All posts by Cynthia Santos

Toxcards: Alcohol Ketoacidosis

Author: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

Case Presentation:

A 45 year old male presents intoxicated, smelling of alcohol and appears disheveled with vomit on his clothes. He is sleepy but arousable to noxious stimuli. His serum ethanol level is 143 mg/dL. Na 135, K 3.9, Cl 97, CO2 20, BUN 33, Cr 1.1. Lactate 3.1. pH 7.35, CO2 28, HCO3 15. His urine is negative for ketones. His vitals are HR 103, RR 30, BP 115/65, O2 98% RA.



Could these laboratory results be consistent with alcohol ketoacidosis (AKA)?


The classic laboratory findings in patients with AKA include an elevated anion gap metabolic acidosis and an elevated lactate. Early in AKA patients may be negative for ketones when the nitroprusside test is used because it does not detect beta-hydroxybutyrate. As patients recover, the nitroprusside test will become positive as beta-hydroxybutyrate gets converted to acetone and acetate.

Acid/base status:

  • Patients with AKA typically have elevated anion gap metabolic acidosis. However, vomiting may cause a primary metabolic alkalosis and a compensatory respiratory alkalosis which may result in a normal or even elevated pH.
  • AKA patients, as compared to DKA patients, typically have higher pH, lower K and Cl, and higher HCO3 in their blood tests.

High Redox State (Excess NADH):

  • As ethanol is metabolized by ADH and ALDH to acetaldehyde and acetate, respectively, an increased amount of NADH forms which causes a high redox state and excess of reducing potential (increased NADH:NAD+ ratio).

ethanol pathway

Increased lactate due to pyruvate shunting:

  • Reduced caloric intake, decreased glycogen stores, and thiamine depletion results in amino acids being converted to pyruvate. The excess pyruvate that forms can then be diverted to gluconeogenesis, be converted to acetyl-CoA, which can enter the Kreb’s cycle, or can enter various biosynthetic pathways (e.g. fatty acids, ketones, etc.). Pyruvate can be diverted to these pathways if there is sufficient NAD+.
  • However ethanol causes a high redox state (excess NADH). In the setting of a high redox state ethanol results in increased lactate due to the conversion of pyruvate to lactate and diverts pyruvate from gluconeogenesis.
pyruvate to lactate

Figure source: Shull P, & Rapoport J.

Anion gap primarily due to beta-hydroxybutyrate:

  • The primary anion contributor in patients with AKA and diabetic ketoacidosis (DKA) is beta-hydroxybutyrate with lactate having less of a role.
  • Decreased caloric intake and glycogen stores results in increased fatty acid mobilization and oxidation resulting in increased acetyl-CoA. In normal states (when there is sufficient NAD+) acetyl-CoA can then enter the Kreb’s cycle or be used in fatty acid synthesis. Thiamine also facilitates the entry of acetyl-CoA into the Kreb’s cycle.
  • However, when there is a high redox state (excess NADH) and thiamine deficiency acetyl-CoA gets converted to acetoacetate which then gets converted to beta-hydroxybutyrate.

ketone production

Ketone production:

  • Early the main anion contributor is beta-hydroxybutyrate, which is not detected well by the nitroprusside test (used to detect ketones in serum and urine). The nitroprusside test does not detect beta-hydroxybutyrate, although it is good for detecting acetoacetate and acetone.
  • It is common for early AKA to have a falsely negative ketone test if the nitroprusside test is used because of the test’s inability to detect beta-hydroxybutyrate. If available, specific assays for beta-hydroxybutyrate should be done.
  • As patients recover and receive glucose and thiamine supplementation, ATP is made which reverses the pyruvate-to- lactate and NAD+-to-NADH ratios.  This allows beta-hydroxybutyrate to be converted to acetoacetate and as patients recover the nitroprusside test will actually become more positive due to the increased production of acetoacetate.

ketone body ratio in alcoholic ketoacidosis

Figure Source:

Main Point:

The classic laboratory findings in patients with AKA include an elevated anion gap metabolic acidosis, and elevated lactate that is insufficient to account for the gap. The main anion contributor early in AKA is beta-hydroxybutyrate, but it will not be detected when evaluating for ketones using the nitroprusside test. As patients recover and are given glucose and thiamine supplementation, the lactate will decrease as pyruvate is no longer shunted to lactate and instead enters the Kreb’s cycle and other biosynthetic pathways. The anion gap decreases as beta-hydroxybutyrate gets converted to acetone and acetate. The nitroprusside test then becomes positive for ketones later as patients recover.

