How low should you go? MAP Goals in Septic Shock

Background:

• Since Rivers’ Early-Goal Directed Therapy, a MAP of 65 mm Hg was been the standard goal for blood pressure in septic shock
• Some studies have suggested a higher target may be better for patients with hypertension
• Potentially less renal failure with a higher target

The Trial:

• 776 adult patients in France; Multi-center; randomized; non-blinded
• All patients had septic shock and on vasopressors
• MAP was maintained for 5 days or when the patient was weaned off pressors
• Primary outcome: Mortality at Day 28
• High target 65-70 mm Hg vs Low target 80-85 mm Hg

Outcome:

• No significant difference in mortality at 28 days: 36.6%  (high target) vs 34% (low target) (95 %CI; 0.84 to 1.38; P=0.57)
• No significant difference at 90 days: 43.8% (high target) vs 42.3% (low target) (95% CI; 0.83 to 1.30; P=0.74)
• Incidence of newly diagnosed atrial fibrillation was higher in the high-target group
• Patients with chronic hypertension: those in the higher target group required less renal-replacement therapy
• Significant percentage of patients in the high target group did not meet goal MAP BUT the trial mirrored actual clinical practice and allowed clinicians the ability to limit blood pressure and differences in actual MAP attained in both groups was significantly different

Bottom Line:

• A MAP goal of 65 is just fine in most patients
• Patients with chronic hypertension and atherosclerosis seem to benefit (less need for renal-replacement therapies) with a higher MAP: so aim higher in these patients or monitor renal function and increase MAP goals accordingly

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Coagulopathies in Critical Illness - DIC

• Disseminated intravascular coagulation (DIC) is an acquired syndrome of intravascular coagulation and is commonly encountered in critically ill patients.
• Think about DIC in the critically ill patient with oozing at vascular sites (or wounds) and the following lab abnormalities:
  • Thrombocytopenia
  • Prolonged PT and aPTT
  • Decreased fibrinogen
  • Elevated fibrin split products and D-dimer
• Guidelines for the management of DIC are primarily based on expert opinion and include:
  • Treat the underlying condition (i.e., sepsis)
  • Transfuse platelets if < 50,000 per mm³
  • Transfuse FFP to maintain PT and aPTT < 1.5 times normal control
  • Transfuse cryoprecipitate to maintain fibrinogen levels > 1.5 g/L
• The use of heparin remains controversial and cannot be routinely recommended.

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Nitric Oxide appears to have NO role in ARDS

Background: The use of inhaled nitric oxide (iNO) in acute respiratory distress syndrome (ARDS) & severe hypoxemic respiratory failure has been thought to potentially improve oxygenation and clinical outcomes.  It is estimated that iNO is used in up to 14% of patients, despite a lack of evidence to show improved outcomes. 

Mechanism: Inhaled NO works as a selective pulmonary vasodilator which has been found to improve P_aO₂/F_iO₂ by 5-13%, but is costly ($1,500 - $3,000 per day) and increases risk of renal failure in the critically ill.

Study: A recent systematic review analyzed 9 different RCTs (N=1142) and compared mortality between those with severe (P_aO₂/F_iO₂ < 100) and less severe (P_aO₂/F_iO₂ > 100) ARDS and found that iNO does not reduce mortality in patients with ARDS, regardless of the severity of hypoxemia.

Bottom Line: Inhaled NO is an intriguing option for the treatment of refractory hypoxemic respiratory failure, however there does not appear to be a mortality benefit to justify it's high cost and potentially negative side effects.  In the ED, it is important to focus on appropriate lung protective ventilation strategies (TV: 6-8 cc/kg IBW) and maintaining plateau pressures < 30 cm H₂O in the initial stages of ARDS to prevent ventilator induced lung injury while awaiting ICU admission.

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In 2001, Rivers et al. published a landmark article demonstrating an early-goal directed protocol of resuscitation that reduced mortality in septic Emergency Department patients.

