Perhaps no topic in the medical literature has received as much attention in the past few years as sepsis and septic shock, the topics for this month’s continuing education presentation. Critical care and infectious disease experts have offered several revisions and modifications with regards to:

• The definition of sepsis: Defined as life-threatening organ dysfunction due to dysregulated host response to infection.

• Removing “severe sepsis” as an actual category of the sepsis continuum.

• The nature, origin, and production of lactate in sepsis: it is believed now that lactate is generated as a byproduct of pyruvate overproduction due to endogenous epinephrine stimulation. This refutes the theory that lactate is produced during “anaerobic metabolism”.

• The cause of acidosis in sepsis (current theories suggest that acidosis in sepsis is not due to “lactic acid” but rather due to chloride and hydrogen ion accumulation and loss of bicarbonate).

• Recommendations regarding whether invasive monitoring of central venous pressure is necessary or beneficial.

Despite the flurry of activity and revisions in the sepsis arena, many of the fundamental aspects remain the same.  Early identification, immediate resuscitation, and antibiotic administration are paramount.  To this end, the EMS provider must be able to suspect sepsis based on the history, including the all-important septic risk factors, physical examination, and ancillary testing. Be aware of sepsis risk factors which include:

• diabetes

• chronic renal failure

• cancer

• post-op patients

• patients with indwelling devices

• patients on immune suppressant medications

Sepsis can be diagnosed at the bedside by an astute clinician. Early identification is essential to a good outcome. Prompt resuscitative and definitive treatment translates to decreased mortality.

We are all familiar with SIRS criteria as an indicator for the presence of sepsis. Any two of these criteria make the patient “SIRS positive”. Although there are several potential causes of Systemic Inflammatory Response Syndrome (SIRS) such as pancreatitis, burns, overdose, trauma, pulmonary embolism, etc., sepsis should always remain a high-level consideration in the differential diagnosis of a SIRS-positive patient.

We have seen the qSOFA score (also known as quick SOFA) as a bedside prompt that may identify patients with suspected infection who are at greater risk for a poor outcome:

The UH protocols include elements of both SIRS and qSOFA are both included on page 6/3, under “SIRS Checklist Clinical Findings”. 

If a patient is SIRS positive, the clinician must “look for the infection”  Common sources of sepsis include the urinary tract, especially in patients who have undergone surgery or instrumentation of the urinary tract and those with a Foley Catheter. Clues for urinary tract infection include dysuria, hematuria, fever, chills, flank pain, and cloudy urine noted in the Foley collection bag. 

The respiratory tract is another common source of sepsis. Patients with pneumonia may have fever, chills, productive cough, shortness of breath, and pleuritic chest pain. Physical findings could include: increased respiratory rate, low pulse oximetry, accessory muscle use, and crackles or wheezes noted on lung auscultation.  

The skin and joints may provide clues for sepsis, and the EMS provider should examine the skin for signs of erythema, warmth, and tenderness to palpation. Wounds can become secondarily infected, and these include non-traumatic (infected foot wounds on diabetics, decubiti on debilitated patients), post-surgical wounds, and post-traumatic wounds such as lacerations and punctures. Signs of septic arthritis (joint infections) include joint swelling, redness, tenderness, and decreased range of motion.  

The GI tract is also a common source of sepsis, and the provider must inquire about vomiting, diarrhea, and abdominal pain. Patients with appendicitis, diverticulitis, ascending cholangitis, acute pancreatitis, mesenteric ischemia, and bowel obstruction and perforation are all examples of gut-related sepsis. The physical finding could include diminished bowel sounds, abdominal distention, tenderness to palpation, and guarding. Rebound tenderness indicates peritonitis, a serious complication often noted in the patient with abdominal sepsis.  

Early recognition and treatment are keys to survival. Treatment includes crystalloid fluids, vasopressors as needed, and early antibiotic administration. More to come later this month. 

Stay well, 

Andrew P. Garlisi MD, MPH, MBA, VAQSF

Sepsis - July  11, 2022

Sepsis diagnosis can often be challenging. Symptoms and signs may be subtle at first, and emergency providers might miss these clues, thereby delaying definitive treatment. It is not uncommon for sepsis victims to complain of general weakness and fatigue, very nonspecific symptoms. Elderly patients often experience a change in mental status or difficulty ambulating. Sepsis should remain high on the list in the differential diagnosis of nonspecific symptoms, especially in those patients who are “high-risk.”  

Risk factors are an essential component of a good history and can lead to a more robust differential diagnosis. Risk factor assessment is important in the assessment of patients with possible acute coronary syndrome, thoracic aortic dissection, cardiac tamponade, or pulmonary embolism. The same is true for sepsis. Patients with high-risk factors include:

• patients with diabetes

• chronic renal failure on dialysis 

• Cancer

• autoimmune diseases (Crohn’s, Rheumatoid Arthritis, Psoriasis, Lupus, etc.) 

• indwelling devices

• frequent hospitalizations, recent invasive procedures, and chronic exposure to health care facilities 

Since sepsis can affect ALL AGES, and have a multitude of presentations, the diagnosis can be difficult. A high index of suspicion coupled with a concise history and physical examination goes a long way in pointing to the diagnosis.  

