UMEM Educational Pearls - By Caleb Chan

Background:

           -Muscle rigidity has been described as a side-effect of fentanyl, specifically activation of expiratory muscles 

           -Excessive expiratory muscle use acts as “anti-PEEP,” causing lung derecruitment and hypoxemia

           -End-expiratory lung volume (EELV) has been used as a surrogate for lung recruitment

Study:

          -Small, two center, observational study (46 patients with ARDS)

          -50% of  patients had a significant increase in EELV after administration of neuromuscular blockade (NMB)

          -Statistically significant correlation between a higher dosage of fentanyl and a greater increase in EELV after NMB

Takeaways:

          -NMB can improve lung recruitment for a subset of patients with ARDS, particularly in patients with significant expiratory muscle use (this can be seen on your physical exam of your intubated ED boarding patient)

          -Although this was not the main point of this study, consider fentanyl-associated “anti-PEEP,” particularly in patients receiving fentanyl whose hypoxemia and/or ventilator mechanics are disproportionate to their imaging

                    -This can be assessed with NMB (but ensure the patient will have adequate minute ventilation first)

                    -Naloxone has also been shown to reverse fentanyl-associated rigidity, but obviously would induce patient discomfort/withdrawal

*Of note, because this was an observational trial, it is possible that the patients with increased work of breathing were simply given more fentanyl. Regardless, these findings are consistent with previously documented physiologic side effects of fentanyl.

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IVC POCUS is often misapplied in attempts to assess volume status and/or volume “responsiveness.” Here are some important concepts to understand when using IVC POCUS to guide management:

  1. IVC measurement is not a reliable predictor of fluid responsiveness
  2. Venodilation and obstructive pathology can decrease and increase (respectively) IVC size without any change in actual blood volume or “volume status”
  3. IVC size/variation is affected by multiple factors including spontaneous breathing vs. mechanical ventilation (AND actual ventilator settings), and degree of respiratory effort (in both spontaneous and mechanically ventilated patients) so there are no true “cut off” points that determine volume responsiveness
  4. Attempting to maximize cardiac output/oxygen delivery (macrocirculation) through IVF can actually cause venous congestion and worsen microcirculation and organ function
  5. Some patients with a plethoric IVC (tamponade or tension pneumothorax) may actually benefit from IVF in the acute setting
  6. Examine the entire IVC (cephalad and distal portion) and in the short and long axis (the IVC is actually elliptoid, rather than a true cylinder)
  7. Interpret IVC size in relation to RA/RV function (pts with chronically elevated RA pressures may have a chronically dilated IVC)

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Background: 
-Initial lactate clearance over 2 hours has been used to measure pt response to resuscitation in sepsis. However, data supporting its prognostic use is lacking.
 
Study:
-Single center, retrospective cohort study in large academic center
-Adult patients (4,775) admitted through ED with suspected infection
-Lactate clearance defined as 10% decrease in 2 to 12 hrs
-Multivariable logistic regression adjusting for age, sex, cirrhosis, ESRD
 
Results:
-Lactate trajectories highly variable
-Lactate clearance was highly confounded by patient comorbidities (particularly cirrhosis)
-24-h change in peak lactate was a better prognostic indicator (but still poor)
 
Takeaway:
-In the ED, caution should be used when using lactate clearance as a single marker for assessment/prognosis, particularly if the pt has other comorbidities such as cirrhosis

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Background:
There has been interest in vitamin C as an adjunctive therapy in patients with systemic inflammation and vasoplegia to reduce inflammation. While it was suggested that vitamin C may have some benefit (along with hydrocortisone and thiamine) in septic shock, the LOVIT trial showed possible harm from high-dose vitamin C administration in septic ICU patients. The  VALENCIA trial sought to evaluate whether vitamin C could reduce the duration of vasopressor therapy in patients with moderate vasoplegic shock.