Many questions have arisen throughout the years with respect to that trial; critics have complained about the overwhelming change in clinical practice based on this one single-center randomized trial.

Challenging Rivers data are the ProCESS (Protocolized Care for Early Septic Shock) investigators, who released the results from a multi-center randomized control trial of 1351 septic Emergency Department patients; the primary end-point was 60-day mortality. Click here for NEJM article.

Patients in this trial were randomized to one of three groups:

• Protocol-based EGDT

• Protocol-based standard (did not require central lines, inotropes, or blood transfusions

• Usual care (no specific protocol; care was left to the bedside clinicians)

Bottom-line: The investigators did not find any difference in mortality between patients in the three groups and comment that the most important aspects of managing the septic patient may be prompt recognition and early treatment with IV fluids and antibiotics.

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• “B-Lines” can be seen in patients with pulmonary edema (see attached image below)
• A “B-line” is a reverberation artifact defined by Lichtenstein as having several properties:

1.     A comet-tail artifact

2.     Arising from the pleural line

3.     Well defined

4.     Hyperechoic

5.     Long (does not fade)

6.     Erases A lines

7.     Moves with lung sliding

• A large amount of B-lines is pathologic
• These artifacts are also called “comet-tails” due to their appearance
• One or two B-lines can be seen in dependent lung zones in normal lungs
• AIS (Alveolar interstitial syndrome) describes a group of conditions including pulmonary edema, interstitial pneumonia, and pulmonary fibrosis that show similar findings on lung ultrasonography
• The most common presentation of this syndrome is from cardiogenic pulmonary edema and is characterized by B-lines in multiple lung zones
•  B lines correspond with interlobular septal thickening on CT scans, which represent pulmonary vascular congestion 

Technique

• B-mode is used with the micro-convex (cardiac) probe scanning in at least 8 lung zones
• Quantify the number of B-lines in each zone
• A lung zone is considered to be “positive” when three or more B-lines are present in a longitudinal plane between two ribs
• Two or more regions bilaterally are required to be defined as AIS
• Bilateral diffuse B-lines have a specificity of 95% and a sensitivity of 97% for the diagnosis of pulmonary edema

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Attachments

• 1403111625_Fig6.1BLINESFINAL.jpg (55 Kb)

Recruitment Maneuvers for ARDS

• Patients with ARDS who are ventilated with lung protective settings are at risk of derecruitment/collapse of lung units.
• Recruitment maneuvers are processes that transiently increase transpulmonary pressure to open collapsed units.
• These maneuvers can improve oxygenation and have been used in patients with ARDS and those with refractory hypoxemia.
• The various types of recruitment methods include:
  • Airway pressure-based maneuver: a continuous positive airway pressure of 35-45 cm H₂O is applied for 30-40 seconds
  • Ventilator modes: Airway pressure release ventilation (APRV) and high-frequency oscillatory ventilation (HFOV)
  • Prone positioning
• Adverse events can occur with recruitment maneuvers and include hypotension, hypoxia, and pneumothorax (rare).

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Intensive BP Control in Spontaneous Intracranial Hemorrhage

Managing the patient with hypertensive emergency in the setting of spontaneous intracerebral hemorrhage (ICH) is often a challenge.  Current guidelines from the American Stroke Association are to target an SBP of between 160 - 180 mm Hg with continuous or intermittent IV antihypertensives.  Continuous infusions are recommended for patients with an initial SBP > 200 mm Hg.
 

An emerging concept is that rapid and aggressive BP control (target SBP of 140) may reduce hematoma formation, secondary edema, & improve outcomes.
 

