Is it possible to have a patient present in diabetic ketoacidosis (DKA) with both negative serum and urinary ketone levels?

A case report published in American Journal of Emergency Medicine by Jehle et al provides a helpful reminder of this phenomenon (1). The degree of acidosis is directly related to the ratio of the various ketones/ketone metabolites: acetone, acetoacetate and beta-hydroxybutyrate present in the serum. The proportion of each respective substance is determined by the existing redox state in the blood. At any given time, acetoacetate and beta-hydroxybutyrate exist in an equilibrium dependent upon the ratio of NAD+ and NADH(fig.1). These substances freely convert with the assistance of the enzyme beta-hydroxybutyrate dehydrogenase (2). This conversion requires the donation of a hydrogen atom from NADH. The balance between beta-hydroxybutyrate and acetoacetate, is determined by the ratio of NADH to NAD+. Acetoacetate will freely degrade into acetone through non-enzymatic decarboxylation. Early in DKA, acetoacetate is the most prevalent substance. As the disease progresses and the serum ratio of NADH to NAD+ increases, the proportion of beta-hydroxybutyrate rises, decreasing the quantity of acetoacetate and acetone.

Traditional serum and urinary ketone assays react strongly to acetoacetate but neither reliably react with beta-hydroxybutyrate. Patients in whom the majority of their anion gap is filled by beta-hydroxybutyrate, urinary or serum ketone levels may be negative. In such cases, serum beta-hydroxybutyrate assays would be positive but are not universally available.

It is important to note, with resuscitation and insulin therapy, the ratio of NADH/NAD+ will start to normalize causing an increase in the quantity of acetoacetate. As the patient improves and the anion gap clears, the degree of ketones detected in the serum and urine will paradoxically increase.

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Zika Virus-associated GBS

• Zika virus has been shown to trigger Guillain-Barre Syndrome (GBS) at a rate similar to Campylobacter jejuni infections.
• In patients with Zika virus-associated GBS, neurologic deterioration has been rapid, with approximately 33% of patients developing respiratory distress.
• For patients who have required intubation, the duration of mechanical ventilation and length of ICU stay has been very long.
• Consider Zika virus-associated GBS in patients with muscle weakness, facial palsy, or paresthesias in the setting of a travel or exposure history to the virus.

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Despite a lack of prospective data, end-tidal CO2 (ETCO2) is often proposed as a viable replacement for the traditional pulse check to identify return of spontaneous circulation (ROSC) in patients presenting to the Emergency Department in Cardiac Arrest. A recent study by Tat et al examined this very question. The authors prospectively enrolled 178 patients suffering out-of-hospital cardiac arrest (OHCA) and examined the accuracy of a rise in ETCO2 at predicting ROSC. The authors examined both a rise of 10 and 20 mm Hg in ETCO2. Of the 178 patients included in this cohort, 60 (34%) experienced ROSC. The sensitivity and specificity of ETCO2 to predict ROSC at a threshold of 10 mm Hg was 33% and 97% respectively. At a threshold of 20 mm Hg ETCO2 performed no better with a sensitivity and specificity of 20% and 99% respectively.

What this data suggests is while a rise of ETCO2 of greater than 10 is highly suggestive of ROSC, the contrary cannot be said. The absence of a spike in ETCO2 does not rule out ROSC, as the large majority of patients experiencing ROSC in this cohort did so without demonstrating a significant rise in ETCO2. This evidence suggests that ETCO2 is a poor surrogate for a pulse check.

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Predicting Fluid Responsiveness with ETCO2

• It is well known that almost 50% of critically ill patients do not respond to fluid resuscitaiton. For those that do not respond, indiscriminate fluid administration may be harmful.
• There is increasing emphasis on the use of dynamic markers of fluid responsiveness, namely passive leg raise (PLR), pulse pressure variation, respirophasic changes in the IVC, and many others.
• ETCO2 can also be used to assess fluid responsiveness in mechanically ventilated patients with no spontaneous respiratory effort.
• An increase in ETCO2 of at least 5% with a PLR has been shown to outperform arterial pulse pressure as a measure of fluid responsiveness.

