Tuesday, June 26, 2018

Clinical Pearl 84: “Normal” Saline vs Balanced Solutions for Fluid Replacement Therapy

Peter Malamet DO

On a daily basis in the emergency care setting, we see patients that require fluid
replacement. From sepsis, diabetic ketoacidosis, dehydration, etc., we obtain intravenous
access and give a few boluses (along with the cocktail of antibiotics, insulin, or
vasopressors that is appropriate for the clinical scenario). However, disagreement exists as
to which type of fluid is best to use for replacement. This pearl aims to summarize the
current evidence comparing the most common crystalloid fluids - Normal Saline and
Lactated Ringers.

Intravenous fluids were first used in 1832 when Robert Lewens administered an
alkalized salt solution to patients with Cholera in an effort to replace lost serum.1 He noted
that the amount of fluids that patients needed appeared to be proportional to the amount
of fluids lost.1 In 1885, Alexis Hartman started giving a modified salt solution to children
with gastroenteritis.1 In 1941, Human Albumin was used as a resuscitative fluid for
patients burned during the Pearl Harbor attack.1 Since then, there have been multiple types
of fluids created in an attempt to replicate human plasma.

The ideal replacement fluid has a composition close to extracellular fluid, is
metabolized and excreted without accumulation, has no adverse effects and is cost
effective.1 Of course, this fluid does not exist. The two categories of fluids created to best
meet the aforementioned requirements are colloids and crystalloids.
Colloids are suspensions of molecules that do not cross a healthy capillary
membrane.1 Popular examples include Albumin and Hyperoncotic Startch.1 These fluids are
not widely used as they have not shown a clear benefit over crystalloids, are expensive and
can be harmful.1,2,3,4,5,6 For these reasons the rest of the discussion will focus on
crystalloids.

Crystalloids are the most frequently used fluids in resuscitation. They are made of
freely permeable ions, such as sodium and chloride, that determine tonicity.1,7 The two
most common types are 0.9% Normal Saline (NS) and Lactated Ringers (LR). These two
types of fluids in particular have been the subject of debate over many years.

Despite the name “normal”, 0.9% Normal Saline has a 10% higher sodium
concentration and 50% higher chloride concentration compared to human serum.7 It was
originally described by Jacob Hamburber, who carried out red blood cell lysis studies in the
early 1880s to determine that it was close to physiologic fluid.1,7 Today, we continue to call
0.9% NS “normal” based on in vitro studies from the 1880’s. The main argument against
normal saline is the adverse effect of a hyperchloremic metabolic acidosis.1,7 This can result
in organ dysfunction, and in particular, renal dysfunction.7

A proposed solution to the problems associated with 0.9% NS were the “Balanced”
or “Physiologic” crystalloid solutions, Lactacted Ringers (LR) or PlasmaLyte. These are
meant to have an electrolyte composition similar to that of human plasma.1,8 Lactated
Ringers are hypotonic to human plasma and also contain potassium, calcium and lactate.1
PlasmaLyte is also hypotonic and contains magnesium, acetate, gluconate without the
addition of lactate.1 For this discussion we will focus on LR, since it is commonly used in the
latest research.

Proponents of LR claim that it will help avoid the metabolic acidosis and renal injury
seen during large volumes of crystalloid infusion.8 However, large volumes of LR can cause
a metabolic alkalosis and hypotonicity.8 A common argument against the use of LR is the
theoretical risk of increasing the potassium level in a hyperkalemic patient. Studies have
shown this to not only be false, but in fact it is normal saline that has a greater risk of
causing hyperkalemia due to pH shifts.7,9,10 Furthermore, the lactate in LR has also been
shown to be beneficial. Research has shown that lactate is one of the preferred substrates
used by the body in energy crisis conditions, such as septic shock and acute heart failure.8,11
Until 2018, the best study comparing 0.9% Normal Saline and Balanced Solutions
was the SPLIT trial. Published in 2015, it was a prospective, blinded, cluster randomized,
crossover study performed in four New Zealand Intensive Care Units.12 Their primary
outcome was the proportion of patients with AKI.12 There were 2278 patients enrolled and
assigned to either buffered crystalloid or normal saline.12 This trial did not find any
significant difference in outcome between the two fluids. However, most patients were
admitted from surgery with only 316 of the patients coming from the Emergency
Department. Furthermore, on average, the study patients only received approximately 2
liters of crystalloid. 12

