In addition to today’s resource, please see:
- *Candidiasis Guidelines from emedicine.medscape.com Updated: Mar 24, 2023
Author: Jose A Hidalgo, MD; Chief Editor: Michael Stuart Bronze, MD
- Link to norepinephrine chapter*in StatPearls. Matthew D. Smith; Christopher V. Maani. Last Update: May 8, 2023.
“It is available as an intravenous solution of 1 mg/mL, 4 mg/250 mL in dextrose 5%, and 8 mg/250 mL in dextrose 5%. Because of its relatively short half-life of 2.5 minutes, the administration of norepinephrine is typically by continuous infusion. The FDA recommends diluting the concentrated norepinephrine in dextrose-containing solutions before infusion, protecting against potential oxidation and subsequent loss of drug potency. The FDA explicitly recommends against using saline as the sole diluent. A common technique is to start the infusion at 8 mcg to 12 mcg per minute and titrate to the desired pressure. The average maintenance dose is around 2 to 4 mcg per minute. If possible, infusions of norepinephrine should use tubing separate from blood products.”
Today, I review, link to, and excerpt from The Curbsiders‘ #419 Rapid Response Series: Sepsis with Dr. Mohleen Kang. December 4, 2023 | By Meredith Trubitt.
All that follows is from the above resource.
A shock to the system
Join us for an infectious conversation about sepsis as we learn about the recognition and initial management of sepsis on the wards. We are joined by Dr. Mohleen Kang (@KangMohleen, Emory University).
- Antibiotics and IV fluids (IVF) should be started within the first hour of onset of suspected sepsis.
- In cases of suspected sepsis, patients should receive 30mL/kg of IVF within the first three hours of identifying suspected sepsis.
- If a patient receives appropriate fluid resuscitation without response, consider transition or addition of vasopressors (even if administration is peripheral). Ideally, peripheral access should be placed above the antecubital vein.
- The CANDIDA score can be used to help determine if antifungal coverage should be added to a patient’s antibiotic regimen*
- Goals of care conversations should take place early in a hospitalization given the difficulty of having such discussions during a rapid response.
It is available as an intravenous solution of 1 mg/mL, 4 mg/250 mL in dextrose 5%, and 8 mg/250 mL in dextrose 5%. Because of its relatively short half-life of 2.5 minutes, the administration of norepinephrine is typically by continuous infusion. The FDA recommends diluting the concentrated norepinephrine in dextrose-containing solutions before infusion, protecting against potential oxidation and subsequent loss of drug potency. The FDA explicitly recommends against using saline as the sole diluent. A common technique is to start the infusion at 8 mcg to 12 mcg per minute and titrate to the desired pressure. The average maintenance dose is around 2 to 4 mcg per minute. If possible, infusions of norepinephrine should use tubing separate from blood products.
Rapid Response Series: Sepsis – Show Notes
Tips and Tricks for Managing a Rapid Response
Similar to identifying roles and responsibilities of the team, it is important to identify the best and fastest route for fluids, antibiotics, and potentially vasopressors. Ideally, this will be a peripheral IV (low gauge number) above the antecubital vein in the event pressors need to be started. If below the antecubital, providers should be more cautious with pressors for risk of extravasation. Dr. Kang reminds us that intraosseous lines (IOs) are an acceptable alternative if a good peripheral cannot be placed. While a central line may be necessary for a patient’s treatment plan in the ICU, it does not need to be placed emergently, as the vast majority of medications can be given peripherally during rapid response.
Definitions and Scoring Systems
According to Sepsis-3, sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Clinically, this is defined as a SOFA score of 2 points or higher (see below for criteria). Septic shock is defined as the subset of sepsis in which there are more profound circulatory, cellular, and metabolic abnormalities. Clinically, this is defined by a vasopressor requirement to maintain MAPs > 65 or serum lactate > 2 in the absence of hypovolemia (Singer, 2016).
There are numerous scoring systems which have been developed over the years to identify sepsis early in patients and to try to improve improve mortality. Below is a list of the scores and their associated criteria.
Systemic Inflammatory Response Score (SIRS) criteria includes:
- Temperature > 38 C or < 36C
- HR > 90
- RR > 20 or PaCO2 < 32
- WBC > 12 or < 4 or differential with > 10% bands
Sequential Organ Failure Assessment (SOFA) criteria includes:
- On mechanical ventilation
- Glasgow Coma Scale
- MAP or use of vasoactive agents
Quick Sequential Organ Failure Assessment (qSOFA) criteria includes:
- Altered mental status
- Resp Rate ≥ 22
- Systolic BP ≤ 100
National Early Warning Score (NEWS) criteria include:
- Resp rate
- Oxygen saturations
- Any supplemental oxygen use
- Systolic BP
- Heart rate
- AVPU score
Modified Early Warning Score (MEWS) criteria include:
- Systolic BP
- Heart rate
- Resp rate
- AVPU score
SIRS was widely used until the Sepsis-3 definition was published in 2016. The downside to SIRS is that it is not specific for sepsis. The Sepsis-3 definition included qSOFA as a screening tool, making it more widely used; however, it has more recently fallen out of favor due to its poor sensitivity (although does have better specificity than SIRS). NEWS performed the best out of the scoring systems (Liu, 2020), but it is cumbersome to use so may not be the best urgent bedside tool. Furthermore, a pooled analysis of three RCTs did not demonstrate a mortality benefit of active screening in inpatient wards (Evans, 2021). Therefore, the scoring systems have noted limitations, and while no single scoring system is ideal for screening, NEWS is most likely the most comprehensive tool available with more evidence to support its use.
