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Septic Shock

February 7, 2017 by Josh Farkas

CONTENTS

Front matterPreamble (#preamble)Brief history of septic shock treatment (#brief_history_of_septic_shock_treatment)

De�nition of septic shock (#de�nition_of_septic_shock)Diagnosis

Clinical Presentations (#clinical_presentations)Differential diagnosis: Sepsis mimics (#sepsis_mimics)

Source of septic shock & evaluation for source (#common_sources_&_evaluation_of_source)Treatment

Vasopressors (#vasopressors)Antibiotics (#antibiotics)Source control (#source_control)Fluid (#�uid)Steroid (#steroid)DVT prophylaxis with heparin (#DVT_prophylaxis_with_heparin)

Interventions of no real value (#interventions_of_no_real_value)Resuscitative endpoints ?? (#resuscitative_endpoints:_general_philosophy)

MAP (#resus_targets:_MAP)Heart rate (#resus_targets:_heart_rate)Urine output (#resus_targets:_urine_output)Fluid balance (#resus_targets:_�uid_balance)Lactate (#resus_targets:_lactate)Skin perfusion (#resus_targets:_skin_perfusion)

Algorithms (#algorithm)Podcast (#podcast)Questions & discussion (#questions_&_discussion)

TOC ABOUT THE IBCC TWEET US IBCC PODCAST

https://emcrit.org/ibcc/toc/https://emcrit.org/author/pulmcrit/https://emcrit.org/ibcc/tochttps://emcrit.org/ibcc/about-guide/http://twitter.com/ibookcchttp://ibccpodcast.libsyn.com/



Pitfalls (#pitfalls)PDF of this chapter (https://emcrit.org/wp-content/uploads/2017/02/sepsis.pdf) (or create customized PDF (https://emcrit.org/ibcc/about-guide/#pdf) )

preamble(back to contents) (#top)

Septic shock is the de�ning illness of medical critical care. It is important because it is common, potentially lethal, and highly treatable. Theimportance of septic shock has attracted attention, guidelines, politics, and controversy. Which makes writing this chapter challenging, because– let's admit it – everyone has a different approach to treating septic shock.

This chapter describes my approach to septic shock. It is evidence-based, but there's inadequate evidence available to prove that it is superior toinnumerable other ways of treating septic shock. Overall, it is a fairly simple approach that doesn't involve a lot of fancy gadgetry. As such, thisapproach should be accessible to a wide variety of practitioners.

Like the remainder of the IBCC, this chapter will be aggressively written and then aggressively revised. Some bold claims will be made. If readers�nd evidence to overturn them, I will make revisions accordingly. The ability to write controversial material and then revise it based on post-publication peer review is a unique strength of this medium. If you disagree with material below, please comment and include citation(s) ofsupporting evidence.

brief history of septic shock treatment(back to contents) (#top)

Rivers Trial, 2001

The history of modern sepsis care can largely be traced back to the Rivers Trial of Early Goal Directed Therapy in septic shock (11794169(https://www.ncbi.nlm.nih.gov/pubmed/11794169) ). This study used an aggressive resuscitative package to decrease mortality from sepsis. The studyhas numerous major �aws, which have grown more apparent over time:

Major con�ict of interest (the primary investigator held a patent for a catheter to measure mixed central venous oxygen saturation).Single-center design with conspicuous lack of blinding (patients in the experimental arm were often treated personally by Dr. Rivers).The mortality rate in the control group (47%) was quite high. This suggests either a statistical anomaly, research misconduct, or lack ofgeneralizability to other contexts.The fragility index was four (very respectable, but also not irrefutable).25 patients were initially included in the study, but then removed for reasons which remain murky and contentious. Notably, the number ofpatients removed from the study is greater than the fragility index of four. According to an investigational report in the Wall Street Journal,an intention-to-treat analysis including these 25 patients would have given study negative results (McKenna 2008(https://www.annemergmed.com/article/S0196-0644(08)01897-0/pdf) ).Attempts to replicate the Rivers trial have failed. Over time, most components of the Rivers Protocol for Early Goal Directed Therapy havebeen explicitly disproven or have fallen out of favor (e.g. central venous pressure monitoring, nitroglycerine for septic shock, transfusion tohemoglobin >10 mg/dL, mixed venous oxygen saturation monitoring). Based on this fact alone, it must be concluded that the Rivers Trialwas invalid (according to science, �ndings which cannot be replicated are not valid).

https://emcrit.org/wp-content/uploads/2017/02/sepsis.pdfhttps://emcrit.org/ibcc/about-guide/#pdfhttps://www.ncbi.nlm.nih.gov/pubmed/11794169https://www.annemergmed.com/article/S0196-0644(08)01897-0/pdf



NINDS-II trial Rivers trial

Fragility index 3 4 for in-hospital mortality3 for 60-day mortality

Published in NEJM NEJM

Number of centers Multicenter Single center

Conflicts of interest? Yes Yes (primary investigator held patentfor catheter to measure svcO2)

Effect on field Widely accepted, believed to be a seminal trial which directed research foryears.

Significant methodologicproblems?

Yes (baseline imbalance, change inendpoints from NINDS-I)

Yes (e.g. patients mysteriouslyremoved, with failure to perform

intention-to-treat analysis)

Re-analysis cast doubt on study Yes (Hoffman et al.) Yes (Unpublished analysis by WallStreet Journal)

Replicated No Failed replication, most findings ofthe study have been disproven(e.g. HgB target >10 mg/dL)

Basis for all future guidelines Yes Yes

Currently, study conclusions arecontroversial

Yes Yes

The Rivers trial is basically the NINDS trial of critical care

-Internet Book of Critical Care, by @PulmCrit

(https://emcrit.org/wp-content/uploads/2017/02/nindsrivers.svg) The Rivers Trial is a cautionary tale in evidence-based medicine. Much like the NINDS trialof tPA in ischemic stroke, this was an inspirational study which sparked widespread enthusiasm, leading to broad acceptance. If the Rivers Trialwere published today, it would be met with considerable criticism and calls for immediate replication. Unfortunately, the exciting results of thetrial and high pro�le of the NEJM allowed the Rivers Trial to misdirect thinking in septic shock for a decade.

The Rivers trial did promote an aggressive stance towards treating septic shock, which is bene�cial. However, most of the interventions from thetrial are incorrect. In order to move forwards with scienti�c and evidence-based therapy for septic shock, we need to have a clear-eyed view ofthis trial.

Surviving Sepsis Campaign

This campaign was initiated as a joint marketing effort by Eli Lilly and Edward Life Sciences to promote activated protein C (XIGRIS) and centralvenous catheters which measure the mixed venous oxygen saturation (yes, the same one Rivers held a patent for). The original backbone of theguidelines was the Rivers Trial.

The Surviving Sepsis Campaign has a track record of being sluggish to change based on the emergence of new data. For example, the SurvivingSepsis Campaign continued to recommend the use of central venous pressure and mixed venous oxygen saturation even after the PROCESS andARISE trials demonstrated that these were non-bene�cial. The campaign also has a history of making strong and arbitrary recommendationspulled out of thin air (e.g. 3-hour and 6-hour bundles of care involving �xed volumes of �uid resuscitation).

In 2018, the Surviving Sepsis Campaign issued an update recommending initiation of antibiotics and 30 cc/kg �uid bolus within sixty minutes ofemergency department triage. This is a bizarre departure from prior recommendations, which came without any solid evidentiary basis. Thisupdate provoked widespread dissent, which led the Surviving Sepsis Campaign to temporarily withdraw it. Subsequently, however, theserecommendations were re-issued.

Currently, the Surviving Sepsis Campaign lumbers on, serving as an impediment to the development of guidelines which are truly evidence-based. The Surviving Sepsis Campaign guidelines have formed the basis of governmental sepsis regulations in the United States (SEP-1), which thwartindividualized care and are frankly dangerous.

going further…

Mythbusting the Surviving Sepsis 2016 guidelines (https://emcrit.org/pulmcrit/sepsis-myths/)Petition to retire the surviving sepsis guidelines (https://emcrit.org/pulmcrit/ssc-petition/)The Survivign Sepsis 1-hour guidelines are… back? (https://emcrit.org/pulmcrit/ssc-1-hour/)Marik et al. Pro-Con debate: Should the Surviving sepsis campaign guidelines be retired? (https://emcrit.org/wp-content/uploads/2019/02/chestprocon.pdf) CHEST 2019; 155:12-20.Kalantari A and Rezaie SR. Challenging the one-hour sepsis bundle (https://emcrit.org/wp-content/uploads/2019/02/kalantari.pdf) . Western Journalof Emergency Medicine, in press.Spiegel R et al. The 2018 Surviving Sepsis Campaign's Treatment Bundle: When guidelines outpace the evidence supporting their use(https://emcrit.org/wp-content/uploads/2019/02/spiegel.pdf) . Annals of Emergency Medicine, 2018.

https://emcrit.org/wp-content/uploads/2017/02/nindsrivers.svghttps://emcrit.org/pulmcrit/sepsis-myths/https://emcrit.org/pulmcrit/ssc-petition/https://emcrit.org/pulmcrit/ssc-1-hour/https://emcrit.org/wp-content/uploads/2019/02/chestprocon.pdfhttps://emcrit.org/wp-content/uploads/2019/02/kalantari.pdfhttps://emcrit.org/wp-content/uploads/2019/02/spiegel.pdf



de�nition of septic shock(back to contents) (#top)

The consensus de�nition of septic shock was updated from Sepsis-II to Sepsis-III recently. These de�nitions may be summarized as follows:

Sepsis II de�nition of septic shock: Infection causing persistent hypotension, despite �uid resuscitation.Sepsis III de�nition of septic shock: Infection causing vasopressor requirement to maintain a MAP > 65 mm (despite �uid resuscitation) plusa serum lactate >2 mM.