This year, 2018, delivered two articles that looked at balanced crystalloid versus
saline in critical and non-critical patients. The Isotonic Fluids and Major Adverse Renal
Events Trial (SMART) and the Saline Against Lactated Ringers or PlasmaLyte in the
Emergency Department (SALT-ED) are both large, single center, randomized trials looking
at the two types of fluids.13,14 The SMART trial studied a primary outcome of major adverse
kidney events within 30 days.13 Out of the more than 15,000 patients, there was a
statistically significant difference in these events, 14.3% vs 15.4% (Balanced Solution to
Normal Saline, respectively).13 The SALT-ED trial enrolled over 13,000 patients with a
primary outcome of hospital free days (which was not statistically significant) but did have
a secondary outcome of Major Adverse Kidney Events within 30 days, which was 4.7% vs
5.6% in favor of balanced solutions.14 It should be noted that the Major Adverse Kidney
Events within 30 days is a composite outcome. A composite outcome combines multiple
endpoints (in this case: death, initiation of Renal Replacement Therapy and persistent renal
dysfunction) and uses them as a primary outcome. This type of statistical analysis does add
some ambiguity to the results. Both trials do have some methodological flaws (non blinded,
single center, most patients receiving LR rather than Plasma-Lyte); however, it is some of
the highest quality of data we have at this point.

Based on the current data, it seems unlikely that the choice of NS vs. LR will have a
major effect on mortality. The data does seem to lean towards LR when it comes to
outcomes like acute kidney injury. LR will not cause a metabolic acidosis, has less chance of
renal injury, does not cause hyperkalemia and may have a benefit by way of the included
lactate. The difference in cost between the two is negligible and both are usually well
stocked. Therefore, this author would suggest that LR is likely the better choice for fluid
resuscitation, especially when using large volumes.

1. Myburgh, J. A., & Mythen, M. G. (2013). Resuscitation fluids. New England Journal of
Medicine, 369(13), 1243-1251.
2. Roberts I, Blackhall K, Alderson P, Bunn F, Schierhout G. Human albumin solution for
resuscitation and volume expansion in critically ill patients. Cochrane Database of Systematic
Reviews. 2011, Issue 11. Art. No.: CD001208. DOI: 10.1002/14651858.CD001208.pub4.
3. SAFE Study Investigators. "Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis." Intensive care medicine 37.1 (2011): 86-96.
4. Wiedermann, Christian J., et al. "Hyperoncotic colloids and acute kidney injury: a meta-analysis of randomized trials." Critical Care 14.5 (2010): R191.
5. Mutter TC, Ruth CA, Dart AB. Hydroxyethyl starch (HES) versus other fluid therapies: effects on
kidney function. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD007594.
DOI: 10.1002/14651858.CD007594.pub3
6. Gattas, David J., et al. "Fluid resuscitation with 6% hydroxyethyl starch (130/0.4 and 130/0.42) in acutely ill patients: systematic review of effects on mortality and treatment with renal replacement therapy." Intensive care medicine 39.4 (2013): 558-568.
7. Li H, Sun S, Yap JQ, Chen J, Qian Q. 0.9% saline is neither normal nor physiological. Journal of
Zhejiang University Science B. 2016;17(3):181-187. doi:10.1631/jzus.B1500201.
8. Ichai, Carole, Jean-Christophe Orban, and Eric Fontaine. "Sodium lactate for fluid resuscitation:
the preferred solution for the coming decades?." Critical Care 18.4 (2014): 163.
9. Khajavi, Mohammad Reza, et al. "Effects of normal saline vs. lactated ringer's during renal
transplantation." Renal failure30.5 (2008): 535-539.
10. Modi, Manisha P., et al. "A comparative study of impact of infusion of Ringer's Lactate solution
versus normal saline on acid-base balance and serum electrolytes during live related renal
transplantation." Saudi Journal of Kidney Diseases and Transplantation 23.1 (2012): 135.
11. Nalos, Marek, et al. "Half-molar sodium lactate infusion improves cardiac performance in acute
heart failure: a pilot randomised controlled clinical trial." Critical Care 18.2 (2014): R48.
12. Young, Paul, et al. "Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial." Jama 314.16 (2015): 1701- 1710.
13. Semler, Matthew W., et al. "Balanced crystalloids versus saline in critically ill adults." New England Journal of Medicine378.9 (2018): 829-839.
14. Self, Wesley H., et al. "Balanced crystalloids versus saline in noncritically ill adults." New England Journal of Medicine378.9 (2018): 819-828

Monday, March 12, 2018

Clinical Pearl 82: The DAWN STUDY-A New Error In Acute Stroke Mangement. Rick Figurasin M.D.



