Synthetic cannabinoids - Careers in Tox - QI/KT: Bites - Urology Troubleshooting - Case Follow-up: CAUTIs - Toxin Review

Visiting Guest Lecturer: Evolution of Synthetic Cannabinoids with Dr. Matt Valento

Synthetic Cannabinoids

Marijuana is listed as a schedule 1 controlled substance by the DEA. However, individual state laws vary on the legality of marijuana. It is important to note that synthetic cannabinoids are not from a plant, like marijuana, but instead are chemical compounds that are created in a lab.

Synthetic cannabinoids are often more structurally similar to methamphetamine than to marijuana. The psychoactive constituent in synthetic cannabinoids is variable and is NOT THC which is the primary psychoactive constituent in cannabis or marijuana. There are multiple adverse reactions associated with synthetic cannabinoids specifically, but not limited to, agitation, psychosis, seizures, and sudden death. In the literature, there is the only one published report that suggests a correlation between marijuana use and death. This is in contrast to multiple case reports which strongly associate synthetic cannabinoids with death

The name "spice", a common slang term for synthetic cannabinoids, is thought to originate from the drug described in the Dune series. In the United States synthetic cannabinoids are also commonly known as "K2". Synthetic cannaboids do not show up in a urine drug screen and their use is often associated with populations that are frequently drug tested, such as prisoners and the military.

History of Synthetic Cannabinoids

Cannabinoid receptors were discovered in the late 1980s and since their discovery, the production of synthetic cannabinoids has significantly increased. Synthetic cannabinoids were first marketed in Europe in the mid 2000s as "spice". About two years later synthetic cannabinoids were confirmed as the active ingredient in "spice". It was also around this time that these drugs made it on the market in the United States as "K2". Synthetic cannabinoids can be purchased, legally as an herb or incense, liquid, or as its parent chemical compound. When abused, synthetic cannabinoids are typically inhaled.

In 2012, President Obama signed the Synthetic Drug Abuse Prevention Act which officially listed multiple synthetic cannabinoids and other stimulants as a schedule 1 controlled substance. However, it is limited by the fact that the active ingredients in marketed synthetic cannabinoids are unknown and unpublished. Only once a chemical compounds is identified as a synthetic cannabinoid can it then be listed as a schedule one controlled substance. The federal government works to determine the active ingredients in various types of synthetic cannabinoids and once it determines the chemical compound of the synthetic cannabinoid, that compound gets passed by the FDA as a schedule 1 drug. However, as quickly as these drugs become illegal, chemists are able to alter the chemical structure of these compounds. By altering the chemical structure of these drugs the chemists are creating analogues that can be sold legally. These analogues compounds often have chemical properties that are similar to amphetamines.

In 2016, NEJM published an article highlighting the increased potency of synthetic cannabinoids. As these chemical compounds have evolved and changed, their potency has increased.

Pathophysiology

The toxicity of synthetic cannabinoids is more similar to amphetamines than to THC. Many of these drugs also have active metabolites so that both the parent compound and active metabolites act on cannabinoid receptors. Synthetic cannabinoids have a markedly higher binding affinity for cannabinoid receptors than THC.

The only preclinical studies chemists are preforming is to show that these chemical binds to cannabinoid receptors. There is no other regulation or testing of these chemicals before they are marketed.

Common adverse effects are CNS depression, agitation, psychosis, and tachycardia. Less often patients present with seizures, chest pain, acute kidney injury, nausea and vomiting, bradycardia, and death. Rare side effects, described in case reports, are mesenteric ischemia, rhabdomyolysis, cardiac dysrrhythmia, myocardial infarction, subarachnoid hemorrhage, hepatotoxicity, and hyperthermia. Autopsy reports of deaths associated with synthetic cannabinoids often list non-cardiogenic pulmonary edema. It is unclear if this is due to patients being in status epileptics or a still unknown property of these compounds.