  1. Yip L. Ethanol, Chapter in Goldfrank’s Toxicological Emergencies. Tenth Edition. Editors: Hoffman R, Howland M, Lewin N, Nelson L, Goldfrank L. McGraw Hill (2015); New York.
  2. Woods W, Perrina D. Alcohol Ketoacidosis, Chapter in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th Edition. Editors: Tintinalli JE, et al. McGraw Hill (2011); New York.
  3. Shull P, & Rapoport J. Life-threatening reversible acidosis caused by alcohol abuse. Nature Reviews Nephrology (2010) 6, 555-559
  4. Diabetic, Alcoholic, and Starvation Ketoacidosis. Chapter 6.17. Available at:

Limitations of CIWA score

Author: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


Case Presentation:

You are working a busy ED shift and are also managing a handful of boarded patients admitted to your ICU. Nursing resources are especially strained today. One of your intubated patients that you admitted for alcohol withdrawal starts having a seizure. His vitals are T 101F, HR 135, BP 175/100, RR 16, O2 sat 89% on 40% O2.


What are some of the limitations of using the CIWA score?


Although the CIWA score is a widely cited example of symptom-triggered therapy it has several important limitations and can be difficult to properly execute in the emergency department setting.

  • Symptom-triggered treatment for alcohol withdrawal using the CIWA score has many benefits including reduced progression to mechanical ventilation requirement, 4-fold decrease in benzodiazepine requirements, shorter duration of treatment, and shorter hospitalization stays by 2 days when compared to fixed-dosing scheduling.(1)
  • However, an important clinical limitation of CIWA as a tool to assess alcohol withdrawal is that it does not incorporate vital sign assessment, which can be an important and sometimes the only clue available in recognizing inappropriately treated DT patients.(2)
  • The CIWA score also does not address choice of benzodiazepines, frequency of administration, use of adjuvant medications and underlying medical conditions (renal failure, liver failure, respiratory failure, cardiac disease, age, etc.) in treating withdrawal.(2)
  • The CIWA score requires patients to be able to respond to questions and follow commands. This can be difficult in patients with language barriers, altered mental status or who are intubated.(2)
    • For example “Do you feel sick to your stomach, have you vomited?”; “Do you have any itching, pins-and-needles sensations, burnings, or numbness…?” and “Are you seeing anything that is disturbing you?” are some questions asked.
  • Many of the studies that have evaluated CIWA have excluded patients with seizures, which is an important sign of severe withdrawal and should be taken into consideration.(3)
  • Moreover, the CIWA score can be especially difficult to execute properly without adequate nursing staff. Many busy EDs are often understaffed and have limited nursing resources. Thorough staff training is required to appropriate use CIWA.(2) Studies have shown that the CIWA score tends to be administered irregularly by nursing staff, often used for patients who are not appropriate for symptom-guided treatment and can have a higher proportion of protocol errors.(4)
  • Scoring systems are important for symptom-triggered therapy and provide the ability for comparison analysis in clinical trials. However, many other scoring systems exist. An example is the Richmond Agitation Sedation Scale (RASS), which is observer based.(5) Many hospitals have their own scoring systems as well.
Main point:

Symptom triggered therapy has been shown to have better outcomes than fixed benzodiazepine scheduling in managing alcohol withdrawal. The CIWA score is a widely cited method of using symptom triggered therapy. However, physicians should not rely on just the CIWA score and other hospital and research protocols exist. The CIWA score has several important limitations including the exclusion of vital signs as an assessment, reliance of the patient’s ability to answer questions and follow commands, and can be time consuming in a busy ED environment.