It is necessary to obtain a complete work-up for the source of infection. This should start with a thorough history and physical for any localizing source of infection. In terms of diagnostic testing, this should include blood cultures, urinalysis/urine culture, chest x-ray, and a basic set of labs (CBC, BMP).
Based on the Surviving Sepsis Campaign (SSC) Guidelines, it is also recommended to get an initial lactate and to trend the lactate to resolution (Evans, 2021).
Lastly, Dr. Kang reminds us that it may be necessary to engage with surgical consultants early, if the source of infection may require surgical intervention.
Antibiotics should be given within one hour of probable sepsis (Evans, 2021). While considering a potential source of infection, it is reasonable to utilize broad spectrum antibiotics. Source control is imperative, so as mentioned above, early consultation with surgical subspecialties is important while concomitantly deciding on antibiotics.
Specific considerations for MRSA coverage, consider whether a patient has related risk factors: prior history of MRSA infection or colonization, recent IV antibiotic use, history of recurrent skin infections or chronic wounds, presence of invasive devices, hemodialysis, recent IV antibiotic use or hospital admissions, and severity of illness (Evans, 2021). Dr. Kang utilizes MRSA nares swabs to de-escalate antibiotic choices after the patient has been stabilized (expert opinion).
Specific considerations for double coverage of multidrug resistant organisms (MDROs) include: “proven infection or colonization with antibiotic-resistant organisms within the preceding year, local prevalence of antibiotic-resistant organisms, probable hospital-acquired infection, broad spectrum antibiotic use within the preceding 90 days, concurrent use selective digestive decontamination, travel to a highly endemic country within the preceding 90 days, and hospitalization abroad within the preceding 90 days” (Evans, 2021).
Regarding antifungal coverage, Dr. Kang utilizes the CANDIDA score (Leon, 2006) to help guide utility of empiric antifungal coverage (expert opinion).
Based on the current SSC guidelines, it is recommended to provide 30 mL/kg of fluid within the first 3 hours of identifying sepsis-induced hypoperfusion hypotension (Evans, 2021). Additionally noted in the guidelines is the recommendation to favor balanced crystalloids instead of normal saline for resuscitation (Evans, 2021). This is based on the SMART trial which provides low quality of evidence due to the study being single center, non-randomized, non-blinded, but showed lower mortality in those who received balanced fluids over normal saline (Semler, 2018).
While the ability to use pressor support on the floor varies across institutions, this practice is supported by the recent CLOVERS trial (Shapiro, 2023) and is also recommended in the SSC guidelines (Evans, 2021) in patients who are not responsive to fluids.
CLOVERS compared a restrictive fluid strategy to liberal fluid strategy. Briefly, if a patient came in with sepsis induced hypotension refractory to 1-3L of fluids, they were randomized to either receive vasopressors with rescue fluids compared to additional fluids alone. There was no difference in mortality between these groups. The study allowed for peripheral catheters for initial vasopressor support and demonstrated only 2 occurrences of extravasation among 500 patients who received peripheral pressors (Shapiro, 2023).
If the patient has already received the recommended fluid resuscitation without response, Dr. Kang prefers to transition to pressor support. She reminds us that in this situation, most patients are in the process of transferring to the ICU. As an additional expert opinion, she recommends using a peripheral access above the antecubital vein while waiting for transfer to ICU and placement of central line. Usually she starts norepinephrine at the lowest dose and titrates up as needed for response (Evans, 2021). Dr. Kang also reminds us that every institution is unique in what may be available in a code cart or on the floor, and that something (i.e. alternative pressor like vasopressors like, dopamine, dobutamine) is better than nothing depending on the severity of the situation.
There are several supportive therapies that are used for sepsis, especially once the patient has transferred to the ICU. Some of these considerations include: oxygen goals, steroids, transfusion requirements, stress ulcer prophylaxis, VTE prophylaxis, acute kidney injury management, bicarbonate, nutrition support, and glucose control (Evans, 2021). However, as this is managed mostly in the ICU, many of these are not discussed in depth during this episode. A few of these measures begin on the wards though so are discussed below.
If there is no evidence of ARDS early on, Dr. Kang recommends using a pulse oximetry goal of > 92%. She does remind us that a pulse ox may not be very accurate during the rapid response as they may not be perfusing well. If there is evidence of ARDS, positive airway pressure (PAP) ventilation therapy should be considered early.
Dr. Kang recommends against using steroids during initial rapid response where sepsis is identified, but is something that may be considered if the patient has known adrenal insufficiency. Additionally, they may be considered in the ICU if the patient is having inadequate response to fluids and pressors (Evans, 2021).
Lastly, the SSC guidelines recommend against using IV vitamin C as part of early management of sepsis (Evans, 2021).