Sepsis and Organ(s) Dysfunction

Abstract

Sepsis is one of the most significant causes of morbidity and mortality in intensive care units. The incidence of sepsis is still frequent, and the high mortality rates associated with the disease is increasing in the critically ill. Worldwide, 13 million people become septic each year and 4 million die. The pathophysiology of sepsis remain an enigma and the natural history is ever evolving.

Appendix from Surviving Sepsis Campaign 2013

	Bundles 2012			Grade
	Initial Resuscitation and Infection Issues
Initial Resuscitation
1	Protocolized, quantitative resuscitation of patients with sepsis-induced tissue hypoperfusion (defined in this document as hypotension persisting after initial fluid challenge or blood lactate concentration ≥4 mmol/L) Goals during the first 6 h of resuscitation: a) Central venous pressure 8–12 mm Hg b) Mean arterial pressure (MAP) ≥65 mm Hg c) Urine output ≥0.5 mL/kg/h d) Central venous (superior vena cava) or mixed venous oxygen saturation 70 or 65 %, respectively			1C
2	In patients with elevated lactate levels targeting resuscitation to normalize lactate			2C
Screening for Sepsis and Performance Improvement
1	Routine screening of potentially infected seriously ill patients for severe sepsis to allow earlier implementation of therapy			1C
2	Hospital–based performance improvement efforts in severe sepsis			UG
	Diagnosis
1	Cultures as clinically appropriate before antimicrobial therapy if no significant delay (>45 min) in the start of antimicrobial(s)			1C
	At least two sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 h) inserted			1C
2	Use of the 1,3 beta-D-glucan assay and mannan and anti-mannan antibody assays if available, and invasive candidiasis is in differential diagnosis of cause of infection			2B
				2C
	Imaging studies performed promptly to confirm a potential source of infection			UG
	Antimicrobial Therapy
1	Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock			1B
	Administration of effective intravenous antimicrobials within the first hour of recognition of severe sepsis without septic shock			1C
2a	Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis			1B
2b	Antimicrobial regimen should be reassessed daily for potential deescalation			1B
3	Use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection			2C
4a	Combination empirical therapy for neutropenic patients with severe sepsis			2B
	Combination empirical therapy for patients with difficult-to-treat, multidrug-resistant bacterial pathogens such as Acinetobacter and Pseudomonas spp.			2B
	Combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone for patients with severe infections associated with respiratory failure and septic shock, for P. aeruginosa bacteremia			2B
	A combination of beta-lactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniae infections			2B
4b	Empiric combination therapy should not be administered for more than 3–5 days. De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known			2B
5	Duration of therapy typically 7–10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, bacteremia with S. aureus; some fungal and viral infections or immunologic deficiencies, including neutropenia			2C
6	Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin			Grade 2C
7	Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause			UG
Source Control
1	A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 h after the diagnosis is made, if feasible			1C
2	When infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred			2B
3	When source control in a severely septic patient is required, the effective intervention associated with the least physiologic insult should be used (e.g., percutaneous rather than surgical drainage of an abscess) (UG)			UG
4	If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established (UG)			UG
Infection Prevention
1a	Selective oral decontamination and SDD should be introduced and investigated as a method to reduce the incidence of ventilator-associated pneumonia; this infection control measure can then be instituted in health care settings and regions where this methodology is found to be effective			2B
1b	Oral chlorhexidine gluconate be used as a form of oropharyngeal decontamination to reduce the risk of ventilator-associated pneumonia in ICU patients with severe sepsis			2B
Fluid Therapy of Severe Sepsis
1	Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock			1B
2	Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock			1B
3	Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids			2C
4	Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid may be needed in some patients			1C
5	Fluid challenge technique be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic (e.g., change in pulse pressure, stroke volume variation) or static (e.g., arterial pressure, heart rate) variables			UG
Vasopressors
