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1. For whom the bell (curve) tolls – important to always describe / show so readers get a sense of middle and spread
a. middle, spread
b. stdev, var, se
c. get to a z-score, standard normal
2. Confidence intervals
a. should always be reported
b. truth of tx effect, precision, frequentist explanation
3. The Testing and Treatment Thresholds
4. Likelihood Ratios
5. Positive/Negative PV; Don’t confuse sensitivity and PPV
a. trade-offs
b. Prevalence matters! (PPV)
c. Sgarbossa papers
6. confusing terminology
a. odds ≠ probabilities,
b. risk, probability, incidence, attributable risk, baseline risk
c. relative, ratio
d. OR = 1
e. correlation = association / how much variance explained, regression = prediction / line
7. No more 2x2 tables
8. Relative and absolute risks: same data, different stories, baseline risk
9. NNT, NNH; estimating NNT from baseline risk, RRR, subtract and invert
10. Odds ratios over-estimate RR! Do not interpret OR as RR!
11. Association ≠ causation
12. Mastering the 2 x 2 table, Part 3: Hypothesis Testing (null hypothesis: tx effect is the same in both groups)
13. Power, false αlarms
14. p value (physicians do not understand), statistical significance, 95% CI including 1
P values are misinterpreted, overtrusted, and mis- used. The language of the ASA statement enables the dis- section of these 3 problems. Multiple misinterpreta- tions of P values exist, but the most common one is that they represent the “probability that the studied hypoth- esis is true.”3 A P value of .02 (2%) is wrongly consid- ered to mean that the null hypothesis (eg, the drug is as effective as placebo) is 2% likely to be true and the al- ternative (eg, the drug is more effective than placebo) is 98% likely to be correct. Overtrust ensues when it is forgotten that “proper inference requires full reporting and transparency.”3 Better-looking (smaller) P values alone do not guarantee full reporting and transpar- ency. In fact, smaller P values may hint to selective re- porting and nontransparency. The most common mis- use of the P value is to make “scientific conclusions and business or policy decisions” based on “whether a P value passes a specific threshold” even though “a P value, or statistical significance, does not measure the size of an effect or the importance of a result,” and “by itself, a P value does not provide a good measure of evidence.”3 These 3 major problems mean that passing a statistical significance threshold (traditionally P = .05) is wrongly equated with a finding or an outcome (eg, an association or a treatment effect) being true, valid, and worth acting on. These misconceptions affect research- ers, journals, readers, and users of research articles, and even media and the public who consume scientific in- formation. Most claims supported with P values slightly below .05 are probably false (ie, the claimed associa- tions and treatment effects do not exist). Even among those claims that are true, few are worth acting on in medicine and health care.
15. Looking at differences: effect size, t tests, ANOVA (preferred over multiple t tests) [PDQ stats]
16. Eponyms beyond t-tests, Ordinal data, compare to expected: χ2, Mann-Whitney, Kruskal-Wallis, McNemar, Wilcoxon, Kolmogorov-Smirnov, (non-parametric)
17. Straight line vs S-shape: Linear and logistic regressions, predictor variables, univariate vs multivariate
18. Study population, inclusion/exclusion criteria
19. Topology / Roadmap of clinical studies
a. caution: observational (successes: Wennberg)