  1. Daeppen J, Gache P, Landry U, et al. Symptom-triggered vs fixed-schedule doses of benzodiazepines for alcohol withdrawal. JAMA. 2002;162(10):1117-1121.
  2. Sankoff J, Taub J, Mintzer D. American College of Medical Quality: Accomplishing much in a short time: use of a rapid improvement event to redesign the assessment and treatment of patients with alcohol withdrawal. Am J Med Qual. 2013; 28(2):95-102.
  3. Saitz R, Mayo-Smith MF, Roberts MS, Redmond HA, Bernard DR, Calkins DR. Individualized treatment for alcohol withdrawal: a randomized double-blind controlled trial. JAMA. 1994;272:519-523.
  4. Hecksel KA, Bostwick JM, Jaeger TM, Cha SS. Inappropriate use of symptom-triggered therapy for alcohol withdrawal in the general hospital. Mayo Clin Proc. 2008;83:274-279. 10.
  5. Sessler CN. The Richmond Agitation-Sedation Scale” validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002; 166:1338-1344.

Tox Cards: Narcan (naloxone)

Author: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


Case presentation:

25-year-old M brought in by EMS after being found not breathing, pupils are pinpoint. HR 61, BP 109/40, RR 6, T98, O2 Sat 70% RA. You ask for Narcan (Naloxone).


What dose Narcan should you give?


Start with small doses, i.e. 0.04 mg, and not the standard dose of 0.4 mg IV/IM.

  • The use of copious amounts of naloxone can precipitate opioid withdrawal.
  • Precipitated opioid withdrawal to an opioid-dependent person does not only cause patient distress and complicate care, but it can be life threatening.
  • Patients with precipitated opioid withdrawal (unlike regular opioid withdrawal) are at risk of seizures and arrhythmias.
  • The often referenced ‘standard dose’ and the dose usually given by EMS is 0.4 mg via the IV or IM route.
  • Although this ‘standard dose’ will reverse opioid-induced respiratory depressant effects in non-opioid-dependent patients, it can precipitate withdrawal in opioid-dependent persons.
  • Life-threatening complications like tonic-clonic seizure, and significant hypotension have occurred with IV/IM doses of 0.2 mg – 1.2 mg.[1, 2, 3]
  • Although severe life-threatening reactions after naloxone administration are relatively rare, it usually occurs when the ‘standard’ naloxone dose of 0.4mg IV/IM is given.

 Main Point:

Naloxone can be lifesaving. However, given the high prevalence of opioid addiction and the rare but potentially dangerous complication of precipitated opioid withdrawal, the use of initial small escalating doses of naloxone can avoid the development of precipitated opioid withdrawal. An appropriate strategy is to start with 0.04 mg and titrate up every 2-3 minutes as needed for ventilation to 0.5 mg, 2 mg, 5 mg, up to a maximum of 10-15 mg.[4, 5]



  1. Buajordet I., Næss A., Jacobsen D., Brørs O. Adverse events after naloxone treatment of episodes of suspected acute opioid overdose. Eur J Emerg Med. 2004;11: 19–23.
  2. Osterwalder J. Naloxone – for intoxications with intravenous heroin and heroin mixtures – harmless of hazardous? A prospective clinical study. Clin Toxicol. 1996;34: 409–416.
  3. Yealy DM, Paris PM, Kaplan RM, Heller MB, Marini SE. The safety of prehospital naloxone administration by paramedics. Ann Emerg Med. 1990; 19(8): 902-5.
  4. Boyer EW: Management of opioid analgesic overdose. N Engl J Med. 2012; 367:146-155).
  5. Kim HK, Nelson LS. Reversal of Opioid-Induced Ventilatory Depression Using Low-Dose Naloxone (0.04 mg): a Case Series. J Med Toxicol. 2016; 12(1):107-10.



Beta Blockers in Sepsis

General Info/Intro

  • In septic shock tachycardia is associated with adverse outcomes. Traditional teaching tells us to treat the root cause of sinus tachycardia, whether it is fever, hypoxia, hypotension, dehydration, pain, or anxiety.
  • The use of β-blockers in sepsis seems counterintuitive but some recent studies have shown that in patients with severe sepsis it may be beneficial.
  • Beta blockers may have a role in attenuating the deleterious effects of β-adrenergic stimulation in septic shock. Beta blockers may also increase microvascular circulation.
  • Beta blockers are not typically used in septic shock because physicians fear their negative inotropic and hypotensive effects in patients with already low blood pressures.