Recently published, the INTERACT 2 trial (n=2,829) compared intensive BP control (target SBP < 140 within 1 hour) to standard therapy (target SBP < 180) found:

• No difference in mortality (11.9% vs 12%, respectively)
• Improved functional status (secondary outcome) with intensive BP control
• Intensive lowering of BP in patients with acute ICH appears safe 

Study flaws: Patients treated with multiple drugs - combinations of urapadil, labetalol, nicardipine, nitrates, hydralazine, and diuretics.  Management variability away from protocol seemed high. (Interesting editorial)
 

A Post-hoc analysis of the INTERACT 2 published just this month suggests that large fluctuations in SBP (>14 mmHg) during the first 24 hours may increase risk of death & major disability at 90 days.

Bottom Line:  INTERACT 2 was a large RCT but not a great study (keep on the look out for ATACH II).  However, in patients with spontaneous ICH, consider early initiation of an antihypertensive drip (preferably nicardipine) in the ED to reduce blood pressure fluctuations early with a target SBP of 140 mmHg.

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• The well-known effects of cocaine toxicity include seizures, cardiac ischemia, and rhabdomyolysis. Abdominal pain, however, is a lesser known side-effect and may occur secondary to ischemia, infarction or perforation of the gastrointestinal tract; such cases tend to occur in younger people without known risk factors for ischemia.
• Ischemia may occur from the direct vasoconstrictive effects of cocaine, but may also occur from its pro-thrombotic effects on the mesenteric vessels; although any segment of the GI tract may be involved, the small bowel is most often affected.
• Symptoms may vary from mild abdominal pain to bloody diarrhea. Physical exam may reveal peritoneal signs if perforation occurs.
• CT scan of the abdomen may reveal the diagnosis although angiography may required for diagnosis or to guide revascularization.
• Management may vary from conservative (i.e., bowel rest and antibiotics) to surgical exploration and bowel resection in selected cases.

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A 50yo man found dow in the snow was brought into our ER last week in cardiac arrest with a bladder temperature of 21° C. Let’s warm him up!

• Passive external warming (good for mild hypothermia > 34° C):  remove all wet clothing, use warm blankets, hot chocolate.
• Active external rewarming (Used for temp between 30-34° C): Radiant heat, electric blankets, Bair-Hugger. Disadvantages: “core temperature after drop” theory: drop in core temp because of peripheral vasodilatation. Therefore, focus on warming the chest and torso area.  May not occur with certain warming techniques.
• Active core rewarming (<30 °C, above techniques and several other options):

1. Heated humidified oxygen via mechanical ventilation at 42-46°
2. IV normal saline warmed to 41-43° C
3. Cardio-pulmonary bypass: 1-2° C increase every 5 minutes
4. ECMO (best option in cardiac arrest): Up to 4-6° C/hr. VV or VA ECMO. Provides Cardio-pulmonary support. Can continue CPR while placing a cannula.
5. CVVH: less costly, more available, 1-4°C/hr. Case reports only. 
6. Artic Sun; external rewarming pads: used in hypothermia protocols. Easy to use. Case reports only.

• Other methods (use if other methods are unavailable):

1. Pleural irrigation: one chest tube in the mid-clavicular line w saline at 42° and another chest tube in the post-axillary line and connected to a pleurovac.
2. Peritoneal lavage: 8 Fr catheter into the peritoneum using a standard paracentesis method. Use 40-45° C dialysate.
3. Gastric, bladder, colonic irrigations

We were able to get ROSC with CPR and ACLS and then used Artic Sun to re-warm successfully.

Other tips/tricks:

• Continue CPR while rewarming (This is debatable: monitor ECG for new rhythms)
• How warm is “warm and dead”? Probably around 32°C
• How fast to rewarm?  Would warm quickly in cardiac arrest and then 1-2° C/hr thereafter; (No good evidence here)
• Arrhythmias corrected by rewarming (bradycardia etc); no need for pacing
• Up to three defibrillations for V. fib/V. tach; hold if no benefit
• Can give epinephrine per ACLS protocol but would be cautious with further dosing
• Pressors: can use epinephrine drip cautiously for hypotension
• Cisaturacurium for paralysis w/ sedation to prevent shivering
• Rule out hypoglycemia, adrenal insufficiency, hypothyroidism, sepsis if patient does not rewarm as expected!
• Avoid IJ lines or irritating the myocardium with a guidewire.
• K>12 mmol /L: consider termination of CPR