Study:
-double-blinded RCT at two tertiary centers, 71 patients (36 to placebo, 35 to vitamin C)
-adult patients with vasoplegic shock of any cause
-vasopressor requirement >10 μg/min of norepi after hypovolemia was excluded
-notable exclusion criteria: end-stage renal failure and expected survival <12 hrs

Results:
-65 pts with septic shock, 6 pts with non-infectious cause
-no significant difference in the duration of vasopressors between the treatment group (median, 44 h [95% CI, 37-54 hrs]) and the control group (55 hrs [95% CI, 33-66 hrs])
-also no statistically significant difference in the vasopressor dose at 12 hourly time points, ICU or 28-day mortality and ICU or hospital length of stay

Take-home points:
Small study that ultimately may be under-powered but did not show that vitamin C reduces vasopressor duration in moderate vasoplegic shock

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Hypoxemic respiratory failure is a common presentation of critically ill patients. If the degree of hypoxemia is severe and disproportionate to the patient's radiographic findings and not responding to increasing FiO2, a right-to-left shunt should be considered. To evaluate for an anatomic shunt, an intravenous agitated saline contrast (ASC) echocardiographic evaluation can be conducted by an ED provider at the bedside.

 

Technique:

  1. Use two operators, nursing can perform the ASC with the physician obtaining the echo views
  2. Set-up:
    • 20 gauge (or larger) PIV in the AC fossa or more proximal is sufficient (does not have to be a CVC)
    • Flush PIV aggressively prior to attempt to make sure it won't blow
    • Obtain 3-way stopcock and 2 10 cc syringes
    • One port is connected to the PIV, and a second port to an empty 10cc syringe with the plunger fully depressed 
    • Third port connected to a syringe filled with 9ccs of saline and 1cc of air (eject 1cc of saline from the syringe of normal saline (NS) and replace it with air)
  3. Echo technique:
    • Any view where the RA, LA, and IAS can be seen will suffice
    • Apical 4-chamber view is favored, with a focus on the bilateral atria (can also do sub-xiphoid)
  4. Procedure:
    • With the equipment connected to the PIV, bubbles are created by turning the stopcock valve to “off” toward the patient and alternately depressing the plungers on the 2 syringes to send the air/NS mixture back-and-forth between them (should be done forcefully)
    • Push ASC completely into one of the syringes and quickly turn the stopcock “off” toward the other, and inject the ASC into patient while maintaining echo view and actively recording

Interpretation:

  1. Quality control check:
    •  A vigorous injection should result in dense opacification of the RA
      • If the chamber is not densely opacified, likely technique issue and the exam should not be interpreted
  2. The LA should be examined for a period of at least 10 full beats
  3. Timing when microbubbles are seen in the LA:
    • Immediately (within 3-6 beats is a typically used cutoff):  likely to be intracardiac (most likely PFO)
      • Under ideal circumstances, bubbles can be seen to transit across the septum in real time
    • After the 3-6 beat cutoff: more likely to be due to a transpulmonary shunt, either an AVM or hepatopulmonary syndrome, depending on the clinical circumstances
      • Further workup might include a CT angiogram of the chest or workup for cirrhosis
  4. Rough qualitative interpretation
    • no bubbles
    • a small number (roughly <10)
    • a large number (roughly >10)
    • enough to completely opacify the LA
    • (Significant continuous hypoxemia requires significant continuous right-to-left shunting, and thus the ongoing passage of many ASC bubbles)

 

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Background: 

There have been a few studies that suggested that there may be some neuroprotective effect with a higher MAP goal in post-arrest patients. However, these studies were small and/or observational. 