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LVADs and RV Failure

• Acute RV failure can be seen in up to 10% of patients after LVAD implantation.
• The treatment of RV failure in the LVAD patient consists of the following:
  • Fluids: avoid aggressive fluid administration, as this can displace the septum and impair LVAD function
  • Inotropes: consider early initiation of dobutamine, milrinone, or epinephrine to augment RV function
  • Vasopressors: target a MAP higher than 60 to 70 mmHg to maintain RV perfusion pressure
• If intubated, avoid hypoxia, hypercarbia, high PEEP, and high ventilator pressures.  These can increase pulmonary vascular resistance and further worsen RV function.

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There are 4 types of respiratory failure that all providers should be familiar with

Type 1: Hypoxemic, PaO2 <50; this can include shunt , V/Q mismatch, or high altitude. Pulmonary edema, ARDS, pneumonia are common causes of this type of failure.

Type 2: Hypercapnic respiratory failure; decreased RR or tidal volume. This includes neuromuscular disorders including GBS or Myasthenia Gravis, in addition to medication overdose. COPD and asthma can lead to this type of respiratory failure as well.

Type 3: Peri-operative; atelectasis; decreased FRC from being supine or obese during the operative period.

Type 4: Shock or hypoperfusion leading to increased work of breathing and respiratory failure.

Heat Stroke

• Heat stroke is critical illness defined as a core body temperature greater than or equal to 40^oC and altered level of consciousness.
• Mortality from heat stroke can be as high as 30%.
• Numerous methods exist to rapidly cool patients below 39^oC.
• Of these methods, ice-water immersion cools patients the fastest and is highly effective in young patients with exertional heat stroke.
• There is currently insufficient evidence to routinely recommend antipyretic agents, intravascular cooling devices, body cavity lavage, or the use of ice packs in the groin/axilla/neck. In addition, dantrolene is not recommended in the treatment of heat stroke.

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• Current guidelines recommend IV proton pump inhibitors in setting of acute upper GI hemorrhage as a bolus + infusion (e.g. 80 mg bolus + 8mg/hr infusion).
• Recent meta-analysis comparing bolus + infusion versus intermittent bolus (most commonly 40 mg BID) demonstrated non-inferiority of intermittent bolus dosing.
• In fact, there was a trend (though not significant) to superiority of intermittent bolus dosing, with decreases in rebleeding, mortality, repeat intervention.
• From a practical standpoint, pantoprazole requires a dedicated IV line, and is not compatible with other common ICU infusions (fentanyl, propofol, norepinephrine, octreotide).

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• Many clinicians use end-tidal CO2 to monitor respirations during procedural sedation or mechanical ventilation
• Typically either the presence (or absence) of a "normal" waveform or the quantitative value is used, however a lot more information can be gathered from the actual shape of the waveform; below are a few examples.
• For more examples of interpreting waveforms, click HERE.

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American Thoracic Society (ATS) Conference Highlights

The ATS conference was last week in San Francisco and a few cool articles were presented. They are briefly summarized below:

1.     Using a helmet vs face mask for ARDS: Non-invasive ventilation is not ideal for ARDS for a variety of reasons. At the same time, endotracheal intubation and ventilation carries some risks as well. Could a new design of a "helmet" device make a difference? This one center study from the Univ of Chicago suggests that it would: decreased rate of intubation, increase in ventilator free days, and decrease in 90 day mortality. http://jama.jamanetwork.com/article.aspx?articleid=2522693

2.     Can aspirin prevent the development of ARDS in at risk patients in the emergency department? Unfortunately, it does not appear to help. http://jama.jamanetwork.com/article.aspx?articleid=2522739

3.     Should you start renal-replacement therapy (HD, CRRT etc) in critically ill patients with AKI sooner or later? Seems to have no difference and may actually lead to patients not needing any dialysis. Really a great read  if you have time.  http://www.nejm.org/doi/full/10.1056/NEJMoa1603017?query=OF&