A patient presents with stroke like symptoms in the prehospital setting.  Patient was last seen normal about 3.5 hours ago.  Prior to that, family state patient was in his usual state of health - ambulating, conversing - without any difficulty.  You perform a quick assessment His medical history is significant for HTN, DM, and hypercholesterolemia.  Blood sugar is 194.  BP is 195/89 with a HR of 97.  The closest primary stroke center is 20 minutes away.  The closest comprehensive stroke center is 45 minutes away.  To make matters worse, a snowstorm is occurring which potentially will further delay transport.  Where do you take him?

According to the Centers for Disease Control and Prevention (CDC), stroke is a major cause of disability in the United States, with approximately 795,000 adults suffering each year [9].  With therapeutic options such as tissue plasminogen activator (tPA) and endovascular therapy, stroke is treatable - given certain inclusion criteria.  The initial National Institute of Neurologic Disorders and Stroke (NINDS) study (1995) found improvement in NIH Stroke Scale if tPA was given within 3 hours of symptom onset [8].  The results of the ECASS III trial (2008) extended the benefit to 4.5 hours [4].  In 2015 alone, multiple clinical trials (MR CLEAN January 2015, EXTEND-IA February 2015, ESCAPE March 2015, Swift Prime June 2015) found a reduction in disability when endovascular therapy was performed within 6 hours of onset of symptoms [1, 2, 3, 12].  At present, acute stroke care is treated on a time-based selection.  When patients exceed the time of symptom onset criteria (4.5 hours for tPA, 6 hours for endovascular therapy), these interventions are not available and the patient is left to suffer the natural progression of the disease.

The recently published DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) trial revealed a significant improvement in functional independence and disability at 90 days for patients who underwent mechanical thrombectomy for large vessel occlusions despite presenting >6 hours after onset of symptoms.  The study found benefit of treatment up to 24 hours with the median patient presentation being 12 hours [10].  With the possibility of endovascular therapy, patients ideally should be brought to a center that can perform such an intervention. 

But should you delay transport to get a patient to a comprehensive stroke center where mechanical thrombectomy can be performed?

Ideally you should get a patient to a center that has all the capabilities of performing stroke management and treatment.  The DAWN Trial only applies to patients with large vessel occlusions.  The only option for patients without a large vessel occlusion is tPA, which remains a time-based treatment option.  Because of this, patients should be transferred to the nearest primary stroke center, especially if time and distance are critical factors.

So you identify a patient with a stroke.  How good are prehospital stroke assessments in identifying large vessel occlusions anyway? 

A retrospective study in Berlin of 3,505 stroke patients (827 of which had a large anterior vessel occlusion) analyzed the various prehospital scoring scales: FAST, GFAST, C-STAT, PASS, and RACE.  The authors concluded that prehospital scoring systems performed similar, if not better, when compared to the NIH stroke scale (in patients with a score >= 6) for identifying large vessel occlusions (sensitivities over 90%) [13].


With an expanded time frame and potential for mechanical thrombectomy, should you then perform a CTA/CT perfusion study on all patients presenting to the ED with a stroke?

You will see arguments for both doing and not doing CTA/CT perfusion, with the biggest detractors citing increased radiation, costs, and contrast induced nephropathy.  Several studies have shown contrast induced nephropathy is minimal [5, 6, 7, 11].  Regarding radiation and costs, this can pale in comparison to a lifetime of disability.  This may be beneficial especially to patients who present with a high NIH stroke score who are outside the window for tPA. As with all things in medicine, a risk versus benefit analysis should be performed to ensure that the benefits outweigh the risks.

Ultimately, what does all this mean?
It is important to remain current on stroke literature to recognize that an intervention exists for patients who present outside the traditional stroke window of 4.5 hours (tPA) or 6 hours (endovascular therapy). The DAWN study provides evidence that the treatment window can be extended up to 24 hours. If a large vessel occlusion can be identified, or is suggested based on prehospital scoring tools, patients should be transported to a comprehensive stroke center (time and distance permitting). Also, seeing how contrast induced nephropathy is a minimal risk, it seems beneficial to get a CTA/CT perfusion study on stroke patients with large deficits, especially if they present outside the traditional treatment window.


REFERENCES:
[1] Berkhemer OA, et al. "A randomized trial of intraarterial treatment for acute ischemic stroke". The New England Journal of Medicine. 2015. 372(1):11-20.

[2] Campbell et al. “Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection.” N Engl J Med 2015 Mar 12;372(11):1009-18.

[3] Goyal M et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016. 387:1723-31.

[4] Hacke W, et al. "Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke". The New England Journal of Medicine. 2008. 359(13):1317-1329.