Neither of these de�nitions is perfect, but they focus our attention on two key bits that together help delineate septic shock:

Bit #1: Overt hypotensionBit #2: Hyperlactatemia – this is generally a re�ection of aerobic lactate production due to endogenous epinephrine. It may be grosslyconceptualized here as a measurement of the patient's endogenous epinephrine release.

Sepsis III requires both bits, which is a mistake because they measure different things:

Lactate is not speci�c to septic shock. Lactate may be elevated by a panoply of conditions (including any shock state, physiologic stress, beta-agonists, seizure, or hepatic dysfunction). Elevated lactate does often identify patients who are at increased risk of mortality, who require moreintensive investigation and treatment.

Ultimately, formal de�nitions are more relevant to clinical trials than bedside management of individual patients. These blunt tools are inadequateto direct patient management. Instead, a diagnosis of septic shock should be made carefully on an individual basis, using clinical judgement andconsideration of the following factors:

(1) Type of underlying infectionSome infections (e.g. necrotizing fasciitis, ascending cholangitis) are more likely to cause septic shock. There should be a lowerthreshold to diagnose septic shock and initiate aggressive management in these patients.

(2) Degree of hemodynamic instabilityShock index (heart rate / systolic blood pressure)Blood pressure, compared to patient's baseline pressureVasopressor requirementEvidence of end-organ hypoperfusion (e.g. urine output, skin perfusion)

(3) Degree of hyperlactatemiaPresence of other factors which may increase lactate levels (e.g. albuterol, hepatic dysfunction).Lactate >4 mM suggests a signi�cant mortality (28248722 (https://www.ncbi.nlm.nih.gov/pubmed/28248722) ).

(4) Other end-organ failures (e.g. delirium, shock liver)

https://www.ncbi.nlm.nih.gov/pubmed/28248722



clinical presentations(back to contents) (#top)

Septic shock encompasses a broad range of infections in a diverse range of patients. The table below shows common signs and symptoms ofsepsis. This can be a di�cult diagnosis, because different patients will present with different constellations of these �ndings.

Labs Signs & symptoms

Non-focalProcalcitoninC-reactive protein

Positive blood cultures

Focal- Urinalysis- Cerebrospinal fluid

Non-focalTemperature

Rigors, night sweats

Focal findings- Cellulitis- Pneumonia- Appendicitis- Meningitis

Lactate & Anion gapGlucose

PaCO2 (respiratory alkalosis)

Blood countWhite blood cell count

Neutrophil/Lymphocyte RatioBands/immature forms

Toxic granulations

RespiratoryRespiratory Rate

CardiovascularHeart rateBlood pressureShock index (HR/SBP)

Renal failureCreatinine, BUN

(Labs will lag behind)

Shock liver ( AST/ALT)

DICPlateletsINR, PTTD-DimerFibrinogen (insensitive)

Warm shock (initially)- Hypotension (usually)- Diastolic Bp- Wide pulse pressure- Warm extremities- Bounding pulses

Cold shock (later)- Hypotension- Mottling- Capillary refill- Narrow pulse pressure- Cool extremities

Delirium

Renal failure- Urine output- Dark urine

diagnostic features of septic shock

Clinical findings in septic shock. Individual presentations varywidely. The most challenging presentation is patients who lackfocal signs or symptoms of infection. Such patients may present ina fairly nonspecific manner with organ failure (e.g. hypotension).


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(https://emcrit.org/wp-content/uploads/2017/02/sepsispresenta.svg)

In many cases, septic shock may be suspected before the underlying infection is de�nitively diagnosed. In such cases, it is generally best toempirically treat as if the patient has septic shock, while obtaining additional information (e.g., culture data, de�nitive CT imaging).

For patients who are clinically in shock with no obvious cause (despite evaluation of history, physical exam, and echocardiography), thereshould be a high index of suspicion for septic shock.

sepsis mimics(back to contents) (#top)

With increased focus on sepsis and septic shock, other disorders are increasingly likely to be misdiagnosed as septic shock (27692840(https://www.ncbi.nlm.nih.gov/pubmed/27692840) ). Common mimics and their evaluation are shown here:

https://emcrit.org/wp-content/uploads/2017/02/sepsispresenta.svghttps://www.ncbi.nlm.nih.gov/pubmed/27692840



Bacterial SepticShock Mimics

Diagnostic clues & evaluation

All bacterial septic shockmimics

Procalcitonin (if normal or only minimally elevated, this shouldincrease suspicion for sepsis mimic)

Infectious

Endocarditis (shock 2/2 valvedysfunction)

Complete echocardiogram

Influenza Respiratory symptoms, influenza season, sick contacts.

Tick-borne illness Clues: Exposure, thrombocytopenia, skin rash, hemolysis

Candidal septicemia Ongoing critical illness, central line, colonization, immunosuppression,GI surg/perf, parenteral nutrition

Aspergillus Prolonged neutropenia, hematologic malignancy, prolonged or high-dose steroid use, pneumonia, hemoptysis

Pneumocystis pneumonia Diffuse pneumonia, immunosuppression (HIV, chronic steroid use,TNF-inhibitor, malignancy)

Endocrine

Adrenal crisis Random serum cortisol level (before steroid tx)

Thyroid storm Signs: tremors, thyromegaly. Labs: TSH, free T4

Diabetic ketoacidosis Beta-hydroxybutyrate level, ketones in urinalysis

Gastrointestinal

Acute mesenteric ischemia CT angiography of abdomen/pelvis

Bowel obstruction CT scan of abdomen/pelvis

Pancreatitis Lipase, CT abdomen/pelvis

Fulminant hepatic failure Liver function tests

Cirrhosis Chronic hypotension, elevated INR, thrombocytopenia

Toxicology

Salicylate intoxication History of salicylate use, tachypnea. Labs: Salicylate level

Beta-blocker / CCB Medication review, disproportionate bradycardia.

Carbon monoxide toxicity Exposure (winter), carboxyhemoglobin level.

Metformin Exposure history, disproportionately severe hyperlactatemia.

Miscellaneous

Anaphylaxis History & Physical (e.g. skin); Rapid resolution over time

HemophagocyticLymphohistiocytosis (HLH)

Labs: Cytopenias, Ferritin

Dermatologic (DRESS or AGEPin severe cases)

Skin exam, review of active medications

Aspiration pneumonitis Rapid recovery over time (faster than true bacterial pneumonia)

A septic shock mimic should be considered in patients without an obvious source of infection,or in patients with unimpressive procalcitonin levels. Evaluation will differ depending on theclinical scenario. The most high-yield tests for most patients are bolded (especially CTabdomen/pelvis and complete echocardiogram).


(https://emcrit.org/wp-content/uploads/2017/02/sepsismimics.svg)

common sources & evaluation of source(back to contents) (#top)

https://emcrit.org/wp-content/uploads/2017/02/sepsismimics.svg



Source Diagnostic clues & evaluation

Meningitis Nuchal rigidity, Lumbar puncture

Pneumonia (~50%) Symptoms, US, CXR (doubt this source if CXR equivocal)

Bloodstream infection (~15%)

Endocarditis Murmur, emboli, abnormal echocardiogram

Line/Hardware infection Erythema/warmpth at central line or port, line clotted

Lemierre’s syndrome Preceding pharyngitis, ultrasound shows jugular thrombus

Gastrointestinal source (~15%)

Cholecystitis Ultrasound: distension, sonographic Murphy’s

Ascending cholangitis Rigors, bilirubin; Ultrasound: Dilated common bile duct

Clostridioides difficile Recent ABX exposure, diarrhea; test stool

Other (appendicitis,diverticulitis, obstruction,perforation)

Pain, anorexia, distension(POCUS signs vary, may include free fluid/air, dilation)

Gynecologic source

Toxic shock Other signs of toxic shock (erythema, nausea/vomiting)

Chorioamnionitis Pregnancy, pain can occur

Urosepsis (~15%) Urgency/dysuria, back pain, abnormal urinalysis

Skin & soft tissue

Group A strep cellulitis Looks like classic cellulitis, but patient in septic shock

Necrotizing fasciitis Severe pain out of proportion to exam, necrosis/bullae

Septic arthritis Severe pain to joint movement; effusion, erythema.

Septic shock can result from infection nearly anywhere in the body, although some areunlikely to cause septic shock (e.g. osteomyelitis). This table merely shows the mostcommon foci of infection.


common sources of septic shock

(https://emcrit.org/wp-content/uploads/2017/02/sepsissources45.svg) source evaluation (https://i0.wp.com/emcrit.org/wp-content/uploads/2016/12/checklist3.gif)

History? Localizing symptoms? Travel to areas with endemic infections (e.g. tick-borne infections, malaria)? Hardware (e.g. prosthetic joints, pacemakers, implanted ports, central lines)

Physical exam: see �gure aboveLabs

Basic labs: Chem-10 (including Ca/Mg/Phos), CBC with differential, Coags, Liver function testsCultures: Blood cultures x2, culture of any indwelling line present >48 hoursProcalcitoninUrinalysis and cultureSpeci�c tests directed at other potential infections (e.g. PCR for anaplasma and ehrlichia; more here (https://emcrit.org/ibcc/tick/#labs) )

ImagingChest X-rayLow threshold to obtain CT abdomen/pelvis if source of infection remains unclear. Especially in elderly patients, severe abdominalpathology may occur with minimal �ndings on history and physical exam. Consider a CT angiogram if mesenteric ischemia is possible.

Additional tests as clinically warranted, for example:CT head and lumbar puncture if altered mental status or nuchal rigidityUltrasound evaluation of any potential sites of infectionParacentesis if ascites (even if previously present)

vasopressors(back to contents) (#top)

increase MAP>65mm promptly with peripheral vasopressor infusion

https://emcrit.org/wp-content/uploads/2017/02/sepsissources45.svghttps://i0.wp.com/emcrit.org/wp-content/uploads/2016/12/checklist3.gifhttps://emcrit.org/ibcc/tick/#labs



Correlational evidence suggests that a longer duration of hypotension increases the risk of renal failure.The traditional strategy of �ogging the patient with �uid for hours before starting pressors is ill-conceived.Peripheral vasopressor may be started without delay to support the blood pressure.