b. case series: hypoxic drive myth
20. Exposure / Outcome: Effect modification vs Confounding
21. Case-Control, lung cancer Doll & Hill, OR
22. Cohort: prospective, retrospective, RR
23. Bias series
a. Cochrane Risk of Bias Tool
b. Recall bias
c. Blinding and allocation concealment – sham arthrocentesis
d. Spectrum bias (don’t compare sick to normal) and verification bias (everyone gets gold standard)
e. Intention to treat, loss to follow-up
f. Selection bias
g. Observer bias / open label (IST-3 tPA stroke)
24. The RCT: overview, Semmelweiss, equipoise/standard of care
25. Table 1 and randomization (Study population)
26. Calling your pocket: primary outcome, endpoints
27. Composite and surrogate endpoints – NINDS, meta-analysis ACS
a. hard to interpret
b. make tx effects seem more important than they really are
c. surrogate = uncertain value
28. Time-to-event: KM, median survival, censoring – Pall care lung cancer
29. Sample size
a. review power
b. α, β, effect size, standard deviation
30. Intention-to-treat vs Per-protocol
31. RCT: Results, internal validity
32. Fishing: post-hoc / secondary analysis, multiple comparisons = bad, Bonferroni
33. External validity, clinical significance: does it apply to my patient, does it make a clinical difference? BASELINE RISK
34. Tree plots / Meta-analysis, publication bias, garbage in, garbage out
35. Stratify the literature as low-, med-, high-quality: screen hierarchy, look for red flags (uncontrolled, unblinded, small n), rule out low-quality studies
a. Orient: gap in knowledge, PICO, study population
b. Methods: study design (look for bias, single location, observational)
c. Results: statistical vs clinical significance (look at endpoints [pt-centered? red flags: surrogate, composite] CIs, adverse events, length of follow-up, similarity to own patients)
36. Phases of Clinical Trials
37. Screening: basic principles, doctors do not understand
a. overdiagnosis
b. lead-time bias
38. Disclosures, conflicts of interest – xigris, vioxx, avandia
39. Tough call: Thrombolysis
a. Thrombolysis for acute stroke
b. Thrombolysis for PE
40. Noninferiority trials – ROCKET AF
# Neuro
- Sedation vacation (Kress, NEJM 2000)
# Cardiovascular
Ischemia:
- COURAGE
- TNT
- WOEST
- PCI vs CABG for 3vCAD :: SYNTAX (NEJM, 2009)
- Early revasc after MI? :: SHOCK (Among patients who developed cardiogenic shock during acute MI, what are the benefits of early revascularization compared to initial medical stabilization on mortality? Trend towards survival at 30 days) (NEJM, 2009)
- IABP? :: SHOCK II (In patients with acute MI complicated by cardiogenic shock, there was no difference in 30-day mortality with IABP placement. ) (NEJM, 2012)
Start oral beta blocker therapy in the first 24 hours of NSTE-ACS therapy if none of the following are present (class I, level A):
● HF signs
● Clinical evidence of a low-output state
● Elevated risk of cardiogenic shock
● General beta blocker contraindications including PR interval >0.24 seconds, second degree heart block, third degree heart block, active asthma, or reactive airway disease
-
Pump:
- BNP :: Faisal, NEJM, 2002
- RAVES
- 3CPO ::
- Continuous vs bolus Lasix :: DOSE (NEJM, 2011)
Rhythm:
- Rhythm vs rate :: AFFIRM (NEJM, 2002)
- Lenient vs strict :: RACE II (NEJM, 2010)
- Peri-op bridging :: (NEJM, 2015)
- Dabigatran vs Warfarin RE-LY (NEJM, 2009)
# Pulm
- SBT
ARDSNet: In 800 pts w/ ARDS, does low tidal volume versus high tidal volume lead to a mortality benefit? (JAMA, 2000)
ESCAPE/PAC-MAN
PROSEVA (NEJM, 2013)
OSCILLATE (NEJM, 2013)
Glucocorticoids in Early Severe ARDS (Chest, 2007)
