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Sepsis: Immune Response Meltdown

Module 8

Supportive Therapy of Severe Sepsis

Supportive therapies include blood product administration, mechanical ventilation, sedation, anesthesia and neuromuscular blockade, glucose control, renal replacement therapy, DVT prophylaxis, and good nutrition.

Blood Product Administration

Guidelines suggest that septic patients with hematocrits below 30% should receive a transfusion of packed red blood cells. After the resuscitation phase of treatment, and when tissue perfusion has improved, red blood cell transfusion should occur only with a hemoglobin concentration of less than 7.0 g/dl (Dellinger et al., 2013b).

Platelets can be given:

  • If the platelet count is <10,000/mm3 in the absence of apparent bleeding or
  • If the platelet count is <20,000/mm3 when there is a significant risk of bleeding or
  • If surgery or invasive procedures are planned, transfusion may occur with platelet counts ≥50,000/mm3 (Dellinger et al., 2013b)

The Guidelines recommend against the use of erythropoietin for anemia and against the use of fresh frozen plasma (FFP) in the absence of bleeding or planned invasive procedure.


The Guidelines recommend against the use of immunoglobulins and selenium because there is not enough evidence of benefit in severe sepsis (Buckman, 2013).

Mechanical Ventilation

In severe sepsis, patients will likely require mechanical ventilation at some point during their hospitalization. Mechanical ventilation reduces the work of the respiratory muscles and can reduce the body’s production of lactic acid. In addition, when patients are being ventilated mechanically, their respiratory muscles need less blood flow, freeing more of the cardiac output for other hypoperfused tissues.

Mechanical ventilation increases intra-airway pressures by actively pushing air into the lungs. Inflating the lungs using internal pressure increases the overall intrathoracic pressure; in turn, the increased intrathoracic pressure can compress the heart and great vessels and lower the mean arterial pressure, especially in conjunction with the relaxant drugs used to maintain intubation.

The hypotension that sometimes occurs with positive pressure mechanical ventilation is more common when the patient is hypovolemic, so additional fluids may improve the blood pressure levels (Kress & Hall, 2008).

To minimize lung injury, patients are usually ventilated using positive end expiratory pressure at low tidal volumes (6 ml/kg body wt) and low plateau pressures <30 cm H2O. Elevating the head of the patient’s bed 30 to 45 degrees helps to prevent aspiration and ventilator pneumonias (Buckman, 2013).


Clinical Indicators of the Need for Mechanical Ventilation

  • Central venous oxygen saturation cannot be maintained >70%
  • Severe acidosis
  • Reduced level of consciousness, making patients unable to protect their airways
  • Work of breathing becomes exhausting. Clinically, fatigue of the respiratory muscles is likely when the rate of respiration is high (>40 breaths/min), the patient is unable to complete a full sentence without taking additional breaths, or the patient is using accessory muscles of respiration
  • ARDS has developed

Source: Ely & Goyette, 2005.



The discontinuation of mechanical ventilation is crucial and should be based on a weaning protocol to assess readiness of successful extubation, reducing the duration and the complications related with it (Boodoosingh, 2012). To recognize when patients can be taken off mechanical ventilation, they should be given daily trials of spontaneous breathing. A trial begins with a check for the necessary baseline conditions:

  • Cough and other airway reflexes working
  • Arousable
  • Hemodynamically stable (without vasopressor agents)
  • No new potentially serious conditions
  • Low ventilatory and end-expiratory requirements
  • Low FIO2 requirements that can be met and safely delivered with a face mask or nasal cannula (Buckman, 2013)

If the spontaneous breathing trial is successful, consideration should be given to extubation. If these conditions are met, the patient is asked to breathe through the endotracheal tube for 30 to 120 minutes without the aid of the ventilator.

A trial is stopped and the ventilator is reattached if the patient’s:

  • Respiratory rate increases to >35 breaths/min for >5 min or
  • Oxygenation saturation drops below 90% or
  • Heart rate increases to >140 beats/min or the heart rate increases or decreases >20% from its baseline
  • Systolic blood pressure drops to <90 mm Hg or rises to >180 mm Hg
  • The patient’s anxiety level or sweating increases
  • A patient who has none of these problems during the test period and who ends with a respiratory rate-to-tidal volume ratio of <105 can then be extubated.

Source: Kress & Hall, 2008; Buckman, 2013.


Answer: C

Test Your Knowledge

In septic patients, mechanical ventilation is:

  1. Used as a last resort because of the difficulty of weaning patients from dependence on the machine.
  2. Needed only when vasopressors are being used to treat hypotension.
  3. Commonly needed.
  4. Rarely needed.