If the patient improves following �uid resuscitation, then pressor may be weaned off.If vasopressor requirements escalate, then transition to a central line may be considered.

choice of the �rst pressor: there is no “�rst-line” agent

Traditional dogma favors a speci�c sequence of vasopressors for all patients (typically beginning with norepinephrine, then with sequentialaddition of vasopressin, and �nally epinephrine). Evidence doesn't really support this:

Initial vasopressor support with vasopressin was potentially bene�cial in the VANISH trial (27483065(https://www.ncbi.nlm.nih.gov/pubmed/27483065) ). This shows that a pure vasoconstrictor can be used as a front-line pressor for septicshock.Epinephrine was shown to yield similar results to norepinephrine in the CAT trial 😺 (18654759(https://www.ncbi.nlm.nih.gov/pubmed/18654759) ) .The only prospective study comparing norepinephrine to phenylephrine found nearly identical hemodynamic responses (19017409(https://www.ncbi.nlm.nih.gov/pubmed/19017409) ).

For most patients, norepinephrine is a good choice. However, the selection of pressors may be individualized based on patient physiology,as shown below.The only pressor which shouldn't be used is dopamine (based on evidence of harm in prospective RCTs)(20200382(https://www.ncbi.nlm.nih.gov/pubmed/20200382) , 26323041 (https://www.ncbi.nlm.nih.gov/pubmed/26323041) ).

possible choices for initial pressor

Alpha-agonist

Beta-agonist

Phenylephrine

- Front-line agent foratrial fibrillation withrapid ventricular rate

- Alternative tonorepinephrine asperipheral pressor ifunable to closelymonitor IV site

Norepinephrine

- Good agent for mostpatients

- Well suited topatients withvasodilatory shock(tachycardia, warmextremities)

Epinephrine

Rational choice in patientswith:

- Inappropriately normalheart rate or frankbradycardia- Signs of low cardiacoutput (e.g. mottling, coolextremities)

Contrary to popular dogma, there is no single vasopressor agent which is “first-line” for everypatient with septic shock. Different patients may respond variably to different agents. Whenin doubt, the best approach is often to trial different agents and carefully monitor the patient’sresponse. Above are some patient characteristics that might suggest which agent the patientis likely to respond favorably to.

-The Internet Book of Critical Care, by @PulmCrit

(https://emcrit.org/wp-content/uploads/2017/02/initialpressor.svg)

peripheral vasopressors

The main concern with peripheral vasopressor infusion is extravasation into the skin leading to necrosis. Fortunately, this is rare. Overall, therisk of skin necrosis should never be prioritized over the risk of systemic hypoperfusion and death.

Skin necrosis is both less common and less important than mortality and systemic hypoperfusion.Norepinephrine is safe for peripheral infusion, but the risk of extravasation does increase if infusions are used for prolonged periods of time(25669592 (https://www.ncbi.nlm.nih.gov/pubmed/25669592) ). Peripheral norepinephrine has been validated in a medical ICU with a rigorousprotocol for placing IV lines and monitoring their function closely (26014852 (https://www.ncbi.nlm.nih.gov/pubmed/26014852) ).Phenylephrine or epinephrine are the safest agents to use peripherally. Both agents have been administered via a subcutaneous routeintentionally in the past. There appear to be no reports (https://emcrit.org/pulmcrit/phenylephrine-epinephrine-central-access/) in the literature of theseagents' causing skin necrosis. It's sensible to avoid infusion into the wrist or hand, but overall these agents are unlikely to cause necrosis ifextravasation occurs.

Note that phenylephrine infusion is physiologically very similar (https://emcrit.org/pulmcrit/phenylephrine-infusion/) to norepinephrine.

https://www.ncbi.nlm.nih.gov/pubmed/27483065https://www.ncbi.nlm.nih.gov/pubmed/18654759https://www.ncbi.nlm.nih.gov/pubmed/19017409https://www.ncbi.nlm.nih.gov/pubmed/20200382https://www.ncbi.nlm.nih.gov/pubmed/26323041https://emcrit.org/wp-content/uploads/2017/02/initialpressor.svghttps://www.ncbi.nlm.nih.gov/pubmed/25669592https://www.ncbi.nlm.nih.gov/pubmed/26014852https://emcrit.org/pulmcrit/phenylephrine-epinephrine-central-access/https://emcrit.org/pulmcrit/phenylephrine-infusion/



Vasopressin administration peripherally should probably be avoided. If vasopressin extravasates, there is no way to counteract its effect(unlike catecholamine extravasation, which can be treated with local in�ltration with phentolamine).

vasopressin

Vasopressin is a non-catecholamine pure vasoconstrictor that may improve renal function (compared to norepinephrine).Drawbacks of vasopressin:

Hard to titrate (half-life of ~30 minutes, so it will take a long time to reach steady state). Vasopressin can be used as a titratablepressor at doses ranging from 0-0.06 U/min, but don't expect dose adjustments to have an immediate effect (27483065(https://www.ncbi.nlm.nih.gov/pubmed/27483065) ).The combination of vasopressin plus norepinephrine can cause digital ischemia and necrosis.

How to use vasopressin?Best for patients with warm extremities (vasodilatory shock) and acute kidney injury.Monitor extremity perfusion and stop vasopressin immediately if digital ischemia occurs.Consider combining vasopressin with epinephrine (rather than norepinephrine). Theoretically, this may allow taking advantage of therenal-perfusion bene�ts of vasopressin while avoiding excessive vasoconstriction.

epinephrine might be the preferred inotrope for septic shock

Traditionally, there has been a preference for catecholamine inotrophes that selectively affect the beta-1 receptor. This is based on thefollowing two concepts, which are both wrong:

(1) The heart has only beta-1 receptors (Actually, the heart has both beta-1 and beta-2 receptors)(2876788(https://www.ncbi.nlm.nih.gov/pubmed/2876788) ).(2) Elevation of lactate levels is harmful (Actually, lactate may serve as a bioenergetic fuel for the heart, improving cardiac function)(24666826 (https://www.ncbi.nlm.nih.gov/pubmed/24666826) )

Epinephrine may actually have advantages over dobutamine:(1) Epinephrine may have greater e�cacy as an inotrope (�gure below).(2) Dobutamine causes vasodilation, which may decrease the blood pressure and exacerbate vasodilatory shock. This can causeproblems if the dobutamine isn't titrated very thoughtfully. In contrast, epinephrine contains alpha-adrenergic stimulation whichprevents it from having a net vasodilatory effect.

https://www.ncbi.nlm.nih.gov/pubmed/27483065https://www.ncbi.nlm.nih.gov/pubmed/2876788https://www.ncbi.nlm.nih.gov/pubmed/24666826



Triple action of epinephrine to support cardiac function?

Epinephrine

-1 receptorstimulation inmyocardium

Improvedcardiacfunction

Increasedchronotropy& inotropy

Release oflactate, usedas metabolicfuel for heart

Lactate is widely feared due to its correlation with mortality. However, lactate may serveas a beneficial source of fuel to the myocardium (prospective studies show that infusion ofsodium lactate improves cardiac function). Therefore, lactate generation from epinephrineisn’t a bug – it’s a feature. Epinephrine may also be more powerful than dobutamine dueto stimulation of cardiac beta-2 receptors. Overall, there are probably good reasons thathumans evolved to secrete epinephrine in the face of physiologic stress.


-2 receptorstimulation

-2 receptor stimulation inmyocardium

(https://emcrit.org/wp-content/uploads/2017/02/epitriple.svg)

multi-pressor titration

Titration of multiple vasopressors involves avoiding excessive vasoconstriction or excessive inotropy (�gure below). The optimal balancewill vary between patients.When in doubt, the best approach is often to empirically up- and down-titrate pressors in order to sort out what the various agents are doing.

If a patient strongly responds to up/down titration of an agent, that drug is more likely to be causing bene�t.If a patient has no/minimal response to adjusting the dose of an agent, that drug probably isn't helping much (and may be causingharm).

Norepinephrine down-titration: In addition to adding pressors, it's also useful to down-titrate pressors which aren't helping. Sometimesnorepinephrine may over-constrict patients, leading to excessive afterload and a drop in ejection fraction (the heart is unable to tolerate theexcessive afterload). If adjusting the norepinephrine dose doesn't affect blood pressure much, that suggests that the norepinephrine dose isexcessive. The goal should always be to use the minimal dose of vasopressor(s) necessary to achieve hemodynamic targets.

considerations in multi-pressor titration

Excess vasoconstriction- Poor urine output- Cool extremities, mottling, reducedcapillary refill

Excess inotropy- Maladaptive tachycardia (>~130 b/m?)- LV ejection fraction pathologically high- Dynamic LV outflow tract obstruction

The appropriate amount of inotropy and vasoconstriction must be balanced for each patient.This will vary between patients, depending on endogenous sympathetic tone and underlyingcardiac dysfunction.


(https://emcrit.org/wp-content/uploads/2017/02/inotropybalance.svg)

epinephrine challenge

Contraindications to epinephrine challenge:Signi�cant tachycardia (e.g. heart rate >120 b/m)Echocardiography shows the left ventricle is already hyperkinetic.

Indications for epinephrine challenge(1) Hypoperfusion (e.g. poor urine output, cold extremities, mottling, poor capillary re�ll)-plus, ideally-(2) Some indicator that epinephrine might help, for example

https://emcrit.org/wp-content/uploads/2017/02/epitriple.svghttps://emcrit.org/wp-content/uploads/2017/02/inotropybalance.svg



i) Bedside echo shows ejection fraction is reduced or (inappropriately) normalii) Heart rate is inappropriately slow or normal (e.g.



Meropenem (https://emcrit.org/ibcc/antibiotics/#carbapenems_(meropenem,_ertapenem)) may be used for nosocomial septic shock or profoundbeta-lactam allergy.Cefepime (https://emcrit.org/ibcc/antibiotics/#cephalosporin_G4:_cefepime) is good, but lacks anaerobic coverage (if abdominal infection ispossible, metronidazole should be added).