# GI
- Rifaximin + Lactulose :: (Am J Gastro, 2013)
- BB in Cirrhosis (Hepatology, 2010)
# Renal
- Losartan :: RENAAL (Arch Int Med, 2003)
- NaHCO3 (Am Soc Nephrology, 2009)
- EPO :: CHOIR (NEJM, 2006), CREATE (NEJM, 2006)
- Darbepoetin :: TREAT (NEJM, 2009)
- ACEi :: REIN-1 (Lancet, 1998), REIN-2 (Lancet, 2005), COOPERATE (Lancet, 2003), ONTARGET (NEJM, 2008)
- Dialysis :: IDEAL (NEJM, 2010)
- Early vs Late (Am J Med, 2011)
# Heme
- Liberal vs Restrictive :: TRICC (NEJM, 1999)
# Endo
DM
- HbA1c control :: ADVANCE (NEJM, 2008)
- ACCORD (NEJM, 2008)
- NICE-SUGAR (NEJM, 2009)
- ACCORD BP (NRJM, 2010)
# Oncology (neutropenic fever)
- 2010 Guideline for Neutropenic Patients (IDSA, 2011)
- MASCC
# Fluids
- Positive fluid balance and mortality
Major studies have failed to demonstrate support of massive IVF resus in sepsis:
○ Multicenter cross-sectional cohort, 198 ICUs, 1,177 patients with sepsis
○ Each 1L of positive fluid balance —> ↑10% odds of mortality
○ Retrospective review of a prospective randomized controlled trial (RCT)
○ 778 patients with septic shock enrolled in vasopressin study
○ Each ↑ quartile of fluid administration associated with ↑ mortality
○ Prospective, cross-sectional cohort, 84 countries, 730 ICUs, 1,808 patients with sepsis (61% septic shock)
■ Survivors had more negative fluid balance
○ After the initial resuscitation, higher hazard ratio for death for each quartile of more fluid
○ 212 patients in Zambia with sepsis
○ RCT sepsis protocol (including aggressive fluids) vs usual care
○ ↑ mortality in protocol group (48% vs 33%)
○ Prospective RCT, 9 Scandinavian ICUs, 151 patients with septic shock
○ Beyond initial resuscitation phase
○ Standard care vs fluid boluses only if severe hypoperfusion
○ Non-significant trend to lower mortality in fluid restriction, less AKI (significant)
○ All 3 trials found that EGDT was equivocal to usual resuscitation
○ 3600 children in Uganda, Kenya, or Tanzania (not in shock), RCT btw 20-40 cc/kg bolus vs. no bolus
○ Fluid boluses significantly increased 48-hour mortality
-
# DVT
- PPI :: (Cochrane, 2012)
- PPI vs H2 (JAMA Int Med, 2014)
- RE-COVER (NEJM, 2009)
- AMPLIFY (NEJM, 2013)
- PREPIC2 (JAMA, 2015)
Plan by Problem
# PNA
- PSI (NEJM, 1997)
- CURB-65 (Thorax, 2002)
- SMART-COP (Clin Inf Dis, 2008)
No Effect on Mortality
- Procalcitonin (Cochrane, 2012)
# PE
- ADJUST-PE (JAMA, 2014)
- YEARS (Lancet, 2018)
- MOPETT (AJC, 2013)
- PEITHO (NEJM, 2014)
# Sepsis
Diagnosis
- SIRS (NEJM, 2015)
- qSOFA
- Sepsis 3.0
EGDT
- RIVERS (NEJM, 2001)
- ProCESS (NEJM, 2014)
- ARISE (NEJM, 2014)
- ProMISe (NEJM, 2015)
Steroids
- COIITS (JAMA, 2013)
- Annane (JAMA, 2002)
- CORTICUS (NEJM, 2008)
- ADRENAL
- APROCHSS
Pressors
- SOAPII (NEJM, 2010)
- CATS (Lancet, 2007)
- VASST (NEJM, 2008)
- Censer
Transfusion
- TRISS (NEJM, 2014)
No Effect on Mortality
- Lipid A antagonist :: ACCESS (JAMA, 2013)
- ATIII :: Antithrombin III (JAMA, 2001)
- rTFPI :: OPTIMIST (JAMA, 2003)
- Activated Prot C :: PROWESS (NEJM, 2001), PROWESS-SHOCK (NEJM, 2008)
# CVA
NINDS (NEJM, 1995)
MR RESCUE (NEJM, 2013)
MR CLEAN (NEJM, 2015)
SBS3-BP (Lancet, 2013)
ACEi :: PROGRESS (Lancet, 2001)
ASA :: ATTC (BMJ, 2002)
Plavix :: CAPRIE (Lancet, 1996)
ASA + Plavix :: CHANCE (NEJM, 2013), CHARISMA (NEJM, 2006), MATCH (Lancet, 2004)
CEA :: NASCET (NEJM, 1998), CREST (NEJM, 2010), CSTC (Lancet, 2016)
Warfarin :: EAFT (Lancet, 1993)
ICM :: CRYSTAL AF (NEJM, 2014)
PICO Format:
In [#] patients ___, does intervention X versus control Y lead to [primary outcome] at [time scale] (Journal, Year)
AIRWAY
CHECKLISTS
