Article

Synthetic drugs: a new trend and the hidden danger

Correspondence / American Journal of Emergency Medicine 31 (2013) 14101417 1413

Table

The varying alteplase dose, duration, and method of administration and time frame for initiating therapy in case of acute ischemic cerebrovascular stroke, STEMI, and PE

[6] Kleczynski P, Dziewierz A, Rakowski T, Rzeszutko L, Sorysz D, Legutko J, et al. Cardioembolic acute myocardial infarction and stroke in a patient with persistent atrial fibrillation. Int J Cardiol 2012;161(3):e46-7.

[7] Chetwood A, Sanders A, Saweirs M, Thapar A, Davies AH. Multiple arterial emboli

Dose and duration of TPA Time frame for administration

secondary to left ventricular thrombus in a 35-year-old obese male. J Cardiovasc Dis Res 2010;1(4):203-5.

Ischemic cerebrovascular stroke

0.9 mg/kg (maximum of 90 mg) infused for 60 min with 10% of the total dose administered as an initial Intravenous bolus for 1 min

Within 3 h of symptom onseta

STEMI The recommended dose administered is 100 mg as a 15-mg intravenous bolus, followed by 50 mg infused over the next 30 min, and then 35 mg infused over the next 60 min.b

PE 100 mg infused for 2 h with 10 mg given as a bolus

Up to 12 h

Longer durationc

Synthetic drugs: a new trend and the hidden danger

Introduction

Designer or synthetic drugs and other recreational type use have

a This period can be extended to 4.5 hours unless any of the following exclusion criteria are present: patients older than 80 years, patients taking oral anticoagulants regardless of the international normalized ratio, patients with baseline NIHSS score higher than 25, and patients with a history of stroke and diabetes.

b For patients weighing 67 kg or less, 15 mg is given as intravenous bolus, followed by 0.75 mg/kg infused over the next 30 minutes not to exceed 50 mg, and then 0.50 mg/ kg over the next 60 minutes not to exceed 35 mg.

c Some studies show that thrombolytic therapy remains to be effective up to 2 weeks after primary embolization.

the alteplase dose, duration of administration, and time frame for initiating therapy in case of ischemic cerebrovascular stroke, STEMI, and PE. Notice the differing total dose of alteplase (100 mg in STEMI and PE vs 90 mg in ischemic stroke), duration of therapy (1 hour in STEMI and ischemic stroke vs 2 hours in PE), way of administration (how the dose is distributed during the delivery period), and the time frame during which therapy can be given (3 hours in ischemic stroke vs up to 12 hours in STEMI). We believe that in cases of simultaneous 2-vessel occlusion, thrombolytic therapy is a reasonable option. Further research is needed for the ideal management modality that provides the best outcome in this rare and devastating clinical scenario.

Hesham R. Omar MD Internal Medicine Department Mercy Hospital and Medical Center

Chicago, IL E-mail address: [email protected]

Devanand Mangar MD Florida Gulf to Bay Anesthesia Tampa General Hospital

Tampa, FL

Enrico M. Camporesi MD

University of South Florida

Tampa, FL

http://dx.doi.org/10.1016/j.ajem.2013.05.046

References

  1. Akyuz S, Sungur MA, Donmez C, Sungur A, Cam N. Rescue thrombolysis in the treatment of Cardiac shock and acute stroke. Am J Emerg Med 2013 [Epub ahead of print].
  2. Omar HR. Myocardial infarction-stroke association. Int J Cardiol 2012;154(3): 340.
  3. Omar HR, Fathy A, Rashad R, Helal E. Concomitant acute right ventricular infarction and ischemic cerebrovascular stroke; possible explanations. Int Arch Med 2010;3: 25.
  4. Omar HR, Huang C, Miller JH, Mangar D, Kabemba A, Camporesi EM. Simultaneous pulmonary embolism and cerebrovascular stroke. Herz 2013 [Epub ahead of print].
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    increased among Young people. The synthetic drugs present difficulty for law enforcement agents as the chemical structure is minimally altered to create a new and almost identical “legal” drug that can be sold as herbal incense or aromatic products. The symptoms of intoxication from these substances include euphoria, palpitations, confusion, anxiety, muscle cramps, depression, Blurred vision, paranoia, insomnia, and altered mental status in extreme cases. They can cause hyperthermia, leading to seizure and liver, kidney, or cardiovascular failure [1-7].