 

Intervention:

-The BOX trial was a double-blind, dual-center (Denmark), randomized trial 

-Study population: >18 yo, OHCA of presumed cardiac cause

-Pts randomized to higher (77 mmHg) vs. lower (63 mmHg) MAP goal

-double-blinded by attaching a module that reported a BP that was 10% higher or lower than the pt’s actual BP

-Notable exclusion criteria:

-unwitnessed asystole or suspected intracranial bleeding/stroke

 

Results/Primary outcome:

-No sig difference in composite of death + Cerebral Performance Category of 3 or 4  (3= severe disability, 4= coma) within 90 days

-133 patients (34%) in the high-target group vs 127 patients (32%) in the low-target group (hazard ratio, 1.08;95%CI, 0.84 to 1.37; P=0.56)

 

Caveats/Takeaways:

-Mean difference in BP was 10.7 mmHg (95[CI], 10.0 to 11.4) which is still relatively clinically significant, but was lower than their goal difference of 14 mmHg

-They used IVF to target a CVP of 10 mmHg prior to initiation of norepi and used dopamine "if necessary"

-Consider generalizability given study population was patients with presumed cardiac cause of arrest

-Keeping a lower MAP goal of >65 mmHg is reasonable in post-arrest patients

 

 

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DOSE VF (DOuble SEquential External Defibrillation for Refractory VF) Trial 

Background - High quality data regarding the use of double sequential external defibrillation (DSED) and vector-change (VC) defibrillation in refractory vfib is limited

Study

-Three-group, cluster-randomized, controlled trial in six Canadian paramedic services

-Study population: 

-OHCA with refractory vfib (initial presenting rhythm of vfib or pulseless VT that was still present after three consecutive rhythm analyses and standard defibrillations separated by 2 minute intervals of CPR) of presumed cardiac etiology (405 patients)

-Some notable exclusion criteria: 

-suspected drug overdose, hypothermia, traumatic cardiac arrest

-Protocol:

-First 3 defib attempts in the standard (anterior-lateral) position

-If remained in vfib after three consecutive shocks randomized to one of:

1. Standard defib for all subsequent attempts (136 pts)

2. VC defib (all subsequent attempts in anterior-posterior position) (144 pts)

3. DSED (applied second set of pads in AP position) with near simultaneously (<1 sec) defib shocks (125 pts)

Results

-Primary outcome: survival to hospital discharge

-38 patients (30.4%) in the DSED group vs. 18 (13.3%) in the standard group (RR 2.21; 95% CI, 1.33 to 3.67) (Fragility index of 9)

-31 patients (21.7%)  in the VC group (RR [vs. standard], 1.71; 95% CI, 1.01 to 2.88) (Fragility index of 1)

-Notable secondary outcome: survival with a good neurologic outcome

-34 patients (27.4%) who received DSED vs. 15 patients (11.2%)  with standard defibrillation (RR, 2.21; 95% CI, 1.26 to 3.88)

 

Takeaways/Caveats:

-68% of arrests witnessed, 58% received bystander CPR, median response time of 7.4-7.8 min

-Did not reach planned sample size 2/2 COVID pandemic

-No reporting of post-arrest care (e.g. TTM, PCI)

-Overall rates of survival and good neuro outcome on the higher side even with standard of care

-More/larger studies needed, but can consider DSED for refractory vfib, particularly if you are in a setting without more advanced circulatory support/resources

 

 

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Point-of-care ultrasound compression of the carotid artery for pulse determination in cardiopulmonary resuscitation

Background:

-shorter (and accurate) pulse/rhythm checks are better
-manual pulse checks are often not reliable and frequently exceed the recommended 10s window
-cardiac POCUS has been used as a possible adjunct but there have been concerns about interruptions in compressions 
 
Study:
-Single center, prospective, 25 patients with OHCA (155 pulse checks total)
-some exclusions: early cessation of CPR (49), "manpower shortage" (35)
-two physicians concurrently performing manual palpation (MP) of femoral artery and POCUS-carotid artery compression (POCUS-CAC) during pulse checks
-each with stopwatch to measure time to pulse judgment
-prev training with hour lecture and hands-on demonstration on how to assess/interpret the compressibility and pulsatility of the carotid artery
 
POCUS-CAC: 
-linear probe placed transversely across patient’s middle neck to identify the carotid artery and internal jugular vein on the screen
-probe pressure was applied until the internal jugular vein was completely compressed
-absent pulse = lack of pulsation and complete compression of the carotid artery under probe pressure
-present pulse = any visual pulsation or incomplete compression of the carotid artery
 
Results:
-the average time for carotid pulse identification per patient significantly different
      -POCUS-CAC was 1.62 (1.14– 2.14) s 
      -MP 3.50 (2.99–4.99) s
-in all 155 pulse checks, the time to complete a pulse check with POCUS-CAC never exceeded 10 s, whereas five cases with MP exceeded this.
 