- Multicenter RCT on checklist for intubation
- No difference on lowest SpO2 or lowest systolic BP during intubation
PREOXYGENATION & APNEIC OXYGENATION- Preoxygenation - Administration of oxygen prior to induction
- Apneic oxygenation - Refers to oxygenation during pre-laryngoscopy and pre-intubation time period in non-spontaneously breathing patient
- Benefit in non-invasive ventilation for pre-ox: Baillard 2006 and Jaber 2016 - OPTINIV trial
- High Flow Nasal Cannula (HFNC) with mixed results - Meta-analysis of these trials with small benefit in lowest SpO2 in preox but limited/no benefit in apneic oxygenation: Baillard 2006, Vourc'h 2015, Simon 2016, Semler 2016 - FELLOW trial, Caputo 2017 - ENDAO trial
SEDATIVES
- Randomized trial of fentanyl, midazolam, and thiopental: Sivilotti 1998
- Fentanyl w/ most hemodynamically neutral profile in RSI; midazolam w/ increase in HR compared to other two agents; thiopental w/ decrease in BP
- 0.3 mg/kg etomidate vs. 2 mg/kg ketamine without difference in intubating conditions: Jabre 2009
NMB
- Only RCT on succinylcholine vs. rocuronium with similar desaturation, intubating conditions. Succinylcholine with shorter duration of intubation sequence; however, many cite that roc dose in this trial is too low (0.6 mg/kg compared to our usual 1.3 mg/kg).
POSITION: SNIFF VS. RAMPED
- Semler 2017 suggested that ramped position may worsen glottic view and increase number of laryngoscopy attempts
- Sniff = entire bed flat; head elevated
- Ramped = upper bed raised 25 deg; head parallel to ceiling
VL VS. DL
- The 9 RCTs evaluated different models of VL: Yeatts 2013, Griesdale 2012, Kim 2016, Goksu 2016, Janz 2016, Driver 2016, Sulser 2016, Lascarrou 2017, and Silverberg 2015
- Time to intubation and first-attempt success with no difference; even when stratifying by operator experience, ED vs. ICU, hyper-angulated vs. non-hyper-angulated there was no difference
- 4 of those 9 RCTs looked at subgroup of anticipated difficult airway; no difference between VL and DL
Airway Preparation Resources
Tier 1 -- Minimal Acceptable Skill Set
● How to Set-Up Your Intubation Box - Weingart runs you through what you need to know to set-up your airway box for the RACC.
● Strayer Airway Management Checklist
○ You must read this, and should understand the reasoning for every step
● How to properly ventilate (BVM/LMA) a patient
○ Its importance:sexiness ratio approaches infinity
○ For the love of God, do not squeeze the bag hard and fast. This is the opposite of chest compressions.
● Direct vs. Video Laryngoscopy (Strayer) - review of DL v VL and differences in blade geometries
● Laryngoscope as Murder Weapon Series
○ We intubate sick patients. Understanding how their physiology is failing and how that interacts with RSI is a necessary part of safely managing the critical airway. These three podcasts are a good introduction, but by no means the end of the story.
○ Intubating the Severe Metabolic Acidosis
○ Intubating the Shocked Patient
○ Intubating the Hypoxic Patient Part I and Part II
● How to do a Cric - by the one and only Ram P.
○ You must know how to set up your bay for a safe intubation. The nurses might or might not know. Your attending might or might not know. If you are the resus resident on a given day, you are responsible for know where every piece of equipment is, if it is stocked, how to work your monitors, etc. Adopt this mindset early, and strive for it during your training.
Tier 2 -- Know By Midway Through PGY2
○ We will all reach this at some point in our career. Having a pre-built mental model of what to do is key.
