Naloxone distribution programs have been expanding to promote the naloxone adminstration by laypersons, usually intranasal (IN) device, to victims of opioid overdose. A recent study analyzed the reports of prehospital naloxone administration reported to a regional poison center.
Opioid toxicity revesal:
However, between 2015 and 2017, the reversal rate decreased (82.1% to 76.4%) while mean administered naloxone dose increased (2.12 mg to 3.63 mg). The cause of this trend is unknown but the dose of commercially available IN naloxone kit increased from 2 mg to 4 mg in 2016.
Bottom line:
Since 2013, the availability of fentanyl has been increasing in the illicit drug supply, especially in heroin supply. Fentanyl and its analogs have been responsible for the dramatic increase in opioid overdose death over the past 5 years.
Two recent cross-sectional studies screened ED patients with opioid use disorder for fentanyl exposure.
Study 1:
Study 2:
Bottom line:
Many chemicals and substances - both legal and illegal - can be purchased from an online retailer. A recent study searched Amazon.com to see if any of the "extremely hazardaous substances" identified by Environmental Protection Agency (EPA) were available for purchase.
Amazon.com was searched over 10-month period.
Result:
Bottom line:
Toxic substances are readily available from many online retailers that can potentially cause serious toxicity. Online retailers should consult with experts and governmental agencies to limit the availability of such products.
Guanfacine is a presynaptic alpha-2 adrenergic receptor agonist (similar to clonidine) that is FDA approved to treat ADHD in pediatric patients 6 years of age and older. A recently published study characterized the pediatric exposure to guanfacine between 2000 and 2016.
Most frequently reported clinical effect (n=10927)
Severe clinical effects (n=10927)
Duration of clinical effect
Conclusion
Single use laundry pods are readily available in many homes. Due to their bright colors, they have been mistaken for edible products (e.g. candy) by children.
A recent study reviewed 4652 laundry pod exposures from United Kingdom.
95.4% involved children aged < 5 years via oral route (89.7%).
Common symptoms in moderate/severe symptom groups, including fatality (n=127)
Conclusion
Intravenous lipid emulsion (ILE) is use as a therapy of last resort in refractory cardiovascular shock from toxicity of select agents (e.g. calcium channel blockers, beta blockers and select Na-channel blocking agents). There are number of case reports/series that showed positive cardiovascular/hemodynamic response after ILE, which are prone to publication bias. Results from limited number of human trials have shown mixed results.
A study reviewed fatal cases of poisoning that received ILE from the National Poison Data System to characterize the clinical response of ILE therapy.
Results
N=459 cases from 2010 to 2015.
Most common substance involved
|
| N (%) | Number with ROSC (%) |
| Ca-channel blockers | 183 (40) | 8 (4.4) |
| Beta blockers | 102 (22) | 5 (4.9) |
| Bupropion* | 53 (12) | 5 (9.4) |
| TCAs* | 48 (10) | 2 (4.2) |
| Citalopram/escitalopram | 36 (8) | 0 |
| Quetiapine | 26 (6) | 1 (3.8) |
| Flecainide | 21 (5) | 5 (23.8) |
| Local anesthetics – parenteral* | 8 (2) | 1 (12.5) |
*Use of ILE supported by Lipid work group
Response rate
Possible adverse reactions (n)
Conclusion
Kratom (Mitragyna speciosa) has been used for centuries in Southeast Asia to manage pain and opium withdrawal. It is increasingly being used in the U.S. for similar purpose. The U.S. DEA lists Kratom as a “drug of concern”.
Effects of Kratom leaves
A study reviewed National Poison Data System (2011 to 2017) to evaluate the clinical effects/outcomes of Kratom exposure.
Finding: (N=1807; single-substance: 1174; multiple-substance: 633])
Common symptoms
Disposition
Bottom line:
Physostigmine is a cholinergic agent that can be administered to reverse delirium associated with anticholinergic toxicity. However, it is infrequenly used since the reports of cardiac arrest in patients with TCA overdose.
A recently published study reviewed 161 articles – involving 2299 patients – to determine the adverse effects and their frequency after the administration of physostigmine.