    This study was conducted after we were contacted by the Department of Health from New York City regarding synthetic and other recreational type substance abuse reported to them by the New York City Poison Control Center during the rave party festival week in 2011 and 2012.

    Materials and methods

    Chart review of all patients who presented to the emergency department (ED) with alcohol- or drug-related complaint on the days of the Electric Zoo festival in New York City in 2011 (September 3 to September 5) and in 2012 (August 31 to September 2). A waiver for chart review was obtained from the institutional review board. Electronic health record was used for patient search and demographics, laboratory results, location of the pick-up, substance used by history, and chief complaints along with the symptoms reported and compli- cations such as seizure and hyperthermia on site as well as laboratory and toxicology results; progress notes about the ED and hospital course of all patients from the list were reviewed and recorded.

    Descriptive statistics were reported using InStat 3.0 software (La Jolla, CA).

    Results

    Eighty-eight patients were seen for substance-related complaints during the Labor Day weekends. Of those 88 patients, 60 (68.2%) were rave party-related substance abuse. The average age for all patients who presented to our ED was 20 years. The average age for male was

    20.5 years, and the average age for female was 19.5 years. Fifty patients had laboratory tests in the ED, ordered at the discretion of the provider based on their initial individual assessment. Twenty-six patients were male, and 34 patients were female. Twenty-five patients were younger than 18 years, and 34 patients were older than 18 years. Five patients (2 males and 3 females) presented with seizure. One female patient had a prior history of seizure, and the other 4 patients had new onset seizure. One patient with a new onset seizure had a sodium level of 113 milliequivalents/liter (mEq/L). She was intubated and treated with 3% sodium chloride solution. A total of 3 patients had to be intubated for airway protection, and one of them developed hyperthermia with a temperature of 106?F. Detailed demographics, substance used by history, and laboratory tests and clinical data are presented in TableA to C.

    1414 Correspondence / American Journal of Emergency Medicine 31 (2013) 14101417

    Table

    Demographics and clinical data

    Demographics

    Sex

    Age

    Male

    Female

    b18 M

    b18 F

    N 18 M

    N 18 F

    2011

    11

    6

    0

    0

    11

    6

    2012

    15

    28

    9

    16

    6

    12

    Total

    26

    34

    9

    16

    15

    18

    Substances used

    2011 2012

    Male Female Male Female

    b18 N 18 b 18 N 18 b18 N 18 b18 N 18

    protection and admitted to intensive care unit. One teenage girl had to be examined by the sexual assault response team as there was a possible assault. She was started on postexposure prophylaxis for HIV infection and Sexually transmitted diseases.

    Most patients in 2012 were teenagers, and they used newer but potent synthetic drugs. Long-term follow-up may reveal delayed sequelae in the psychobehavioral or psychosocial and organ-related side effects of these agents. Moreover, these teenagers are susceptible to sexual and other assaults from diminished consciousness.

    5. Limitation

    Our study is limited by small sample size and its retrospective nature. laboratory examinations were not consistent on and sequelae ld not be followed up after discharge on all patients.

    Adderall

    1

    1

    of the drugs cou

    Ecstasy

    4

    4

    1

    1

    2

    2

    ETOH

    7

    4

    6

    5

    15

    11

    6. Conclusion

    Ketamine

    2

    1

    1

    1

    Marijuana 1 1 1 1

    Molly 3 1 4 2

    PCP 1 1

    Ritalin 1

    Clinical data

    2011 2012

    Male Female Male Female

    Synthetic drug is consumed at special occasion such as rave parties in large quantities and for several days continuously. They pose a serious hazard as they can cause seizure, kidney injury, rhabdomyolysis, and acute coronary syndrome. Synthetic and other recreational drugs pose a serious hazard as shown by this review and a review of the literature. Health care providers should be aware and counsel these patients.