[5] Hopyan JJ, et al.  Renal safety of CT angiography and perfusion imaging in the emergency evaluation of acute stroke.”  Am J Neuroradiol. 2008 Nov; 29(10):1826-30.

[6] Krol AL, et al.  “Incidence of radiocontrast nephropathy in patients undergoing acute stroke computed tomography angiography.”  Stroke. 2007 Aug; 38(8):2364-6.

[7] Lima FO, et al.  “Functional contrast-enhanced CT for evaluation of acute ischemic stroke does not increase the risk of contrast-induced nephropathy.”  Am J Neuroradiol. 2010 May; 31(5):817-21.

[8] Marler JR, et al. "Tissue Plasminogen Activator for Acute Ischemic Stroke". The New England Journal of Medicine. 1995. 333(24):1581-1587.

[9] Mozzafarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al.  “Heart disease and stroke statistics—2016 update: a report from the American Heart Association.” Circulation 2016;133(4):e38–360.

[10] Nogueira, R.G., et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct.” The New England Journal of Medicine, vol. 378, no. 11-21, 4 Jan. 2018, doi:10.1056/NEJMoa1706442.

[11] Oleinik A, et al. “CT angiography for intracerebral hemorrhage does not increase risk of acute nephropathy.”  Stroke. 2009 Jul; 40(7):2393-7.

[12] Saver JL, et al. "Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke". The New England Journal of Medicine. 2015. 372(24):2285-2295.

[13] Scheitz, Jan F, et al. “Clinical Selection Strategies to Identify Ischemic Stroke Patients With Large Anterior Vessel Occlusion.” Stroke, vol. 48, 2017, doi:10.1161/STROKEAHA.116.014431.

Tuesday, January 23, 2018

Clinical Pearl 81: What Is The Best Location for Needle Decompression of a Pneumothorax

Case: A 58 year-old male who was the restrained driver of a vehicle struck on the
driver’s side with no LOC, no airbag deployment and no other injured parties. The
patient is complaining of shortness of breath and left sided chest pain. The patient
appears to be in mild respiratory distress on arrival. During the history and while
obtaining vitals the man becomes increasingly short of breath and anxious appearing.
Initial vitals: HR: 101bpm, RR: 20, SpO2: 98% and BP: 125/80. During your physical
exam decreased breath sounds are appreciated over the left chest and no bleeding,
ecchymosis or deformities are noted. You now appreciate moderate retractions with
his inspirations, JVD, a distended left chest wall and tracheal deviation to the right
with repeat vitals: HR: 135bpm, RR: 28, SpO2: 94% and BP: 95/70.

The current Advanced Trauma Life Support (ATLS) guidelines for tension
pneumothorax recommend needle thoracostomy (NT) with a 5cm angiocatheter at
the second intercostal space (ICS2) in the midclavicular line (MCL) over the affected
side of the chest (1).

Over the past couple of decades the US military has made identifying preventable
causes of death a priority and identified tension pneumothorax as the second
leading cause of preventable death in combat behind hemorrhage from isolated limb
loss. Due to the identification of being a major cause of preventable casualties in
combat, research has been advancing on the subject of tension pneumothorax(2-4).
Research has shown that a 5cm angiocatheter may not be of adequate length to
reach the pleural space and that the ICS2-MCL may not be the best location for
needle decompression (5-8).

Studies in both civilian and military populations have shown that using a 5cm
angiocatheter results in only a 50-75% success rate in gaining access to the pleural
cavity (5,6). Autopsy studies conducted by the military in service members
demonstrated an angiocatheter of at least 8cm to penetrate the chest wall and gain
access to the pleural cavity with a 99% success rate (6,7). This need in the military
population for longer angiocatheters to increase the success rate of entering the
pleural cavity can easily be translated to the civilian population where treatment
guidelines must include all body habitus types in a population. Studies utilizing
computed tomography have shown that the area of minimal chest wall thickness to
be the fourth or fifth intercostal space (ICS4/5) at the anterior axillary line (AAL) (8).
Studies have also shown higher success rates and fewer complications utilizing the
ICS4/5-AAL when compared to the ICS2-MCL for NT (8). There may also be a
decreased chance of lung injury at the ICS4/5-AAL as compared to the ICS2-MCL
because a Pneumothorax would have to be very large to have the airspace make it
all the way to the ICS2-MCL. Although air in the pleural space from a pneumothorax
can collect anteriorly to the lung, laterally or both.

