UMEM Educational Pearls

Exericse as preventative medicine!

A recent cohort study of over 2,000 adults (mean age approx. 45) over approximately 11 years of follow-up investigated the association of step count with mortality.

This study found that those participants taking at least 7,000 steps per day compared to those taking fewer steps had a 50%-70% lower risk of mortality. They did not find an association with step intensity.

Another recent study investigated the dose-response association between daily step count and intensity and the incidence of all-cause dementia.

Uk based study of >78,000 adults aged 40 to 79 years with approximately 7 years of follow-up. Data from wrist accelerometer and registry-based dementia diagnoses.

Optimal step dose was 9826 steps. Minimal dose was 3826 steps (value at which the risk reduction was 50% of the observed max).

In this study, steps performed at higher intensity (112 steps/min) resulted in stronger associations.

Conclusions:  A great exercise goal for middle aged and older adults is just under 10,000 steps per day to decrease risks of both overall mortality and dementia.

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Take Home:

This is essentially a secondary analysis of a previous prospective observational cohort study with high quality methods. The authors have an excellent discussion of the previous studies on this topic (which for those with an interest I highly recommend you read). They conclude that this study supports previous literature which I would think would be seemingly obvious, which is that those who are more ill to begin with have less tolerance of propofol (in a dose-independent relationship) in this and previous studies. Their use of IPTW extends the analysis on this large international population by addressing confounders in a novel way.

Their overall conclusion is that propofol is bad for the critically ill, and especially bad for those with pre-existing risk factors for intubation complications. I agree: This study suggests in even stronger terms that propofol should be used carefully and probably only in unhealthy patients when other options are unavailable.

Study Background and Characteristics

• INTUBE study¹ was a prospective cohort study conducted from October 1, 2018, to July 31, 2019
• Enrolled consecutive “critically ill” patients over 8 week period at 197 clinical sites from all over the world. Critically ill was defined as those with “an underlying life-threatening condition causing cardio–respiratory failure or neurologic impairment”.
• Outcome of “cardiovascular instability/collapse” as one or more of the following events within 30 minutes of intubation start: (1199 of 2760 enrolled patients; 43.4%)
  • systolic arterial pressure <65 mm Hg recorded at least once (collapse criteria) – 12.8%
  • cardiac arrest (collapse criteria) – 7.8%
  • systolic arterial pressure <90 mm Hg for >30 minutes – 24%
  • new requirement or increase of vasopressors – 87.8%
  • fluid bolus >15 ml/kg to maintain the target blood pressure – 13.2%
• STROBE Compliant

Findings

• CV-instability group were significantly older, high SOFA scores, and higher rates of ischemic heart disase, NYHA 3/4 heart failure, poor oxygenation (SPO2/FIO2 ration), pressors, fluid bolus/total, systolic/diastolic BP, and more commonly respiratory failure and cardiovascular instability as the reason for intubation.
• CV-stability group was less likely to receive propofol and at lower doses and more likely receive ketamine.
• Notably, CV-instability patients were less likely to be intubated by emergency physicians versus anesthesiology.
• Anesthesiologists were more likely to use propofol and more emergency medicine physicians using ketamine.
• Higher incidence of CV-instability in ischemic heart disease and heart failure, noninvasive ventilation and apneic oxygenation, and in the 30–45° head-up position.
• ICU mortality associated with:
  • vasopressors/fluids without hypotension (OR, 1.47; 95% CI, 1.21–1.79)
  • systolic blood pressure <90 mm Hg for >30 min despite vasopressors (OR, 2.65; 95% CI, 1.87–3.75)
  • systolic blood pressure <65 mm Hg (OR, 1.89; 95% CI, 1.31–2.71)
  • cardiac arrest (OR, 8.79; 95% CI, 5.46–14.7)
• Inverse Probability Treatment Weighting² (IPTW) analysis found that the only treatment effect with significance associate with the entire CV-instability group was propofol usage (OR, 1.23; 95% CI, 1.02–1.49).
  • No treatment effect, including propofol use or dosage, was associated with those meeting cardiovascular collapse criteria.