Avoid third-generation cephalosporins (https://emcrit.org/ibcc/antibiotics/#cephalosporin_G3:_ceftazidime) (e.g. ceftazidime or ceftriaxone) for thefollowing reasons:

Sub-optimal gram-positive coverage (even if vancomycin is given, vancomycin levels will often be inadequate).Failure to cover gram-negatives with inducible beta-lactamase (e.g. Serratia or Enterobacter spp.) – even if they may appear to coverthese organisms on an antibiogram (more on this here (https://emcrit.org/ibcc/antibiotics/#AmpC_inducible_beta-lactamase) ).

MRSA coverage?

Not every septic patient needs vancomycin!MRSA isn't a pathogen involved in urosepsis or community-acquired intra-abdominal infection. Patients with these sources of infectiondon't need MRSA coverage.MRSA coverage should be considered for patients with pneumonia, soft-tissue infection, line infection, or endocarditis.

Either vancomycin or linezolid may be used.If vancomycin is chosen, it should be dosed correctly (ideally with pharmacokinetic monitoring (https://emcrit.org/pulmcrit/vanco/) ).Linezolid has no risk of nephrotoxicity and is easier to dose adequately.

coverage of other pathogens

Atypical pulmonary pathogens should be covered in patients with pneumonia (https://emcrit.org/ibcc/pneumonia/#antibiotic_selection) (azithromycin(https://emcrit.org/ibcc/antibiotics/#macrolides_(azithromycin,_clarithromycin)) or doxycycline (https://emcrit.org/ibcc/antibiotics/#doxycycline) ).Possible tick-borne illness (https://emcrit.org/ibcc/tick/) may be covered with doxycycline.Clostridioides di�cile (https://emcrit.org/ibcc/cdiff/) coverage in patients with colitis or diarrhea (especially if recent antibiotic exposure).Clindamycin (https://emcrit.org/ibcc/antibiotics/#clindamycin) may be considered for toxin suppression in patients with necrotizing fasciitis, toxicshock syndrome, or severe group A streptococcal infections (e.g. streptococcal cellulitis).

going further…

Approach to allergy to various beta-lactam antibiotics (https://emcrit.org/ibcc/penicillin/) (IBCC chapter)Antibiotics (https://emcrit.org/ibcc/antibiotics/) (IBCC chapter)

source control(back to contents) (#top)

Failure to achieve source control might be the most common cause of death from septic shock within a modern healthcare system. All otherinterventions described in this chapter will often fail if there is inadequate procedural source control.

common examples of source control

Infected hardware (e.g. catheter) may need to be removed.Nephrolithiasis causing obstruction and infection may require decompression.Ascending cholangitis requires ERCP or percutaneous intervention for decompression.Perforated or obstructed bowel requires surgical repair.Necrotizing fasciitis may require debridement.

investigation regarding possible need for source control

Ensure that the source has been fully investigated (e.g. a patient with urosepsis should be imaged to exclude obstruction).For patients in whom no infection is identi�ed, aggressive imaging may be helpful to search for the source (e.g. CT abdomen/pelvis).

�uid(back to contents) (#top)

https://emcrit.org/ibcc/antibiotics/#carbapenems_(meropenem,_ertapenem)https://emcrit.org/ibcc/antibiotics/#cephalosporin_G4:_cefepimehttps://emcrit.org/ibcc/antibiotics/#cephalosporin_G3:_ceftazidimehttps://emcrit.org/ibcc/antibiotics/#AmpC_inducible_beta-lactamasehttps://emcrit.org/pulmcrit/vanco/https://emcrit.org/ibcc/pneumonia/#antibiotic_selectionhttps://emcrit.org/ibcc/antibiotics/#macrolides_(azithromycin,_clarithromycin)https://emcrit.org/ibcc/antibiotics/#doxycyclinehttps://emcrit.org/ibcc/tick/https://emcrit.org/ibcc/cdiff/https://emcrit.org/ibcc/antibiotics/#clindamycinhttps://emcrit.org/ibcc/penicillin/https://emcrit.org/ibcc/antibiotics/



Rivers of ink have been spilled discussing the optimal strategy for �uid administration in septic shock. However, there's little evidence that �uidadministration is truly bene�cial. Excessive �xation on �uid status may serve to divert attention from other more important aspects of care.

foundational concepts of �uid management in septic shock

1. The primary physiologic problems in septic shock are vasodilation and maldistribution of blood to organs (sometimes with cardiacdysfunction as well). None of these problems can be solved with �uid administration.

2. The vast majority of crystalloid administered will leak out of vasculature into the interstitial tissue (for example, 95% in some studies of �uidboluses!)(22165353 (https://www.ncbi.nlm.nih.gov/pubmed/22165353) ).

3. Fluid bolus therapy isn't evidence-based (https://emcrit.org/pulmcrit/bolus/) and should arguably be avoided when possible (partially due to #2above).

4. There is no high-quality evidence that large-volume �uid resuscitation is bene�cial in septic shock. Available RCT evidence shows that �uidadministration may be harmful (27686349 (https://www.ncbi.nlm.nih.gov/pubmed/27686349) , 28973227 (https://www.ncbi.nlm.nih.gov/pubmed/28973227) ).

5. A low central venous pressure and collapsed inferior vena cava may result from vasodilation and distribution of blood out of the central veins(rather than true hypovolemia; explained further here (https://emcrit.org/pulmcrit/mythbusting-empty-ivc-hyperkinetic-heart-%E2%89%A0-volume-depletion/) ). Therefore, a collapsed IVC shouldn't be interpreted as an indication to give �uid.

6. Fluid responsiveness has never been shown to improve clinical outcomes in septic shock (likely due to #1-3 above). Likewise, sophisticatedhemodynamic monitoring (e.g. Swan-Ganz catheter, vigelo FloTrac) has never been shown to improve clinical outcomes (29149934(https://www.ncbi.nlm.nih.gov/pubmed/29149934) ).

7. Every physician is convinced that they understand how to apply �uids to bene�cial effect, yet there is zero agreement on this topic. Thisdemonstrates the existence of widespread over-estimation of our ability to use �uids in a bene�cial manner.

video explaining why �uid boluses are rarely helpful (more on this here (https://emcrit.org/pulmcrit/bolus/) )

initial �uid resuscitation (generally in the emergency department)

00:00 01:14

https://www.ncbi.nlm.nih.gov/pubmed/22165353https://emcrit.org/pulmcrit/bolus/https://www.ncbi.nlm.nih.gov/pubmed/27686349https://www.ncbi.nlm.nih.gov/pubmed/28973227https://emcrit.org/pulmcrit/mythbusting-empty-ivc-hyperkinetic-heart-%E2%89%A0-volume-depletion/https://www.ncbi.nlm.nih.gov/pubmed/29149934https://emcrit.org/pulmcrit/bolus/



History & exam indicates true hypovolemia- nausea/vomiting/diarrhea- reduced PO intake for several days- diabetic ketoacidosis or severe hypercalcemia- over-diuresis

Average patient Contraindications to fluid, e.g.:- Evidence of systemic congestion- Severity of lung failure > severitycardiac dysfunction- Dialysis patients (use caution)

You’re done! Great job! Stop giving fluid.

Key point: IV medications (especially those given via continuous infusion) will provide a substantial fluid volume ontheir own without any added crystalloid. To provide additional fluid beyond this, consider initiation of enteralnutrition. Persistent administration of fluid following initial resuscitation may cause harm.

initial resuscitation of hypotensive patients with septic shock

- Provide ~1-2 liters fluid(~30 cc/kg ideal body wt)- Consider giving fluid slowly(over several hours)

Provide little or nocrystalloid resuscitation.

- Consider larger volume fluidresuscitation (e.g. 2-4 liters)- Give fluid slowly, followhemodynamics.

Assess volume status- Clinical history (? Significant nausea/vomiting/diarrhea or reduced oral intake or diabetic ketoacidosis)- Known cardiac dysfunction (e.g. cardiomyopathy, aortic stenosis, pulmonary hypertension)- Bedside echocardiography- Increased risk of harm from hypervolemia? (e.g. pneumonia with risk of evolving into ARDS)

Moderate volume resus Low volume resus

Nobody actually knows how much fluid to use in septic shock. This seems like a reasonable approach in the absence ofdefinitive evidence. Note that this approach only applies to patients who are hypotensive or on vasopressors.


Large volume resus

(https://emcrit.org/wp-content/uploads/2017/02/�uidschema.svg)

The optimal strategy for initial volume resuscitation is unknown. This is currently the subject of ongoing clinical trials (e.g. CLOVERS trial(https://clinicaltrials.gov/ct2/show/NCT03434028) ).The above schema seems reasonable, but will obviously need to be tailored to the individual patient.For patients with pneumonia and mild hypotension, their primary physiologic problem is often hypoxemia. If you're concerned primarilyabout pulmonary decompensation then �uid won't help – such patients may bene�t from vasopressor support rather than �uids.

management of �uid status following initial resuscitation

Unless the patient has substantial ongoing �uid losses (e.g. severe diarrhea), it may be wise to stop giving additional crystalloid following theinitial resuscitation.Most patients will receive ~1.5 liters per day of �uid along with various infusions and antibiotics. The addition of enteral nutrition will oftenincrease this to >2-3 liters per day! This �uid alone is already excessive (without the use of any additional crystalloid).Follow electrolytes daily. If hypernatremia (https://emcrit.org/ibcc/hypernatremia/) develops then the patient has a free water de�ciency whichmust be treated with enteral water or intravenous D5W.A common mistake is to continue large-volume �uid resuscitation for too long. For example, a patient may receive 2-3 liters of �uid in theemergency department (appropriately), and then the ICU team will re-resuscitate with an additional 2-3 liters of �uid (inappropriately). Thena different ICU team will rotate on shift and resuscitate the patient a third time!