1	Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg			1C
2	Norepinephrine as the first choice vasopressor			1B
3	Epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure			2B
4	Vasopressin 0.03 units/min can be added to norepinephrine (NE) with intent of either raising MAP or decreasing NE dosage			UG
5	Low dose vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension and vasopressin doses higher than 0.03–0.04 units/min should be reserved for salvage therapy (failure to achieve adequate MAP with other vasopressor agents)			UG
6	Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (e.g., patients with low risk of tachyarrhythmias and absolute or relative bradycardia)			2C
7	Phenylephrine is not recommended in the treatment of septic shock except in circumstances where:			1C
	(a) norepinephrine is associated with serious arrhythmias
	(b) cardiac output is known to be high and blood pressure persistently low or
	(c) as salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target
8	Low-dose dopamine should not be used for renal protection			1A
9	All patients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available (UG)
Inotropic Therapy
1	A trial of dobutamine infusion up to 20 μg/kg/min be administered or added to vasopressor (if in use) in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP			1C
2	Not using a strategy to increase cardiac index to predetermined supranormal levels			1B
Corticosteroids
1	Not using intravenous hydrocortisone to treat adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (see goals for Initial Resuscitation). In case this is not achievable, we suggest intravenous hydrocortisone alone at a dose of 200 mg per day			2C
2	Not using the ACTH stimulation test to identify adults with septic shock who should receive hydrocortisone			2B
3	In treated patients hydrocortisone tapered when vasopressors are no longer required			2D
4	Corticosteroids not be administered for the treatment of sepsis in the absence of shock			1D
5	When hydrocortisone is given, use continuous flow			2D
Blood Product Administration
1	Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, such as myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic heart disease, we recommend that red blood cell transfusion occur only when hemoglobin concentration decreases to <7.0 g/dL to target a hemoglobin concentration of 7.0–9.0 g/dL in adults			1B
2	Not using erythropoietin as a specific treatment of anemia associated with severe sepsis			1B
3	Fresh frozen plasma not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures			2D
4	Not using antithrombin for the treatment of severe sepsis and septic shock			1B
5	In patients with severe sepsis, administer platelets prophylactically when counts are <10,000/mm3 (10 × 109/L) in the absence of apparent bleeding. We suggest prophylactic platelet transfusion when counts are <20,000/mm3 (20 × 109/L) if the patient has a significant risk of bleeding. Higher platelet counts (≥50,000/mm3 [50 × 109/L]) are advised for active bleeding, surgery, or invasive procedures			2D
Immunoglobulins
	Not using intravenous immunoglobulins in adult patients with severe sepsis or septic shock			2B
Selenium
	Not using intravenous selenium for the treatment of severe sepsis			2C
History of Recommendations Regarding Use of rhAPC
	The specific mechanisms by which drotrecogin alfa (activated) exerts its effect on survival in patients with severe sepsis are controversial, not completely understood and the evolution of SSC RECOMENDATIONS not recommended the use of rhAPC
Mechanical Ventilation of Sepsis-Induced ARDS
1	Target a tidal volume of 6 mL/kg predicted body weight in patients with sepsis-induced ARDS (vs. 12 mL/kg)			1A
2	Plateau pressures be measured in patients with ARDS and initial upper limit goal for plateau pressures in a passively inflated lung be ≤30 cm H2O			1B
3	Positive end-expiratory pressure (PEEP) be applied to avoid alveolar collapse at end expiration (atelectotrauma)			1B
4	Strategies based on higher rather than lower levels of PEEP be used for patients with sepsis-induced moderate or severe ARDS			2C
5	Recruitment maneuvers be used in sepsis patients with severe refractory hypoxemia			2C
6	Prone positioning be used in sepsis-induced ARDS patients with a Pao2/Fio2 ratio ≤100 mm Hg in facilities that have experience with such practices			2B
7	That mechanically ventilated sepsis patients be maintained with the head of the bed elevated to 30–45° to limit aspiration risk and to prevent the development of ventilator-associated pneumonia			1B
8	That noninvasive mask ventilation (NIV) be used in that minority of sepsis-induced ARDS patients in whom the benefits of NIV have been carefully considered and are thought to outweigh the risks			2B
9	That a weaning protocol be in place and that mechanically ventilated patients with severe sepsis undergo spontaneous breathing trials regularly to evaluate the ability to discontinue mechanical ventilation when they satisfy the following criteria:			1A