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Intraosseous (IO) administration uses bone marrow to deliver fluids and medications during cardiac resuscitation or other emergent situations where IV access cannot be established.

IV versus IO

• No statistically significant difference between the pharmacokinetics!
• Flow rates of IV cannula typically range from 20 to 200 mL/min versus IO ranging from 0.33 to >50 mL/min under pressure
  • Maximum rate of administration through IO is comparable to a 21G peripheral cannula.

Considerations When Using IO Access

• Single line, ensure all drugs running through the IO are compatible with one another.
  • For example: plasmalyte is not compatible with most medications
• If trying to quickly administer fluids utilize a pressure bag.
  • If medication administration (i.e. vasopressors) pump should be used
• Contraindications to IO include:
  • Placement in fractured bone with vascular injury
  • Compartment syndrome
  • Cellulitis/burns at the site
  • Underlying bone disease
  • Soft tissue infection
  • Recent orthopedic surgery
• Once a bone has been punctured by an IO attempt, it should not be used again for at least 48 hours. 
• Intraosseous aspiration of blood is usable for lab tests, though accuracy has varied in studies. 

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Traditionally, internal jugular and subclavian central line placement has required chest x-ray confirmation of correct placement (venous cavoatrial junction placement) as well as demonstrating lack of complication (no pneumothorax) prior to use of that central line. However, current evidence supports similar if not superior complication identification and placement confirmation with ultrasound,^(1-7) allowing for a much quicker confirmation time than traditional chest x-ray, which can be vital in critically ill patients who need immediate medication administration.

Venous placement is confirmed with prompt visualization of microbubbles in the right atrium and ventricle with a rapid flush of 5-10 ml of agitated saline via the distal central line port. Additionally, if the opacification occurs <2 seconds after injection then the catheter tip is sufficiently distal in the central venous system to not require additional verification. Additional confirmation of lung sliding in both lung apices will rule out pneumothorax.

Some authors recommend checking the contralateral internal jugular vein to ensure that the central line catheter has not traveled up the internal jugular towards the head, however this may be redundant as long as the time from agitated saline injection to right atrial visualization of microbubbles is clearly less than 2 seconds.

Bottom Line: Utilization of ultrasound for central line placement confirmation is a relatively simple, rapid, safe, and accurate means of confirmation of venous catheter placement and catheter tip location, as well as ruling out pneumothorax complications.

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Approximately 284,000 immigrants reside in Baltimore (10% of the total population). In April 2022, Governor Abbott of Texas began sending migrants from the US southern border to Washington, DC, with Arizona joining soon after. It is important for emergency providers to be aware of these changes and how new disparities may arise.

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Limited data are available to guide recommendations re screen time after concussion.

A recent ED study looked at screen time effects on concussion recovery.

Population:  125 patients aged 12 to 25 years presenting to the ED <24h after injury. Mean age 17. Approximately 51% male.

Intervention:  Patients were placed in a screen time allowed group and a screen time not allowed group for the first 48 hours. Total minutes reported after the study were 630 minutes vs 130 minutes.

Outcome:  Time to symptom resolution. Patients took daily symptom scoring tests for 10 days.

Result: Screen time allowed group had a significantly longer time to recovery (8 days) vs screen time not allowed (3.5 days).

Strength: Good attempt at quantifying effects on early screen time exposure on symptom recovery in an ED population.

Weakness:  This was a small study. Many patients (>25%) were lost to follow-up and it relies on symptom self-reporting.

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Deep sedation in the ED has previously been associated with longer duration of mechanical ventilation, longer lengths of stay, and higher mortality.¹ Current guidelines recommend light sedation, consistent with a goal RASS of -2 to 0, for most critically-ill patients in the ICU.²

The ED-SED³ multicenter, pragmatic, before-and-after feasibility study implemented an educational initiative (inservices, regular reminders, laminated sedation charts) to help target lighter sedation depths in newly-intubated adult patients without acute neurologic injury or need for prolonged neuromuscular blockade.