    Acknowledgment

    b18

    N 18

    b 18

    N 18

    b18

    N 18

    b18

    N 18

    Seizure

    2

    2

    1

    We would like to thank Drs Bania and Shaw for reviewing

    Hypokalemia 1 1 3

    Hyponatremia 1

    Hypoglycemia 1

    Hypomagnesiumia 1

    Elevated Crea 1

    Elevated CK 1 1 1

    Hyperthermia 1

    Intubation 1 1 1

    Admission to ICU 1 1 1

    the manuscript.

    Getaw Worku Hassen MD, PhD Farzaneh Ghobadi MD Hossein Kalantari MD, MPH

    Department of Emergency Medicine

    NYMC, Metropolitan Hospital Center Emergency Medicine, NY 10029, USA

    Abbreviations: F, female; M, male; CK, Creatinine kinase; Crea, creatinine; ICU, intensive

    care unit.

    Discussion

    Emergency department visits for serious and sometimes fatal side effects have increased significantly in the last 2 years. These drugs are usually sold and used at rave parties and other big events such as the one at Electric Zoo festival in New York City. Overall ED visits due to 3, 4-methylenedioxy-N-methylamphetamine (MDMA), also known as Ecstasy, were less than 4% in 2009. The national Drug Abuse Warning Network found a 123% increase in the number of ED visits involving MDMA taken alone or in combination with other drugs from 2004 to 2009 [8]. Molly, the powder or crystal form of MDMA, has been a popular drug at music festivals in 2012.

    Seizure has been reported from drug overdose, poisoning, and use of recreational drugs such as Ecstasy [9-11]. Seizure is partially from hyponatremia. The hyponatremia is partially from rehydration with free water and partially the result due to the effects of these drugs on antidiuretic hormone [9,12,13]. Seizures and delayed seizures from the use of synthetic drugs pose significant health and behavioral risk [11]. Other complications such as multisystem organ failure; rhabdo- myolysis; cases of acute coronary syndrome and acute kidney injury, ischemic stroke, Hepatic injury, and renal failure; and death have been reported from the use of recreational and synthetic drugs [2,3,6,14-17]. The results of our study showed that multiple drug types were used, and complications such as electrolyte derangements and seizure were also noted (Table). One patient was hyperthermic with temperature of 106?F. Three patients were intubated for airway

    E-mail addresses: [email protected], [email protected]

    [email protected] http://dx.doi.org/10.1016/j.ajem.2013.05.047

    References

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  6. Bhanushali GK, Jain G, Fatima H, Leisch LJ, Thornley-Brown D. AKI associated with synthetic cannabinoids: a case series. Clin J Am Soc Nephrol 2013;8:523-6.
  7. Borek HA, Holstege CP. Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med 2012;60:103-5.
  8. Coppola M, Mondola R. 3,4-methylenedioxypyrovalerone (MDPV): chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online. Toxicol Lett 2012;208:12-5.
  9. Hermanns-Clausen M, Kneisel S, Szabo B, Auwarter V. Acute toxicity due to the confirmed consumption of synthetic cannabinoids: clinical and laboratory findings. Addiction 2013;108:534-44.
  10. Mir A, Obafemi A, Young A, Kane C. Myocardial infarction associated with use of the synthetic cannabinoid K2. Pediatrics 2011;128:e1622-7.
  11. Wood DM, et al. Dissociative and Sympathomimetic toxicity associated with recreational use of 1-(3-trifluoromethylphenyl) piperazine (TFMPP) and 1- benzylpiperzine (BZP). J Med Toxicol 2008;4:254-7.
  12. Center for Behavioral Health Statistics and Quality. 2009. http:

    //www.samhsa.gov/data/2k11/DAWN/2k9DAWNED/HTML/DAWN2k9ED.htm.

    Giorgi FS, et al. MDMA and seizures: a dangerous liaison? Ann N Y Acad Sci 2006;1074:357-64.

