• Amiodarone and lidocaine are commonly used antiarrhythmics for ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT). Their efficacy towards survival to hospital discharge and neurological outcome, however, has been questioned.
• A recently published study in the NEJM evaluated these drugs by performing a double-blind, randomized, placebo-control trial. The trial evaluated patients presenting with out of hospital cardiac arrest secondary to VF or pulseless VT that is refractory to one or more shock.
• The trial randomized 3,026 patients to receive amiodarone (974), lidocaine (993), or normal saline (i.e., placebo) (1,059); the primary outcome was survival to hospital discharge and the secondary outcome was favorable neurological outcome at hospital discharge. Several sub-group analyses were planned a priori.
• No statistically significant difference was found in hospital survival or neurologic outcomes between any of the groups. Patients who had a witnessed arrest and bystander CPR had higher rates of survival with either lidocaine or amiodarone compared to saline while there was no difference between the two.

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What is cardio-renal syndrome CRS?

• Covers disorders where acute or long-term dysfunction of one organ can cause acute or long-term dysfunction of the other
• Worsening renal failure, diuretic resistance in heart failure, and worsening kidney function during heart failure are all characteristic of the disease process

There are 5 types

1. Acute CRS: abrupt worsening of heart function leading to kidney injury

2. Chronic CRS: chronic heart failure leads to progressive kidney disease

3. Acute renocardiac syndrome: abrupt kidney dysfunction leading to acute cardiac disorder

4. Chronic renocardiac syndrome: chronic kidney disease leading to decreased cardiac function

5. Systemic CRS: Systemic condition leading to both heart and kidney disease

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Cerebral Venous Thrombosis

• Approximately 25% of patients with cerebral venous thrombosis (CVT) will experience neurologic deterioration.
• This is most commonly due to an increase in ICP that results in transtentorial herniation.
• While heparin remains the treatment of choice for CVT, consider the following alternative strategies in the acutely decompensating patient:
  • Endovascular thrombolysis
  • Mechanical thrombectomy
  • Decompressive hemicraniectomy

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There are multiple vasoactive infusions available for acute hypertensive emergencies, many having serious side effect profiles or therapeutic disadvantages.

Clevidipine (Cleviprex) is rapidly-titratable, lipid-soluable dihydropyridine calcium channel blocker which has become increasingly used in the ICU in recent years [1]:

• Onset of action 2-4 minutes
• Duration of action 5-15 minutes (half-life of 1 minute)
• Clevidipine is relatively inexpensive ($108/50mL bottle)
• Side effects include hypertriglyceridemia, hypotension and reflex tachycardia

ECLIPSE trial compares clevidipine, nicardipine, nitroglycerin and nitroprusside in cardiac surgery patients. .

Clevidipine was as effective as nicardipine at maintaining a pre-specified BP range, but superior when that BP range was narrowed (also studied in ESCAPE-1 and ESCAPE2 with similar results) [2-3]

TAKE-HOME: Clevidipine is an ultra short-acting, rapidly-titratable vasoactive with favorable cost, pharmacokinetics, and side-effect profile. Consider its use in hypertensive emergencies.

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• The RUSH exam is a rapid way to identify the cause of shock using ultrasound. What's the RUSH exam? Click here
• The RUSH exam does not include an assessment of volume responsiveness (VR), but a new article by Blaivas, Aguiar, and Blanco suggests that it should be.
• VR has classically been assessed by determining the stroke volume before and after a passive leg raise or a fluid bolus. Click here for a video on how to calculate the stroke volume (skip to 21:30 in the video)
• The authors claim that VR can further be simplified by not measuring the left ventricular outflow tract (LVOT) and only comparing changes in the velocity-time integral (VTI). The assumption is that the LVOT is constant and doesn't change in most circumstances; a change of VTI that is greater than 15% suggests that the patient is VR
• Further validation is required to determine the degree of benefit to adding VTI to the RUSH exam, however measuring VTI is a skill that can be done with relatively little training and is clinically helpful.

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• A recent observational study was published looking at the ICU incidence and outcome of ARDS
• This international prospective cohort study looked at 459 ICUs and over 29,000 patients
• Incidence: 10.4% met ARDS criteria
• Severe ARDS occurred in 23.4%
• Clinical recognition of mild ARDS was only 51%
• Less than 2/3rds of patients with ARDS received a TV of 8 mL/kg or less
• Prone positioning was used in 16% of patients with severe ARDS
• Recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockers, and prone positioning
• Mortality ranged from 35% to 46%
• Pneumonia was the biggest risk factor for ARDS

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Sepsis-3

• After nearly 2 decades, the definitions for sepsis and septic shock have been updated.
• Key findings from the Task Force convened by SCCM and ESICM include:
  • Sepsis
    • Definition: life-threatening organ dysfunction due to a dysregulated host response to infection
    • ICU patients: organ dysfunction is defined as an increase of 2 points or more in the Sequential Organ Failure Assessment (SOFA) score
    • ED patients: 2 or more of the following new qSOFA (quickSOFA) score may identify patients with increased mortality
      • SBP less than or equal to 100 mm Hg
      • RR greater than or equal to 22
      • Altered mental status
  • Septic Shock
    • Definition: a subset of patients with sepsis and profound circulatory, cellular, and metabolic abnormalities
    • Clinical Criteria:
      • Persistent hypotension requiring vasopressors to maintain MAP greater than or equal to 65 mm Hg despite adequate volume resuscitation
      • Lactate greater than or equal to 2 mmol/L
  • The term "severe sepsis" is no longer used

