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Sepsis and the Inflammatory Response to Injury

Ilya Shnaydman, MD and Matthew Bronstein, MD

Division of Trauma and Acute Care Surgery, New York Medical College, Westchester Medical Center, Valhalla, NY, USA

A 78‐year‐old woman recently discharged from the hospital after ventral hernia repair presents to the emergency department with a 5‐day history of fever, chills, and productive cough. The patient’s family reports poor oral intake and altered mental status. The patient’s vital signs are temperature 38.5 °C; heart rate 125 beats/min; respiratory rate 30 breaths/min; blood pressure 80/60 mm Hg; and oxygen saturation 85% on room air. A chest radiograph demonstrates multifocal pneumonia and the urinalysis shows leukocyte esterase and nitrites. She is appropriately volume resuscitated and requires norepinephrine to maintain a mean arterial blood pressure of 65 mm Hg. Her serum lactate is 4 mmol/L.

The patient’s clinical condition can best be defined as:
1. Sepsis.
2. Septic Shock.
3. Severe Sepsis.
4. Multiorgan dysfunction syndrome.
5. Systemic inflammatory response syndrome (SIRS).
The Society of Critical Care Medicine task force produced the new definition for sepsis and septic shock (Sepsis‐3) in 2016. Sepsis is defined as life‐threatening organ dysfunction caused by a dysregulated host response to infection. This is identified by a score of 2 points or more on the Sequential Organ Failure Assessment (SOFA) score and is associated with 10% mortality or greater. Patients with septic shock are defined as requiring a vasopressor to maintain a MAP > 65 mmHg and having a serum lactate level >2 mmol/L in the absence of hypovolemia and is associated with 40% mortality or greater (choice B). Severe sepsis (choice C) and Multiorgan dysfunction syndrome (choice D) are not definitions recommended by the new guidelines. SIRS (choice E) is defined as two of the following: tachycardia (HR > 90 bpm), tachypnea (RR > 20 breaths/min), fever (>39 °C or <36 °C), and leukocytosis (WBC > 12 or <4 or >10% bands). SIRS would be correct if there was no identified or suspected source. A quick bedside score, qSOFA, can also be used (respiratory rate > 22/min, altered mental status or systolic blood pressure 100 mmHg or less). Using these new definitions, the patient has Septic Shock (choice B).

Answer: B

Gyawali B, Ramakrishna K, Dhamoon, A. Sepsis: the evolution in definition, pathophysiology, and management. SAGE Open Med. 2019; 7:205031211983504. doi: https://doi.org/10.1177/2050312119835043.

Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis‐3). JAMA. 2016; 315(8):801.
What is the first step in the initial management of the patient in the above question?
1. Antibiotic Therapy.
2. Transfer to Intensive Care Unit.
3. Intravenous fluid bolus.
4. Checking serum lactate level.
5. Supplemental oxygen administration.
Just as in trauma, the initial management of any critically ill patient should involve establishing an adequate airway, evaluating breathing (which may require supplemental oxygen and/or mechanical ventilation), and restoring adequate perfusion with volume resuscitation and/or vasopressors (choice E). The patient will also require antibiotics (choice A), ICU care (choice B), intravenous fluids (choice B) as well as measurement of serum lactate (choice D).

Answer: E

Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017; 43(3):304–377.

Holmes CL, Walley KR. The evaluation and management of shock. Clin Chest Med. 2003; 24(4):775–789.
An 80‐year‐old man is admitted to the surgical intensive care unit with perforated diverticulitis after a Hartmann procedure. He has received appropriate fluid resuscitation but is requiring high doses of norepinephrine and vasopressin. His labs are significant for white blood cell count 18 000/μL and hemoglobin 10 g/dL. Bedside critical care ultrasound demonstrates a non‐collapsible inferior vena cava and an appropriate ejection fraction.

The next best intervention should be:
1. Transfusion of 2 units packed red blood cells.
2. Continued fluid resuscitation.
3. Addition of Epinephrine.
4. Initiation of stress dose steroids.
5. Placement of intra‐aortic balloon pump.
Intravenous “low dose” corticosteroids (200 mg hydrocortisone daily) are recommended in patients with sepsis in which adequate fluid resuscitation and vasopressor therapy are unable to restore hemodynamic stability. Steroid use should also be considered in patients at risk of adrenal dysfunction due to exogenous steroid use. Packed red blood cell transfusion is recommended only when hemoglobin decreases to <7.0 g/dL in the absence of extenuating circumstances, such as myocardial infarction, severe hypoxemia, or acute hemorrhage (choice A). Additional intravenous fluids would not be helpful if the patient is already adequately fluid resuscitated as evidenced by his non‐collapsible inferior vena cava (choice B). Intra‐aortic balloon pump and epinephrine can be useful in cardiogenic shock, but the patient has an appropriate ejection fraction, indicating the absence of cardiogenic shock (choice C/E).

Answer: D

Annane D, Renault A, Brun‐Buisson C, et al. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med. 2018; 378(9):809–818.

Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017; 43(3):304–377.

Cecconi M, De Backer D, Antonelli M, et al. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014; 40(12):1795–1815.

