, platelet dysfunction, risk of bleeding, and presence of concomitant disorders. P. 864

High tidal volumes, > 6 ml/kg, coupled with high plateau pressures, > 30 cm H2O, should be avoided Hypercapnia can be tolerated in patients with ALI/ARDS if required to minimize plateau pressures and tidal volumes A minimum amount of positive end expiratory pressure should be set to prevent lung collapse at end-expiration9.Mechanical Ventilation of Sepsis-Induced Acute Lung Injury (ALI)/ARDSGrade BGrade CGrade E23Start a reduction in tidal volumes over 1-2 hours to a low tidal volume (6 mL per kilogram of predicted body weight) as a goal in conjunction with the goal to maintain end inspiratory plateau pressures < 30 cm H2O.The largest trial of a volume- and pressure-limited strategy showed a 9% decrease of all-cause mortality in patients ventilated with tidal volumes of 6 mL/kg of predicted body weight (as opposed to 12 mL/kg) while aiming for a plateau pressure < 30 cm H20 above two goals reduce mortality in ventilated patients. p. 864 Hypercapnia is contraindicated in patients with elevated intracranial pressure and should be limited in patients with preexisting metabolic acidosis.Sodium bicarbonate infusion may be considered in select patients to facilitate use of permissive hypercarbia. P. 864

In experienced facilities, prone positioning should be considered in ARDS patients requiring potentially injurious levels of FiO2 or plateau pressure who are not at high risk for adverse consequences to positioning changes

Unless contraindicated, mechanically ventilated patients should be maintained semirecumbent with the head of the bed raised to 45 to prevent ventilator associated pneumoniaMechanical Ventilation of Sepsis-Induced Acute Lung Injury (ALI)/ARDSGrade EGrade C24Potentially life threatening complications to prone positioning include accidental dislodgement of the endotrachael tube and central venous catheters.Several studies have demonstrated that a majority of patients with ALI/ARDS respond to the prone position with improved oxygenation.

A weaning protocol should be in place and mechanically ventilated patients should undergo spontaneous breathing trial when they satisfy the following criteria: ArousableLow ventilatory and end expiratory pressure requirementsNo new potentially serious conditionsHemodynamically stable without vasopressorsRequiring levels of FiO2 that could be delivered with a face mask or nasal cannula Mechanical Ventilation of Sepsis-Induced Acute Lung Injury (ALI)/ARDSGrade A25Spontaneous breathing trial options include a low level of pressure support with continuous positive airway pressure 5 cm H2O or a T-pieceProtocols should be used when sedation of critically ill mechanically ventilated patients is required The protocol should include the use of a sedation goal, measured by a standardized subjective sedation scale

Intermittent bolus or continuous infusion sedation are recommended to predetermined end points With daily interruptions/lightening of continuous infusion sedation with awakening and retitration, if necessary9.Sedation, Analgesia, and Neuromuscular Blockade in SepsisGrade BGrade B26The use of protocols and daily interruption/lightening of continuous sedative infusion have shown to reduce the duration of mechanical ventilation and length of stay and tracheostomy rates.

Neuromuscular blockers should be avoided in the septic patient due to the risk of prolonged neuromuscular blockadeIf needed for more than the first hour of mechanical ventilation, either intermittent bolus as required or continuous infusion with monitoring of depth of block with train of four monitoring should be used Sedation, Analgesia, and Neuromuscular Blockade in SepsisGrade E27Prolonged skeletal weakness has been reported in critically ill patients following the use of intermediate and long acting neuromuscular blockers.Intermittent assessment of the depth of neuromuscular blockade reduces the risk of prolonged paralysis.Following initial stabilization of patients with severe sepsis, maintain blood glucose to < 150 mg/dLBest results obtained when blood glucose was maintained between 80 and 110 mg/dLGlycemic control strategy should include a nutrition protocol with the preferential use of the enteral routeMinimize the risk of hypoglycemia by providing a continuous supply of glucose substrate Accomplished by using 5% or 10% dextrose IV infusion and followed by initiation of feeding preferably by enteral route

10.Glucose ControlGrade DGrade E28This recommendation stems from a large, single center trial of postoperative surgical patients but the panel sees no reason to think that these data are not generalizable to all severely septic patients.Glucose monitoring should be frequent every 30-60 minutes after initiation of the protocol and on a regular basis once the blood glucose concentration has stabilized (e.g., every 4 hrs).Risk of hypoglycemia.Note the glycemic goal in the clinical trial was 80-110 mg/dL but generalized to 150 mg/dL in this guideline to reduce risk of hypoglycemia. Post hoc data analysis revealed that best results were obtained when glucose was maintained at 80-110 mg/dL; however, glucose of < 150 mg/dL also showed improved outcome compared to higher glucose concentrations.The frequency of blood glucose determinations may require the use of central or arterial catheters for blood sampling.Continuous hemofiltration offers easier management of fluid balance in hemodynamically unstable septic patients 11.Renal ReplacementGrade B Continuous venovenous hemofiltration and intermittent hemodialysis are considered equivalent in acute renal failure (in the absence of hemodynamic instability)

29There is no current evidence to support the use of continuous venovenous hemofiltration for the treatment of sepsis independent of renal replacement needs. p. 865 No difference revealed in vasopressor requirements or hemodynamic variables between bicarbonate and normal saline for treating hypoperfusion-induced acidemiaEffects of bicarbonate therapy at pH levels < 7.13 have not been studied12.Bicarbonate TherapyGrade C Bicarbonate is not recommended for the purpose of improving hemodynamics or reducing vasopressor requirements for the treatment of hypoperfusion induced lactic acidemia with pH 7.15Use a mechanical prophylactic device or intermittent compression in patients with contraindications to heparin Use a combination of pharmacological and mechanical therapy in very high risk patients (eg, severe sepsis and history of DVT)12.Deep Vein Thrombosis (DVT) Prophylaxis Grade A DVT prophylaxis with either low-dose unfractionated heparin or low molecular weight heparin should be used in severe sepsis patients31Examples of heparin contraindications: thrombocytopenia, severe coagulopathy, active bleeding, and recent intracerebral hemorrhage.Mehanical prophylactic device examples: graduated compression stockings and intermittent compression devices.Contraindication for use of mechanical prophylactic device includes the presence of peripheral vascular disease.There are no studies performed specifically in patients with severe sepsis; however, large trials confirm the benefit of DVT prophylaxis in general ICU populations that included significant numbers of septic patients.H2 receptor blockers are more efficacious than sucralfate and are the preferred agents Proton pump inhibitors compared to H2 blockers have not been assessed

13.Stress Ulcer ProphylaxisGrade AStress ulcer prophylaxis should be given to all patients with severe sepsis

32Proton pump inhibitors and H2 blockers equivalently lower gastric pH.Other conditions that benefit from stress ulcer prophylaxis that are also present in severe sepsis are coagulopathy, mechanical ventilation, hypotension. Decisions for less aggressive support or withdrawal of support may be in the patients best interest (Withholding or Withdrawing)

Consideration for Limitation of SupportGrade EAdvance care planning, including the communication of likely outcomes and realistic goals of treatment, should be discussed with patients and families

33It is too frequent that inadequate physician/family communication characterizes end-of-life care in the ICU. The level of life support given to ICU patients may not be consistent with their wishes. Early and frequent caregiver discussions with patients who face death in the ICU and their loved ones may facilitate appropriate application and withdrawal of life-sustaining therapies. p. 866Thank You