Another related mistake is not keeping track of �uid inputs during transitions in care.Available evidence supports a �uid-restrictive strategy following initial resuscitation (CLASSIC & FACT trials). In the CLASSIC trial, additional�uid caused no improvement in hemodynamics, vasopressor dose, or urine output. In fact, a liberal �uid strategy seemed to increase therisk of kidney injury (27686349 (https://www.ncbi.nlm.nih.gov/pubmed/27686349) ).

Rory Spiegel@EMNerd_

Replying to @PulmCrit and 3 othersYep, looks something like this: Is the pt in the ICU? I I I Yes I I I Stop giving fluid!

11 9:04 AM - Jun 7, 2019 · Washington, DC

See Rory Spiegel's other Tweets

https://emcrit.org/wp-content/uploads/2017/02/fluidschema.svghttps://clinicaltrials.gov/ct2/show/NCT03434028https://emcrit.org/ibcc/hypernatremia/https://www.ncbi.nlm.nih.gov/pubmed/27686349https://twitter.com/EMNerd_https://twitter.com/EMNerd_https://twitter.com/EMNerd_/status/1136982170470440960https://twitter.com/_/status/1136981188927733761https://twitter.com/intent/like?tweet_id=1136982170470440960https://twitter.com/EMNerd_/status/1136982170470440960https://twitter.com/search?q=place%3A01fbe706f872cb32https://support.twitter.com/articles/20175256https://twitter.com/EMNerd_



Serial assessment of �uid responsiveness may lead to a vicious cycle of perpetual �uid administration (�gure below).Fluid administration does often cause a transient improvement in hemodynamics, which reinforces this misguided behavior.Fluid micro-management (e.g. serial echocardiography with �uid boluses) is extremely time-consuming and probably not bene�cial(see: futility of �uid boluses above #2).

by @PulmCrit

Vicious cycle of repeated fluid boluses for “fluid responsiveness”

Repeated assessments of fluid responsiveness may lead to perpetual administration of fluidboluses in an endless cycle. This cycle is reinforced by transient improvement following eachbolus. Unfortunately the net effect of this spiral is volume overload and endothelial damage.

Patient evaluated and foundto be intravascularly volume

depleted and volumeresponsive

Fluid bolus given. Patientimproves transiently with

better cardiac output, urineoutput, blood pressure, etc.

Fluid third-spaces out ofvasculature within a few

hours.

Hemodynamic deterioration(decrease in blood

pressure, urine output, etc.)

traditional dogma: over-resuscitation followed by de-resuscitation

A traditional concept is that septic patients should initially be volume overloaded, and subsequently diuresed during their recovery (“you needto swell to get well, you need to pee to be free”).There is no evidence to support this concept. Volume overload isn't a viable therapeutic strategy. A better strategy seems to be targetingeuvolemia and then keeping patients there.

If the patient does become volume overloaded, diuresis should be performed as soon as it is safe to remove �uid. Diuresis can oftenbe commenced ~24-48 hours after admission, once the patient is stabilizing hemodynamically and vasopressor doses are decreasing. Signs of intravascular volume overload (e.g. distension of the inferior vena cava, portal vein pulsatility) support the safety of diuresis.

�uid choice

Non-anion-gap metabolic acidosisUremic acidosis

Acute metabolic alkalosis No pH disorder treatable withcrystalloid

Reassess electrolytes & volume status

IF remains substantially hypovolemic then repeat…

Patient who requires large-volume fluid resuscitation

pH-guided resuscitation

0.9% saline Lactated ringers orplasmalyteIsotonic Bicarbonate

Assess metabolic acid-base abnormalities

alkalinize acidify maintain

pH-guided fluid resuscitation refers to the concept that resuscitation represents a one-time opportunity to fix certain pHabnormalities that are responsive to acidic or alkali fluid infusion. Since such therapies typically require a large volume of infusedfluid, treatment of the pH abnormality must occur simultaneous with the initial fluid resuscitation.


(https://emcrit.org/wp-content/uploads/2017/02/phguidedresus.svg)

Fluid choice can be guided by the presence of pH abnormalities (pH-guided �uid resuscitation (https://emcrit.org/ibcc/�uid/) ).For most patients, a balanced crystalloid is a good choice (e.g. Lactated Ringers or Plasmalyte).For patients with spontaneous bacterial peritonitis and/or hepato-renal syndrome, albumin is generally the �uid of choice.

going further…

Landmark trialsFEAST trial (https://www.thebottomline.org.uk/summaries/icm/feast/) (David Slessor)

https://emcrit.org/wp-content/uploads/2017/02/phguidedresus.svghttps://emcrit.org/ibcc/fluid/https://www.thebottomline.org.uk/summaries/icm/feast/



CLASSIC trial (https://www.thebottomline.org.uk/summaries/icm/classic/) (Segun Olusanya)Simpli�ed Severe Sepsis Protocol 2 (https://www.thebottomline.org.uk/summaries/icm/sssp2/) (Fraser Magee)

Fluid Responsiveness (https://emcrit.org/emcrit/assessing-�uid-responsiveness/) (EMCrit podcast 162)Empty IVC doesn't prove volume depletion (https://emcrit.org/pulmcrit/mythbusting-empty-ivc-hyperkinetic-heart-%E2%89%A0-volume-depletion/)Myth-busting the �uid bolus (https://emcrit.org/pulmcrit/bolus/)pH-guided resuscitation (https://emcrit.org/ibcc/�uid/) (IBCC chapter)Get SMART: 9 reasons to quit using normal saline (https://emcrit.org/pulmcrit/smart/)

steroid(back to contents) (#top)

risk of steroid

Stress-dose steroid (50 mg hydrocortisone IV q6hr) is equivalent to 50 mg prednisone daily. This dose of steroid is routinely used foroutpatients with a myriad of diagnoses, without much fuss (e.g. asthma or COPD exacerbation).Stress-dose steroid doesn't increase the risk of super-infection. This concept was promoted by inappropriate interpretation of secondaryoutcomes in the CORTIUS trial (18184957 (https://www.ncbi.nlm.nih.gov/pubmed/18184957) ). This fear has been debunked in meta-analyses, aswell as in the much larger ADRENAL trial (19489712 (https://www.ncbi.nlm.nih.gov/pubmed/19489712) , 29347874(https://www.ncbi.nlm.nih.gov/pubmed/29347874) ).Large RCTs haven't detected a risk of steroid-induced myopathy. However, such a risk may exist in patients who are undergoing therapeuticparalysis.Steroid does increase the rate of hyperglycemia (shown in numerous RCTs above).

bene�t of steroid

Both the meta-analysis and ADRENAL trial show that steroid reduces the time on vasopressors, the duration of intubation, and the length ofICU stay (29347874 (https://www.ncbi.nlm.nih.gov/pubmed/29347874) , 29761216 (https://www.ncbi.nlm.nih.gov/pubmed/29761216) ). These are importantoutcomes which may hasten recovery, avoid iatrogenic harms, and reduce costs.A potential mortality bene�t of steroid is debated. It's possible that one may exist, if steroid is initiated early and in the sickest patients(29490185 (https://www.ncbi.nlm.nih.gov/pubmed/29490185) ). Logistically, it is nearly impossible (https://emcrit.org/pulmcrit/mortality/) to prove whethersuch a mortality bene�t exists, so this may be the wrong question to �xate upon.

rationale for early steroid administration

(1) For years, it was believed that a subset of patients with pressor-refractory shock would experience a mortality bene�t from steroid, basedon subgroup analysis within the Annane 2002 (https://www.ncbi.nlm.nih.gov/pubmed/12186604) trial. This suggested that only the sickest subset ofpatients would bene�t from steroid. However, the more recent ADRENAL trial showed that patients on any dose of vasopressor couldbene�t (as discussed above). This suggests that steroid therapy may be used more broadly.(2) The entire concept of sepsis resuscitation is to proactively support the patient and prevent further deterioration – not to wait for thepatient to deteriorate further before trying to salvage them in a reactive fashion. This is why every single therapy in sepsis care is institutedrapidly – ideally including steroid.(3) Starting steroid immediately eliminates the decision about when to start steroids, shifting greater focus on other issues.(4) Immediately initiating maximal medical therapy can help rapidly clarify whether the patient can respond to medical therapy. This mayexpedite decisions about whether to move to a more aggressive surgical procedure for source control.(5) Antibiotics often cause bacterial cell lysis, which releases bacterial products into the bloodstream, causing clinical deterioration (Jarisch-Herxheimer reaction). Front-loaded steroid therapy could theoretically blunt this phenomenon.

https://www.thebottomline.org.uk/summaries/icm/classic/https://www.thebottomline.org.uk/summaries/icm/sssp2/https://emcrit.org/emcrit/assessing-fluid-responsiveness/https://emcrit.org/pulmcrit/mythbusting-empty-ivc-hyperkinetic-heart-%E2%89%A0-volume-depletion/https://emcrit.org/pulmcrit/bolus/https://emcrit.org/ibcc/fluid/https://emcrit.org/pulmcrit/smart/https://www.ncbi.nlm.nih.gov/pubmed/18184957https://www.ncbi.nlm.nih.gov/pubmed/19489712https://www.ncbi.nlm.nih.gov/pubmed/29347874https://www.ncbi.nlm.nih.gov/pubmed/29347874https://www.ncbi.nlm.nih.gov/pubmed/29761216https://www.ncbi.nlm.nih.gov/pubmed/29490185https://emcrit.org/pulmcrit/mortality/https://www.ncbi.nlm.nih.gov/pubmed/12186604



approach to steroid administration in septic shock

Septic shock

Stress dose steroid

- Hydrocortisone 50 mg IV q6

(If hydrocortisone unavailable,may use methylprednisolone40 mg IV daily)

Yes

No

No

Yes

Yes

Withhold steroid, follow hemodynamics

No If develops refractory shock


Known/probable adrenal insufficiency?- Addison’s disease- Chronic steroid use

Relative contraindication(s) to steroid?- Brittle diabetes- Delirium- Fungal/mycobacterial infection- Severe immunocompromise (e.g. neutropenia)

Patient is refractory to low-moderate doseof vasopressors?