• 415 patients (196 pre-, 219 post-intervention), majority white (50%) and black (40%)
• Main reasons for intubation: sepsis, trauma, airway protection
• Majority of patients on fentanyl (85%) and propofol (76%), midazolam (20%)

After educational intervention:

• 21% fewer patients with deep sedation & 20% more patients achieving light sedation
  • 10% decrease in comatose levels of sedation (RASS -4 to -5)
• Lower hospital mortality (20.4 vs 10%, p < 0.01)
• Similar rates of self-extubation and paralysis awareness
• More patients extubated in the ED, downgraded from ICU admission, and discharged from the ED

Even with the caveats of the confounding and bias that can exist in before-and-after studies, these results are consistent with prior sedation-related studies and offer more evidence to support for avoiding deep sedation in our ED patients. The study also demonstrates the importance of nurse-driven sedation in achieving sedation goals.

Bottom Line: Our initial care in the ED matters beyond initial stabilization and compliance with measures and bundles. Avoid oversedating intubated ED patients, aiming for a goal RASS of -2 to 0. 

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This was a multistate, prospective, observational cohort of children and teachers attending in person schools in kindergarden through 12th grade where the school districs had the ability to perform contact tracing and determine primary vs secondary infections.  During the study period (6/21-12/21) 46 districts had universal masking policies and 6 districts had optional masking policies.  

Districts that optionally masked had 3.6x the rate of secondary transmission compared to universally masked school districts.  Optionally masked districts had 26.4 cases of secondary transmission per 100 community acquired cases compared to only 7.3 cases in universally masked districts.

Bottom line: Universial masking was associated with reduced secondary transmission of SARS-CoV2 compared with optional masking policies. 

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We previously posted on the COCA trial, which looked at empiric calcium administration in cardiac arrest.  They studied 391 adult Danish cardiac arrest patients.  The immediate and 30 day outcomes showed no benefit, and in fact strongly trended towards calcium being WORSE than placebo.  This article provides the 6 month and 1 year follow up data.  Surprise, surprise... calcium is still not looking good.  

At 6 months survival non-significantly favored the placebo group, and at 1 year it significantly favored the placebo group.  Neurologic outcome for those who survived was also no better, and perhaps slightly worse, in the calcium group. 

Importantly, the trial excluded patients with "traumatic cardiac arrest, known or suspected pregnancy, prior enrollment in the trial, adrenaline prior to possible enrollment, and clinical indication for calcium at the time of randomization."

Bottom Line:  The evidence continues to not support the routine empiric administration of calcium in cardiac arrest.  Patients in whom there is an indication to give calcium (e.g. known ESRD, suspected hyperkalemia, etc) are excluded from these trials, and should likely still receive empiric calcium, but in undifferentiated cardiac arrest you can probably skip the calcium.

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The hip joint is a very strong and stable structure requiring great force to produce a dislocation

Most hip dislocations are posterior (80-90%)

Mechanism:  MVC generating force onto an adducted flexed hip (most commonly)

Associated injuries occur both locally (acetabular fx) and distant (knee bone and ligamentous)

                Significant associated injuries in >70%

The hip joint has a very precarious blood supply.

One of the risk factors for AVN is total dislocation time

                <6 hours - 5% incidence

                >6 hours – up to 53% incidence

Examine the sciatic nerve carefully with posterior dislocations (10% incidence)

                Motor – EHL/ankle dorsiflexion

                Sensory – sensation dorsum of foot

There are many reduction maneuvers including the East Baltimore Lift technique

https://www.youtube.com/watch?v=1zvelGbVn04

Demonstrated at 30 seconds in above video

Place patient supine with affected leg flexed to 90 degrees at knee and hip. 2 providers position themselves on opposite sides of the patient and each places their arm under the patient’s calf/popliteal region and their hand on the opposite providers shoulder. A 3^rd person is required to stabilize the pelvis. Axial traction is generated by the providers slowly standing up. Gentle internal and external rotation can facilitate successful reduction