Attachments

• 1402111256_nejm_hypothermia2012.pdf (581 Kb)

Mechanical Ventilation During ECMO

• ECMO is a rapidly emerging therapy for critically ill patients with severe acute respiratory failure (VV-ECMO) and circulatory failure (VA-ECMO).
• Mechanical ventilation (MV) settings may have important effects on patients receiving either VV- or VA-ECMO.
• Though no large, randomized trials, consensus guidelines and expert opinion recommend the following initial settings for patients receiving VV-ECMO:
  • Tidal volume: < 4 ml/kg predicted body weight
  • Plateau pressure: < 25 cmH₂O
  • PEEP: 10-15 cmH₂O
  • F_iO₂: titrated to maintain sats > 85%
  • RR: 4 to 6 breaths per minute

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NSSTIs occur secondary to toxin-secreting bacteria; NSSTIs are surgical emergencies with a high-morbidity / mortality

Risk factors: immunocompromised host (DM, AIDS, etc.), intravenous drug use, malnourishment, peripheral vascular disease

Type I (polymicrobial; most common), Type II (monomicrobial; typically clostridia, streptococci, staph, or bacteroides), Type III (Vibrio vulnificus; seawater exposure)

Signs / Symptoms: pain out of proportion to exam (occasionally no pain at all), skin findings (blistering / bullae, gray-skin discoloration, or “Dishwater-like” discharge), or systemic toxicity (altered mental status, elevated lactate, etc.)

Diagnostic radiology

• Xray (shows gas); low sensitivity; CT scan (gas / tissue stranding); sensitivity is also low
• MRI can over-diagnose NSSTI and should not be used routinely
• Bedside ultrasound may demonstrate fluid or gas collections in deeper tissues (see clip below)

Treatment is emergent surgical debridement with simultaneous hemodynamic resuscitation PLUS broad-spectrum antibiotics; consider clindamycin becuase it has anti-toxin activity

Adjunctive therapies include Intravenous intraglobulin (neutralizes toxins secreted by bacteria) and hyperbaric oxygen

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Arterial Catheter-Related Blood Stream Infections

Whether arterial lines are a potential source of catheter-related blood stream infections (CRBSIs) is highly-debated; however, based on a recent systematic review they are an under recognized and significant source of CRBSIs.

• Incidence: In systematically cultured arterial catheters, the infection rate was 1.6 infections/1,000 catheter days which is similar to what has been reported for infections associated with short-term CVC's.
   
• Location: Femoral a-lines are more likely than radial a-lines to be a source of a CRBSI. Femoral a-line CRBSIs occurred in 1.5% of all catheters (95% CI, 0.8–2.2%), which is higher than radial CRBSI, with a relative risk of infection 1.94 times greater than those placed at the radial site.
   
• Technique: Only one study specifically evaluated the impact of full barrier precautions versus using sterile gloves only for peripheral a-lines, and it did not find any significant difference in BSI. No study has evaluated the impact of maximal barrier precautions for femoral, axillary, and brachial arterial catheters.
   
• Dressing: The risk of infection was significantly decreased with the use of chlorhexidine-impregnated dressings (ex: BioPatch).

Bottom Line(s) 

1. Arterial lines appear to be a significantly under recognized source of CRBSI's in critically-ill patients.  If you are deciding to place an a-line for invasive blood pressure monitoring, strongly consider the radial site and use a chlorhexidine sponge or dressing to try and minimize the risk of future BSI.
    
2. There is a paucity of data regarding the utility of maximal barrier techniques when inserting peripheral arterial lines.  With arterial catheter infection rates approaching that of central venous catheters, we should probably be inserting a-lines with the same sterile technique.