(https://emcrit.org/wp-content/uploads/2017/02/steroidinsepsis.svg) one possible approach

Above is one potential approach to steroid in septic shock. This strategy prioritizes liberation from pressors and ventilation over the risk ofhyperglycemia.Please note that patients with known adrenal insu�ciency or chronic steroid use should de�nitely be treated with stress-dose steroid.

steroid dose in septic shock

The best studied dose of steroid in septic shock is 200 mg hydrocortisone total daily.Clinical studies often use a continuous infusion of hydrocortisone. However, in clinical practice the use of divided IV doses (50 mg IV q6hr)has the following advantages:

(1) Immediately establishes effective drug level (rather than an infusion that takes time to reach steady state).(2) Doesn't tie up an intravenous line, making it easier to administer.(3) One small RCT demonstrated that intermittent administration of hydrocortisone resulted in improved shock resolution compared toa continuous infusion (30628950 (https://www.ncbi.nlm.nih.gov/pubmed/30628950) ).

If hydrocortisone isn't immediately available, any equivalent dose of steroid may be used. A nice option is methylprednisolone 40 mg IVdaily, because this is widely available in emergency departments.

�udrocortisone is unnecessary

The APROCHSS trial used a combination of hydrocortisone and �udrocortisone. This has led some to question the value of adding�udrocortisone on top of hydrocortisone.Using �udrocortisone currently doesn't seem justi�ed for several reasons:

(1) Hydrocortisone itself has mineralocorticoid effects, making the addition of �udrocortisone unnecessary.(2) Fludrocortisone administration to critically ill patients often fails to achieve a measurable serum drug level – so it's probably notdoing much (27416887 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099539/) ).(3) The ADRENAL trial demonstrated numerous bene�ts of steroid – without �udrocortisone administration.(4) Septic patients are typically treated with an excessive quantity of exogenous sodium, making �udrocortisone-induced sodiumretention unnecessary.

going further…

The Bottom Line reviews:ADRENAL trial (https://www.thebottomline.org.uk/summaries/icm/adrenal/)APROCCHSS trial (https://www.thebottomline.org.uk/summaries/icm/aprocchss/)

Steroid in septic shock: Four misconceptions and one truth (https://emcrit.org/pulmcrit/steroids-in-septic-shock-four-misconceptions-and-one-truth/)ADRENAL trial & implications for metabolic resuscitation (https://emcrit.org/pulmcrit/adrenal/) (PulmCrit)APROCCHSS vs. ADRENAL: Really discordant? (https://emcrit.org/pulmcrit/aprocchss/) (PulmCrit)

https://emcrit.org/wp-content/uploads/2017/02/steroidinsepsis.svghttps://www.ncbi.nlm.nih.gov/pubmed/30628950https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099539/https://www.thebottomline.org.uk/summaries/icm/adrenal/https://www.thebottomline.org.uk/summaries/icm/aprocchss/https://emcrit.org/pulmcrit/steroids-in-septic-shock-four-misconceptions-and-one-truth/https://emcrit.org/pulmcrit/adrenal/https://emcrit.org/pulmcrit/aprocchss/



DVT prophylaxis with heparin(back to contents) (#top)

heparin may protect the endothelial glycocalyx

The endothelial glycocalyx is composed of heparinoids, which have a similar molecular structure compared to exogenous heparin. Thisraises the possibility that exogenous heparin could potentially inhibit the activity of endogenous heparinase enzymes that degrade theendothelial glycocalyx (thereby protecting the glycocalyx). Some laboratory studies suggest that low molecular-weight heparin may protectthe endothelial glycocalyx (28347755 (https://www.ncbi.nlm.nih.gov/pubmed/28347755) , 30046671 (https://www.ncbi.nlm.nih.gov/pubmed/30046671) ,22507823 (https://www.ncbi.nlm.nih.gov/pubmed/22507823) , 22310127 (https://www.ncbi.nlm.nih.gov/pubmed/22310127) ). Bene�ts from heparin mayextend beyond this, to include immunomodulation as well (28832958).Patients with septic shock are at high risk of deep vein thrombosis (DVT), so they merit treatment for DVT regardless of the above data. Apotential bene�t of heparin in septic shock argues for initiating this therapy sooner rather than later.

interventions of no real value(back to contents) (#top)

serial �uid bolus after initial resuscitation

This is explored brie�y above in the section on �uid management (#�uid) .Further discussion regarding why �uid boluses are unlikely to help patients in septic shock is here (https://emcrit.org/pulmcrit/bolus/) . Thisintervention has neither diagnostic nor therapeutic merit.

central venous pressure (CVP) transduction

Central venous pressure is an extremely complex variable, which re�ects a nexus of volume status, cardiac function, and vascular tone.The concept that central venous pressure re�ects volume status has been thoroughly debunked (18628220(https://www.ncbi.nlm.nih.gov/pubmed/18628220) ).Measuring the central venous pressure should be avoided, as this value will almost invariably be misinterpreted.

mixed venous oxygen saturation (%svcO2)

Similar to central venous pressure, the mixed venous oxygen saturation is a highly complex variable which re�ects numerous contributingfactors.Based on the number of factors affecting svcO2%, there is a dramatic error range (https://emcrit.org/pulmcrit/central-venous-saturation/) in the value.Measurement of mixed venous oxygen saturation should be avoided because it is extremely complex, subject to considerable random error,and easily misinterpreted. Furthermore, numerous RCTs revealed that measuring svcO2% didn't improve outcomes compared toconventional therapy (the PROCESS, PROMISE, and ARISE trials).

resuscitative endpoints: general philosophy(back to contents) (#top)

Resuscitative endpoints are targets which we would ideally like our patients to reach. The evidentiary basis for most resuscitative endpoints canbe summarized roughly as follows:

There is usually excellent retrospective evidence that a resuscitative endpoint correlates with improved outcomes.There is usually minimal prospective RCT evidence that tailoring resuscitation to intentionally reach a speci�c endpoint improves outcomes.

Prospective RCTs tend to compare different resuscitative endpoints, which is extremely murky (because none of these endpoints is supported byany hard data). These studies often build upon one another, with an exquisitely shaky foundation. For example:

1. The Rivers trial used resuscitative endpoints including central venous pressure (CVP) and mixed venous oxygen saturation. As discussedabove, this is a profoundly �awed trial which at this point has been largely disproven (discussed above (#brief_history_of_septic_shock_treatment) ).

2. The Jones trial (https://www.ncbi.nlm.nih.gov/pubmed/20179283) showed equivalence between mixed venous oxygen saturation and lactate. This isprobably demonstrating the equivalence of two awful resuscitative endpoints.

https://www.ncbi.nlm.nih.gov/pubmed/28347755https://www.ncbi.nlm.nih.gov/pubmed/30046671https://www.ncbi.nlm.nih.gov/pubmed/22507823https://www.ncbi.nlm.nih.gov/pubmed/22310127https://emcrit.org/pulmcrit/bolus/https://www.ncbi.nlm.nih.gov/pubmed/18628220https://emcrit.org/pulmcrit/central-venous-saturation/https://www.ncbi.nlm.nih.gov/pubmed/20179283



3. The ANDROMEDA-SHOCK trial (https://www.ncbi.nlm.nih.gov/pubmed/30772908) suggested that capillary re�ll could be superior to using lactate asa resuscitation target. Given the lack of evidence supporting lactate as an endpoint, this trial is nearly impossible to interpret. It's possiblethat this trial reveals more about the harm of chasing lactate than the bene�t of chasing capillary re�ll.

how to use resuscitative endpoints wisely?

As discussed above, the science behind resuscitative endpoints is very weak. This creates a risk of harm if we chase these endpoints tooaggressively.(1) Using resuscitative endpoints as a trigger for �uid administration is generally not a good idea.

It's well established that the vast majority of �uid administered will rapidly extravasate out of the vasculature.Unless there is a source of ongoing �uid loss (e.g. diarrhea or high-output �stula), ongoing �uid resuscitation is unlikely to be bene�cial.More discussion on �uid resuscitation above (#�uid) .

(2) Resuscitative endpoints may be most useful for titrating vasopressors and inotropes.Exactly how patients will respond to vasopressors or inotropes may be impossible to predict from an initial echocardiogram (whichrepresents a snapshot of cardiac function in time).The optimal hemodynamic targets (e.g. MAP goal) may vary between patients.The best way to determine the optimal MAP goal and vasopressor dose for any speci�c patient may be empiric titration with closeobservation of the effects.

(3) Failure to meet resuscitative endpoints should prompt overall re-evaluation of the patient, for example:Is there a failure to detect the correct source of sepsis?Is the antibiotic selection correct?

resus targets: MAP(back to contents) (#top)

why MAP is generally the most useful blood pressure parameter:

It is the mean pressure driving perfusion.It is what noninvasive oscillometric blood pressure cuffs actually measure.It is the most reproducible parameter when measured in different locations and via different techniques (e.g. noninvasive vs. invasivemonitoring).Septic patients with vasodilation often have low diastolic blood pressure – so an adequate systolic blood pressure may be falselyreassuring.

conventional MAP target (>65 mm)

MAP > 65mm is the usual target.This is generally a reasonable place to start – particularly in an undifferentiated patient whose baseline hemodynamics are unclear.

higher MAP targets (e.g. >75-80 mm)

SEPSISPAM trial (https://www.ncbi.nlm.nih.gov/pubmed/24635770) showed that a MAP goal of >80-85 mm improved renal function in the subset ofpatients with chronic hypertension, but higher MAP targets were associated with increased risk of atrial �brillation.Higher MAP targets may be trialed in patients with chronic hypertension and sluggish urine output. If there is an improvement in urineoutput at higher MAP, then this strategy may be continued; otherwise, the MAP target may be decreased (vasopressor challenge).Patients with cirrhosis and renal failure who have a component of hepatorenal syndrome might bene�t from higher MAP targets.

lower MAP targets (e.g. >60 mm)

Situations where lower MAP targets may be sensible:Patients with chronic hypotension (e.g. younger women, patients with cirrhosis without hepatorenal syndrome).Patients with end-stage renal failure on hemodialysis (main concern with low MAP is renal injury, which isn't an issue here).

