HWN Suggests

A Paradigm shift: re-thinking sepsis, and maybe shock in general

My (very) humble opinion on this is a rather simple, almost philosophical one: why are we seemingly obsessed with treating a predominantly vasodilatory pathology with large amounts of volume? I’ve said this in previous posts and podcasts, but this, in my opinion, is largely cultural and dogmatic. “Levophed – Leave’em dead” is something I heard as a student and resident, and came to take for granted that I should give lots of fluid in hopes of avoiding pressors… But there’s no evidence at all to support this. The common behavior of waiting until someone has clearly failed volume resuscitation before starting pressors befuddles me (think how long it takes to get two liters of fluid in most ERs…).…

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 A Potent Medication Administered in a Not So Viable Route

In summary, when faced with a patient in shock refractory to adequate fluid resuscitation, the administration of vasopressors can be lifesaving. These medications can safely be administered through peripheral IVs if the IV is in a proximal location such as the antecubital fossa, has good blood return, and flushes easily. Such peripheral infusion can allow the rapid stabilization of the patient and facilitate the orderly insertion of a central line in a stable environment. The site of vasopressor infusion should be monitored regularly for signs of complications, and the duration of vasopressor infusion should be kept to no more than 2 hours. If extravasation or ischemic complications occur, they can be treated with administration of phentolamine and nitroglycerine paste to the area.

 Vasopressors in the ED

Norepinephrine ONE LINER: THE “BEES KNEES” OF VASOPRESSORS - Mechanism: ⍺/β agonism - Dose: Initial dose 5mcg/min (0.05mcg/kg/min) - Indication: Any shock, the best agent in (ALMOST) all circumstances: SOAP II (NEJM 2010) – Norepi vs dopamine for shock (primarily sepsis); Levy et al (JACC 2018) – Norepi vs epi for post AMI cardiogenic shock; VASST (NEJM 2008) – More norepi vs norepi + vasopressin - Good/bad: (+) Literally the best, (+) Safe for peripheral administration, (-) Can cause arrhythmias.

Articles of Interest

Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial

Early norepinephrine was significantly associated with increased shock control by 6 hours. Further studies are needed before this approach is introduced in clinical resuscitation practice.

Peripheral Vasopressors: Do I need that central line?

This study shows that administration of vasopressors peripherally is feasible with a low risk if proper precautions are taken. The risk of extravasation and tissue necrosis is still present especially in ED’s and ICUs where such rigorous protocols are not in effect. However, this study demonstrates that vasopressor use may not be an automatic indication for central venous catheter insertion.

Association Between Early Administration of Norepinephrine in Septic Shock and Survival

The study aimed at evaluating the association between early administration of norepinephrine in septic shock and survival rate using a retrospective single-center observational study in a sample drawn from the Kingdom of Saudi Arabia. Findings identify that early norepinephrine administration was linked to a reduction in mortality rate and improvement in survival rate for patients in intensive care units for the treatment of sepsis and septic shock.

Blood pressure - Do Better, Keep Rising with Norepi

Early Norepinephrine can change some MOOs ( MAP, Lactate, Urinary output) but does not seem to change any POOs ( In-hospital or 28 day mortality) in adult patients with septic shock.

CENSER: Early use of Norepinephrine in Septic Shock Resuscitation

Overall the results seem encouraging and would certainly provide a basis to conduct a larger, multi-centre trial to explore the important question of timing of initiation of vasopressor therapies in septic shock

Get Rid of Dopamine in EMS!, What about Levophed?

In the end, studies have not shown a huge difference in morbidity and mortality associated with the use of Dopamine vs. Levophed. However, the upside to Levophed is evident and its broad range of positive effects makes it the go-to Inopressor for most clinical presentations needing hemodynamic support.

How many mcg of push-dose norepinephrine is needed to prevent hypotension?

A group of investigators published a study of 42 women in Anesthesia & Analgesia in 2017. The women were undergoing elective cesarean delivery under spinal anesthesia. Patients received intermittent norepinephrine boluses of either 3, 4, 5, 6, 7, or 8 mcg every time their systolic blood pressure fell to below 100% of baseline. The authors determined that the minimum dose of norepinephrine to prevent postspinal hypotension in 90% of women undergoing elective cesarean delivery was 6 mcg.

Levophed-openia

The debate on the treatment of circulatory shock is over(-ish?). Ever since the NEJM put out its big RCT on the treatment of all-comer shock[i], we know that norepinephrine is the vasopressor of choice. Septic, cardiogenic….doesn’t matter. Norepinephrine is superior to dopamine. Bummer, right? Choice of vasoactive agent was so sexy. And now, it’s so easy. Shock-y? Start Levo’…[ii]

The CENSER Trial: Early Norepinephrine in Septic Shock

Although, this study confirms my own biases of initiating vasopressor therapy earlier in the course of patients with septic shock, it should be remembered that this study still requires external validation with patient oriented outcomes before implementation into routine clinical practice. Currently, in my practice, in patients with septic shock, I am starting with a Lactated Ringers bolus and assessing fluid status with RUSH exam. If my patient is euvolemic or hypervolemic, I am beginning my norepinephrine infusion at a much sooner time than waiting for 30cc/kg to be completed.

Resources

Picmonic

Norepinephrine (Levophed) is an adrenergic agonist with alpha-1, alpha-2, and beta-1 specificity.

StatPearls

Norepinephrine's predominant use is as a peripheral vasoconstrictor. Specifically, the FDA has approved its use for blood pressure control in specific acute hypotensive states, as well as being a potential adjunct in the treatment of cardiac arrest with profound hypotension. Also, norepinephrine generally has more predictive pharmacologic properties than other alpha agonists. This predictive quality, in combination with some of its beta-agonism (which improves cardiac function relative to pure alpha agonists), makes norepinephrine a widely used vasoactive agent.