  • A recent randomized clinical study published in JAMA by Morelli et al in a cohort of 77 septic shock patients showed that “use of esmolol after initial hemodynamic optimization resulted in maintenance of heart rate within the target range of 80/min to 94/min. Compared with standard treatment, esmolol also increased stroke volume, maintained MAP, and reduced norepinephrine requirements without increasing the need of inotropic support or causing adverse effects on organ function. There was an associated improvement in 28-day survival.”
  • The primary outcome in the Morelli et al study was heart rate, while the secondary outcomes were hemodynamic and organ function measures; norepinephrine dosages at 24, 48, 72, and 96 hours; and adverse events and mortality occurring within 28 days after randomization. As for any conclusions obtained from any secondary outcomes, the benefit of β-blockers on hemodynamics, organ preservation, norepinephrine requirements, and mortality should be further investigated before it becomes routinely used.
  • Whether β-blockers have a role in the emergency department setting is unclear. The study above was done in a cohort of patients in an ICU setting that were already stabilized after 24 hours. Patients were enrolled after 24 hours once they were deemed hemodynamically optimized, which was defined as having a pulmonary artery pressure of ≥ 12 mm Hg and central venous pressures of ≥ 8 mm Hg.
  • Another study published by Balik et al showed that the use of esmolol did not result in a significant change in norepinephrine requirements or lactate levels. This study was done in ten septic patients. There was a significant decrease in heart rate and the stroke volume was insignificantly increased. The authors concluded that the use of beta-blockade was cardioprotective in septic shock patients with high cardiac output.
  • The importance of the β receptors in septic shock is not entirely new. In the late 1960s, Berk published an article entitled “the treatment of endotoxin shock by beta adrenergic blockade.” This study was done in dogs that were injected with E. coli. The dogs were divided in several groups 1) no treatment 2) fluids, sodium bicarb, calcium, atropine intermittently to maintain hemodynamics AND propranolol 3) same as group 2 but without propranolol.
  • The dogs did better with fluids and propranolol, the group 3 dogs needed twice as much fluids as the group 2 dogs but all the dogs were still sacrificed after 72 hours anyways. The post-mortem analysis of group 2 dogs showed less organ damage than the other groups.


Bottom Line/Pearls & Pitfalls

  • Excessive adrenergic stimulation in septic patients can result in poor outcomes through direct autonomic dysfunction, myocardial damage, vascular shock, insulin resistance, and increased susceptibility to infection and thrombus formation.
  • Tachycardia can be an indicator of excessive adrenergic stress in a septic patient. High plasma catecholamine levels, the use of pressor therapy, and tachycardia are all independently associated with poor outcomes in critically ill patients.
  • Beta blockers may improve hemodynamics, organ preservation, pressor requirements, and mortality, but should be further investigated before it becomes routinely used!!
  • Although counterintuitive to our traditional approach to treating sinus tachycardia, β-blockers may have a role in septic patients once you have stabilized using your standard approach to sepsis.  Although, it is probably not wise to use β blockers on your crashing sepsis patient who recently arrived to your ED, who would benefit more from generous fluids, antibiotics, airway management, and pressors.

Further Reading

Edited by Alex Koyfman

Airway Subtleties in Critically Ill Patients

Airway Subtleties in Critically Ill Patients: Salicylate Poisoning, Hypotensive/Septic, and Obtunded DKA

‘Fish in the oropharynx.’ Sim training on Kangaroo Island, rural Australia via Reposted with permission (thanks!).

Salicylate-Poisoned Patients

When salicylate-poisoned patients are ventilated using standard settings you may harm your patients by diminishing the respiratory alkalosis, which facilitates the passage of salicylate into the CNS. Also the use of sedatives and paralytics can result in CO2 retention and respiratory acidosis, which can further facilitate the shift of salicylate into the CNS.

Because of this many toxicologists believe that intubation should be avoided if possible and performed only if the patient has true respiratory failure (worsening acidosis, hypoxemia). Endotracheal intubation and mechanical ventilation can be associated with rapid worsening of clinical salicylate toxicity and increased mortality unless a normal or slightly alkalemic blood pH is maintained via hyperventilation and achievement of a low PCO2 and/or intravenous sodium bicarbonate.