Ancillary testing can be a valuable adjunct in diagnosing sepsis, which results in organ dysfunction. The brain is often the target organ which reveals early signs of sepsis.  Recall that a urinary tract infection in the susceptible chronic nursing home patient frequently manifests as an “acute mental status change.” Glucose testing should be obtained in all patients with encephalopathy. Patients could experience hypoglycemia, especially if they are chronically malnourished or if they have had frequent vomiting and reduced food intake.  

The other extreme, hyperglycemia, can also be a consequence. Patients under the stress of sepsis have increased adrenal cortisol production, which increases blood glucose.  Furthermore, endogenous epinephrine production (a result of the septic process) breaks down glycogen into glucose.  

The 12 lead EKG may reveal tachyarrhymias and signs of ischemia in patients with underlying heart disease. As a result of sepsis, lung dysfunction could manifest by impairment in oxygen exchange resulting in decreased oxygen saturation on pulse oximetry. As systemic perfusion decreases during the septic process, cells are impaired in their ability to produce ATP and Carbon Dioxide. Reduction in CO2 is detected by waveform capnography. As ATP energy diminishes, the cells and tissues break down and eventually die. Organ dysfunction is the consequence. Capnography remains an important index of perfusion at the cellular level. Some squads have utilized pre-hospital point-of-care lactate testing. The CAUSE of lactate excess in sepsis is debated by the experts. Recently, many researchers have postulated that Lactate (not Lactic Acid) is produced by the release of endogenous epinephrine which breaks down glycogen into glucose. In the past, Lactate was believed to be the product of anaerobic metabolism (without oxygen), but in fact, most patients with sepsis have adequate oxygen supplies and still produce lactate.  

Normally, the glucose would be utilized in the metabolic pathway known as glycolysis to make pyruvate, which enters the Krebs Cycle. When excess pyruvate is produced, the Krebs Cycle pathway is overwhelmed. Therefore, some of the glucose excess converts into lactate. These scientists contend that lactate, not lactic acid, is the actual chemical (the difference is one hydrogen ion in lactic acid which lactate lacks).  Regardless of how or why lactate accumulates, it remains an important indicator of sepsis severity, and serial lactate measurements provide insight into patient response to treatment.  Thank you to all of my EMS and ED colleagues!  

Stay well, 

Andrew P. Garlisi MD, MPH, MBA, VAQSF                              

 Septic Shock - July 18, 2022

Septic Shock –Circling the Drain

Septic Shock is the extreme consequence of the septic process, much as anaphylactic shock is the most severe form of allergic reaction. Septic shock typically begins as a bacterial invasion. The bacteria and their toxins trigger an immune reaction which involves white blood cells, antibodies, the complement system, and a host of proteins and chemicals. The immune reaction is intended to protect the body, contain and eradicate the bacteria, neutralize the effect of the bacterial toxins, and assist in damage repair. Unfortunately, all too often, the immune reaction is “dysregulated” or essentially “out of control” resulting in a series of events which lead to damage to end organs such as the brain, lungs, kidneys, heart, and the vascular system. Ultimately, blood vessels become dilated, leaky, and clotted –resulting in decreased perfusion to cells, and decreased cellular perfusion results in decreased ATP production. Without ATP energy, the organs cannot function and irreparable damage is the consequence. Furthermore, diminished cellular perfusion leads to a decrease in carbon dioxide (CO2) production which is detected by waveform capnography. 

Septic shock falls into the Distributive Shock category, along with anaphylactic and neurogenic shocks. Profound Adrenal Insufficiency is another cause of distributive shock, although it is not often mentioned as such.  Distributive shock is characterized by widespread vasodilation and decreased blood flow to the organs as already described. Furthermore, due to damage to the endothelial lining, blood vessels become “leaky” with plasma fluid seeping into intersitial tissue.  

Because of the diverse presentations and widespread age distribution of septic shock, it is THE most commonly missed shock type in the EMS and ED world. The septic shock process can affect newborns, relatively healthy individuals, chronically ill, or incapacitated patients, and of course the elderly. The septic process often begins insidiously, and symptoms could be vague such as general weakness, fatigue, and behavioral change in the elderly. All too often these patients are misdiagnosed initially. Delays in diagnosis and treatment have deadly consequences. Septic shock has mortality rates of up to 50%.  

Treatment of septic shock includes the initiation of basic and advanced interventions in the field and the ED. Patients require close monitoring of cardiac rhythm, oxygen saturation, capnography, clinical course, and VITAL SIGNS. Intravenous crystalloid fluid bolus should be provided.  Some patients will require 30 mL/kg or more of fluids to maintain mean arterial pressure of 65 mm Hg.  Some patients will respond to the fluid challenge with an improvement in blood pressure, reduction of heart rate, and an increase in capnography levels.  