Takeaways/caveats:
-larger study is needed and focus should be on rhythm checks, but if staffing allows, can consider utilizing POCUS-CAC as an adjunct for pulse checks 
-the MP time in this study is much shorter than in prev studies
-would be interesting to see if the findings would be even more exaggerated in a larger patient population (average BMI in the study was 23!)
-small sample, did not address carotid stenosis/atherosclerosis, no standardization for intensity of compression applied

 

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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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-If the patient is able to maintain mentation/airway/SpO2/hemodynamics and cough up blood, intubation is not immediately necessary

  • an ETT will actually reduce the diameter of the airway and can impede clearance and precipitate respiratory failure

-If you do intubate, intubate with the largest ETT possibly to faciliate bronchoscopic interventions and clearance of blood

  • Men: 8.5 or above; Women: 8.0 or above

-The CT scan that typically needs to be ordered is a CTA (not CTPA) with IV con

  • 90% of life-threatening hemoptysis from the bronchial arteries

-See if you can find prior/recent imaging in the immediate setting (e.g. pre-existing mass/cavitation on R/L/upper/lower lobes) 

  • having a level of suspicion for location/lateralization is helpful for the performing bronchoscopist to allow them to empirically occlude a location with an endobronchial blocker in a crashing hypoxemic patient if visualization is difficult 2/2 blood

-Get these meds ready before the bronchoscopist gets to the bedside to expedite care: 

  • iced/cold saline, thrombin, code-dose epi (which will be diluted)
  • there is also some (not great) data for intravenous TXA and improved outcomes

-If the pt's vent suddenly has new high peak pressures or decreased volumes after placement of endobronchial blocker, be concerned that the blocker has migrated

  • this can happen even with 1 cm movement of the ETT or blocker, or extension of the patient's neck
  • know where the ETT is secured as well as the endobronchial blocker (analagous to locking of a transvenous pacer)
  • pts with endobronchial blockers should also be on continuous neuromuscular blockade

 

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Clinical Pearls for Variceal Hemorrhage

-lower mortality with “restrictive” (Hgb 7-9 g/dL) rather than liberal strategy

  • although you should c/w your blood resuscitation according to hemodynamics

-antibiotic “prophylaxis” reduces mortality

  • use ceftriaxone rather than quinolone 2/2 increasing resistance

-no need to correct INR with FFP

  • FFP transfusions may actually be associated with worse outcomes (e.g. inc’d mortality)

-vasoactives (i.e. octreotide, somatostatin, terlipressin) alone may actually control bleeding

-for your ICU boarders...if persistent or severe rebleeding (despite endoscopic therapy), rescue TIPS is therapy of choice (call IR)

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Clinical Question:

  • Does dexmedetomidine lead to better short-term and long-term outcomes than propofol in mechanically ventilated adults with sepsis?

Methods:

  • Multicenter (13 US hospitals), double-blinded, 422 mechanically ventilated patients with sepsis
  • Notable exclusion criteria: pregnant, 2nd- or 3rd-degree heart block or persistent bradycardia requiring intervention, indication for bzds, expected to have NMB > 48 hrs, already had received mechanical ventilation >96 hrs
  • Pain was treated with opioid pushes or fentanyl gtt
  • Primary end point: number of calendar days alive without delirium or coma during the 14-day intervention period
    • Secondary efficacy end points included ventilator-free days at 28 days, death at 90 days, and global cognition at 6 months

Results:

  • No sig difference in adjusted number of days alive without delirium or coma over the 14-day intervention period  (dexmedetomidine: 10.7 days vs. propofol: 10.8 days; OR, 0.96; 95% CI, 0.74 to 1.26; P = 0.79
    • No sig differences in the number of ventilator-free days at 28 days, in death at 90 days, or global cognitiion at 6 months
  • Other notable findings:
    • Fewer patients in the dexmedetomidine group had ARDS or signs of trial drug withdrawal
    • Fewer patients in the propofol group extubated themselves
    • Open-label propofol received by 13% in the dexmedetomidine group and 8% in the propofol group) and dexmedetomidine (4% in the dexmedetomidine group and 3% in the propofol group)
    • Rescue midazolam was used in about half the patients, most often for procedural sedation or during NMB, 42% received antipsychotics
    • Similar proportions of patients had organ dysfunction, hypotension, or severe lactic acidosis
    • Symptomatic bradycardia requiring discontinuation of the trial drug was similar in the two groups

Take-home points:

  • Dexmedetomidine or propofol are reasonable options for septic patients requiring mechanical ventilation without notable differences in delirium or mortality

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Study Question: What is the association of relative hypotension (degree and duration of MPP deficit) in patients with vasopressor-dependent shock with the incidence of new significant AKI and major adverse kidney events (MAKE)? 

  • Mean Perfusion Pressure (MPP) = MAP - CVP
  • MAKE-14: composite measure of death, new initiation of RRT, or doubling of serum creatinine from the premorbid level at Day 14
  • Basal MPP estimated using pre-illness BP readings in the chart, basal CVP estimated using prior echo findings or estimated mean values

Methods:

  • Multicenter, prospective observational cohort study with 302 patients
  • Notable exclusion criteria:
    • age < 40, trauma as primary reason for ICU admission, active bleeding, unavailability of at least two preillness BP readings, pregnancy, "any condition specifically requiring a higher or a lower blood pressure target in the view of a treating clinician"

Results:

  • for every percentage increase in the time-weighted average MPP deficit, the odds of developing new significant AKI and MAKE-14 increased by 5.6% (95% CI, 2.2–9.1; P = 0.001) and 5.9% (95% CI, 2.2–9.8; P = 0.002), respectively.
  • Relationships between the risks of developing new significant AKI or MAKE-14 and the percentage of time spent with a MAP < 65 mm Hg were not statistically significant 

Take-aways:

  • Critically ill patients in shock who had higher and longer degrees of relative hypotension compared to their baseline BPs had a higher incidence of adverse kidney outcomes
  • Sidenote: also consider venous congestion/volume overload when thinking about end-organ damage (e.g. MPP not just MAP)

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Significance: 
There have been few high-quality studies regarding slow continuous infusion (SCI) of hypertonic vs. rapid intermittent bolus (RIB) therapy for patients with symptomatic hyponatremia
 
Study Design:
Multicenter, open-label RCT with 178 patients (both ED and inpatient) with corrected Na of 125 mml/L or lower with moderate/severe symptoms
-Moderate symptoms:  nausea, headache, drowsiness, general weakness, and malaise
-Severe symptoms: vomiting, stupor, seizure, and coma (Glasgow Coma Scale [GCS] score ≤8)
Relevant excluded patient populations: liver disease/cirrhotics, uncontrolled diabetics, primary polydypsia, anuric, hypotensive
 
Intervention:
Slow continuous infusion (SCI) of hypertonic vs. Rapid intermittent bolus (RIB) therapy 
(see treatment algorithms  for specifics)
 
Results:
Primary outcome: No difference in rates of overcorrection 
15 of 87 (17.2%) patients in the RIB group vs.  22 of 91 (24.2%) patients in the SCI group 
-(absolute risk difference, −6.9% [95% CI, −18.8% to 4.9%]; P = .26)
 
Other outcomes:
RIB group showed a lower incidence of relowering treatment than the SCI group 
-(absolute risk difference, −15.8% [95% CI, −30.3% to −1.3%]; P = .04; NNT, 6.3)
 