  13. Olson KR, Kearney TE, Dyer JE, Benowitz NL, Blanc PD. Seizures associated with poisoning and drug overdose. Am J Emerg Med 1994;12:392-5.
  14. Wood DM, et al. Delayed onset of seizures and toxicity associated with recreational use of Bromo-dragonFLY. J Med Toxicol 2009;5:226-9.
  15. Campbell S,QureshiT.Taking Ecstasy…it’s child’splay!Paediatr Anaesth 2005;15:257-9.
  16. Sue YM, Lee YL, Huang JJ. Acute hyponatremia, seizure, and rhabdomyolysis after ecstasy use. J Toxicol Clin Toxicol 2002;40:931-2.
  17. Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol 2012;8:33-42.

    Correspondence / American Journal of Emergency Medicine 31 (2013) 14101417

    Wolff V, et al. Cannabis-related stroke: Myth or reality? Stroke 2013;44:558-63.

    1415

    Subramanian Senthilkumaran MD

    Duchene C, et al. Cannabis-induced cerebral and myocardial infarction in a young woman. Rev Neurol (Paris) 2010;166:438-42.

  18. Singh NN, Pan Y, Muengtaweeponsa S, Geller TJ, Cruz-Flores S. Cannabis-related stroke: case series and review of literature. J Stroke Cerebrovasc Dis 2012;21: 555-60.

    Atropine resistant bradycardia and hyperkalemia: our experiences?,??

    To the Editor,

    We read the report of Srivali et al [1] with great interest and wish to share our experiences with Atropine-resistant bradycardia. Symp- tomatic bradycardia is a frequent presentation in the emergency department (ED), although the causes may not readily be demon- strable during the early phase of management. Invariably, atropine is administered to treat such cases, and many respond well. However, a few continue to have persistent Symptomatic bradycardia and are often referred for temporary cardiac pacing.

    Bradycardia secondary to hyperkalemia is a frequently overlooked electrocardiographic finding [2]. Here, we wish to share some of the clinical characteristics of 55 cases of symptomatic bradycardia referred to our ED over a period of 2 years. None were on ?-blockers, verapamil, digoxin, or any poisoning. In this population, maximal dosage of atropine failed to enhance the heart rate significantly in 11. The mean age of nonresponders was 52.3 years (SD, 10.3) with male preponderance and was similar to those who responded to atropine. Heart rate at presentation varied from 30 to 48, and the initial ECG findings were junctional rhythm in 5, sinus rhythm in 4, and nonspecific in 2 others. serum potassium level varied from 6.4 to 8 with a median of 6.8 mEq/dL. Of 11, 9 improved within 10 to 15 minutes after commencement of Antihyperkalemic therapy. Urgent hemodialysis was carried out in 2 patients (4%). Discharge diagnoses was “Adverse drug effect” and attributable to angiotensin- converting enzyme inhibitors, potassium-sparing diuretics, and Cycloox- ygenase-2 inhibitors in 8, 2, and 1, respectively.

    Hyperkalemia causes various ECG changes including shortening of QT interval to asystole. However, these patterns may not correlate clinically or with the serum potassium levels [3]. Absence of ECG changes despite markedly elevated serum potassium [4] was noticed in patients with renal insufficiency. Therapeutic agents have been noted to be a major cause for hyperkalemia in 35% to 75% of hospitalized patients [5], and some of them were on a combination of angiotensin-converting enzyme inhibitors with potassium-sparing diuretics or potassium supplements.