Early antibiotic administration, ideally within one hour of diagnosis, is an essential component of the treatment algorhythm. Some patients who are critically ill and in profound shock may require fluid boluses and vasopressors. These are medications that cause vasoconstriction, thereby reversing the vasodilation, which is characteristic of distributive shock. In the field, we have replaced dopamine with push dose Epinephrine, 10 micrograms IV or IO. The dosage can be repeated every 2 to 5 minutes if needed to maintain a MAP of 65 mm Hg or greater.  Epinephrine works on beta-1 receptors in the heart to stimulate cardiac contractility (force of contraction) as well as heart rate. Epinephrine also acts upon alpha-1 receptors in peripheral blood vessels to cause vasoconstriction.  With septic shock, “Time is Organs” thus, we battle yet another time-sensitive lethal condition. Truly, septic shock is the STEMI of infectious disease. Hope your summer is fantastic! 

Andrew P. Garlisi MD, MPH, MBA, VAQSF

Sepsis - July 25, 2022

The Insidious and Devastating Nature of Sepsis

Sepsis and septic shock are often insidious diseases with subtle initial presentations which masquerade as less ominous conditions. Early symptoms and signs can be nonspecific and non-alarming. These can cause delays in diagnosis and definitive treatment. Such delays can be catastrophic.

Elderly cases:

• General weakness, fatigue, chills, mild change in mental status

Infant cases:

• Feeding difficulties and change in behavior

An example of an adult case is a 42-year-old female who presented to the emergency department at 4 pm with abdominal pain, nausea, and vomiting. This woman had been diagnosed with rheumatoid arthritis and placed on Humira. She was an otherwise healthy woman, working as a free-lance journalist and mother of two children. 

She presented with stable vital signs—RR 18, blood pressure 118/68, heart rate 92, temp 37.4, room air pulse oximetry 96% room air.  Her physical examination revealed lower abdominal tenderness. The emergency physician ordered an IV fluid bolus, pain medication, Zofran, labs, urinalysis, and a CT scan of the abdomen and pelvis. No orders were entered for continuous monitoring.  

Two hours later, the evening change-of-shift occurred. The ED was full, and multiple patients were handed off to the oncoming physician. Two squads arrived at the change-of-shift with one critical patient, which immediately consumed the time and attention of the night shift doctor.  

Meanwhile, our 42-year-old patient was still waiting for the CT scan. Five other patients were waiting for CT scans ahead of her.  Newly arriving nurses were scrambling to catch up on the influx of patients which included 4 patients on hallway stretchers.  

At 8 pm the patient was transported to the radiology department for her CT. Labs had resulted, remarkable only for an elevated white blood count of 15,500 and a lactate level of 2.4. The oncoming physician had not yet had the opportunity to examine the patient who had been handed off at the change of shift.  

The patient returned from the CT department. By 9:30 pm, the emergency physician was able to reassess the patient complaining of increasing abdominal pain. She exhibited LLQ tenderness and guarding. Noting the elevated white blood count, the physician ordered IV Zosyn and requested that the patient be placed on a cardiac monitor. He ordered repeat vital signs, which revealed a heart rate of 108 and blood pressure of 102/60. Because of the deluge in CT studies, the radiologists were running behind in CT interpretations.  

Unfortunately, due to staffing issues and an overburdened ED, the nurse (who was also caring for the critically ill respiratory failure patient who required emergency intubation and multiple medications) was not able to place the patient on the cardiac monitor or hang the Zosyn.  

At 10:30 pm, a family member arrived and screamed out for help. A nurse and the ED doctor rushed into the room to find the 42-year-old patient lethargic and diaphoretic with a thready pulse. The patient was not on the cardiac or blood pressure monitor. A flurry of activities included vital signs, heart monitor, placement of second IV line, and order for two liters fluid bolus. The patient’s blood pressure was 70 systolic. Zosyn was finally initiated. Norepinephrine was ordered. At that time, the radiologist called the ED to alert the staff that the patient had evidence of diverticular abscess and perforation on the CT. The on-call surgeon was paged.  

The patient deteriorated despite resuscitation efforts and expired in the emergency department. 

This case illustrates how a septic patient can present with subtle signs and symptoms and rapidly progress to septic shock and death within hours. This case also demonstrates the importance of RISK FACTOR assessment.  

• This young woman was on HUMIRA for rheumatoid arthritis. (Humira is an immune modulator, also used in Crohn’s disease, psoriasis, ankylosing spondylitis, etc., which suppresses the patient’s innate immune system making her susceptible to infections).  

• Because her symptoms and vitals initially were not dramatic, the staff was lulled into a false sense of security.  

• Cardiac rhythm and vital signs were not closely monitored.  The nurses and physician were distracted by multiple other patients and activities in the department.  

• The patient’s nurse was preoccupied with another critical patient who required intubation and post-ventilator intensive care monitoring.  

• Antibiotic administration was seriously delayed. The CT interpretation was delayed. 

• The patient’s deterioration was unnoticed by the staff until a family member raised the alarm. 

Unfortunately, It was the perfect storm for pitfalls and miscues resulting in a tragic preventable death.  

Thank you for taking the time to review Sepsis this month.

Andrew P. Garlisi MD, MPH, MBA, VAQSF