Findings
Adverse effects were observed in 415 patients (18.1%)
Specific adverse effects
Of 394 TCA overdose, adverse effects occurred in 14 patients (3.6%)
Conclusion
Therapeutic use or overdose of tramadol has been associated with seizure. However, it is unknown if there are any specific predisposing factor that increases a patient’s risk of seizure after tramadol use/overdose.
In a recently published study, eighty patient data with single ingestion of tramadol were reviewed.
Risk of seizure
Conclusion
In this small study, Asian patients and patients with abuse/misuse were at higher risk of developing seizure compared to patients who overdose tramadol.
Take home naloxone (THN) programs have been expanded to help reduce the opioid overdose-related deaths. A study was done in Australia to characterize a cohort of heroin overdose deaths to examine if there was an opportunity for a bystander to intervene at the time of fatal overdose.
235 heroin-overdose deaths were investigated during a 2 year study period in Victoria, Australia.
Conclusion
Taking a double-dose of a single medication is presumed to be safe in most cases. However, there is limited data to support this assumption.
A retrospective study of the California Poison Control System was performed to assess adverse effects of taking double dose of a single medication. During a 10-year period, 876 cases of double-dose ingestion of single medication were identified.
Adverse effects were rare (12 cases). However, medication classes that were involved in severe adverse effects included:
Conclusion:
Selective serotonin reuptake inhibitors are the most common anti-depressant used today. However, the use bupropion in adolescents is increasing due the belief that it has fewer side effects than TCAs.
Using the National Poison Data System (2013 – 2016), the adverse effects of bupropion were compared to TCA in adolescents (13 – 19 years old) with a history of overdose (self harm).
Common clinical effects were:
TCA: n=1496; Bupropion: n=2257
| Clinical effects | TCAs | Bupropion |
| Tachycardia | 59.9% | 70.7% |
| Drowsiness/lethargy | 51.5% | 18.1% |
| Conduction disturbance | 22.2% | 15.6% |
| Agitation | 19.1% | 16.4% |
| Hallucination/delusions | 4.2% | 23.9% |
| Seizure | 3.9% | 30.7% |
| Vomiting | 2.7% | 20.0% |
| Tremor | 3.7% | 18.1% |
| Hypotension | 2.7% | 8.0% |
| Death | 0.3% | 0.3% |
Conclusion:
Bupropion overdose results in significant adverse effects in overdose; however, death is relatively rare.
Alcohol withdrawal syndrome is frequently treated with benzodiazepines following CIWA-Ar (Clinical Institute Withdrawal Assessment of Alcohol scale). There are other medications that are used as either second line or as adjunctive agents along with benzodiazepines. A retrospective study compared the clinical outcomes between phenobarbital vs. benzodiazepines-based CIWA-Ar protocol to treat AWS.
The primary was ICU length of stay (LOS); secondary outcome were hospital LOS, intubation, and use of adjunctive pharmacotherapy.
Study sample: 60 received phenobarbital and 60 received lorazepam per CIWA-Ar.
Phenobarbital protocol:
Results
|
| Phenobarbital | CIWA-Ar |
| ICU LOS | 2.4 days | 4.4 days |
| Hospital LOS | 4.3 days | 6.9 days |
| Intubation | 1 (2%) | 14 (23%) |
| Adjunctive agent use | 4 (7%) | 17 (27%) |
Conclusion
Phenobarbital therapy appears to be a promising alternative therapy for AWS. However, additional studies are needed prior to adapting phenobarbital as first line agent for AWS management.
The management of pediatric hydrocarbon ingestion has not changed significantly over the past several decades. One of the earlier study that helped established the management approach is by Anas N et al. published in JAMA, 1981.
It was a retrospective study of 950 children who ingested household hydrocarbon containing products.
Discharged patients: n=800
Admitted patients: n=150
This study recommended that hospitalization is required in patients…
Analphylatoid reaction is caused by non-IgE mediated histamine released. Intravenous N-acetylcysteine (NAC) infusion is well known to cause analphylatoid reaction. However, it’s incidence is unknown.