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Determination of Brain Death

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Attachments

• 1401141409_pitfalls_in_brain_death,_wijdicks.pdf (93 Kb)

Pearls for the Crashing LVAD Patient

• Left ventricular assist devices (LVAD) are placed as a bridge to transplant, bridge to recovery, or as destination therapy.
• As thousands of LVADs have been implanted, it is likely that a sick LVAD patient will show up in your ED or ICU.
• In addition to pump thrombosis (UMEM pearl 12/31/13), two complications to also consider in the crashing LVAD patient include infection and arrhythmias.
• Infection:
  • The driveline and pump pocket are the most common locations for device infection.
  • Most are caused by Staphylococcus and Enterococcus organisms.
  • For pump pocket and deeper wound infections be sure to also add coverage against Pseudomonas species. 
• Arryhthmias:
  • The highest incidence is within the first month after implantation.
  • Consider a "suction event," where the inflow cannula contacts the ventricular septum.
  • Suction events can be caused by hypovolemia, small ventricular size, or RV failure and are treated with fluid resuscitation and decreasing the LVAD speed.

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VAD thrombosis: A Must Know VAD Complication

The HeartMate left ventricular assist device (LVAD) is one of the most frequently placed LVADs today. Originally, it was thought to have a lower incidence of thrombosis due to its mechanical design. However, a recent multi-center study published in the NEJM reported a dramatic increase in the rate of thrombosis since 2011 in the HeartMate II device.  The report found:

• An increase in pump thrombosis at 3 months after implantation from 2.2% to 8.4%

• The median time from implantation to thrombosis was 18.6 months prior to March 2011, to 2.7 months after.

Pump thrombosis is a major cause of morbidity and mortality (up to almost 50%!!) and is a can't miss diagnosis.  It's important to keep thrombosis on the differential for any VAD patient presenting with:

• Power spikes or low pump flow alarms on the patient's control box

• Pump (VAD) failure

• Recurrent/new heart failure

• Altered mental status

• Hypotension (MAP < 65)

• Signs of peripheral emboli (including acute CVA)

Useful lab findings suggestive of thrombosis include:

• Evidence of hemolysis

• LDH > 1,500 mg/dL or 2.5-3 times the upper limit of normal

• Hemoglobinuria

• Elevated plasma free hemoglobin

Bottom Line: In the patient with suspected VAD thrombosis, it is important to contact the patient's VAD team immediately (CT surgeon, VAD coordinator/nurse, VAD engineer).  Treatment should begin with a continuous infusion of unfractionated heparin, while other treatment options can be discussed with the VAD team.

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The morbidity and mortality from pseudomonas aeruginosa infections is high and empiric double-antibiotic coverage (DAC) is sometimes given; quality evidence for this practice is lacking.

Although there is little supporting data, the following reasons have been given for DAC:

• DAC provides better empiric coverage through differing mechanisms of antibiotic action
• DAC prevents the emergence of antibiotic resistance during therapy

The potential harm of antibiotic overuse cannot be ignored, however, and include adverse reaction, microbial resistance, risk of super-infection with other organisms (e.g., Clostridium difficile), and cost.

There may be a signal in the literature demonstrating a survival benefit when using DAC for patients with shock, hospital-associated pneumonia, or neutropenia. The IDSA guidelines, however, do not support DAC for neutropenia alone; only with neutropenia plus pneumonia or gram-negative bacteremia.

Bottom line: Little data supports the routine use of DAC in presumed pseudomonal infection. It may be considered in patients with shock, hospital-associated pneumonia, or neutropenia (+/- pneumonia), but consult your hospital’s antibiogram or ID consultant for local practices.

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Hepatic Encephalopathy (HE)

Pathogenesis: Several theories exist that include accumulation of ammonia from the gut because of impaired hepatic clearance that can lead to accumulation of glutamine in brain astrocytes leading to swelling in patients with hepatic insufficiency from acute liver failure or cirrhosis.