Lower MAP values may be tolerated in the face of adequate perfusion (e.g. urine output and peripheral perfusion).

resus targets: heart rate

https://www.ncbi.nlm.nih.gov/pubmed/30772908https://www.ncbi.nlm.nih.gov/pubmed/24635770



(back to contents) (#top)

optimal heart rate?

Septic patients should have a bit of tachycardia. This is a compensatory response that improves cardiac output.Remember: Cardiac Output = (Heart Rate)(Stroke Volume)

The optimal heart rate for a patient with septic shock is unknown, and may vary between patients (e.g. patients with diastolic dysfunctioncould do better with a slightly slower heart rate). In general, a heart rate of ~90-110 might be reasonable for most patients.

management of bradycardia or “inappropriate normocardia” (e.g. 140 b/m)

Excessive tachycardia probably isn't great either:May impair ventricular �lling (especially with diastolic dysfunction).Over time, may increase the risk of stress cardiomyopathy.

Potential interventions which may be considered:Transition to vasopressors with less beta-adrenergic stimulation (e.g. vasopressin or phenylephrine).Digoxin initiation in patients with chronic atrial �brillation.Removal of other stimuli which may be driving tachycardia (e.g. under-treated agitation, pain, or withdrawal).Esmolol infusion was found to be bene�cial in one study, but generalization from that study is impossible (because patients were onhigh-dose pressors and often levosemindan)(24108526 (https://www.ncbi.nlm.nih.gov/pubmed/24108526) ). It's possible that the bene�t fromesmolol re�ected excessive beta-adrenergic administration. Esmolol infusion in septic shock generally isn't generally recommended.

resus targets: urine output(back to contents) (#top)

typical urine output

The usual goal is >0.3-0.5 cc/kg/hr ideal body weight.There is no single, speci�c cutoff rate for the urine output. The risk of renal failure increases based on how low the urine output is, and howlong oliguria persists. For example:

Urine output 0.4 cc/kg for an hour with subsequent improvement is probably �ne.Urine output



potential approach to oliguria

After the initial resuscitation, additional �uid boluses should be avoided unless there is compelling evidence of hypovolemia (e.g. �uid lossfrom diarrhea).Depending on the current hemodynamics, vasopressor or inotrope challenges may be useful. If there is evidence of systemic congestion ora high suspicion for intrinsic renal failure, a furosemide stress test (https://emcrit.org/pulmcrit/furosemide-stress-test/) may be performed.

This is discussed further in the chapter on acute kidney injury (https://emcrit.org/ibcc/acute-kidney-injury/#approach_to_oliguria) .

resus targets: �uid balance(back to contents) (#top)

Keep track of the net �uid balance of the patient, which includes the volume of crystalloid given, as well as the volume of antibiotics andother infusions.Very high �uid balance correlates with increased mortality (28130687 (https://www.ncbi.nlm.nih.gov/pubmed/28130687) ). Unless there is strongevidence of pre-existing hypovolemia, avoid running the �uid balance above ~5 liters positive.

resus targets: lactate(back to contents) (#top)

general philosophy

Lactate is not an indicator of perfusion, systemic oxygenation, organ failure, or anaerobic metabolism. In most cases it serves as an indexof endogenous epinephrine production.Cycling the lactate and trying to “normalize” it isn't evidence-based (for more on this, see Myth #3 here (https://emcrit.org/pulmcrit/sepsis-myths/) ).Following the lactate is reasonable until it falls, but this data should be used in an intelligent and thoughtful fashion.

following lactate in patients not on epinephrine

If the lactate is continuing to increase, this may be a sign of “missed injury”Undrained source of infection.Inappropriate antibiotic selection.Incorrect diagnosis entirely.

A rising lactate isn't an indication to blindly give �uid or inotropes, but rather should be a sign that something is wrong and the entirepatient needs to be reconsidered carefully.

Omnintensivist@GoodishIntent

*Breezing into the adult ICU for my first day of service*

https://emcrit.org/pulmcrit/furosemide-stress-test/https://emcrit.org/ibcc/acute-kidney-injury/#approach_to_oliguriahttps://www.ncbi.nlm.nih.gov/pubmed/28130687https://emcrit.org/pulmcrit/sepsis-myths/https://twitter.com/GoodishIntenthttps://twitter.com/GoodishIntenthttps://twitter.com/GoodishIntent/status/1113627993652359168



following lactate in patient on epinephrine

Epinephrine should cause the lactate to increase. In fact, rising lactate following initiation of epinephrine is generally a positive prognosticsign! (20016405 (https://www.ncbi.nlm.nih.gov/pubmed/20016405) ).However, if the lactate increases to very high levels (e.g. >10 mM), then the epinephrine infusion should be down-titrated (and replaced bydobutamine if an inotropic agent remains necessary).

going further…

Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia (https://ccforum.biomedcentral.com/articles/10.1186/s13054-014-0503-3) . Critical Care 2014; 18(5) 503 (open access).Understanding lactate and using it to our advantage (https://emcrit.org/pulmcrit/understanding-lactate-in-sepsis-using-it-to-our-advantage/) (PulmCrit)

resus targets: skin perfusion(back to contents) (#top)

(1) loss of pulse oximetry waveform

If the extremities are very poorly perfused, then the pulse oximeter becomes unable to recognize any pulsatile blood �ow in the digits.This isn't sensitive for poor perfusion (because pulse oximeters are designed to amplify small pulsations).When encountered, this should be recognized as an objective sign of terrible perfusion.

(2) mottling

Galbois A 2015 (https://www.sciencedirect.com/science/article/abs/pii/S0168827814007417)

Lab tech: Oh, um hello

Me: Whatcha doin

LT: A reflex lactate

Me:

LT: I'll just go ahead and cancel it

Me:

LT: I'll cancel all of the reflex lactates

Me: no more lactates forever

481 10:22 PM - Apr 3, 2019

54 people are talking about this

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Mottling refers to extreme vasoconstriction of cutaneous blood vessels, which creates a patchwork appearance (skin areas with very poorperfusion will appear violaceous).Mottling has been linked to poor prognosis (including mortality) in several studies. Patients with mottling are extremely sick and should betaken very seriously.

(3) capillary re�ll time

Preferred technique:Compress �ngertip using a slide with enough pressure to cause blanching for ten seconds. (Any clear surface can also be used, suchas a plastic urine specimen container.)Release and measure the time until return of normal color using a chronograph (watch or smartphone).Normal capillary re�ll time is 5 seconds is delayed capillary re�ll (27908340(https://www.ncbi.nlm.nih.gov/pubmed/27908340) ).

In the ANDROMEDA-SHOCK trial, patients were resuscitated with a goal of decreasing the capillary re�ll time below



skin perfusion may be used to guide the selection and titration of vasopressors







(1) Signs of skin hypoperfusion may re�ect excessive vasoconstriction (above). In some patients, these will improve with a shift towardsuse of an inotrope.(2) Vasopressin

One of the most feared complications of using vasopressin is digital ischemia, which may lead to necrosis and digit loss.Cool digits may be a sign of excess vasoconstriction and the need to down-titrate vasopressin.Digital ischemia (e.g. blue �ngers) should be an indication to immediately stop vasopressin.

refractory shock(back to contents) (#top)

The above interventions will su�ce to stabilize the vast majority of patients. However, rare patients may remain in refractory shock. Below is alist of potential interventions for such patients.

earlier considerations

Metabolic resuscitation if not already initiated (see above).Placement of a central arterial line (femoral or axillary)

Radial arterial lines may under-estimate blood pressure (https://emcrit.org/pulmcrit/a-line/) .Transition to more hemodynamically stable analgo-sedative regimen

Propofol or dexmedetomidine are excellent sedatives, but they do tend to reduce the blood pressure.In the face of refractory shock, more hemodynamically stable agents may be preferable (e.g. ketamine infusion).

Trial of various different pressor agents (e.g. epinephrine challenge, addition of vasopressin).Vasopressin has been demonstrated to be safe at doses of 0.06 U/min and could likely be titrated higher (VASST trial(https://www.nejm.org/doi/full/10.1056/NEJMoa067373) ).High-dose norepinephrine (there is no maximal dose (https://emcrit.org/pulmcrit/high-dose-vasopressor/) ).

For patients with right ventricular dysfunction and hypoxemia on mechanical ventilation, inhaled pulmonary vasodilators could be trialed(e.g. inhaled epoprostanol).

last-ditch considerations

Intravenous calcium (often causes transient improvements in blood pressure which are short-lived).Reducing MAP target

If very high doses of norepinephrine are required to achieve a MAP >65 mm (e.g. >1 ug/kg/min), this may be causing more harm thangood. Reducing the MAP target to >55 or >60 could potentially represent a more bene�cial balance of vasopressor bene�t vs harm.

Nitric oxide inhibitors

https://emcrit.org/wp-content/uploads/2017/02/inotropybalance.svghttps://emcrit.org/pulmcrit/a-line/https://www.nejm.org/doi/full/10.1056/NEJMoa067373https://emcrit.org/pulmcrit/high-dose-vasopressor/



Avoid these if possible (in one RCT, inhibition of nitric oxide increased mortality)(14707556 (https://www.ncbi.nlm.nih.gov/pubmed/14707556) ). Should be used only as a last-ditch effort for profound vasodilatory shock.Methylene blue:

Dose: bolus 1-2 mg/kg q4-6 hours; infusion of 0.25-1 mg/kg/hr.Can increase pulmonary vascular resistance

HydroxocobalaminDose: 5 grams IV x1.