Recently, a large retrospective study of all patients who received 21-hour IV NAC in 34 Canadian hospitals (1980 to 2005) was performed.
Anaphylactoid reaction was documented in 528 (8.2%) of 6455 treatment courses
Over 90% patients developed analphylatoid reaction within 5 hours.
Onset of reaction:
Administered medication for treatment
Patient characteristics that were associated with higher incidence of Anaphylactoid reaction includes
Bottom line
Various intial doses of naloxone (0.4 to 2 mg) are administered to reverse the signs and symptoms of opioid toxicity. However, there is limited data regarding the duration of action of naloxone is correlated to the administered dose.
A recently published retrospective study investigated whether initial naloxone doses (IV), low-dose (0.4 mg) vs. high-dose (1-2 mg), lead to different time to recurrence of opioid toxicity.
Study sample: 274 patient screened but 84 patients were included.
Higher rate of adverse effects (withdrawal symptoms - vomiting, agitation, tachycardia, etc.) were observed in high-dose group (41% vs. 31%) but this was not statistically signficant.
Conclusion:
Elevated transaminases are found in both rhabdomyolysis and delayed acetaminophen (APAP) toxicity. Establishing the cause of elevated transaminase can be difficult when there is unclear history of acetaminophen ingestion.
A retrospective study of patients with delayed acetaminophen toxicity or rhabdomyolysis from 2006 to 2011 was recently published.
The authors compared AST/ALT, CK/AST and CK/ALT ratio of
Results
AST/ALT ratio
CK/AST ratio
CK/ALT ratio
Conclusion
From 1960s to 1970s, physostigmine was routinely administered as part of the "coma cocktail." Since the publication of two cases by Pentel (1980) that resulted in asystole after administration of physostigmine in TCA poisoned patient, its use has declined significantly.
However, physostigmine still possess limited but clinically useful role in the management of patients with antimuscarinic/anticholinergic induced delirium.
Recently, a prospective observational study was performed in the use of physostigmine when recommended by a regional poison center.
In 1 year study period, physostigmine was recommended by a regional poison center in 125 of 154 patients with suspected antimuscarinic/anticholinergic toxicity.
common exposures were
57 of 125 patients received physostigmine per treating team.
Of the remaining patients,
Delirium control
Adverse events (physostigmine group vs. non-physo group) - no statistically significant difference.
Conclusion:
Physostigmine can safely control antimuscarinic/anticholinergic-induced delirium.
Acutely agitated patients in the emegency room receive single or combination of benzodiazepine (lorazepam vs. midazolam) and antipsychotic (e.g. haloperidol) agents. Recently, use of ketamine has also been advocated to sedate agitated patients.
A recently published article compared IM administration several medications to treat acutely agitated patients in the ED. According to established protocol, each medication was administered in predetermined 3 week blocks:
Results
N=737 with median age of 40 years, 72% men.
Midazolam resulted in greater proportion of patients with "adequate" sedation (altered mentatl status scale <1) compared to antipsychotics at 15 min post administration. Among antipsychotics, olanzapine resulted in greater proportion of patient with sedation.
Adverse effect were limited
Conclusion:
Midazolam 5 mg IM achieve more effective sedation at 15 min in agitated ED patients than antipsychotics.
On May 3, the FDA approved adexanet alfa, the reversal agent for factor Xa inhibitors - apixaban and rivaroxaban. It received both U.S. Orphan Drug and FDA Breakthrough Therapy designations.
Unlike indarucizumab (a monoclonal antibody fragment) to reverse dabigatran (direct thrombin inhibitor) associated bleeding, adexanet alfa is a recombinant modified human factor Xa decoy protein.
A phase 3 study showed that adexanet alfa decreased the anti-factor Xa activity of rivaroxaban by 92% from baseline and by 94% in apixaban treated participants.
ANNEXA-4 study involving participants with acute major bleeding (GI and intracranial) showed a significant decrease in the anti-factor Xa activity after the bolus dose of adexanet alfa and "effective" hemostasis was noted in 79% of the participants at 12 hours post infusion.
Andexanet alfa is expected to become available in June 2018.