Hébert PC, Wells G, Blajchman, MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999; 340(6):409–417. doi: https://doi.org/10.1056/NEJM199902113400601. Erratum in: N Engl J Med 1999 Apr 1;340(13):1056. PMID: 9971864.
A 64‐year‐old man presents with left lower quadrant abdominal pain and fever. His exam does not show peritonitis. He has a white blood cell count of 16 000/μL. He undergoes CT abdomen & pelvis and is found to have diverticulitis with a 3 cm pelvic abscess. He is immediately started on antibiotics and undergoes percutaneous drainage by interventional radiology. How long should antibiotic therapy be continued?
1. 7 days
2. 4 days
3. 10 days
4. Until his symptoms and fever resolve
5. Until his leukocytosis resolves
Duration of therapy for complicated intra‐abdominal infections is a frequent problem to manage for the acute care and critical care surgeon. Antimicrobial therapy guidelines continue to evolve from high‐quality evidence. Traditionally, surgeons have treated patients until all evidence of SIRS have resolved, typically for 1–2 weeks (choice A/C/D/E). The Study To Optimize Peritoneal Infection Therapy (STOP‐IT) trial was a multicenter randomized trial that examined 4 day therapy vs. 2 days after the resolution of physiologic abnormalities related to SIRS. The primary endpoint was surgical site infection, recurrent intra‐abdominal infection, or death. There was no significant difference between the groups, so they concluded that a 4 day duration of antibiotic therapy was sufficient after obtaining source control.

Answer: B

Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short‐course antimicrobial therapy for intraabdominal infection. N Engl J Med. 2015; 372(21):1996–2005.
A 55‐year‐old male trauma patient who remained intubated 4 days after laparotomy undergoes bronchoscopy for suspected mucous plugging seen on a chest radiograph. Purulent secretions are encountered and a bronchoalveolar lavage (BAL) and quantitative culture is performed.

Which of the following supports a diagnosis of ventilator associated pneumonia (VAP)?
1. Negative gram stain but high clinical suspicion.
2. Protected brush specimen culture growing 10² CFU.
3. Bronchoscopic BAL culture growing 10³ CFU.
4. Endotracheal aspirate growing 10⁴ CFU.
5. Bronchoscopic BAL culture growing 10⁵ CFU.
Pulmonary cultures can be obtained via bronchoscopy BAL, protected brush specimen (PSB) or blind tracheal suctioning. The following criteria confirm a diagnosis of VAP: blind tracheal suctioning (endobronchial aspirate) ≱ 10⁵ CFU, PSB ≱ 10³ CFU, bronchoscopic BAL ≱ 10⁴ CFU (choice E). The trauma literature supports a diagnosis of VAP with BAL ≱ 10⁵ CFU/mL, while CDC uses ≱ 10⁴ CFU/mL.

Answer: E

Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital‐acquired and ventilator‐associated pneumonia: 2016 clinical practice guidelines by the infectious diseases society of America and the American thoracic society. Clin Infect Dis. 2016; 63(5):e61–e111.

Martin‐Loeches I, Rodriguez AH, Torres A. New guidelines for hospital‐acquired pneumonia/ventilator‐associated pneumonia: USA vs. Europe. Curr Opin Crit Care. 2018; 24(5):347–352.

Croce MA, Fabian TC, Mueller EW, et al. The appropriate diagnostic threshold for ventilator‐associated pneumonia using quantitative cultures. J Trauma: Inj, Infect, Crit Care. 2004; 56(5):931–936.

National Healthcare Safety Network, Center for Disease Control. Pneumonia (Ventilator‐Associated [VAP] and Non Ventilator‐Associated Pneumonia [PNEU]) Event. Table 5: Threshold Values for Cultured Specimens Used in the Diagnosis of Pneumonia, 2021.

Rea‐Neto A, Youssef N, Tuche F, et al. Diagnosis of ventilator‐associated pneumonia: a systematic review of the literature. Crit Care. 2008; 12(2):R56.
The BAL culture from the patient above grows an extended spectrum beta lactamase (ESBL) producing strain of Klebsiella. Which antibiotic would be most likely to be effective?
1. Piperacillin/tazobactam
2. Vancomycin
3. Ampicillin/sulbactam
4. Cefepime
5. Meropenem
Cefepime and piperacillin/tazobactam demonstrate antipseudomonal activity but have limited activity against ESBL organisms (choice A/D). Vancomycin has no activity against Klebsiella (choice B). Ampicillin/sulbactam is not effective for ESBL organisms or Pseudomonas (choice C). Carbapenems are first‐line therapy for extended‐spectrum beta‐lactamase (ESBL) organisms (choice E).

Answer: E

Harris PNA, Tambyah PA, Lye DC, et al. Effect of piperacillin‐tazobactam vs meropenem on 30‐day mortality for patients with E coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance. JAMA. 2018; 320(10):984.

What is the next best step in management?

A 52‐year‐old woman presents to the emergency department with right upper quadrant pain and weakness. On admission, her vital signs are temperature 39 °C; heart rate 130 beats/min; respiratory rate 22 breaths/min; blood pressure 80/50 mm Hg; oxygen saturation 97% on room air. On examination, she is disoriented and her skin is jaundiced. Laboratory studies demonstrate white blood cell count 20 000/μL and an elevated bilirubin. Ultrasound examination reveals cholelithiasis and intrahepatic biliary ductal dilatation.

Emergent laparoscopic cholecystectomy.
GI consultation.
Parenteral antibiotic.
ICU admission.
Emergent MRCP.

The patient is in septic shock from cholangitis. The Surviving Sepsis Campaign Guidelines recommend administration of IV antimicrobials to be initiated as soon as possible after recognition of sepsis and within 1 hour for both sepsis and septic shock (choice C). They recommend obtaining microbiological cultures prior to starting antimicrobial therapy; if doing so, results in no substantial delay in the start of antimicrobials. For fluid resuscitation, the guidelines recommend 30 mL/kg of IV crystalloid be given within the first 3 hours. The patient will require emergent decompression of the biliary tract with either ERCP (choice B), PTC, or surgical common bile duct decompression. While these choices would address source control, it would take time and initiating antibiotics should be done first. The patient should undergo cholecystectomy (choice A) during that hospitalization (non‐emergently) after bile duct decompression, the cholangitis has resolved and the patient has stabilized. This patient is appropriate for admission to the ICU (choice D), but this would not be the next best step.