	(a) arousable
	(b) hemodynamically stable (without vasopressor agents)
	(c) no new potentially serious conditions
	(d) low ventilatory and end-expiratory pressure requirements
	(e) low Fio2 requirements which can be met safely delivered with a face mask or nasal cannula
	If the spontaneous breathing trial is successful, consideration should be given for extubation
10	Against the routine use of the pulmonary artery catheter for patients with sepsis induced ARDS			1A
11	A conservative rather than liberal fluid strategy for patients with established sepsis-induced ARDS who do not have evidence of tissue hypoperfusion			1C
12	In the absence of specific indications such as bronchospasm, not using beta 2-agonists for treatment of sepsis-induced ARDS			1B
Sedation, Analgesia, and Neuromuscular Blockade in Sepsis
1	Continuous or intermittent sedation be minimized in mechanically ventilated sepsis patients, targeting specific titration endpoints			1B
2	Neuromuscular blocking agents (NMBAs) be avoided if possible in the septic patient without ARDS due to the risk of prolonged neuromuscular blockade following discontinuation. If NMBAs must be maintained, either intermittent bolus as required or continuous infusion with train-of-four monitoring of the depth of blockade should be used			1C
3	A short course of NMBA of not greater than 48 h for patients with early sepsis-induced ARDS and a PaO2/Fio2 <150 mm Hg			2C
Glucose Control
1	A protocolized approach to blood glucose management in ICU patients with severe sepsis commencing insulin dosing when 2 consecutive blood glucose levels are >180 mg/dL. This protocolized approach should target an upper blood glucose ≤180 mg/dL rather than an upper target blood glucose ≤110 mg/dL			1A
2	Blood glucose values be monitored every 1–2 h until glucose values and insulin infusion rates are stable and then every 4 h thereafter			1C
3	Glucose levels obtained with point-of-care testing of capillary blood be interpreted with caution, as such measurements may not accurately estimate arterial blood or plasma glucose values			UG
Renal Replacement Therapy
1	Continuous renal replacement therapies and intermittent hemodialysis are equivalent in patients with severe sepsis and acute renal failure			2B
2	Use continuous therapies to facilitate management of fluid balance in hemodynamically unstable septic patients			2D
Bicarbonate Therapy
	Not using sodium bicarbonate therapy for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥ 7.15			2B
Deep Vein Thrombosis Prophylaxis
1	Patients with severe sepsis receive daily pharmacoprophylaxis against venous thromboembolism (VTE) with daily subcutaneous low-molecular weight heparin (LMWH)			1B
		(a) versus twice daily UFH		1B
		(b) versus three times daily UFH		2C
	If creatinine clearance is < 30 mL/min, use	(a) dalteparin		1A
		(b) another form of LMWH that has a low degree of renal metabolism		2C
		(c) UFH		1A
2	Patients with severe sepsis be treated with a combination of pharmacologic therapy and intermittent pneumatic compression devices whenever possible			2C
3	Septic patients who have a contraindication for heparin use (e.g., thrombocytopenia, severe coagulopathy, active bleeding, and recent intracerebral hemorrhage)
	a) not receive pharmacoprophylaxis			1B
	b) receive mechanical prophylactic treatment, such as graduated compression stockings or intermittent compression devices, unless contraindicated.			2C
	c) When the risk decreases start pharmacoprophylaxis			2C
Stress Ulcer Prophylaxis
1	Stress ulcer prophylaxis using H2 blocker or proton pump inhibitor be given to patients with severe sepsis/septic shock who have bleeding risk factors			1B
2	When stress ulcer prophylaxis is used, proton pump inhibitors rather than H2RA			2D
3	Patients without risk factors do not receive prophylaxis			2B
Nutrition
1	Administer oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock			2C
2	Avoid mandatory full caloric feeding in the first week but rather suggest low dose feeding (e.g., up to 500 calories per day), advancing only as tolerated			2B
3	Use intravenous glucose and enteral nutrition rather than total parenteral nutrition (TPN) alone or parenteral nutrition in conjunction with enteral feeding in the first 7 days after a diagnosis of severe sepsis/septic shock			2B
4	Use nutrition with no specific immunomodulating supplementation rather than nutrition providing specific immunomodulating supplementation in patients with severe sepsis			2C
Setting Goals of Care
1	Discuss goals of care and prognosis with patients and families			1B
2	Incorporate goals of care into treatment and end-of-life care planning, utilizing palliative care principles where appropriate			1B
3	Address goals of care as early as feasible, but no later than within 72 h of ICU admission			2C