The following are recommendations for salicylate-poisoned patients based on a retrospective case series using the New York City Poison Control Center (NYCPCC) database for cases of salicylate poisoning, defined as a peak serum concentration >50 mg/dL, who had mechanical ventilation:

  • Avoid intubation if possible. Intubation should only be performed if patient truly has respiratory failure (worsening acidosis, hypoxemia).
  • Ensure that alkalinization of plasma and urine are initiated early and prior to intubation if possible.
  • Avoid paralytics and high doses of sedatives during rapid sequence intubation. Try to minimize the time that patient’s ventilatory drive is compromised.
  • Place an arterial line for frequent blood gas monitoring.
  • Frequent blood gas monitoring to ensure that an appropriately high minute ventilation is achieved. The goal is to maintain an arterial pH of 7.5–7.6.
  • Consider pressure-controlled ventilation. Adjust the rate to obtain the desired minute ventilation. This will allow delivery of maximal tidal volumes while controlling peak airway pressures. Any mode can be used as long as physiologic goals are being met. Adjust the settings based on the arterial blood gas to achieve goal pH.
  • Monitor closely for ‘‘breath-stacking’’ and ventilator asynchrony due to tachypnea.
  • Collaboration with intensivist recommended.

Further Reading

  1. American College of Medical Toxicology, Guidance Document: Management Priorities in Salicylate Toxicity, Available at:
  2. Stolbach AI, Hoffman RS, Nelson LS. Mechanical ventilation was associated with acidemia in a case series of salicylate-poisoned patients. Acad Emerg Med 2008;15(9):866-9.

Sepsis-Induced ARDS

Sepsis is the leading cause of death in U.S. hospitals, affecting 750,000 Americans and killing between 28 and 50 percent of those people each year. Managing the airway and ventilation settings in a patient with sepsis-induced ARDS can be challenging. The following are guidelines from the Surviving Sepsis Campaign, a joint collaboration of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine committed to reducing mortality from severe sepsis and septic shock worldwide.

Mechanical Ventilation

  • Target a tidal volume of 6 mL/kg predicted body weight in patients with sepsis-induced ARDS (grade 1A vs. 12 mL/kg).
  • Plateau pressures should be measured in patients with ARDS and initial upper limit goal in a passively inflated lung be ≤ 30 cm H2O (grade 1B).
  • Positive end-expiratory pressure (PEEP) should be applied to avoid alveolar collapse at end expiration (atelectotrauma) (grade 1B).
  • Strategies based on higher rather than lower levels of PEEP should be used for patients with sepsis-induced moderate or severe ARDS (grade 2C).
  • Recruitment maneuvers should be used in sepsis patients with severe refractory hypoxemia (grade 2C).
  • Prone positioning should be used in sepsis-induced ARDS patients with a PaO2/FiO2 ratio ≤100 mm Hg in facilities that have experience with such practices (grade 2B).
  • Mechanically ventilated sepsis patients should be maintained with the head of the bed elevated to 30-45 degrees to limit aspiration risk and to prevent the development of ventilator-associated pneumonia (grade 1B).
  • Noninvasive mask ventilation (NIV) should be used in that minority of sepsis-induced ARDS patients in whom the benefits of NIV have been carefully considered and are thought to outweigh the risks (grade 2B).
  • A weaning protocol should be in place and that mechanically ventilated patients with severe sepsis undergo spontaneous breathing trials regularly to evaluate the ability to discontinue mechanical ventilation when they satisfy the following criteria: a) arousable; b) hemodynamically stable (without vasopressor agents); c) no new potentially serious conditions; d) low ventilator and end-expiratory pressure requirements; and e) low FiO2 requirements which can be met safely delivered with a face mask or nasal cannula. If the spontaneous breathing trial is successful, consideration should be given for extubation (grade 1A).
  • Against the routine use of the pulmonary artery catheter for patients with sepsis-induced ARDS (grade 1A).
  • A conservative rather than liberal fluid strategy for patients with established sepsis-induced ARDS who do not have evidence of tissue hypoperfusion (grade 1C).

Sedation, Analgesia, and Neuromuscular Blockade in Sepsis

  • Continuous or intermittent sedation should be minimized in mechanically ventilated sepsis patients, targeting specific titration endpoints (grade 1B).
  • Neuromuscular blocking agents (NMBAs) should be avoided if possible in the septic patient without ARDS due to the risk of prolonged neuromuscular blockade following discontinuation. If NMBAs must be maintained, either intermittent bolus as required or continuous infusion with train-of-four monitoring of the depth of blockade should be used (grade 1C).
  • A short course of NMBA of not greater than 48 hours for patients with early sepsis-induced ARDS and a PaO2/FiO2 < 150 mm Hg (grade 2C).