Angiotensin II may be considered if your hospital has this.

algorithm(back to contents) (#top)

Part I: Initial resuscitation (Primary Survey)

Investigations [more on source evaluation (#common_sources_&_evaluation_of_source) ]Electrolytes, CBC with differential, Coags, Liver function testsUA/UCx, peripheral blood culture x2, culture of any line in place >48 hoursChest X-rayProcalcitonin, LactateExam with ultrasonographyCT abdomen/pelvis if source unclearAdditional tests as warranted (e.g. CT head/LP if concern for meningitis)

Antibiotics [more on antibiotics (#antibiotics) ]Review prior cultures & antibiotic exposure data if availableKey is a good beta-lactam backbone (piperacillin-tazobactam, meropenem, or cefepime).MRSA coverage only if soft tissue infection, infected line, nosocomial infection, or possibly for PNA (not for community-acquiredabdominal or urinary source).Additional antibiotics depending on source (e.g. azithromycin if pneumonia).

Source control [more on source control (#source_control) ]Consider hardware removal (e.g. port, tunneled line, central line).Otherwise depends on source (e.g., decompress hydronephrosis, ERCP for cholangitis, abscess drainage).

HemodynamicsPressors: Early peripheral vasopressors to maintain MAP >65 [more (#vasopressors) ]Fluid: Give a fair amount, then STOP giving �uid. Avoid giving >3 liters �uid unless there is a compelling reason [more (#�uid) ]

Adjunctive therapiesHydrocortisone 50 mg IV q6hr unless contraindicated [more (#steroid) ]DVT prophylaxis with low molecular weight heparin (if GFR >30 ml/min) or otherwise unfractionated heparin [more(#DVT_prophylaxis_with_low_molecular-weight_heparin) ]

Part II: Follow-up after initial resuscitation (Secondary Survey)

Correct diagnosis? Right antibiotics & source control measures?Review imaging & lab data.If there is no clear source of sepsis consider sepsis mimics (#sepsis_mimics) & further measures to identify the source(#common_sources_&_evaluation_of_source) .

Review medicationsHave antibiotics been administered? Are they scheduled & dosed optimally?

Resus targets: Overall philosophy [more (#resuscitative_endpoints:_general_philosophy) ]It's generally unclear how hard to chase resuscitative targets.Additional �uid should usually not be given based on these targets. Resuscitation targets might be best utilized to �ne-tune the doseand choice of vasopressors & inotropes (�gure below).

Resus targets: MAP [more (#resus_targets:_MAP) ]

https://www.ncbi.nlm.nih.gov/pubmed/14707556



Usually target >65 mm.Vasopressor challenge: For patients with chronic HTN and poor urine output, increase MAP target to >80mm and determine whetherthis improves urine output.Patients with chronic hypotension and excellent urine output: may target MAP >60 mm

Resus targets: Heart rate [more (#resus_targets:_heart_rate) ]Hypoperfusion & heart rate 140 b/m): Consider vasopressors with less beta-agonist activity (e.g. phenylephrine, vasopressin)

Resus targets: Fluid balance [more (#resus_targets:_�uid_balance) ]Keep track of net �uid balance (inputs – outputs).Avoid running net �uid balance greater than +5 liters (unless history of severe volume depletion prior to admission).

Resus targets: Skin perfusion [more (#resus_targets:_skin_perfusion) ]Evaluate for mottling, cool extremities, and sluggish capillary re�ll.Poor skin perfusion may be an indication that the patient is receiving excess vasoconstrictors (and perhaps could bene�t from anepinephrine challenge (#epichallenge) ).

Resus targets: Lactate [more (#resus_targets:_lactate) ]The use of lactate as a resuscitative target is extremely dubious, but this will conventionally be measured.Rising lactate should prompt global re-evaluation of the patient (e.g. echocardiography & adequacy of source control and antibiotics).Epinephrine infusions will increase lactate, making lactate measurements meaningless in such patients.

Resus targets: Urine output [more (#resus_targets:_urine_output) ]Falling urine output is concerning regarding hypoperfusion. However, this is nonspeci�c (may re�ect hypoperfusion or intrinsic renalfailure).Oliguria requires thoughtful evaluation, ideally including echocardiogram and bladder ultrasound.







Most Important Tables & Figures

beware of sepsis mimics:

https://emcrit.org/wp-content/uploads/2017/02/inotropybalance.svg



Bacterial SepticShock Mimics

Diagnostic clues & evaluation

All bacterial septic shockmimics

Procalcitonin (if normal or only minimally elevated, this shouldincrease suspicion for sepsis mimic)

Infectious

Endocarditis (shock 2/2 valvedysfunction)

Complete echocardiogram

Influenza Respiratory symptoms, influenza season, sick contacts.

Tick-borne illness Clues: Exposure, thrombocytopenia, skin rash, hemolysis

Candidal septicemia Ongoing critical illness, central line, colonization, immunosuppression,GI surg/perf, parenteral nutrition

Aspergillus Prolonged neutropenia, hematologic malignancy, prolonged or high-dose steroid use, pneumonia, hemoptysis

Pneumocystis pneumonia Diffuse pneumonia, immunosuppression (HIV, chronic steroid use,TNF-inhibitor, malignancy)

Endocrine

Adrenal crisis Random serum cortisol level (before steroid tx)

Thyroid storm Signs: tremors, thyromegaly. Labs: TSH, free T4

Diabetic ketoacidosis Beta-hydroxybutyrate level, ketones in urinalysis

Gastrointestinal

Acute mesenteric ischemia CT angiography of abdomen/pelvis

Bowel obstruction CT scan of abdomen/pelvis

Pancreatitis Lipase, CT abdomen/pelvis

Fulminant hepatic failure Liver function tests

Cirrhosis Chronic hypotension, elevated INR, thrombocytopenia

Toxicology

Salicylate intoxication History of salicylate use, tachypnea. Labs: Salicylate level

Beta-blocker / CCB Medication review, disproportionate bradycardia.

Carbon monoxide toxicity Exposure (winter), carboxyhemoglobin level.

Metformin Exposure history, disproportionately severe hyperlactatemia.

Miscellaneous

Anaphylaxis History & Physical (e.g. skin); Rapid resolution over time

HemophagocyticLymphohistiocytosis (HLH)

Labs: Cytopenias, Ferritin

Dermatologic (DRESS or AGEPin severe cases)

Skin exam, review of active medications

Aspiration pneumonitis Rapid recovery over time (faster than true bacterial pneumonia)

A septic shock mimic should be considered in patients without an obvious source of infection,or in patients with unimpressive procalcitonin levels. Evaluation will differ depending on theclinical scenario. The most high-yield tests for most patients are bolded (especially CTabdomen/pelvis and complete echocardiogram).


(https://emcrit.org/wp-content/uploads/2017/02/sepsismimics.svg)

meticulous search for the source:

https://emcrit.org/wp-content/uploads/2017/02/sepsismimics.svg



Source Diagnostic clues & evaluation

Meningitis Nuchal rigidity, Lumbar puncture

Pneumonia (~50%) Symptoms, US, CXR (doubt this source if CXR equivocal)

Bloodstream infection (~15%)

Endocarditis Murmur, emboli, abnormal echocardiogram

Line/Hardware infection Erythema/warmpth at central line or port, line clotted

Lemierre’s syndrome Preceding pharyngitis, ultrasound shows jugular thrombus

Gastrointestinal source (~15%)

Cholecystitis Ultrasound: distension, sonographic Murphy’s

Ascending cholangitis Rigors, bilirubin; Ultrasound: Dilated common bile duct

Clostridioides difficile Recent ABX exposure, diarrhea; test stool

Other (appendicitis,diverticulitis, obstruction,perforation)

Pain, anorexia, distension(POCUS signs vary, may include free fluid/air, dilation)

Gynecologic source

Toxic shock Other signs of toxic shock (erythema, nausea/vomiting)

Chorioamnionitis Pregnancy, pain can occur

Urosepsis (~15%) Urgency/dysuria, back pain, abnormal urinalysis

Skin & soft tissue

Group A strep cellulitis Looks like classic cellulitis, but patient in septic shock

Necrotizing fasciitis Severe pain out of proportion to exam, necrosis/bullae

Septic arthritis Severe pain to joint movement; effusion, erythema.

Septic shock can result from infection nearly anywhere in the body, although some areunlikely to cause septic shock (e.g. osteomyelitis). This table merely shows the mostcommon foci of infection.


common sources of septic shock

(https://emcrit.org/wp-content/uploads/2017/02/sepsissources45.svg)

podcast(back to contents) (#top)

(https://i1.wp.com/emcrit.org/wp-content/uploads/2016/11/apps.40518.14127333176902609.7be7b901-15fe-4c27-863c-7c0dbfc26c5c.5c278f58-912b-4af9-

88f8-a65fff2da477.jpg)

Follow us on iTunes (https://itunes.apple.com/ca/podcast/the-internet-book-of-critical-care-podcast/id1435679111)

The Podcast Episode

Want to Download the Episode?Right Click Here and Choose Save-As (http://tra�c.libsyn.com/ibccpodcast/IBCC_Episode_49_Septic_Shock.mp3)

questions & discussion(back to contents) (#top)

To keep this page small and fast, questions & discussion about this post can be found on another page here (https://emcrit.org/pulmcrit/sepsis/) .

00:00 00:00 (javascript:void(0);)

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(https://i0.wp.com/emcrit.org/wp-content/uploads/2016/11/pitfalls2.gif)

Inadequate focus on antibiotic selection and source control. Failure of either of these is most likely to cause morbidity or mortality.Blind administration of 30 cc/kg �uid is often not the best treatment. For morbidly obese patients, 30 cc/kg should be be dosed based onideal body weight, not actual weight.Delaying the initiation of vasopressors while waiting to see if �uid-loading works. If the patient is really in septic shock, delayinghemodynamic stabilization isn't advisable.Incorrect diagnosis of sepsis due to pneumonia (in response to minor CXR abnormalities from atelectasis) or urosepsis (due to UAabnormalities re�ecting asymptomatic bactiuria). CXR and UA are often abnormal, so be careful of premature diagn

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