Diastolic Blood Pressure

• The diastolic blood pressure (DBP) is determined by vascular tone and remains relativley constant throughout the arterial system.
• A low DBP (< 50 mm Hg) suggests vasodilation and may be associated with an increased risk of myocardial ischemia and left ventricular dysfunction.
• In a recent trial, Ospina-Tascon and colleagues described the diastolic shock index (heart rate/DBP) and found that a DSI > 2.2 was associated with higher mortality in patients with septic shock.
• Take Home Point: pay attention to the DBP and, when low, consider initiation of vasopressors concomitant with fluid resuscitation.

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• TXA has been used for pediatric non-traumatic (surgical) bleeding with good evidence
• Currently used in around 1/3 of pediatric trauma centers based on survey data
• PED-TRAX (retrospective review of pediatric trauma admissions in a combat zone) showed an association between use of TXA and decreased mortality, with no increase in thromboembolic events
• Dosing strategies in the literature and in practice have been variable (bolus at variable dosing versus bolus + infusion)
• The TIC TOC trial was recently completed - a multicenter randomized pilot study looking at 2 dosing strategies of TXA versus placebo which demonstrated feasibility of a larger study and will hopefully serve as a model for further research to determine efficacy as well as ideal dosing

Bottom line: There is not clear evidence for efficacy, but trends are positive and the documented rates of adverse effects in this population are low. It is reasonable to give, especially in patients requiring massive transfusion or who are critically ill.

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Hemodynamic instability and cardiac arrest are major complications following endotracheal intubation.  The mantra “resuscitate before you intubate” has prompted several studies of how to prevent this.

The PREPARE II trial is a multicenter ICU-based trial studying the effect of 500cc of crystalloid versus no crystalloid pre-emptively to prevent hypotension following endotracheal intubation. The study enrolled 1067 critically ill patients in United States ICUs. Some 60% of patient were intubated for respiratory failure and 20% were already on vasopressor.  The primary induction drugs we etomidate and rocuronium. Importantly, urgent intubation was an exclusion. There were no differences in multiple endpoints including hypotension, new need for vasopressors, cardiac arrest, or 28-day mortality. 

This was in some ways this in not unexpected and patients already in an ICU setting have typically received some form of fluid loading already. Being ICU based and primarily a more smoldering medical population this has limited application to more emergent and undifferentiated settings, but study underscores the need for a broad and nuanced view of what “resuscitate” means. Positive pressure may exacerbate hypovolemia, but the patient’s underlying disease, the effect of anesthetic drugs both by direct action via relief of pain, discomfort, or dyspnea may predominate if you think the patient is euvolemic.

Remember to dose anesthetics/sedatives/RSI drugs with an eye toward hemodynamics and consider starting vasopressors prior to intubation

Bottom Line:

-In a broad well-conducted ICU-based study a 500cc peri-intubation bolus doesn’t prevent hypotension

-Have a broad view of what resuscitation for intubation might entail

-Having fluid ready for intubation is helpful, hemodynamic dosing of drugs and having a plan for vasopressors might be even more helpful

-Applicability to ED environments is limited in this ICU-based trial

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Have you ever wonder what patients feel after being intubated in the ED?

The study " Awareness With Paralysis Among Critically Ill Emergency Department Patients: A Prospective Cohort Study" aimed at answering just that.

Settings: Emergency Departments from 3 hospitals; This was a secondary analysis of a prospective trial.

Patients:

Patients who received neuromuscular blockade in ED

Intervention: None.

Comparison: None.

Outcome: Primary outcome was Awareness while paralyzed, secondary outcome was Perceived threat, which is considered the pathway for PTSD.

Study Results:

The study evaluated 388 patients.  There were 230 (59%) patients who received rocuronium.

Patients who received rocuronium (5.5%, 12/230) were more likely to experience awareness than patients receiving other neuromuscular blockade (0.6%, 1/158).