Use of Etomidate

The Surviving Sepsis Campaign Guidelines also discourage the use of etomidate if adrenal suppression is suspected. “Although the clinical significance is not clear, it is now recognized that etomidate, when used for induction for intubation, will suppress the hypothalamic-pituitary-adrenal axis. Moreover, a subanalysis of the CORTICUS trial revealed that the use of etomidate before application of low-dose steroids was associated with an increased 28-day mortality rate. An inappropriately low random cortisol level (< 18μg/dL) in a patient with shock would be considered an indication for steroid therapy along traditional adrenal insufficiency guidelines.”

Further Reading

  1. Surviving Sepsis Campaign, International Guidelines for Management of Severe Sepsis and Septic Shock. Crit Care Med. 2013 Feb;41(2):580-637. Available at

Diabetic Ketoacidosis with Severe Metabolic Acidosis

Diabetic Ketoacidosis is very common and is responsible for more than 500,000 hospital days per year at an estimated cost of 2.4 billion USD. Patients in DKA can look terrible. They may be obtunded, hypotensive, have respiratory fatigue after compensating for a while with Kussmaul breaths, and may have underlying sepsis. Their electrolytes are usually off and they can have severe metabolic acidosis. Patients are usually breathing at a maximum for respiratory compensation and trying to intubate them using standard approaches can cause a period of apnea which can kill your patient who is dependent on that respiratory compensation.

Fluid Therapy

The ADA recommends a gradual correction of glucose and osmolality as well as the judicious use of isotonic or hypotonic saline, depending on serum sodium and the hemodynamic status of the patient. In the absence of cardiac compromise, isotonic saline (0.9% NaCl) is infused at a rate of 15–20 ml/kg during the first hour. Subsequent choice for fluid replacement depends on hemodynamics, the state of hydration, serum electrolyte levels, and urine output. In general, 0.45% NaCl infused at 250–500 ml/h is appropriate if the corrected serum sodium is normal or elevated; 0.9% NaCl at a similar rate is appropriate if corrected serum sodium is low.  Once the plasma glucose is 200 mg/dl, 5% dextrose should be added to replacement fluids to allow continued insulin administration until ketonemia is controlled while at the same time avoiding hypoglycemia.


You can feel confident sending off a VBG instead of an ABG. A VBG gives you the same information as an ABG except for the PO2 and O2 sat, but we have our monitors that we can use instead to give us this information (EMRAP May 2013).

Electrolyte Repletion

After IVF the next step in management is electrolyte repletion, especially potassium. Repleting electrolytes should be done prior to starting a patient on an insulin drip.  The ADA recommends that potassium replacement should begin with fluid therapy, and insulin treatment should be delayed until potassium concentration is restored to >3.3 mEq/l to avoid life-threatening arrhythmias and respiratory muscle weakness. The ADA also recommends repleting phosphate to avoid cardiac and skeletal muscle weakness and respiratory depression due to hypophosphatemia.

Sodium Bicarbonate

The use of sodium bicarbonate is controversial. Studies have shown that it may have little effect on patient outcome and can actually cause harm by causing increased risk of hypokalemia, decreased tissue oxygen uptake, cerebral edema, and development of paradoxical central nervous system acidosis. The ADA recommends that adult patients with a pH <6.9 should receive 100 mmol sodium bicarbonate (two ampules) in 400 ml sterile water (an isotonic solution) with 20 mEq KCI administered at a rate of 200 ml/h for 2 h until the venous pH is >7.0. If the pH is still <7.0 after this is infused, they recommend repeating infusion every 2 h until pH reaches >7.0. Some believe that giving sodium bicarbonate won’t work as patients are already breathing at their maximum. Unless they blow off the bicarb-generated CO2, they won’t increase their pH significantly (EMCrit Episode 3; EMRAP May 2013).

Insulin Bolus vs Insulin Drip

The ADA recommends an insulin bolus for adults, but no bolus in pediatrics when you start an insulin infusion. Some recommend not giving the bolus since studies have shown that patients are more likely to have hypoglycemic episodes when started with a bolus and have no difference in the change of anion gap (EMRAP May 2013).