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• Transthoracic echocardiography (TTE) is an essential tool during cardiac arrest because it identifies potentially reversible causes (e.g., tamponade, massive PE, etc.).
• One of the limitations of TTE is that it is sometimes difficult to assess the heart in less than ten seconds (i.e., during a pulse check) and good views of the heart sometimes hard to obtain. Transesophageal echocardiography (TEE) offers the potential to overcome these obstacles.
• TEE not only allows continuous visualization and better imaging of the heart during arrest, but it also allows the assessment of compression depth, and whether the heart is being correctly compressed during CPR.
• Here is what a TEE probe looks like, here is an example of a TEE during arrest, and here is a podcast by @ultrasoundpodcast on the literature for using TEE during cardiac arrest.

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• AKI can be seen in up to 40% of ICU patients
• Around 5-10% require treatment with renal replacement therapies
• The most common cause is acute tubular necrosis
• Definition by KDIGO:

1. Increase in Creatinine by 0.3 or more within 48 hours OR
2. Increase in Cr to >1.5 x baseline, presumed to have occured within the prior 7 days
3. Urine volume <0.5 mL/kg/hr x 6 hours

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Shock Index

• The shock index (SI) is calculated as the ratio of heart rate to systolic blood pressure and is often used in the assessment of critically ill patients.
• A SI > 0.8 has been shown to be an independent predictor of post-intubation hypotension during emergency airway management.
• Kristensen and colleagues performed a retrospective review in a single-center in Denmark to evaluate the ability of SI to predict 30-day mortality.
• In over 110,000 patients, they found a weaker association of SI with 30-day mortality in patients > 65 years of age, those taking a beta-blocker or calcium channel blocker, or those with a history of hypertension.
• Notwithstanding, a SI > 1 was a significant predictor of mortality across all patient populations and should be considered a warning of serious illness.

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What classifies "submassive PE"?

• Echocardiographic signs of RV strain (RV dilation/systolic dyfunction, decreased TAPSE)
• Hemodynamic stability (SBP >90)
• Patients may or may not have abnormal cardiac biomarkers (elevated troponin, BNP)

Submassive PE has early benefit from systemic thrombolysis at the cost of increased bleeding [1].

Ultrasound-accelerated, catheter-directed thrombolysis (USAT) [the EKOS catheters] has been shown to be safe, with low mortality and bleeding risk, as well as immediately improved RV dilation and clot burden [2-4]. USAT may improve pulmonary hypertension [4].

USAT is superior to heparin/anti-coagulation alone for submassive PE at reversing RV dilation at 24 hours without increased bleeding risk [5].

Long-term studies evaluating chronic thromboembolic pulmonary hypertension (CTEPH) need to be done, comparing USAT with systemic thrombolysis and surgical thombectomy.

Take-home: In patients with submassive PE, USAT should be considered over systemic thombolysis or anti-coagulation alone.

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There are so many variables to monitor during CPR; speed and depth of compressions, rhythm analysis, etc. But how much attention do you give to the ventilations administered?

The right ventricle (RV) fills secondary to the negative pressure created during spontaneously breathing. However, during CPR we administer positive pressure ventilation (PPV), which increase intra-thoracic pressure thus reducing venous return to the RV, decreasing cardiac output, and coronary filling. PPV also increases intracranial pressure by reducing venous return from the brain.

So our goal for ventilations during cardiac arrest should be to minimize the intra-thoracic pressure (ITP); we can do this by remembering to ventilate "low (tidal volumes) and slow (respiratory rates)"

• Low: Use only one-hand while bagging, this will give the patient 500-600cc per breath. Using two-hands provides ~900-1,000cc per squeeze (more than we normally ventilate patients who have a pulse).
• Slow: Ventilate patients at 8-10 breaths per minute. The less you ventilate the less time the patient spends with positive ITP. Observational studies have demonstrated that providers ventilate too fast during code so the use of a metronome or timing light provides critical feedback.

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Happy New Year!!!

My new year's resolution is to use less antibiotics (and eat more Cap'n Crunch Berries)

Will I be successful?

A multi-center, ICU, observational study looking at over 900 patients from 67 ICUs showed that half of all empiric antibiotics ordered in patients are continued for at least 72 hours in the abscence of adjudicated infection.