RIB group had higher proportion of patients achieving target correction rate within 1 hour than the SCI group 
-(absolute risk difference, 14.6% [95% CI, 2%-27.2%]; P = .02; NNT, 6.8)
 
No significant differences between the groups were observed in:
- symptoms at 24 and 48 hours after treatment initiation
- first time to an increase in sNa 5 mmol/L or greater after treatment initiation
- incidence of target correction rate
- time from treatment initiation to achievement of sNa greater than 130 mmol/L
- length of hospital stay 
 
There were no cases of osmotic demyelination syndrome in either group
 
Take-home point:
Rapid intermittent boluses of hypertonic saline may be just as effective as slow continuous infusions for certain patient populations with moderate/severe symptomatic hyponatremia (and may actually have decreased rates of need for re-lowering treatment)
 
Limitations:
-smaller study
-high number of dropout due to protocol violation
-remember that ODS is multifactorial (liver disease, chronic alcoholism, malnutrition)

 

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Systematic review and meta-analysis of 5 studies with a total of 929 patients comparing early vs. late initiation of norepinephrine in patients with septic shock

  • all were single-center studies
  • included RCTs, prospective and retrospective cohort studies

Primary outcome:

  • short-term mortality of the early group was lower than that of the late group ([OR] = 0.45; 95% CI, 0.34 to 0.61)

Secondary outcome:

  • no difference in ICU LOS
  • time to achieved target MAP of the early group was shorter than that of the late group (mean difference = − 1.39; 95% CI, −1.81 to −0.96)
  • in the three studies that assessed the volume of intravenous fluids within 6 h, the volume of intravenous fluids within 6 h of the early group was less than that of the late group (mean difference = − 0.50L; 95% CI, −0.68 to −0.3)

Caveat:

  • no clear definition of “early” initiation (ranged from within 1 to 6 hrs)

Take home point:

Early norepinephrine usage may improve mortality in septic shock

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Design
-Two-center prospective observational study with 157 patients admitted to the ICU for pneumonia and being treated with HFNC
-ROX (Respiratory rate-OXygenation) index = ratio of SpO2/FIO2 to RR

Results:
-ROX index ≥4.88 at 12 hours after HFNC onset with a sensitivity of 70.1%, a specificity of 72.4%, PPV of 89.4%, NPV of 42%, LR+ of 2.54, and LR- of 0.41 in predicting treatment failure

Validation study: Roca, 2019
-results similar, but ROX index ≥4.88 at 12 hour with LR+ of only 1.82
-also found that a ROX index of <3.85 at 12 hours had a sensitivity of 23.5%, specificity of 98.4%, PPV of 88.9, NPV 69.9, LR+ of 14.47, and LR- 0.78

Pitfalls:
-decision to intubate was not made based on ROX index
-criteria for intubation was also part of the ROX index
-NIV was not part of their treatment algorithm
-created and validated prior to current COVID-19 pandemic

Takeaways:
- The ROX index can be a tool to help predict whether a patient with pneumonia on HFNC may need mechanical ventilation or higher level of care
- May be most helpful with patients with pneumonia on HFNC boarding in the ED
- At 12 hours of HFNC, ROX index of >4.88 suggests patient likely to succeed with HFNC vs. <3.85 which suggests likely need for mechanical ventilation

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Question

Clinical Question: Will resuscitation guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes?

Methodology:

Design: Randomized, unblinded clinical trial among adults with sepsis-associated hypotension comparing PLR-guided SV responsiveness as a guide for fluid management (intervention) versus “usual care” at 13 hospitals in the United States and the United Kingdom (randomization was in a 2:1 allocation of SV-guided to usual care).

 

Inclusion criteria:

-patients presenting to the ED with sepsis or septic shock and anticipated ICU admission.