4.    Should I extubate at night? Lastly, probably don’t extubate at night if you can avoid it. Or just be cautious. http://www.atsjournals.org/doi/abs/10.1164/ajrccmconference.2016.193.1_MeetingAbstracts.A6150

Situations Where ECMO Will Likely Fail

• As many EDs and ICUs begin to develop protocols for the use of ECMO, it is important to note select conditions when this therapy is unlikely to be succesful.
  • Chronic respiratory or cardiac disease with no hope of recovery
  • OHCA with prolonged no blood flow
  • Severe aortic regurgitation
  • Type A aortic dissection
  • Refractoroy septic shock with preserved LV function
  • Stem cell transplant patients
  • Advanced age with ARDS
  • Prolonged pre-ECMO mechanical ventilation (> 7 days)
  • Center inexperienced with ECMO

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Zika virus has received significant media attention in the US due to its recent link with teratogenicity. But Zika is also associated with critical and life-threatening complications, including death. Differentiating it from other Flavivirus diseases such as Dengue or Chikungunya can be challenging.

Diagnosis

• Clinical -- low-grade fever, maculopapular pruritic rash, arthralgias (small joints of hands and feet), non-purulent conjunctivitis [1,4]
• Serum RT-PCR
• Dengue --high fever, severe myalgias, no conjunctivitis, cytopenia common [2,4]
  • Dengue is a hemorrhagic fever, Zika and Chikungunya are not.
• Chikungunya -- high fever, severe polyarthralgias, no conjunctivitis, no hemorrhage [2,4]

Complications

• Guillian-Barre Syndrome (GBS) [1,3]
  • Responsible for majority of Zika deaths worldwide
  • Estimated at 1 in 4000 cases of Zika in French Polynesian study [3]
  • WHO estimates up to 4M cases in the Americas this year (~1k cases GBS)
• Immune Thrombocytopenic Pupura (ITP) [2]
  • Thrombocytopenia leading to bleeding. Responsible for lone US death and deaths in Columbia
• Meningoencephalitis, transverse myelitis, fetal microcephaly [2]

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Attachments

• 1605101507_Zika_Dengue_Chikungunya.jpg (131 Kb)

A recent survey looked at resuscitation practices that could help improve survival during in-hospital cardiac arrest

• Monitoring for interruptions in chest compressions
• Reviewing cardiac arrest cases monthly
• Adequate resuscitation training

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Can NIV be Used in ARDS?

• Mechanical ventilation can cause lung injury and increase patient morbidity and mortality.
• Noninvasive ventilation (NIV) is well-known to decrease intubation rates and improve patient outcome in select disease states (i.e., COPD, acute CHF).
• For patients with acute respiratory distress syndrome (ARDS), NIV may reduce the work of breathing by opening collapsed alveoli, increasing FRC, and improving oxygenation.
• To date, there are only a few RCTs that have evaluated the use of NIV in ARDS.
• Unfortunately, these trials have failed to demonstrate improved patient outcome or decreased intubation rates in patients with ARDS.
• Clinical Bottom Line: Intubate patients with ARDS who are difficult to oxygenate with standard oxygen therapy.

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Disclaimer: Talking about seizures/status that is NOT due to eclampsia

• Propofol (Class B) -- though not recommended for obstetric use by manufacturer
• Benzodiazepines (Class D) -- mostly due to fetal withdrawal syndrome, but some teratogenicity to prolonged exposure inconsistent in literature
• Ketamine (No FDA class assigned but likely Class B Austrailia equivalent)
• Levetiracetam (Class C) -- no clear evidence of major fetal malformations in humans
• Phenytoin, phenobarbitol, carbemazepine, valproic acid and most other common AEDs (Class D due to teratogenicity)

TAKE HOME: While no AEDs are completely safe in pregnancy, treatment and stabilization of maternal status epilepticus is paramount for fetal health. Involve neurology/epileptology and OB/maternal-fetal medicine.

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• 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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