We currently recommend a 14 or 16 gauge 8cm (3.15 inch) angiocatheter at the
ICS4/5-AAL inserted perpendicular to the skin for needle decompression in
pneumothorax.
.
References:

1. American College of Surgeons. Advanced Trauma Life Support ATLS Student Course Manual. The ninth edition. 2012; 119.

2. McPherson JJ, Feigin DS, Bellamy RF. Prevalence of tension pneumothorax in fatally wounded combat casualties. J Trauma. 2006;60:573-8.

3. Holcomb JB, McMullen NR, Pearse LA, et al. Causes of death in Special Operations Forces in the Global War on Terror. Ann Surg. 2007;245:986-91.

4. Mark AC, Wimberger N, Sztajnkrycer MD. Incidence of tension pneumothorax in police officers feloniously killed in the line of duty: a ten-year retrospective analysis. Prehosp Disaster Med. 2012 Feb;27(1):94-7.

5. Givens ML, Ayotte K, Manifold C. Needle thoracostomy: implications of computed tomography chest wall thickness. Acad Emerg Med. 2004 Feb;11(2):211-3.

6. Harcke HT, Pearse LA, Levy AD, Getz JM, Robinson SR. Chest wall thickness in military personnel: implications for needle thoracentesis in tension pneumothorax. Mil Med. 2007 Dec;172(12):1260-3.

7. Clemency BM, Tanski CT, Rosenberg M, May PR, Consiglio JD, Lindstrom HA. Sufficient catheter length for pneumothorax needle decompression: a meta-analysis. Prehosp Disaster Med. 2015 Jun;30(3):249-53.

8. Laan DV, Vu TD, Thiels CA, Pandian TK, Schiller HJ, Murad MH, Aho JM. Chest wall thickness and decompression failure: A systematic review and meta-analysis comparing anatomic locations in needle thoracostomy. Injury. 2016 Apr;47(4):797-804.

Monday, December 4, 2017

Clinical Pearl 80: Does Albuterol help in Bronchiolitis?


An 11 month old male is having difficulty breathing. The baby appears comfortable but with intercoastal retractions, and nasal congestion. His RR is 42 bmp,  SpO2 is 93% on RA, HR is 120bpm. He has wheezing throughout both lung fields and mother tells you that this is his 4th day with this symptoms. Would Albuterol be your next step in treatment?

The scenario clearly shows a child that meets criteria for bronchiolitis; for years we’ve been trying to figure out what can we do to make this patient better, and for years bronchodilators have been one of the first line treatments, but does it really work?

Scribani MB et al. (Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2014.) suggests that bronchodilators may provide modest short-term clinical improvement but do not affect overall outcome, may have adverse effects, and increase the cost of care. This is a meta-analysis of randomized trials and systematic reviews that included 30 trials representing 1992 infants with bronchiolitis. It demonstrated that oxygen saturation did not improve with bronchodilators. Outpatient bronchodilator treatment did not reduce the rate of hospitalization, and inpatient bronchodilator treatment did not reduced length of stay in the hospital. The clinical score and oximetry outcome showed significant heterogeneity with questionable clinical importance. Multiple adverse effects where recorded such as tachycardia, oxygen desaturation and tremors. The review concluded that given the adverse side effects and the expense associated with these treatments, bronchodilators are not effective in the routine management of bronchiolitis.

Per American Academy of Pediatrics most recent guidelines (Ralston SL, Lieberthal AS, Meissner HC, et al. Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis. Pediatrics. 2014) Clinicians should not administer albuterol or epinephrine to infants and children with a diagnosis of bronchiolitis (Evidence Quality: B; Recommendation Strength: Strong Recommendation)

But, should I at least try it?

A one-time trial of inhaled bronchodilators (albuterol or epinephrine) may be warranted for infants and children with bronchiolitis and severe disease, as this group generally was excluded from trials evaluating inhaled bronchodilators in children with bronchiolitis.

In addition, a subset of young children with the clinical syndrome of bronchiolitis may have virus-induced wheezing or asthma and may benefit from inhaled bronchodilator therapy. In a prospective multicenter study by Jonathan M. Mansbach et al. (Children hospitalized with rhinovirus bronchiolitis have asthma-like characteristics. J Pediatr. 2016 May) of children hospitalized with bronchiolitis, children with rhinovirus-associated bronchiolitis were more likely than those with respiratory syncytial virus-associated bronchiolitis to respond to bronchodilators as they present similar to asthmatic patients, and are usually excluded from other studies as it is more common on patients >12 months of age. 

In conclusion, after reviewing the available literature, the use of albuterol in patients with bronchiolitis might be attempted once and evaluate for response, but if no desirable response, the continued use of bronchodilators will only increase side effects and cost with no added benefit, and will give wrong reassurance to parents that there is an effective treatment for Bronchiolitis besides letting the disease run its course.