Management

The corner stone of management focuses around control of the patient's agitation. Because of this, intoxication is treated similarly to amphetamine intoxication. Benzodiazepines are commonly used for treatment but ketamine, haldol, and precedex can also be used. When evaluating these patients it is important to look for signs of end organ damage.

Visiting Guest Lecturer: Careers in toxicology with Dr. Matt Valento

Toxicology Careers

Most fellowship graduates spend a majority of their careers working clinically in the ED. Medical toxicology is a two year fellowship that is compromised of clinical work in the ED, daily teaching rounds, clinical consultant services, and rarely inpatient services. Fellowship in toxicology culminates in a board exam with a 50-70% pass rate.

A 'traditional' toxicology career involves working in an academic Emergency Department, publishing scholarly work, and taking call with your local poison control center. Being the medical director of a poison center is typically a full time job. It is focused on teaching and administrative work. It is important to know that poison centers are totally dependent on local, state, or federal funding.

QI/KT: Mammalian bites WITH DRs. Habib and Ham

Epidemiology

There are 3-6 million mammalian bites that occur yearly in the United States however, only a small percentage of these present to the ED. The majority of mammalian bites are due to dogs and cats, representing 80-90% and 5-15% of bites respectively.

In Ohio, it is mandatory to report all non-human mammalian bites to the Department of Health.

Dog bites

Most commonly seen in males ages 5-9 years old
Lower infectious risk
Wounds often occur on the face, scalp or neck

Cat bites

Most commonly seen in elderly females
Carry a high infectious risk
Wounds usually occur on the upper extremities

Managment

History and Physical - It is important to determine how long prior to presentation the bite occurred, the immunization status of the animal, and the type of mammal that inflicted the bite. With any wound it is important to ask the past medical history of the patient as well as the vocation and handedness of the patient. Physical exam should focus on the if there is any evidence of neurovascular, ligamentous, joint involvement, and or deep tissue compromise.

Wound closure - It is ok to consider primary wound closure in mammalian bites but it is important to weight each patient's individual risk factors for infection against the cosmetic and functional benefit gained from wound closure. Depending on follow up available for the patient, delayed primary wound closure is also an option. Wounds that are considered high risk for developing infection are those on the hand or genitals, overlying a joint, non-dog bites, and puncture wounds. Patients who are at high risk for develop infection are those who are immunocompromised, splenic, have diabetes, or those whose social situation makes close follow up difficult.

Antibiotics - When considering prophylaxis it is important to consider each patient's risk factors for infection and complication. When treating for an infected wound or when considering prophylaxis is it important to cover for gram positive, gram negative, and anaerobic organisms. Amoxicillin-clavulanic acid is considered first line for PO antibiotics, typically for 3-5 days. Second line oral antibiotics are doxycycline, sulfamethoxazole-trimethoprim, and cefuroxime plus metronidazole. First line IV antibiotics are ampicillin-sulbactam or piperacillin-tazobactam.

Tetanus - Toxoid vaccine should be given if unknown or incomplete vaccination status, if last booster >10 years in the setting of minor or clean wound, or if last booster >5 years in the setting of severe wounds. Immune globulin should be given if the patient's vaccination status is unknown or incomplete.

Rabies - Post-exposure prophylaxis should involve rabies immune globulin and the rabies vaccine in patients who have never been vaccinated against rabies. The decision to initial post-exposure prophylaxis depending on the type of animal bite and type of exposure. The rabies virus is transmitted through exposure from saliva or neural tissue. Rabies immune globulin is given at days 0, 3, 7, 14 for immunocompetent patients. Rabies immune globulin is dosed 20 units/kg and should be given in and around the wound if possible.

