Shock and Sepsis

Shock + Septic Shock: How to Beat the Odds

What is Shock: 

Cell and tissue hypoxia due to reduced O2 delivery, increased O2 consumption, or inadequate O2 utilization

Signs of Shock:

hypotension/tachycardia/tachypnea 

Altered mental status

Weak pulses

Poor urine output

Lactic acidosis

What Causes Shock:

A little Reminder of Hemodynamics:

Management of Septic Shock

Early Goal Directed Therapy??

Rivers trial (Early Goal Directed Therapy in the Treatment of Severe Sepsis and Septic Shock) was completed on 263 patients in 2001. This was a single center RCT in Michigan. Patients were placed in 2 groups, standard therapy or “Early Goal Directed Therapy”. In the EGDT arm, patients received an arterial line and a central line with continuous central venous oxygen saturation (ScvO2). The EGDT group consisted of several sequential goals in the ER prior to ICU admission:

1.     CVP 8-12mmHg, achieved with fluid boluses

2.     MAP >65mmHg, achieved with vasopressors if necessary

3.     ScvO2 >70%, achieved with packed RBC transfusions and dobutamine if necessary

4.     UOP >0.5mL/kg/hr

The results showed mortality increased by 8% per hour w/o volume and antibiotics. This EGDT was widely adapted across the US. The bottom line was this trial showed giving early antibiotics and fluids (30 mL/kg) in septic shock significantly improved mortality outcome. The other interventions would be disputed in large multi-center RCTs that were completed ~15 years later.

The ProCeSS trial (2014), the ARISE trial (2014), the ProMISE trial (2015), and the PRISM trial (2017) all showed that having the standardized “Rivers” EGDT protocol didn’t change outcomes when compared to patients getting early sepsis fluids (30 mL/kg) and early antibiotics.

So, the long story of EGDT made short, give antibiotics and fluids early.

What’s the Pressor? What’s the (MAP) Goal?

SEPSISSPAM Trial in 2014 was an RCT of 29 ICU’s in France. Randomized to a MAP of 65-70 and 80-85 with no difference in morality. Showed that a MAP 65< is reasonable.

SOAP-2 trial in 2010 compared Dopamine vs NE. No difference in mortality. NE was mentioned to be preferred due to 35% of dopamine patients having arrhythmias.

VASST trial in 2008 showed that vasopressin can be safely added to NE in patients with refractory shock

What Fluid Should I Use?

SMART trial in 2018 looked at balanced crystalloids (LR) vs saline in septic shock patients. This was an unblinded single center trial at Vanderbilt. Patients who received LR had slightly more RRT free days, but not by much. This was backed up by the SALT-ED trial in 2018, which included 5 ICUs.

Neither of these trials were blinded and they did not have a difference in mortality, but you may be able to buy yourself some preserved kidney function using LR instead of NS.

What About Albumin?

The ALBIOS trial in 2014 was an RCT which looked at 20% albumin vs NS. No difference in mortality, but did show less days of vasopressin overall. Suggested that albumin is safe to use and may be a vasopressin sparing agent.

Roid Rage

Steroids in septic shock patients has been something people have looked at repeatedly for a number of years now. We can start with the ANNANE trial in 2002 which looked at steroid “responders” vs “non-responders” via ACTH stim test in septic shock patients after getting IV steroids. Patients who were “responders”, had a slightly improved 28 day mortality (p = .04)

The next large trial was CORTICUS which randomized to hydrocortisone vs placebo. 28 day mortality was the same, but the time to shock reversal was better (3.3 vs 5.8 days). They also looked at “responders” and “non-responders”, with no difference in the two groups.  One big difference between these trials is the time to randomization and how sick the patients were. ANNANE included patients after 8 hours of shock vs 72 hours in CORTICUS. The patients were also much sicker in the ANNANE trial. So, perhaps patients who are sicker may benefit from steroids.

The ADRENAL trial in 2018 was another hydrocortisone vs placebo in septic shock. Primary outcome here was death at 90 days. Mortality p = .5. However, the p <.001 in favor of hydrocortisone for time to ICU exit and need for RRT.

The APROCCHSS trial in 2018 also looked at death at 90 days in hydrocortisone vs placebo. This study favored the steroid group for MORTALITY with a p = .03.

Bottom-line of steroids = may provide some benefit, especially in very ill patients. They may be able to buy you less RRT time and less time in the ICU. I’m sure in the future we will continue to bang our head against the wall with new steroid in septic shock studies and different end-points. Until then, when a critically ill patient is climbing on their pressor requirements, 50mg of IV hydrocortisone Q8H doesn’t sound so bad.

- Brandon Temte

Thanks to Emma White and Grant Farr for helping with this post!