Sedation, Anesthesia, and Neuromuscular Blockade

The Guidelines recommend:

  • Minimal use of sedation during mechanical ventilation
  • Avoiding neuromuscular blocking agents in patients without ARDS
  • A short course of neuromuscular blockers in patients with ARDS (Buckman, 2013)

Glucose Control

Hyperglycemia is induced by stress and infection, and it is common in critically ill patients, even patients who have no history of diabetes (Schmidt & Mandel, 2013). Hyperglycemia worsens sepsis by many routes. Hyperglycemia promotes inflammation, it hinders normal immune functioning, and it activates the extrinsic blood coagulation pathway. Consistently high levels of blood glucose also alter the body’s fluid balance and directly damage the kidneys and the peripheral nerves, among other tissues (Munford, 2008).

The prevalence of hyperglycemia in critically ill patients can be as high as 50% to 75%. Historically, moderate hyperglycemia was considered at best to be an adaptive response to critical illness, and at worst a marker of severity of disease. However, several studies have clearly demonstrated an association between hyperglycemia and mortality in both adult and pediatric nondiabetic critically ill patients (Choong, 2012).

It is recommended that blood glucose levels be kept <180mg/dl for septic patients and that insulin should be used after two consecutive readings that are >180 to control episodes of hyperglycemia. Patients on intravenous insulin need a scheduled source of glucose calories, and their blood glucose levels must be monitored regularly (every 1–2 hours at first, and every 4 hours when the blood values are stable) (Buckman, 2013).

Renal Replacement Therapy

Acute kidney injury (AKI), a complex disorder with clinical manifestations ranging from a minimal elevation in serum creatinine to anuric renal failure, is a frequent and serious complication of sepsis in ICU patients. Septic AKI, which accounts for 50% or more of AKI cases in ICUs, is associated with a very high mortality. Although medical practice has advanced in the last decade, the pathophysiology of sepsis-induced AKI is incompletely understood. Current treatments for sepsis-induced AKI including intensive insulin therapy and early goal-directed therapy have been reported to be beneficial; however, there are still no radical treatments to completely treat septic AKI (Choong, 2012).

The Surviving Sepsis Guidelines for 2012 recommend continuous renal replacement therapies (CRRT) or intermittent hemodialysis as equivalent therapies in patients with severe sepsis and acute renal failure (Dellinger et al., 2013b). CRRT is continuous extracorporeal blood purification with target replacement fluid rates of 20 to 30 ml/kg/hr. Bicarbonate or citrate-based replacement solutions are used. A 1:1 nursing ratio is employed for all patients on CRRT (Allegretti et al., 2013).

There are currently no drugs that can protect the kidney during an episode of sepsis. The best the clinician can do is to avoid additional damage. When under-perfused, the kidneys are especially vulnerable to injury from drugs, so physicians should avoid administering any medicines that are kidney stressors or are potentially nephrotoxic. According to Ely and Goyette (2005), the use of nonsteroidal anti-inflammatory drugs used to treat fever can actually inhibit prostaglandin production and impair the kidney’s ability to regulate blood flow and pressure.

Therefore, when a required drug is potentially nephrotoxic (eg, the aminoglycosides), it should be given in doses adjusted for the patient’s level of kidney function.

If it appears that acute kidney failure is beginning (lab results show high BUN, high serum creatinine, hyperkalemia, acidosis, or volume overload) either intermittent hemodialysis or continuous renal replacement therapy can be instituted for most patients. Patients who are hemodynamically unstable, though, do better on continuous renal replacement therapy (Dellinger et al., 2013b). It can take weeks for survivors of sepsis to regain their normal kidney function.

DVT Prophylaxis

Immobile patients are at risk for developing thrombi in the deep veins of their lower limbs with the potential for emboli to the lungs and elsewhere. The pneumonic is often used “Legs to Lungs and Heart to Head, ” which is a reminder that a leg DVT will generally move to the lungs and an embolism of the heart will travel to the head. This risk increases in a septic patient, who is likely to be elderly and to have a central venous access device in place. Remember that in patients with severe sepsis the coagulation system is usually headed toward clotting rather than fibrinolysis.

The recommended deep-vein thrombosis prophylaxis for patients with sepsis begins with a combination of low molecular weight heparin (LMWH) and intermittent mechanical compression devices. If heparinization is contraindicated, such as when the patient has active bleeding, low platelet counts, or a recent intracerebral hemorrhage, compression stockings or other compression devices are recommended (Buckman, 2013).