    Hyperkalemia reduces myocardial excitability, suppresses Sino- atrial node activity, and blocks the conduction at the Atrioventricular node, which eventually attenuates the response to atropine. Slade et al [6] reported 2 cases of atropine-resistant bradycardia due to hyperkalemia and suggested rapid bedside assessment of potassium by arterial Blood gas analyzer in the ED and ensure early intervention. From the point of patient safety, hyperkalemia needs to be investigated, in those receiving hyperkalemia-prone therapeutic agents, and considered at as a bedside investigation, if the pulse rate reduces significantly. Hyperkalemia may also manifest without ECG changes. Therefore, timely recognition and intervention not only avoid referral but also avert expensive pacemaker therapy. Interestingly, the etiology for predilection toward hyperkalemia and the frequent absence of ECG changes in such individuals warrant further exploration. Emergency physicians shall remember that bradycardia is not always a primary cardiac issue and, hence, consider or suspect hyperkalemia for bradyarrhythmia, if not responding to atropine or failure to capture

    the beat, in the absence of other demonstrable causes.

    Department of Emergency & Critical Care Medicine, Sri Gokulam Hospitals & Research Institute, Salem-636004, Tamil Nadu, India

    E-mail address: [email protected]

    Suresh S. David MS

    Department of Emergency Medicine, Christian Medical College and

    Hospital, Vellore, India

    Rishya Manikam MD

    Department of Emergency Medicine, University Malaya

    Kuala Lumpur, Malaysia

    Ponniah Thirumalaikolundusubramanian MD

    Department of Internal Medicine, Chennai Medical College and

    Research Center, Irungalur, Trichy, India

    http://dx.doi.org/10.1016/j.ajem.2013.06.020

    References

    Srivali N, Ratanapo S, Cheungpasitporn W, Chongnarungsin D, Bischof EF. Hyperkalemia-induced pacemaker dysfunction. Am J Emerg Med 2013;31:879-80.

  19. Mattu A, Brady WJ, Robinson DA. electrocardiographic manifestations of hyperka- laemia. Am J Emerg Med 2000;18:721-9.
  20. Montague BT, Ouellette JR, Buller GK. Retrospective review of the frequency of ECG changes in hyperkalemia. Clin J Am Soc Nephrol 2008;3:324-30.
  21. Aslam S, Friedman EA, Ifudu O. Electrocardiography is unreliable in detecting potentially lethal hyperkalaemia in haemodialysis patients. Nephrol Dial Trans- plant 2002;17:1639-42.
  22. Stevens MS, Dunlay RW. Hyperkalemia in hospitalized patients. Int Urol Nephrol 2000;32:177-80.
  23. Slade TJ, Grover J, Benger J. Atropine-resistant bradycardia due to hyperkalaemia. Emerg Med J 2008;25:611-2.

    Takotsubo syndrome and chest pain units?

    To the Editor,

    Patients presenting with suspected takotsubo syndrome (TTS) are mostly evaluated by emergency department (ED) physicians, except if such illness occurs in the already hospitalized patients, admitted for a diverse array of medical/surgical conditions or in the setting of Diagnostic and therapeutic procedures or perioperatively. Because the most prevalent presenting symptom of patients with suspected TTS is chest pain, which is indistinguishable from the one experienced with an acute coronary syndrome (ACS), such patients may be admitted and observed in Chest pain units (CPUs) [1-4]. Such CPUs staffed by ED physicians, with available prompt consultation by a cardiologist at the discretion of the ED physicians, provide for admission, observation, and triage of patients with chest pain, most of whom do not have ACS but noncardiac chest pain. Some of the patients presenting with chest pain turn out to have TTS, and such occurrences are being identified with accelerating frequency [5]. The crux of the matter, in reference to differential diagnosis of ACS and TTS, is to distinguish anterior ST- elevation myocardial infarction (a subtype of ACS) from TTS because the former requires expeditious referral for coronary revascularization, with thrombolysis and preferably percutaneous coronary intervention, whereas the latter is managed currently with nonspecific supportive (based on symptoms) therapies [5]. Patients with both syndromes show ST-elevations primarily in precordial electrocardiographic (ECG) leads in their admission ECG, but this Diagnostic modality does not appear to differentiate between the 2 [5,6]. What is being currently done, besides obtaining a targeted history and performing a focused physical examination, is to record the ECG and sample for blood biomarker

    ? Financial support: Nil.

    ?? Conflict of interest: Nil.

    ? Disclosures: The author has disclosed no conflicts of interest.

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