R3 Small Groups: Urology WITH DRs. Baez, Bernardoni, randolph, and shaw

Trouble-shooting Difficult Foleys

Women

Difficulty is often due to issues with visualization of the urethra. In obese patients try lifting the hips up and the labia up and outwards to improve visualization

Men - There are three parts to the male urethra - the prostatic, membranous, and spongy

For improved pain control consider using lidocaine jelly, this may also help the sphincter to relax
If you are considered about prostate hypertrophy as the etiology for difficult foley placement consider up sizing the foley or using a coude catheter
If you are concerned there is a stricture in urethra consider downsizing the foley or using a silicone foley which is stiffer

General

Encourage the patient to take slow deep breaths to help relax sphincter
Always hub catheter
If urine is not flowing through the catheter, flush it
If the patient complains of a painful foley, reinsert the catheter all the way to Y-hub, then inflate balloon

Suprapubic catheter insertion

Indications

Urethral injury or foreign body
Obstructing urethral/bladder neck lesions
Urethral stricture
Enlarged prostate
Obstructing phimosis

Contraindications

Latex allergy
Coagulopathy

Relative contraindications

History of pelvic cancer or radiation
Previous abdominal surgeries
Ascites
UTI
Morbid obesity

Technique

Palpate the distended bladder 4-5 cm above the pubic symphysis
Use ultrasound to confirm bladder location and ensure no loops of bowel are present
Apply antiseptic solution from the pubis to the umbilicus x 3 and use standard sterile technique from this point on
Inject local anesthetic at the site of insertion
Make a single stab incision at predetermined insertion site with an 11-blade
With US guidance, advance your suprapubic catheter with dilator attached at 20 to 30 degrees from true vertical, caudally towards the patient until you encounter the black mark on the needle
Aspirate urine with a 10cc syringe to confirm placement of your needle within the bladder
Unscrew the purple lock at the top of the catheter in order to unlock it
Advance the catheter until it is hubbed at the skin, the pigtail loop will keep it within the bladder
Suture the suprapubic catheter to the skin
Attach the foley bag using the adaptor included within the kit

Complications

Bowel perforation
Hemorrhage
Peritonitis
Catheter misplacement or migration
Gross hematuria common and transient
Infection

Urology Quick Hits

Cryptorchidism, or maldescended/undescended testicles, is a congenital abnormality that increases your risk for testicular cancer
Phimosis is a condition of the uncircumcised penis in which constriction of the foreskin prevents retraction of the prepuce from the glans
Struvite stones are the type of kidney stones commonly caused by Proteus urinary tract infections.
Diabetics are predisposed towards balanitis, so POC glucose should be checked in those with diagnosis.
Bell-Clapper Deformity, or incomplete anchoring of the tunica vaginalis, predisposes males to testicular torsion with a 1/25 prevalence
6 weeks of antibiotics is the length of treatment for chronic (non-STD) bacterial prostatitis
The most common risk factor for Fournier's Gangrene is diabetes
Prehn’s sign is a physical exam finding where pain is relieved with testicular elevation.
Torsion of appendix testis is associated with a “blue dot” sign on the testicle. This structure has no function, so treatment is supportive
Following the diagnosis of traumatic posterior urethral injury, suprapubic catheter placement is indicated
“Cannonball metastasis” is seen on chest x-ray, which is pathognomonic for metastatic testicular cancer

R4 Case follow up: Medical management of indwelling GU catheters WITH DR. Titone

When to Worry about a Catheter Associated Urinary Tract Infection (CAUTI)?

The IDSA describes CAUTI as a patient with symptoms, a source, and urine culture with >1000 colonies. Symptoms are described as fevers, rigors, altered mental status, or lethargy without other source of infection. Pyruia, odorus, or cloudy urine alone are not an indication for UTI treatment. This is because all catheters will become bacteruric by one month. If the patient is asymptomatic and is well appearing a urinalysis and urine culture are not indicated. As long as the urine is appropriately draining through the patient's catheter, the risk of CAUTI is low. In order to assess if the urine draining appropriately you can bladder scan, examine and flush nephrostomy tubes, preform a renal POCUS to evaluate for hydro, or CT scan the patient. Generally, it is very rare for ileal conduits to obstruct.