Stress Ulcer Prophylaxis

Patients with severe sepsis are at risk for developing upper GI bleeds. This risk is greatest in a patient who is on mechanical ventilation, who has a coagulopathy, or who has a history of peptic ulcer disease. Therefore, an H2-blocker (eg, ranitidine) or a proton pump inhibitor (eg, omeprazole) should be considered as part of the routine for sepsis. More recent meta-analyses suggest that proton pump inhibitors may provide more protection against GI bleed than H2 blockers. A qualifier to this recommendation is that a decrease in stomach acid production will increase the risk of pneumonia in a ventilated patient (Dellinger et al., 2013b).


A patient with sepsis will be in the ICU for 1 to 2 weeks. Proper nutrition can shorten the stay. Feeding via the gastrointestinal tract is preferred. According to Ely and Goyette (2005):

Enteral nutrition offers several advantages, including lower cost, preservation of the GI mucosal barrier, buffering of gastric acid, preservation of enteral hormone secretion, provision of unique nutrients, decreased incidence of infections, improved wound healing, and avoidance of parenteral nutritional catheters and their complications.

For patients receiving enteral feedings, the head of the bed should be elevated 30 to 40 degrees (Morrell et al., 2009).

Secondary positive outcomes of enteral feedings include (Buckman, 2013):

  • Reductions in infectious complications
  • Reduced length of mechanical ventilation
  • Reduced ICU and hospital stays

The 2012 nutritional guidelines for septic patients include (Buckman, 2013):

  • Administer oral or enteral feedings rather than complete fasting or administration of IV glucose within the first 48 hours after diagnosis.
    • Enteral feedings are given through a nasogastric (NG) tube for short-term use or through a tube surgically placed into the stomach
  • Avoid full-caloric feedings during the first week. Low dose feedings are recommended of up to 500 calories/day if the patient can tolerate them.
  • Use IV glucose and enteral nutrition rather than total parenteral nutrition (TPN) alone or TPN with enteral feeding in the first days after diagnosis.


Answer: A

Test Your Knowledge

Combating hyperglycemia by limiting blood glucose levels in septic patients to <180 mg/dl:

  1. Should be done using insulin.
  2. Is critical for diabetic patients but not necessary for non-diabetics.
  3. Will worsen survival rates and should be avoided.
  4. Should be done by restricting glucose intake.

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Body Temperature

Sepsis often produces an abnormal body temperature—either fever (>38°C) or hypothermia (<36°C). Typically, the body corrects its temperature after the septic infection has been controlled.


Usually, mild fever in a septic patient can simply be watched cautiously, but higher temperatures (>40°C) should be treated, especially in patients with pre-existing heart, lung, or brain disease. Feverish patients can be given antipyretics (eg, acetaminophen). Alternately, cooling blankets or tepid water sponging can be used. Fever increases the body’s consumption of energy and oxygen, and this will worsen the effects of poor tissue perfusion from sepsis.

Hypothermia and Shivering

Mild hypothermia usually improves with a blanket. Shivering increases the patient’s energy and oxygen use, and persistent shivering is often treated with meperidine.

Setting Goals of Care

Vincent and colleagues report (2011):

Death in the ICU is now often preceded by a decision to withhold or withdraw potentially life-sustaining treatments. . . [One recent analysis found that] potentially life-sustaining treatments were withheld or withdrawn before death [for 91% of the patients who eventually died]. Approximately two-thirds of these patients had treatments withdrawn because death was imminent and one-third because the treatments were judged to be inappropriate.

The technical support of a gravely ill patient in an ICU can dominate the patient’s last days and nights and leave little room for the human interactions that many patients and their families want. It is important for ICU doctors and nurses to talk with their patients and the patients’ families about their desires for continued treatment. It may be in the patient’s best interest to provide less-aggressive life-sustaining treatments or to withdraw life-sustaining treatments (Dellinger et al., 2013b).

Giving realistic information early and allowing patients and families to talk about their wishes can reduce the levels of anxiety and depression that the circumstances can produce (Dellinger et al., 2013b).

The Guidelines recommend that goals of care and prognosis be discussed with the patient and family and that they be incorporated into the treatment and end-of-life planning. Palliative care principles should be used where appropriate. These goals need to be addressed as soon as feasible, but no later than 72 hours after ICU admission (Buckman, 2013).

The guidelines promote early and repeated care-conferencing with consideration of spiritual and cultural differences. Palliative care includes:

  • Pain management
  • Symptom control
  • Improved patient comfort
  • Improved family communication (Buckman, 2013)
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