RSI Medications

In cases requiring intubation, the ADA recommends that the paralytic succinylcholine should not be used if hyperkalemia is suspected; it may acutely further elevate potassium.

Airway Pearls

In Scott Weingart’s EMCrit Episode 3 he describes his method for intubating a DKA patient with severe metabolic acidosis. For preoxygenation he recommends using the “pseudo-NIV technique,” which is placing a NIV mask on the patient and connecting it to a ventilator on SIMV mode to allow the patient to take spontaneous breaths. Below are notes from his podcast.

Vent Settings during Preoxygenation

  • Mode Volume SIMV
  • Vt 550 ml
  • FiO2 100%
  • Flow Rate 30 lpm “aim nice, slow breaths, over 1 second (on normal ventilator setting usually less <1sec)”
  • PSV 5-10
  • PEEP 5
  • RR 0 (most important part, pt breaths on their own)

Getting ready to intubate

  • Attach ETCO2 and observe value (try and keep this value at all times)
  • Push the RSI Meds
  • Turn the Resp Rate to 12 (note we are giving breaths at all times so there is no apneic period)
  • Perform jaw thrust (while the pt is still wearing the BiPAP mask)
  • Wait 45 seconds. This violates the tenets of RSI, but keeping the pt alive is probably more crucial right now.
  • Most experienced operator should intubate the patient (first pass success most important).
  • Attach the ventilator
  • Confirm tube placement by observing ETCO2
  • Immediately increase Respiratory Rate to 30
  • Change Vt to 8 cc/kg predicted IBW
  • Change Flow Rate to 60 lpm, this is the normal setting for intubated patients

Why 30 BPM? To maintain eucapnea (normal capnea) you need 60 cc/kg/min. After intubation you need 120 cc/kg/min (because of additional dead space) to stay at a PCO2 of 40. But we want a PCO2 of at least 20 so we need to double it so 240 cc/kg/min, which when divided by 8 cc/kg comes out to 30 BPM to get the tidal volume we need.

  • Make sure ETCO2 is at least as low as it was when you started
  • Check blood gas (check pH and pCO2)
  • Pat yourself on the back

Further Reading

  1., Episode 3, Intubating the Patient With Severe Metabolic Acidosis. Available at
  2., May 2013 Episode, DKA Myths
  3. American Diabetic Association Consensus Statement, Kitabchi A, et al. Hyperglycemic Crises in Adult Patients With Diabetes. Diabetes Care. 2009 July; 32(7): 1335–1343. Available at
  4. Viallon A et al. Does bicarbonate therapy improve the management of severe diabetic ketoacidosis? Crit Care Med. 1999 Dec;27(12):2690-3.
Edited by Alex Koyfman, MD

Synthetic Cannabinoids



  • Synthetic cannabinoids were first designed after the structure of the primary psychoactive compound in marijuana, 9-tetrahydrocannabinol (9-THC), was figured out in the 1960s.
  • Synthetic cannabinoids have been used as a tool to study endocannabinoid biochemistry and also to design cannabinoid derivatives for medicinal use, for example in appetite stimulants and pain medications.
  • In the late 1990s, The John W. Huffman research group at Clemson University began to synthesize over 450 cannabinoids. JWH-018 was one such synthetic cannabinoid that his group created for research purposes but in 2004 it first appeared in Europe in recreational smoke blends under the marketed name “Spice” or “K2.”


Synthetic Cannabinoid Types

  • There are many types of synthetic cannabinoids. More and more continue to be created to either produce a “better high” or evade detection in drug screens. Each has their own distinct binding affinity to the cannabinoid receptor subtypes (CB1 and CB2).
  • For example, HU210 is reported to bind to the CB1 and CB2 receptors with 100 times the affinity of 9-THC.
  • Blends of K2 contain JWH-018 (a full agonist at the CB1 and CB2 receptor), JWH-073 (somewhat selective for CB1), and JWH-250 (CB1 and CB2 agonist).
  • First generation synthetic cannabinoids are believed to be more benign than the newer generation cannabinoids, which are more likely to cause cardiotoxicity and neurotoxicity. One such newer generation synthetic cannabinoid is ADB-PINACA (N-[1-amino-3,3-dimethy-1-oxobutan-2-yl]-1-pentyl-1H-indazole-3-carboxamide), the compound identified in the recent Colorado outbreak known locally as Black Mamba.