-refractory hypotension (MAP ≤ 65mmHg after receiving ≥ 1L and < 3L of fluid)

Exclusion criteria:

-infusion of > 3L of IV fluid prior to randomization

-hemodynamic instability due to active hemorrhage

-pregnancy or being incarcerated

-indication for immediate surgery

-acute CVA, acute coronary syndrome, acute pulmonary edema, status asthmaticus, major cardiac arrhythmia, drug overdose, injury from burn or trauma, status epilepticus

-inability or contraindication to passive leg raising

Intervention (in ICU):

-PLRs were performed prior to any treatment of hypoperfusion with either fluid bolus or vasopressors for the first 72 hours after ICU admission or until ICU discharge (whichever occurred first)

-If patient was FR (increase in SV ≥10%) a 500 ml crystalloid fluid bolus was given with repeat PLRs after every fluid bolus

-If the patient was non-FR, initiation or up-titration of vasopressors was prompted with repeat PLRs after significant escalation (an increase of 1 mcg/kg/min norepinephrine)

 

Results:

-83 patients in Intervention arm, 41 in Usual Care arm

-Both arms received a similar volume of resuscitation fluid prior to enrollment (2.4 ± 0.6 L Intervention vs. 2.2 ± 0.7L Usual Care)

-Positive fluid balance at 72 hours or ICU discharge, was significantly less in the Intervention arm (-1.37L favoring Intervention, 0.65 ± 2.85L Median: 0.53L Intervention vs. 2.02 ± 3.44L Median: 1.22L Usual Care, p=0.02).

-Fewer patients required RRT (5.1% vs 17.5%, p=0.04) or MV in Intervention arm compared to Usual Care (17.7% vs 34.1%, p=0.04)

-ICU length of stay was similar in the two arms  

-There was no difference in overall 30-day mortality (6.3% difference, Intervention: 15.7% vs. Usual Care: 22.0%, 95% CI -21.2%, 8.6%)

 

Implications:

Although this is a smaller, unblinded (also funded by maker of SV monitoring device) study, Douglas et al. demonstrate that limiting fluid administration using dynamic assessments of fluid responsiveness to guide resuscitation in patients in septic shock is likely safe. In fact, this may actually decrease the need for renal replacement therapy and mechanical ventilation amongst this patient population. At the very least, this study adds to the body of literature showing the harms of excessive fluid administration and positive fluid balance.

 

Bottom line:

If possible, use dynamic assessments of fluid responsiveness in patients with septic shock to guide interventions, particularly for further resuscitation beyond initial fluid resuscitation (~2 liters in this study).

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Clinical Question: Does a lower MAP target (60-65 mmHg) for ICU patients ≥ 65 years-old reduce 90-day mortality?

 

Methodology:

-Design: multicenter (across 65 UK ICUs), randomized clinical trial (not blinded), ultimately with 2598 patients

-Inclusion criteria: ICU patients ≥ 65 years-old receiving vasopressors for vasodilatory hypotension with adequate fluid resuscitation

-Exclusion criteria: vasopressors being solely used for bleeding or acute RV/LV failure or post-cardiopulmonary bypass vasoplegia, ongoing treatment for brain/spinal cord injury, death perceived as imminent

-Intervention:

  • Permissive hypotension group – MAP target of 60-65 mmHg
  • Usual care group – received vasopressors at discretion of treating clinician
  • Choice of vasopressor (norepi, vaso, terlipressin, phenylephrine, epi, dopamine, and metaraminol) left to discretion of treating clinician

 

Results:

-Patients in the permissive hypotension group had a lower exposure to vasopressors compared with those in the usual care group

  • median duration 33 hours compared with 38 hours (difference, –5.0; 95% CI, –7.8 to –2.2)
  • mean duration, 46.0 hours compared with 55.9 hours (mean difference, –9.9 hours; 95% CI, –14.3 to –5.5)

-Mean MAP was on average 6 mmHg lower in permissive hypotension group

-At 90 days, there was no statistically significant difference in all-cause mortality

  • 500 deaths (41.0%) among of 1221 patients in the permissive hypotension group compared with 544 (43.8%) among 1242 patients in the usual care group (absolute risk difference, −2.85%, 95% CI, −6.75 to 1.05; P = .15)