○ See also: The Shock Trauma Failed Airway Algorithm
● Vomit SALAD - Techniques during Massive Regurg, Emesis, Bleeding
● The Awake Airway
○ Sometimes stopping someone’s breathing is bad idea
■ This is an advanced maneuver, but knowing it is out there and thinking about when it is indicated will make you better
● What is this orotracheal intubation bias? You will come across tracheostomies and laryngectomies in your career, and need to know how to troubleshoot these airways as well.
Tier 3 -- Suggested
● Levitan on the Psychology of the Difficult Airway
○ As PGY2s you will be put in a lot more critical situations that take you to a psychological place you don’t really reach as PGY1s. You will always have backup and you’re never as alone as you might feel, but learning how to recognize, wrangle, and respond to your own stress is critical in your growth as an emergency physician.
■ See also The Day I Didn't Use Ultrasound
Breathing:
Tier 1 -- Minimal Acceptable Skill Set
1. Non-Invasive Ventilation - if you can master this, you can prevent intubations for several patients, and/or maximally preoxygenate them if they need to be intubated.
2. Dominating the Vent - Part 1 and Part 2 - This is an excellent lecture that goes over the basics of ventilator management. Weingart reviews how to set up a ventilator, what settings to dial in for your intubated patients, and the logic behind these choices. Essential Viewing.
a. See also Weingart’s Ventilator review article in the Annals (just 4 pages)
3. Setting up the Vents at Elmhurst - A step-by-step walkthrough on how to actually set up the ventilators at EHC.
4. The Post-Intubation Package - whew, you successfully intubated your sick patient in cardiac/resus. Don’t stop now though, there is a boatload of stuff you need to do in order to optimize their care.
5. Post-Intubation Sedation and Analgesia - This lecture by Emcrit will get you through the basics of how to set up an adequate sedation package for your intubated patients.
6. Troubleshooting the Ventilator (DOPES) - Uh oh, your patient is hypoxic on the ventilator. What do you do? This is an easy mnemonic that reviews how to troubleshoot post-intubation complications.
Tier 2 -- Know By Midway Through PGY2
1. Ventilator Assisted Preoxoygenation (VAPOX) - how to use the ventilator to provide preoxygenation in a smooth, controlled way.
a. NIV For Preox (Featurinng Elmer Siong!) - https://vimeo.com/31311379 AND https://vimeo.com/148790744
2. Standard BVM Doesn’t Work for Shunted Lungs - it is sometimes difficult to bag a patient with shunted lungs (lungs that have fluid/pus in them, which is hindering oxygenation). This video directly shows what happens to a cadaver’s lungs when you add some PEEP onto your standard BVM.
3. High Flow Nasal Cannula - why would you use it, and when?
4. Management of the Severe Asthmatic - an intubated asthmatic is an “oh shit” moment for any medical intensivist. They get more dangerous when intubated. Here is a great podcast reviewing the nuances of their management pre and post-intubation.
a. NIV For Obstructive Lung Disease - read this to get a sense about how to combat hypercapnea in your obstructed patient. TLDR - increase your IPAP to assist in work of breathing.
5. Oxygen Physiology and Pulse Ox Latency - essential information you should know about how the pulse ox works
Tier 3 -- Suggested (CC Nerds)
1. DSI - What is Delayed Sequence Intubation, and why would you consider using it for a patient in the ED?
2. Proning for ARDS - review the benefits of prone positioning for your severe ARDS patients. Something you can try in the MICU/SICU.
SEDATION & ANALGESIA GUIDELINES FOR MECHANICALLY VENTILATED PATIENTS
PRIORITIZE ANALGESIA-FIRST SEDATION STRATEGY1
AVOID BENZODIAZEPINES1
SEDATION TARGET
RASS (Richmond Agitation Sedation Scale)
-1 = Awakens to voice (eye opening/contact) > 10 sec
-2 = Briefly awakens to voice (eye opening/contact) < 10 sec
OK TO BE DEEPER IN IMMEDIATE POST-INTUBATION PERIOD
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