Clinical Features:

• Impaired mental status
• impaired neuromotor function (hyperreflexia, hypertonicity, asterixis)
• Subtle signs include personality changes, decreased energy level, and impaired sleep-wake cycle

Diagnostic tests: Ammonia levels are routinely drawn but must be drawn correctly without the use of a tourniquet, transported on ice, and analyzed within 20 minutes to get an accurate result. Severity of HE does not correlate with increasing levels.

Management:

1.     Airway protection as needed

2.     Correct precipitating factors (GI bleed, infection-SBP, hypovolemia, renal failure)

3.     Consider neuro-imaging if new focal neurologic findings are found on exam

4.     Correct electrolyte imbalances

5.     Lactulose by mouth (PO/Naso-gastric tube or Rectally)

a.     10-30 g every 1-2 hours until bowel movement or lactulose enema (300 mL in 1 L water)

b.     Facilitates conversion of NH3 to NH4+, decreases survival of urease-producing bacteria in the gut

6.     Rifaximin 550 mg by mouth BID (minimally absorbed antibiotic with broad-spectrum activity)

7.     Do not limit protein intake acutely

8.     TIPS reduction in certain patients with recurrent HE

9.     Transplant referral as needed

10.  Consider other causes if patient does not improve within 24-48hrs. 

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The Concentrated Overview of Resuscitative Efforts (CORE) Scan

• Ultrasound has become an essential tool in the evaluation and management of the crashing patient.
• The CORE scan utilizes emergency bedside ultrasonography to systematically evaluate and resuscitate the rapidly deteriorating patient.
• Essentially steps in the CORE scan include:
  • Endotracheal tube assessment
  • Lung assessment
    • Pneumothorax?
    • Pleural effusion?
    • Hemothorax?
  • Cardiac assessment
    • Pericardial effusion?
    • Massive PE?
    • Estimated ejection fraction?
  • Aorta assessment
    • Abdominal aortic aneurysm?
    • Aortic dissection?
  • IVC assessment
  • Abdominal assessment
    • Intraperitoneal fluid?

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Vent Management: Finding the AutoPEEP!

OK, so we all know not to, "...Fall asleep on Auto-PEEP" thanks to Dr. Mallemat's pearl that can be seen here.  But now the question is, how do you know if your patient is air-trapping?

There are 3 ways you can look for evidence of Auto-PEEP on the ventilator:

1. Do an end-expiratory hold:  If the measured PEEP is more than the PEEP set on the vent after a 2-3 second hold, the difference is your Auto-PEEP.


2. Look at the expiratory flow waveform:  If the waveform does not return to baseline (still expiring when inspiratory ventilation occurs), there's Auto-PEEP!


3. Compare the inspiratory vs. expiratory volumes.  If the inspiratory volumes are much higher then the expiratory volumes, consider Auto-PEEP.

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The management of alcohol withdrawal syndrome (AWS) includes supportive care focusing on the ABC’s and administration of benzodiazepines (BDZ). 

While BDZ are effective in the treatment of AWS, some patients may require very high doses of BDZ to control symptoms (tachycardia, hypertension, diaphoresis, etc.); unfortunately, high-doses of BDZ may lead to suppression of the respiratory drive and endotracheal intubation.

Dexmedetomidine (DEX) is a sedative agent that is an intravenous alpha2-agonist (it's like clonidine); it reduces sympathetic outflow from the central nervous system and it may help treat withdrawal syndromes. The major benefit of DEX is that it does not suppress the respiratory drive, thus intubation is not required.

Smaller trials and case series have shown that patients with AWS who were treated with BDZ in addition to DEX had better symptom control, lower overall BDZ doses, and less respiratory depression/intubation.

Bottom-line: While more trials are needed, consider adding DEX for patients with AWS who require high-doses of BDZ.

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