Patients who experienced awareness during paralysis had a higher threat perception score that those who did not have awareness (15.6 [5.8] vs. 7.7 [6.0], P<0.01).

A multivariable logistic regression, after adjustment for small sample size, showed that Rocuronium in the ED was significantly associated with awareness (OR 7.2 [1.39-37.58], P = 0.02). 

Discussion:

With the increasing use of rocuronium for rapid sequence intubation in the ED, clinicians should start to pay more attention to the prevalence of awareness during paralysis.  According to the study, patients reported pain from procedures, being restrained, and worst of all feelings of impending death.

One of the risk factors for awareness during paralysis would be the long half-life of rocuronium, compared to that of succinylcholine.  Therefore, clinicians should consider prompt and appropriate dosage of sedatives for post-intubation sedation.  Previous studies showed that a mean time from intubation till sedatives was 27 minutes (2), and propofol was started at a low dose of 30 mcg/kg/min for ED intubation (3). 

Conclusion:

Approximately 5.5% of all patients or 4% of survivors of patients who had invasive mechanical ventilation in the ED experienced awareness during paralysis.  They also were at high risk for PTSD.

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Tachyarrhythmias in the setting of high-dose vasopressors due to septic shock are not uncommon. Aside from amiodarone, some providers may not know of alternative therapeutic options in the setting of septic shock. In addition, some may view the use of a beta-blocker as counter-intuitive or counter-productive in the setting of norepinephrine usage.

However, there have been multiple smaller studies evaluating using esmolol (and other short-acting beta-blockers) in the setting of tachycardia, septic shock and pressors. Outcomes regarding the theoretical benefits of beta-blockade in sepsis (i.e. decreased mortality/morbidity 2/2 decreased sympathetic innervation, inflammation, myocardial demand etc.) have been varied. However, esmolol has been demonstrated multiple times to be effective at reducing heart rate without significant adverse outcomes (i.e. no sig diff in mortality, refractory shock, or time on vasopressors).  

Caveats/pitfalls

-most of the studies discuss “adequate resuscitation” prior to initiation of esmolol

-not studied in patients that also had significant cardiac dysfunction 

-be aware that esmolol gtts can be a lot of volume and pts can become volume overloaded if boarding in the ED for an extended period of time

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Balanced crystalloids:  So Hot Right Now

Brief Read:

The use of balanced crystalloids has been the subject of several RCTs with conflicting results. However, recent post-hoc and meta-analyses of these same trials suggest that balanced crystalloids may be the best choice initially. See nice summary at: https://www.atsjournals.org/doi/full/10.1164/rccm.202203-0611ED.

Long Read:

While I had thought about summarizing the recently published data on EPR from the CRITICAL trial in Japan, JournalFeed today covered the recent post-hoc analysis of the BaSICS trial originally seen on CC Pearls back in August 31, 2021 by Dr. Sjelocha. This subject is as important as it is confusing. There are large and relatively well done RCTs that point in opposite and sometimes strange directions. However, as the authors of the SMART trial summarized, even an NNT of 94 in this population could be a huge number of patients!

The use of balanced crystalloids (e.g. Plasmalyte) has been the subject of several previous RCTs (SMART and SALT-ED) with conflicting results. Recently the PLUS RCT and BaSICS trials seemed to push the literature towards to concluding there was no difference, but there are caveats for both trials now in the literature:

• While the PLUS RCT found no difference, a concurrently published meta-analysis seemed to conclude the opposite (https://doi.org/10.1056/EVIDoa2100010).
• Further confusing the issue, apost-hoc analysis of the similarly negative BaSICS RCTcame out in March 2022 suggesting that overall there was a benefit for patients who received balanced crystalloid when they hit the door, but that those who arrived with sepsis and were unplanned admissions benefited most!
  • The authors note that their original analysis is likely affected by the fact that 68% of the original BaSICS study population had already received balanced fluid, saline, or both before randomization.