-No significant difference in mean duration of ICU and hospital stay, duration and days alive and free from advanced respiratory and renal support to day 28

-No significant different in number of serious adverse events (severe acute renal failure, supraventricular and ventricular cardiac arrhythmia, myocardial injury, mesenteric ischemia, and cardiac arrest)

 

Bottom line:

A lower MAP goal of 60-65 mm Hg appears to be safe for ICU patients ≥ 65 years-old being treated for vasodilatory hypotension

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(*It is important to note that many of the percentages in these early studies will change as more asymptomatic or minimally symptomatic patients are identified with increased testing)

 

Epidemiology

Among more than 44,000 confirmed cases of COVID-19 in China as of Feb 11, 2020:

- 30–69 years: ~78%

- severely or critically ill: ~19%

 

Case-fatality proportion: 

-60-69 years: 3.6%

-70-79 years: 8%

-≥80 years: 14.8%. 

-With no underlying medical conditions: overall case fatality of 0.9%

-With comorbidities: 

-cardiovascular disease (10.5%), diabetes (7%)

-chronic respiratory disease, hypertension, and cancer (6% each)

 

Presentation

For patients admitted to the hospital, many non-specific signs and symptoms: 

- fever (77–98%) and cough (46%–82%) were most common

- of note, gastrointestinal symptoms (~10%) such as diarrhea and nausea present prior to developing fever and lower respiratory tract signs and symptoms.

 

Diagnosis

No general lab tests have great sensitivity or specificity            

A normal CT scan does NOT rule out COVID-19 infection

-In an early study, 20/36 (56%) of patients imaged 0-2 days (‘early’) after symptom onset had a normal CT with complete absence of ground-glass opacities and consolidation

 

Treatment-

Mainstay of treatment will be management of hypoxemia including early intubation if necessary. However, specifically:

-Steroid therapy is controversial and the WHO is currently recommending against it unless it is being administered for another reason

-has not been associated with any benefit

-associated with possible harm in previous smaller studies with SARS and MERS

-associated with prolonged viremia

-intravenous remdesivir (a nucleotide analogue prodrug with promising in-vitro results against SARS-CoV and MERS-CoV) is available for compassionate use

            -lopinavir-ritonavir has been used without any associated benefit

 

 

Show References



Category: Airway Management

Title: Critical Care Pearls for Adrenal Crisis

Keywords: Adrenal Crisis (PubMed Search)

Posted: 1/7/2020 by Caleb Chan, MD (Updated: 5/24/2024)
Click here to contact Caleb Chan, MD

Adequate treatment of adrenal crisis (AC) is often delayed, even when a h/o adrenal insufficiency is known.

  • most important predictor of AC is a h/o of AC

 

Besides refractory hypotension, also consider in pts with:

  • critically ill pts with eosinophilia (cortisol typically suppresses eosinophil counts)
  • cancer patients who are on check-point inhibitor immunotherapy (they can cause severe hypophysitis or adrenalitis)
  • (inhaled glucocorticoids and topical creams also cause a degree of adrenal insufficiency)

 

Beware of triggers:

  • trauma, recent surgery, even emotional stress/exercise
  • recent initiation of medications that increase hydrocortisone metabolism (avasimibe, carbamazepine, rifampicin, phenytoin, and St. John’s wort extract)
  • recent withdrawal of medications that decrease hydrocortisone metabolism (voriconazole, grapefruit juice, itraconazole, ketoconazole, clarithromycin, lopinavir, nefazodone, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and conivaptan)

 

Treatment:

  • 100 mg IV hydrocortisone STAT as a loading dose, followed by 50 mg IV hydrocortisone q6h
  • can also give 40 mg IV methylprednisolone if hydrocortisone is not immediately available
  • can also give 4-6 mg IV decadron instead (will preserve integrity of ACTH stim test to diagnose adrenal insufficiency if it is performed later)

 

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