Ureteral Stents

All patients with a symptomatic ureteral stent require a KUB to confirm stent position. It is almost important to note that all of these patients will have hydronephrosis as a sequelae of their ureteral stent so renal POCUS is not helpful. Additionally, flank pain, dysuria, and hematuria are known side effects that are common in patients with ureteral stents and are unreliable as symptoms of stent migration or infection. If you have a clinical suspicion for UTI AND the stent has migrated OR the patient looks ill checking a urinanlysis is indicted. However, it is important to know that urine microscopy is unreliable in this patient population as they will all have microscopic hematuria. Treatment for UTI in this patient population should be limited to culture positive results.

R1 Clinical knowledge : Toxins WITH DR. Koehler

Ciguatera

Ciguatera is found in reef fish. It is the most frequently reported seafood-toxin and is most commonly seen in the Caribbean and Pacific. It accumulates in the food chain as fish eat each other. It is a heat stable toxin that activates voltage gated sodium channel. Symptoms are usually GI or neurological in nature. GI symptoms are commonly nausea, vomiting, diarrhea. Neurological symptoms are usually unique sensitization symptoms. Patients will eat hot food yet describe that it feels cold. They may also describe a feeling like your teeth are falling out. Treatment is usually IV mannitol for the neurologic symptoms and supportive care for the GI symptoms. If you are concerned about ciguatera poisoning this should be reported to health department. It is important to inform patients that symptoms can recur from weeks to month.

Scombroid

Scombroid is a pseudo-allergic poisoning, commonly seen in Mahi-Mahi and tuna fish. It occurs when the fish is poorly preserved allowing for the histadine in the fish to convert to histamine. Presenting symptoms are often a metallic or peppery taste that occurs 20-30 minutes after ingestion and last <6 hours. It is also associated with flushing, urticaria, headache, palpitations, and diarrhea. Oral swelling is a rare presenting symptom. The main stay of treatment is antihistamines however, epinephrine should also be used if airway swelling is present.
It is importnat to inform patients that this is not a fish allergy. Scrombroid posioning should be reported to health department. These patients should be observe in the ED for worsening of symptoms.

Tetrodotoxin

Commonly found in puffer fish and in newts. It accumulates through the food chain and acts by inhibiting voltage gated sodium channels. Symptom onset is usually between 0.5-6 hours after exposure and symptoms usually resolve within 24 hours. Symptoms are characterized by weakness, dysarthria, dysphagia, and skeletal weakness however, in severe cases this can progress to paralysis, hypotension and cardiovascular collapse. Unfortunately, no antidote exists and managment is supportive care only. Regardless of the severeity of a patient's symtpoms if you suspect tetrodotoxin posioning they should be admitted to the hospital for observation.

Mushrooms

Most commonly present with GI irritation. It is important when patients present after mushroom ingestion to determine how long ago their ingestion occurred. Patients who presents with GI irritation only should be given supportive care only. It is important to not give anti-diarrheals as this may prolong patient's symptoms.

Amatoxin is highly fatal (90-95%) and acts by selectively inhibiting RNA polymerase which inhibits protein synthesis. It is a heat stable toxic which initially presents with GI symptoms in the first 6 hours but, can progress to hepatotoxicity causing hemorrhagic hepatic necrosis and hepatorenal syndrome. Treatment options include MARS (albumin dialysis), n-acetylcysteine (NAC), high dose penicillin, cimetidine, and silibiinin. These patients need to be transported to a liver transplant center.
Gyromitrin is found in "false morels" and is water soluble and volatile toxin. Its metabolites cause CNS depletion of B6 leading to seizures. In addition to neurologic symptoms, it can also cause hepatotoxicity. Seizures should be treated with IV pyridoxine give grams and patients should be admitted to the ICU.

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