This paper makes a nice point which I think is important for us in the ED: the evidence is suggesting a commonality in many critical care concepts, which is that decisions made in early resuscitation may have an outsized impact on patient outcomes. However, this will not be the last we hear on this subject, but for the time being, I agree with Dr. Lacy that “It might not matter as much what fluids you choose when patients are on their third, fourth, or fifth liter of fluid – but especially for the sickest patients, it sure seems like the initial resuscitation fluid makes a difference.”

BaSICS post hoc: https://www.atsjournals.org/doi/full/10.1164/rccm.202111-2484OC (See JournalFeed post from today and the accompanying editorial)

• 68% (10,520) of enrolled patients had balanced crystalloids (3,202), saline (2,096), or both (1,862) prior to enrollment
• “There was a high probability that balanced solution use was associated with lower 90-day mortality in patients who exclusively received balanced solutions before study enrollment.”

BASICS: https://jamanetwork.com/journals/jama/fullarticle/2783039 (summary stolen from Dr. Sjeklocha’s  August 31, 2022 CC Pearl)

• No difference in 90 days mortality (P-Lyte 26.4% v NS 27.2, aHR p=0.47), AKI or RRT out to 7-days, or in duration of MV, ICU LOS or hospital LOS
• Signal for possible harm in TBI population with balanced crystalloids compared to normal saline

PLUS: https://www.nejm.org/doi/10.1056/NEJMoa2114464

• 5,037 critically ill patients
• No statistically significant difference in the primary outcome of death within 90 days of randomization in the BMES group compared to the saline group (21.8% vs 22.0%, 95% CI -3.6 to 3.3; P=0.90).
• Subgroup analyses were conducted based on illness severity before randomization, presence of sepsis, kidney injury, age, sex, and ICU admission after surgery, and did not show a significant difference between the two groups.

SMART: https://www.nejm.org/doi/full/10.1056/nejmoa1711584

• 7942 patients in the balanced-crystalloids group,
• Balanced: 1139 (14.3%) versus Saline: 1211 of 7860 patients (15.4%) had a major adverse kidney event in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04).
• “Our results suggest that the use of balanced crystalloids rather than saline might prevent 1 patient among every 94 patients admitted to an ICU from the need for new renal-replacement therapy, from persistent renal dysfunction, or from death.”

SALT-ED: https://www.nejm.org/doi/full/10.1056/nejmoa1711586

• 13,347 patients
• The number of hospital-free days did not differ between the balanced-crystalloids and saline groups (median, 25 days in each group; adj. OR, 0.98; 95% CI, 0.92 to 1.04; P=0.41).
• Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P=0.01).

https://journalfeed.org/article-a-day/2022/back-to-basics-first-fluid-choice-matters-a-reanalysis-of-the-basics-rct/

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Prior studies have found that patients are at an increased risk for hypoglycemia when administered insulin for the acute management of hyperkalemia when they have renal dysfunction.  A new single-center, retrospective study investigated the risk of hypoglycemia and the overall effect of potassium lowering in patients with renal dysfunction and stratified outcomes based on the CKD level.

Patients were included if they were ordered insulin for hyperkalemia using a hospital driven order set and had CKD stages 3a, 3b, and 4.  They were excluded if they had dialysis within 6h of insulin administration, had DKA, or no repeat labs.  The hospital order set encourages 5 units of insulin instead of 10 when “renal failure” is present without clear guidance.

377 patients were included: 186 received 5 units and 191 received 10 units.  The average age was 65 years old, predominantly male, weighing 90 kg.  In the 5 unit group, significantly more patients had CKD stage 4 (60% v 30%) and in the 10 unit group, significantly more patients were CKD stage 3a (p<0.001).  The baseline serum potassium was 6 in each group.

The hypoglycemia incidence was not different between groups, with severe hypoglycemia occurring twice per group.  All patients received dextrose according to the protocol.

There was a significant difference in the reduction of serum potassium between the 5 and 10 unit groups: -0.63 mmol/L vs -0.9 mmol/L (p 0.001).

Bottom line:  Hypoglycemia occurred even with insulin dose reduction.  Potassium lowering was higher in patients who received the 10 unit dose.

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