Street Names

  • K2, Spice, Black Mamba, Blaze, Bliss, Bombay Blue, Fake Weed, Genie, Moon Rocks, Mr. Nice Guy, Skunk, Yucatan Fire and Zohai.

Legal Status

  • In July 2012, the Synthetic Drug Abuse Prevention Act of 2012 was signed into law, which banned 26 substances commonly found in synthetic marijuana, placing them under Schedule I of the Controlled Substances Act.
  • Despite legislation banning its use, synthetic cannabinoid use is becoming increasingly popular and is still readily available. Synthetic cannabinoids have been found in smoke shops, gas stations, and can be found for sale on the internet. They can be found in legal retail stores and packaged as incense or potpourri and may be labeled “not for human consumption.”

Growing Popularity and Media Attention

  • In 2010, the DEA reported that 30–35% of specimens submitted by juvenile probation departments tested positive for synthetic cannabinoids.
  • According to the 2011 National Institutes of Drug Abuse (NIDA)-sponsored Monitoring the Future survey, 11% of high school seniors reported smoking synthetic marijuana, making it one of the most commonly abused drugs in this population — second only to marijuana.
  • 4.5% of urine specimens collected from 5,956 U.S. athletes tested positive for synthetic cannabinoids, the highest of all drug classes detected.
  • A recent NEJM letter to the editor described an outbreak in Colorado where a total of 263 cases of possible synthetic cannabinoid exposure were identified during August 21-September 19 2013, however only 15 of these cases were reported to the state poison control center. Of the 263 cases, 76 sought medical attention in emergency departments and 7 were admitted to intensive care units. Colorado health officials identified a novel synthetic cannabinoid, ADB-PINACA, which was associated with neurotoxicity and cardiotoxicity.

Clinical Highlights

Route of Ingestion

  • Synthetic cannabinoids can be smoked, insufflated, or orally ingested.


  • The psychoactive effects are similar to 9-THC and include altered time perception, anxiety, changes in mood, confusion, hallucinations, and psychomotor agitation. There have been case reports of induced psychoses, unmasking of underlying psychiatric disease, and suicidal attempts especially in individuals with a personal or family history of psychiatric conditions. Additional undesirable effects include dry mouth, nausea, vomiting, tachycardia, palpitations.
  • Life-threatening neurotoxic effects, like seizures or ischemic stroke, and cardiotoxic effects, like arrhythmia or acute coronary syndrome / myocardial infarction, rarely occur with synthetic cannabinoid intoxication and likely occur more often with the newer synthetic cannabinoids presumably due increased potency to the cannabinoid receptors.


  • Similar to marijuana intoxication, patients typically do not need measures other than symptomatic or supportive treatment. No antidote exists for synthetic cannabinoid poisoning. Seizure control and agitation can be treated with benzodiazepines. Gastrointestinal decontamination typically has no role in patients using synthetic cannabinoids, but it may be considered in large-quantity ingestions.
  • For severe intoxication, especially with the newer generation synthetic cannabinoids, intensive care monitoring and management for seizures, ischemic stroke, and possible cardiotoxicity may be required. Death due to neurotoxicity or cardiotoxicity as well as suicidality has been reported with synthetic cannabinoid use.


  • Synthetic cannabinoids do not show up in the standard urine drug screens available in most hospitals, which test for Tetrahydrocannabinol. The best methods for detecting synthetic cannabinoids are liquid chromatography / tandem mass spectrometry (LC-MS/MS) and gas chromatography / mass spectrometry (GC/MS) and are only available in select laboratories.
  • The inability to detect synthetic cannabinoids using standard urine drug screens adds to its growing popularity.

Bottom Line

  • Suspect synthetic cannabinoids in your patients who present with marijuana-like symptoms but screen negative for cannabis using standard urine drug screens. Most patients require symptomatic support as you would normally do for your patient presenting with marijuana intoxication.
  • However, there have been a growing number of cases associated with life-threatening neurotoxic effects (seizures, strokes) and cardiotoxic effects (arrhythmia, acute coronary syndrome / myocardial infarction), presumably due to increased potency to the cannabinoid receptors in the newer synthetic cannabinoids.

Further Reading

Edited by Alex Koyfman, MD