• We have been well trained to start antibiotics but stopping or limiting use can be difficult
• The greater the severity of illness, the longer the antibiotics were continued in this study

Things to consider:

The same way we try and limit central line use, we should try and decrease antibiotic usage on a daily basis

Tips to decrease use: daily clinical pharmacist input, ID specialist involvement, automated stop dates, 72 hour vancomycin cessation protocols, incentives for de-escalation, educational resources

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Acute Chest Syndrome

• Acute chest syndrome (ACS) accounts for the most common cause of ICU admission and the most common cause of death in sickle cell patients.
• Important pearls for ACS include:
  • Chlamydophila pneumonia is the most common bacterial cause of ACS in adults, whereas Mycoplasma pneumonia is the most common bacterial cause in children.
  • CXR abnormalities may be absent early in disease.
  • Children are more likely to have middle lobe disease, in contrast to adults who often have lower lobe involvement.
  • Acute RV failure is a well recognized complication of ACS - use ultrasound to evaluate the RV and be careful with fluids.

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The EuroTherm3235 Trial was a randomized, multi-center trial to study hypothermia (32-35^oC) in severe, traumatic brain injury¹:

• Hypothermia was compared with hyperosmolar therapies (hypertonic saline and mannitol) as "Stage 2" management.
• While hypothermia did successfully reduce ICP, functional outcomes (as measured in Extended Glasgow Outcome Score [GCS-E]) trended towards harm at six months (though not significantly different).
• Take-home: The study design has significant flaws, but the lack of clear benefit of hypothermia is consistent with previous studies² and suggests that fever prevention or controlled normothermia (36^oC) may be ideal for severe TBI patients, but needs further study.

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• What type of fluid we use in critical care resuscitation has been hotly debated for some time
• The most recent battles have been played out between NS and plasmalyte or buffered solutions
• There has been some evidence that high chloride solutions can lead to renal injury requiring renal replacement therapy (RRT)
• Does a buffered crystalloid reduce renal complications compared with normal saline in patients admitted to the ICU?
• The SPLIT Trial (Saline vs Plasma-Lyte) from New Zealand ICU's adds more to our knowledge about this topic while enrolling over 2,000 patients
• Summary:

1. Primary outcome was a rise in creatinine
2. There was no difference in the primary outcome or incidence of AKI
3. There was no difference in use of RRT or mortality
4. Suggesting that is doesnt make too much of a difference

• There were some limitations: 90% of patients were given fluid before enrollment that was buffered crystalloid and patients were only given around 2 liters on average of fluid in the ICU

The Bottom Line: This was a nicely designed study to evaluate the safety of both fluids. It does suggest that either fluid type is for the most part OK. But in patients requiring hefty fluid boluses, we should be cautious in what type of fluid we choose.

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Mechanical Ventilation for Septic Patients in Resource-Limited Settings

• An international team of physicians just published a series of recommendations for ventilatory support of septic patients in resource-limited settings.
• Pearls from these recommendations include:
  • Elevate the head of the bed to 30^o - 45^o
  • Consider tidal volumes of 5 - 7 ml/kg PBW in all patients
  • Use minimum levels of PEEP ( 5 cm H₂O) in all patients with sepsis and acute respiratory failure (unless the patient has moderate to severe ARDS)
  • Lower F_iO₂ to target SpO₂ > 88% or PaO₂ > 60 mm Hg
  • Use lung ultrasound to evaluate pulmonary edema when CXR is not available
  • Consider using SpO₂ to FiO₂ (S/F) as an alternative to P/F when blood gas analyzers are not available

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--The role of antibiotics in acute exacerbations of COPD remains controversial in many settings. However, a recent Cochrane review concludes that antibiotics have "large and consistent" benefit in ICU admissions [1]:

• decreased length of hospital stay
• decreased treatment failure
• decreased mortality

--However, patients on antibiotics had increased side effects, are at risk for increased drug-drug interaction (think azithromycin/levofloxacin), and the effect on multi-drug resistance is unclear.

--GOLD Guidelines are a bit more liberal with their recommendations for antibiotics [2], recommending antibiotics based on symptoms or in patients needing mechanical support.

--TAKEAWAY -- if your patient needs BiPAP or ICU, they should also get antibiotics!

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• Invasive candidal infections can carry a high mortality (up to 40%) and can hard to diagnose
• In the ICU it is important to know which patients are at risk for developing invasive candidal infections

Risk factors for invasive candidal infections

• Critical illness (long ICU stays)
• Abdominal surgery (anastomotic leaks, repeat laporatomies)
• Necrotizing pancreatitis
• Hematologic malignencies
• Solid organ transplant
• Solid organ tumors
• Neonates (low birth wt, preterm)
• Use of broad spectrum antibiotics
• Central lines/PICC lines
• TPN
• Hemodialysis
• Steroid use
• Candidal colinization (urine, sputum)  

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Pain Management in the Critically Ill Patient

• Pain is common, often underappreciated, and routinely undertreated in our critically ill patients.
• Poorly treated pain has been shown to adversely affect both short- and long-term outcomes.
• Key pearls when treating pain in the critically ill:
  • Vital signs should not be used in isolation to assess pain
  • Use a validated assessment tool to objectively quantify pain (i.e., Critical Care Pain Observation Tool)
  • An analgosedation strategy (analgesics before sedative medications) has been shown to decrease duration of mechanical ventilation and decrease ICU LOS
  • Opioids have no maximum or ceiling dose. The appropriate dose is that which controls pain with the fewest side effects.

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